WILBERT

Wildauer Bücher+E-Medien Recherche-Tool

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Daniel O’Keefe, Anna Wilkinson, Campbell Aitken, Paul Dietze Distance to health services is known to be negatively associated with usage and needle and syringe programs (NSPs) for people who inject drugs (PWID) are no different. Australia has a mixture of NSP modalities (primary or secondary fixed-site NSPs), which may present unique barriers to access. In this study, we explore 1) the effect of distance to NSPs on individual-level needle and syringe coverage, and 2) differences in coverage dependent on NSP modality. Using data from 219 PWID in an ongoing cohort study in Melbourne, Australia, we measured the straight-line distance from participants’ residence to their nearest primary or secondary fixed-site NSP. We analysed the relationship between geographical distance and coverage via regression analysis. The median distance to any type of NSP was 1872 metres. Regardless of service type, 52% of participants lived within 2 kms of a fixed-site NSP and 87% lived within 5 kms. We found no association between distance to NSPs and syringe coverage or a significant difference in coverage by nearest service type. Our findings suggest that the number and distribution of NSPs in Melbourne, Australia caters adequately for the population of PWID.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Xupo Ding, Wenli Mei, Shengzhuo Huang, Hui Wang, Jiahong Zhu, Wei Hu, Zehong Ding, Weiwei Tie, Shiqing Peng, Haofu Dai Dragon’s blood collected from the genus Dracaena is used as a renowned traditional medicine in various cultures worldwide. However, the genetics of the genus Dracaena and the formation mechanism of dragon’s blood remain poorly understood. Here, we generate the first draft genome reference assembly of an elite Chinese Dracaena species, Dracaena cambodiana , from next-generation sequencing data with 89.46× coverage. The reads were assembled into 2,640,704 contigs with an N50 length of 1.87 kb, and a 1.05 Gb assembly was finally assembled with 2,379,659 scaffolds. Furthermore, 97.75% of the 267,243 simple sequence repeats identified from these scaffolds were mononucleotide, dinucleotide, and trinucleotide repeats. Among all 53,700 predicted genes, 158 genes involved in cell wall and plant hormone synthesis and reactive oxygen species scavenging showed altered regulation during the formation of dragon’s blood. This study provides a genomic characterization of D . cambodiana and improves understanding of the molecular mechanism of dragon’s blood formation. This report represents the first genome-wide characterization of a Dracaena species in the Asparagaceae.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Elisa Castaldi, Anne Mirassou, Stanislas Dehaene, Manuela Piazza, Evelyn Eger Dyscalculia, a specific learning disability that impacts arithmetical skills, has previously been associated to a deficit in the precision of the system that estimates the approximate number of objects in visual scenes (the so called ‘number sense’ system). However, because in tasks involving numerosity comparisons dyscalculics’ judgements appears disproportionally affected by continuous quantitative dimensions (such as the size of the items), an alternative view linked dyscalculia to a domain-general difficulty in inhibiting task-irrelevant responses. To arbitrate between these views, we evaluated the degree of reciprocal interference between numerical and non-numerical quantitative dimensions in adult dyscalculics and matched controls. We used a novel stimulus set orthogonally varying in mean item size and numerosity, putting particular attention into matching both features’ perceptual discriminability. Participants compared those stimuli based on each of the two dimensions. While control subjects showed no significant size interference when judging numerosity, dyscalculics’ numerosity judgments were strongly biased by the unattended size dimension. Importantly however, both groups showed the same degree of interference from the unattended dimension when judging mean size. Moreover, only the ability to discard the irrelevant size information when comparing numerosity (but not the reverse) significantly predicted calculation ability across subjects. Overall, our results show that numerosity discrimination is less prone to interference than discrimination of another quantitative feature (mean item size) when the perceptual discriminability of these features is matched, as here in control subjects. By quantifying, for the first time, dyscalculic subjects’ degree of interference on another orthogonal dimension of the same stimuli, we are able to exclude a domain-general inhibition deficit as explanation for their poor / biased numerical judgement. We suggest that enhanced reliance on non-numerical cues during numerosity discrimination can represent a strategy to cope with a less precise number sense.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Anders P. E. Backman, Josefin Halin, Henrik Nurmi, Anna Möuts, Matti A. Kjellberg, Peter Mattjus The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER). We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions. We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide. We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts. Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability. It has long been postulated that GLTP would be a sensor in the sphingolipid synthesis machinery, but how this mechanistically occurs has not been addressed before. It is unclear what proteins the GLTP VAP association would influence. Here we found that if GLTP has a bound GlcCer the association with VAP-A is weaker. We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Karin Törnbom, Anna Danielsson Objectives It is well known that physical activity levels for persons after stroke or acquired brain injuries do not reach existing recommendations. Walking training is highly important since the ability to walk is considered to be a meaningful occupation for most people, and is often reduced after a brain injury. This suggests a need to innovate stroke rehabilitation, so that forms of walking training that are user-friendly and enjoyable can be provided. Method An interview study was carried out with persons after stroke (n = 8), or acquired brain injury (n = 2) at a rehabilitation unit at Sahlgrenska University Hospital. We used a semi-structured interview guide to investigate experiences and thoughts about walking on a treadmill with non-immersive virtual reality feedback. The contents were analyzed through an inductive approach, using qualitative content analysis. Results The virtual reality experience was perceived as enjoyable, exciting, and challenging. Participants stressed that the visual and auditory feedback increased their motivation to walk on a treadmill. However, for some participants, the virtual reality experience was too challenging, and extreme tiredness or fatigue were reported after the walking session. Conclusions Participants’ thoughts and experiences indicated that the Virtual Reality walking system could serve as a complement to more traditional forms of walking training. Early after a brain injury, virtual reality could be a way to train the ability to handle individually adapted multisensory input while walking. Obvious benefits were that participants perceived it as engaging and exciting.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Charlotte Vanden Hole, Silke Cleuren, Chris Van Ginneken, Sara Prims, Miriam Ayuso, Steven Van Cruchten, Peter Aerts Intrauterine crowding (IUC) considerably influences postnatal traits in a polytocous species such as the pig. Previously, our group described how IUC affects locomotion during the piglet’s first days of life (until 96 h after birth). We noted a reduced motor performance in piglets with a low birth weight and low vitality (L piglets), compared to piglets with a normal birth weight and normal vitality (N piglets), indicating L piglets are unable to produce enough force. Our current study investigates whether this observed force deficit in L piglets is caused by a reduced force generating capacity in the muscles and/or a lower percentage of type II (fast-contracting) fibers. Volume and fiber length of the main extensor muscles of the hind limb were used to estimate the physiological cross-sectional area (PSCA) and hence calculate the maximal isometric force generating capacity (F iso-max ) of the hind limb. To check for developmental differences between the muscles of L and N piglets, F iso-max was normalized to body weight (BW), thus yielding a dimensionless variable F’ iso-max . To check for differences in muscle composition, m. vastus lateralis was stained immunohistochemically in order to determine the percentage of type II fibers through image analysis. Our results indicate that L piglets have a reduced absolute force generating capacity due to a lesser muscle mass, compared to N piglets. However, when normalized to BW L piglets actually show a larger force generating capacity, suggesting their muscles are more voluminous, given their body mass, than those of N piglets. However, no differences between L and N piglets were detected with regard to muscle composition of the m. vastus lateralis. Based on our data, we can say that neither normalized force generating capacity, nor muscle composition (of the m. vastus lateralis) can explain the observed force deficit in L piglets and as such the effect of IUC on locomotor performance.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Suroso Rahutomo, John L. Kovar, Michael L. Thompson Sediments in streams that drain agricultural watersheds may be sinks that can adsorb P from the stream or sources that can release P to the stream. Sediment characteristics and environmental factors, including the oxidation-reduction (redox) potential of the water associated with the sediment, determine whether P will be adsorbed or released by the sediment. We investigated P adsorption and release by four sediments [three Holocene-age sediments (Camp Creek, Roberts Creek and Gunder) as well as Pre-Illinoian-age Till] that occur in Walnut Creek, a second-order stream in Jasper County, Iowa, that is representative of many small streams in the glaciated upper Midwest of the US. The effects of two redox potentials on phosphorus buffering capacity (PBC) and equilibrium phosphorus concentration (EPC) were evaluated in batch adsorption experiments. We also simulated aerobic and anerobic conditions over a 24-day period and measured solution-phase P concentrations in stirred systems where the sediments were isolated from the water by dialysis tubing. The batch experiment indicated that the EPCs of the three Holocene-age sediments were similar to one another and increased with decreasing redox potential. In the stirred flow reactors, more dissolved P was released from the Camp Creek and Roberts Creek sediments under anaerobic conditions than from the other sediments. This observation suggests that these two sediments, which are younger and higher in the stratigraphic sequence, are more likely to be P sources in suboxic settings. The P buffering capacity was greatest in the till. Where it is in contact with the stream water, the till is likely to serve as an adsorbing sink for P in the water column.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Deok Gie Kim, Hoon Young Choi, Ha Yan Kim, Eun Ju Lee, Kyu Ha Huh, Myoung Soo Kim, Chung Mo Nam, Beom Seok Kim, Yu Seun Kim Background Serum uric acid (UA) level has been reported to be associated with chronic allograft nephropathy and graft failure in patients who undergo kidney transplantation (KT). However, the role of serum UA level in renal graft survival remains controversial. Objective This study aimed to investigate the effect of mean serum UA level during two different post-KT periods on long-term renal graft outcomes in a large population cohort in which living donor KT prevails. Material and methods A retrospective cohort study was performed using KT data prospectively collected at a single institution. Patients (n = 2,993) were divided into low-, normal-, and high-UA groups according to the mean serum UA level within the first year (1-YR) and 1–5 years (5-YR) after transplantation. Results In the 1-YR Cox proportional hazards analysis, the low- and high-UA groups had a significantly decreased and increased risk, respectively, for overall graft failure (OGF), death-censored graft failure (DCGF), and composite event (return to dialysis, retransplantation, death from graft dysfunction, and 40% decline in estimated glomerular filtration rate) compared with the normal-UA group. Similarly, in the 5-YR analysis, the low-UA group had a significantly reduced risk of DCGF compared with the normal-UA group, whereas the high-UA group had a significantly increased risk of all three graft outcomes. In a marginal structural model, hyperuricemia had a significant causal effect on worsening graft outcomes, with consideration of all confounding variables (OGF: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.33–3.78; DCGF: HR 2.38, 95% CI 1.09–4.9; composite event: HR 3.05, 95% CI 1.64–5.49). Conclusions A low-to-normal serum UA level within the first year and 1–5 years after KT is an independent factor for better renal allograft outcomes in the long-term follow-up period rather than high serum UA level.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Johan J. Bolhuis, Gabriel J. L. Beckers, Marinus A. C. Huybregts, Robert C. Berwick, Martin B. H. Everaert In this Formal Comment the authors respond to objections to their previous Essay, reiterating that comparative linguistics is not an easy undertaking.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Britt Koskella Host populations are under continual selection by parasites due to reduced fitness of infected individuals relative to uninfected individuals. This should select for host resistance against parasites, and ample evidence from the laboratory and natural populations demonstrates that hosts can respond rapidly to parasitism by evolving resistance. Why then do parasites still exist? In part, this is due to ongoing arms races as parasites evolve counteradaptations to overcome resistance and to the presence of spatial structure and refuges. However, host–parasite coexistence can also be explained through loss of resistance over time due either to selection against costly resistance mechanisms or constant loss of resistance via reversion mutations.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 11
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Tomotsune Ameku, Yuto Yoshinari, Michael J. Texada, Shu Kondo, Kotaro Amezawa, Goro Yoshizaki, Yuko Shimada-Niwa, Ryusuke Niwa Stem cell maintenance is established by neighboring niche cells that promote stem cell self-renewal. However, it is poorly understood how stem cell activity is regulated by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Here, we show that neuropeptide F (NPF) signaling plays an important role in the pathway regulating mating-induced germline stem cell (GSC) proliferation in the fruit fly Drosophila melanogaster . NPF expressed in enteroendocrine cells (EECs) of the midgut is released in response to the seminal-fluid protein sex peptide (SP) upon mating. This midgut-derived NPF controls mating-induced GSC proliferation via ovarian NPF receptor (NPFR) activity, which modulates bone morphogenetic protein (BMP) signaling levels in GSCs. Our study provides a molecular mechanism that describes how a gut-derived systemic factor couples stem cell behavior to physiological status, such as mating, through interorgan communication.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 12
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Hélène Chabas, Sébastien Lion, Antoine Nicot, Sean Meaden, Stineke van Houte, Sylvain Moineau, Lindi M. Wahl, Edze R. Westra, Sylvain Gandon The emergence and re-emergence of pathogens remains a major public health concern. Unfortunately, when and where pathogens will (re-)emerge is notoriously difficult to predict, as the erratic nature of those events is reinforced by the stochastic nature of pathogen evolution during the early phase of an epidemic. For instance, mutations allowing pathogens to escape host resistance may boost pathogen spread and promote emergence. Yet, the ecological factors that govern such evolutionary emergence remain elusive because of the lack of ecological realism of current theoretical frameworks and the difficulty of experimentally testing their predictions. Here, we develop a theoretical model to explore the effects of the heterogeneity of the host population on the probability of pathogen emergence, with or without pathogen evolution. We show that evolutionary emergence and the spread of escape mutations in the pathogen population is more likely to occur when the host population contains an intermediate proportion of resistant hosts. We also show that the probability of pathogen emergence rapidly declines with the diversity of resistance in the host population. Experimental tests using lytic bacteriophages infecting their bacterial hosts containing Clustered Regularly Interspaced Short Palindromic Repeat and CRISPR-associated (CRISPR-Cas) immune defenses confirm these theoretical predictions. These results suggest effective strategies for cross-species spillover and for the management of emerging infectious diseases.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 13
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Anne Cori, Pierre Nouvellet, Tini Garske, Hervé Bourhy, Emmanuel Nakouné, Thibaut Jombart Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 14
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Gary Wilk, Rosemary Braun Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain unclear. It has been hypothesized that SNPs in microRNA binding sites may disrupt gene regulation by microRNAs (miRNAs), short non-coding RNAs that bind to mRNA and downregulate the target gene. While several studies have predicted the location of SNPs in miRNA binding sites, to date there has been no comprehensive analysis of their impact on miRNA regulation. Here we investigate the functional properties of genetic variants and their effects on miRNA regulation of gene expression in cancer. Our analysis is motivated by the hypothesis that distinct alleles may cause differential binding (from miRNAs to mRNAs or from transcription factors to DNA) and change the expression of genes. We previously identified pathways—systems of genes conferring specific cell functions—that are dysregulated by miRNAs in cancer, by comparing miRNA–pathway associations between healthy and tumor tissue. We draw on these results as a starting point to assess whether SNPs on dysregulated pathways are responsible for miRNA dysregulation of individual genes in tumors. Using an integrative regression analysis that incorporates miRNA expression, mRNA expression, and SNP genotype data, we identify functional SNPs that we term “regulatory QTLs (regQTLs)”: loci whose alleles impact the regulation of genes by miRNAs. We apply the method to breast, liver, lung, and prostate cancer data from The Cancer Genome Atlas, and provide a tool to explore the findings.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 15
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Caitlin D. French, Rodney E. Willoughby, Amy Pan, Susan J. Wong, John F. Foley, L. Joseph Wheat, Josefina Fernandez, Rafael Encarnacion, Joanne M. Ondrush, Naaz Fatteh, Andres Paez, Dan David, Waleed Javaid, Ioana G. Amzuta, Anne M. Neilan, Gregory K. Robbins, Andrew M. Brunner, William T. Hu, Darya O. Mishchuk, Carolyn M. Slupsky Background Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample. Methodology/Principal findings 1 H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity. Conclusions/Significance These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 16
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Warren Tennant, Mario Recker Background The required efforts, feasibility and predicted success of an intervention strategy against an infectious disease are partially determined by its basic reproduction number, R 0 . In its simplest form R 0 can be understood as the product of the infectious period, the number of infectious contacts and the per-contact transmission probability, which in the case of vector-transmitted diseases necessarily extend to the vector stages. As vectors do not usually recover from infection, they remain infectious for life, which places high significance on the vector’s life expectancy. Current methods for estimating the R 0 for a vector-borne disease are mostly derived from compartmental modelling frameworks assuming constant vector mortality rates. We hypothesised that some of the assumptions underlying these models can lead to unrealistic high vector life expectancies with important repercussions for R 0 estimates. Methodology and principal findings Here we used a stochastic, individual-based model which allowed us to directly measure the number of secondary infections arising from one index case under different assumptions about vector mortality. Our results confirm that formulas based on age-independent mortality rates can overestimate R 0 by nearly 100% compared to our own estimate derived from first principles. We further provide a correction factor that can be used with a standard R 0 formula and adjusts for the discrepancies due to erroneous vector age distributions. Conclusion Vector mortality rates play a crucial role for the success and general epidemiology of vector-transmitted diseases. Many modelling efforts intrinsically assume these to be age-independent, which, as clearly demonstrated here, can lead to severe over-estimation of the disease’s reproduction number. Our results thus re-emphasise the importance of obtaining field-relevant and species-dependent vector mortality rates, which in turn would facilitate more realistic intervention impact predictions.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 17
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 18
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by José-Daniel Aroca-Aguilar, Ana Fernández-Navarro, Jesús Ontañón, Miguel Coca-Prados, Julio Escribano Myocilin is an extracellular glycoprotein with a poorly understood biological function and typically known because of its association with glaucoma. In this study, we analyzed the expression and biological activity of human myocilin in some non-ocular tissues. Western immunoblot showed the presence of myocilin in blood plasma as well as in liver and lymphoid tissues (thymus and lymph node). Quantitative PCR confirmed the expression of MYOC in these lymphoid organs and revealed that its mRNA is also present in T-lymphocytes and leukocytes. In addition, detection of 30 kDa C-terminal myocilin fragments in thymus and liver suggested that myocilin undergoes an in vivo proteolytic processing that might regulate its biological activity. The presence of myocilin in blood was further corroborated by peptide mass fingerprinting of the HPLC-isolated protein, and gross estimation of its concentration by Western immunoblot indicated that it is a medium-abundance serum protein with an approximate concentration of 0.85 mg/ml (15.5 μM). Finally, in vitro analyses indicated that myocilin acts as an anti-adhesive protein for human circulating leukocytes incubated with endothelial cell monolayers. Altogether, these data provide insightful information on new biological properties of myocilin and suggest its putative role as a blood matricellular protein.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 19
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Brian Lawlor, Ricardo Segurado, Sean Kennelly, Marcel G. M. Olde Rikkert, Robert Howard, Florence Pasquier, Anne Börjesson-Hanson, Magda Tsolaki, Ugo Lucca, D. William Molloy, Robert Coen, Matthias W. Riepe, János Kálmán, Rose Anne Kenny, Fiona Cregg, Sarah O'Dwyer, Cathal Walsh, Jessica Adams, Rita Banzi, Laetitia Breuilh, Leslie Daly, Suzanne Hendrix, Paul Aisen, Siobhan Gaynor, Ali Sheikhi, Diana G. Taekema, Frans R. Verhey, Raffaello Nemni, Flavio Nobili, Massimo Franceschi, Giovanni Frisoni, Orazio Zanetti, Anastasia Konsta, Orologas Anastasios, Styliani Nenopoulou, Fani Tsolaki-Tagaraki, Magdolna Pakaski, Olivier Dereeper, Vincent de la Sayette, Olivier Sénéchal, Isabelle Lavenu, Agnès Devendeville, Gauthier Calais, Fiona Crawford, Michael Mullan, for the NILVAD Study Group Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. Methods and findings NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged 〉50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 20
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-25
    Description: by Garazi Labayru, Irati Arenzana, Jone Aliri, Miren Zulaica, Adolfo López de Munain, Andone Sistiaga A. Aims The cognitive profile of Myotonic Dystrophy type 1 (DM1) has been described in recent decades. Moreover, DM1 patients show lowered social engagement and difficulties in social-cognitive functions. The aim of the present study is to explore whether social cognition impairment is present in DM1 taking into account the overall cognitive condition. Method 38 patients and a control group paired in age and gender participated in the study. All the participants had an IQ within the normal range. Subjects were administered an abbreviated neuropsychological battery which comprised a facial emotion recognition test (POFA) and Faux Pas Test, as well as a self-report questionnaire on cognitive and affective empathy (TECA). Results Statistically significant differences were found only for facial emotion recognition ( U = 464.0, p = .006) with a moderate effect size (.31), with the controls obtaining a higher score than the patients. Analyzing each emotion separately, DM1 patients scored significantly lower than controls on the recognition of anger and disgust items. Emotion recognition did not correlate with genetic load, but did correlate negatively with age. No differences were found between patients and controls in any of the other variables related to Theory of Mind (ToM) and empathy. Conclusion DM1 does not manifest specific impairments in ToM since difficulties in this area predominantly rely on the cognitive demand of the tasks employed. However, a more basic process such as emotion recognition appears as a core deficit. The role of this deficit as a marker of aging related decline is discussed.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 21
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-25
    Description: by Meenakshi A. Chellaiah, Sunipa Majumdar, Hanan Aljohani Sealing ring formation is a requirement for osteoclast function. We have recently identified the role of an actin-bundling protein L-plastin in the assembly of nascent sealing zones (NSZs) at the early phase of sealing ring formation in osteoclasts. TNF-α signaling regulates this actin assembly by the phosphorylation of L-plastin on serine -5 and -7 residues at the amino-terminal end. These NSZs function as a core for integrin localization and coordinating integrin signaling required for maturation into fully functional sealing rings. Our goal is to elucidate the essential function of L-plastin phosphorylation in actin bundling, a process required for NSZs formation. The present study was undertaken to determine whether targeting serine phosphorylation of cellular L-plastin would be the appropriate approach to attenuate the formation of NSZs. Our approach is to use TAT-fused small molecular weight amino-terminal L-plastin peptides (10 amino acids) containing phospho- Ser-5 and Ser-7. We used peptides unsubstituted (P1) and substituted (P2- P4) at serine-to-alanine residues. Immunoblotting, actin staining, and dentine resorption analyses were done to determine cellular L-plastin phosphorylation, NSZ or sealing ring formation, and osteoclast function, respectively. Immunoblotting for bone formation markers, Alizarin red staining and alkaline phosphatase activity assay have been done to determine the effect of peptides on the mineralization process mediated by osteoblasts. Transduction of unsubstituted (P1) and substituted peptides at either Serine 5 or Serine 7 with Alanine (P3 and P4) demonstrated variable inhibitory effects on the phosphorylation of cellular L-plastin protein. Peptide P1 reduces the following processes substantially: 1) cellular L-plastin phosphorylation; 2) formation of nascent sealing zones and sealing rings; 3) bone resorption. Substitution of both Serine-5 and -7 with Alanine (P2) had no effects on the inhibitory activities described above. Furthermore, either the L-plastin (P1-P5) or (P6) control peptides had a little or no impact on the a) assembly/disassembly of podosomes and migration of osteoclasts; b) mineralization process mediated by osteoblasts in vitro. Small molecular weight peptidomimetics of L-plastin inhibits bone resorption by osteoclasts via attenuation of NSZ and sealing ring formation but not bone formation by osteoblasts in vitro. The L-plastin may be a valuable therapeutic target to treat and prevent diseases associated with bone loss without affecting bone formation.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 22
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-25
    Description: by Xu-Sheng Zhang, Giovanni Lo Iacono Hepatitis A is caused by hepatitis A virus and occurs worldwide. Estimating the transmissibility, which is usually characterized by the basic reproductive number R 0 , the mean number of secondary infectious cases generated by a single primary infectious case introduced into a totally susceptible population, provides crucial information for the effort required to stop infection spreading. Hepatitis A virus is usually transmitted indirectly through contaminated food and environment. An outbreak from March to June 2011 was reported to have occurred at an elementary school of 698 pupils in China and it was found that the outbreak was due to direct transmission between school children. Based on the symptom onset date and the social contact network of the children, in this study we estimate the serial interval (i.e. the gap in symptom onset between an infectee and its infector) and use different statistical methods to estimate R 0 . Combining with the positivity of IgG antibodies tests, we develop a compartmental transmission dynamics model which includes both asymptomatic and symptomatic infections to estimate the overall R 0 . Our analysis suggests a serial interval of mean = 23.9 days and standard deviation = 20.9 days. The different statistical methods suggest estimates for R 0 in the outbreak varying from 2.1 to 2.8, and the estimates from the transmission dynamics model are consistent with this range. Our estimates are in agreement with that from one study in England but are higher than that from one study in the United States. Our transmission dynamics model suggests that the proportion of symptomatic infections is about 9%, implying that there were about 344 asymptomatic infections along with the 32 observed symptomatic cases. Furthermore, it is shown that the inclusion of asymptomatic infection in the epidemic process increases the estimate of R 0 but does not do so greatly provided that the proportion of symptomatic infections is constant over the outbreak and there is no difference in transmissibility between symptomatic and asymptomatic infections.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 23
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-25
    Description: by Robert Larribau, Hélène Deham, Marc Niquille, François Pierre Sarasin Objective The implementation of cardiopulmonary resuscitation guidelines, updated every five years, appears to improve patient survival rates after Out-Of-Hospital Cardiac Arrest (OHCA). The aim of this study is: 1) to measure the level of improvement in the prognosis of OHCA patient survival rates for the years 2009 and 2010 and the following two years 2011 and 2012; and 2) correlate the improvement in prognosis with the updated 2010 Advanced Cardiovascular Life Support (ACLS) Guidelines. Method We performed a retrospective observational study based on Geneva’s OHCA register that includes data from January 1, 2009 to December 31, 2012. We compared the evolution of prognostic factors that influenced survival at hospital discharge between the periods before and after the implementation of the 2010 guidelines. We then compared the survival rates between each period. Finally, we adjusted the effects on survival in the second period to prognostic factors not linked with the care provided by Emergency Medical Services (EMS) teams, using a multivariable logistic regression model. Changes in advanced resuscitation treatment provided by EMS personnel were also examined. Results 795 OHCA were resuscitated between 1 st January, 2009 and 31 st December, 2012. The prognosis of patient survival at the time of hospital discharge rose from 10.33% in 2009–2010 to 17.01% in 2011–2012 (p = 0.007). After making adjustments for the effect of improved survival rates on the second period with factors not related to care provided by EMS teams, the odds ratio (OR) remains comparable (OR = 1.87, 95% CI [1.08–3.22]). Measured changes in treatment provided by EMS personnel were minor. Conclusions Survival rate for OHCA patients improved significantly in 2011–2012. This study suggests that it was probably the improvement in the quality of care provided during CPR and post-cardiac arrest care that have contributed to the increase in survival rates at the time of hospital discharge.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 24
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-25
    Description: by Tianhua Hu, Qingzhen Wei, Wuhong Wang, Haijiao Hu, Weihai Mao, Qinmei Zhu, Chonglai Bao Floral induction that initiates bolting and flowering is crucial for reproductive fitness in radishes. CONSTANS -like ( CO -like, COL ) genes play an important role in the circadian clock, which ensures regular development through complicated time-keeping mechanisms. However, the specific biological and functional roles of each COL transcription factor gene in the radish remain unknown. In this study, we performed a genome-wide identification of COL genes in the radish genome of three cultivars including ‘Aokubi’, ‘kazusa’ and ‘WK10039’, and we analyzed their exon-intron structure, gene phylogeny and synteny, and expression levels in different tissues. The bioinformatics analysis identified 20 COL transcription factors in the radish genome, which were divided into three subgroups (Group I to Group III). RsaCOL-09 and RsaCOL-12 might be tandem duplicated genes, whereas the others may have resulted from segmental duplication. The Ka/Ks ratio indicated that all the COL genes in radish, Arabidopsis , Brassica rapa , Brassica oleracea , Capsella rubella and rice were under purifying selection. We identified 6 orthologous and 19 co-orthologous COL gene pairs between the radish and Arabidopsis , and we constructed an interaction network among these gene pairs. The expression values for each COL gene during vegetable and flower development showed that the majority of Group I members had similar expression patterns. In general, the expression of radish COL genes in Groups I and III decreased during development, whereas the expression of radish COL genes in Group II first increased and then decreased. Substantial numbers of radish COL genes were differentially expressed after vernalization treatment. The expression levels of RsaCOL-02 and RsaCOL-04 were significantly increased during vernalization treatment, while the expression of RsaCOL-10 was significantly decreased. These outcomes provide insights for improving the genetic control of bolting and flowering in radish and other root vegetable crops, and they facilitate genetic improvements to radish yields and quality.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 25
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Laxman Ghimire, Sagar Paudel, Liliang Jin, Pankaj Baral, Shanshan Cai, Samithamby Jeyaseelan Gram-positive bacteria, including Staphylococcus aureus are endemic in the U.S., which cause life-threatening necrotizing pneumonia. Neutrophils are known to be critical for clearance of S . aureus infection from the lungs and extrapulmonary organs. Therefore, we investigated whether the NLRP6 inflammasome regulates neutrophil-dependent host immunity during pulmonary S . aureus infection. Unlike their wild-type (WT) counterparts, NLRP6 knockout (KO) mice were protected against pulmonary S . aureus infection as evidenced by their higher survival rate and lower bacterial burden in the lungs and extrapulmonary organs. In addition, NLRP6 KO mice displayed increased neutrophil recruitment following infection, and when neutrophils were depleted the protective effect was lost. Furthermore, neutrophils from the KO mice demonstrated enhanced intracellular bacterial killing and increased NADPH oxidase-dependent ROS production. Intriguingly, we found higher NK cell-mediated IFN-γ production in KO mouse lungs, and treatment with IFN-γ was found to enhance the bactericidal ability of WT and KO neutrophils. The NLRP6 KO mice also displayed decreased pyroptosis and necroptosis in the lungs following infection. Blocking of pyroptosis and necroptosis in WT mice resulted in increased survival, reduced bacterial burden in the lungs, and attenuated cytokine production. Taken together, these novel findings show that NLRP6 serves as a negative regulator of neutrophil-mediated host defense during Gram-positive bacterial infection in the lungs through regulating both neutrophil influx and function. These results also suggest that blocking NLRP6 to augment neutrophil-associated bacterial clearance should be considered as a potential therapeutic intervention strategy for treatment of S . aureus pneumonia.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 26
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Daniela Niemeyer, Kirstin Mösbauer, Eva M. Klein, Andrea Sieberg, Robert C. Mettelman, Anna M. Mielech, Ronald Dijkman, Susan C. Baker, Christian Drosten, Marcel A. Müller SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 27
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-25
    Description: by Calum Forrest, Andrew D. Hislop, Alan B. Rickinson, Jianmin Zuo Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life, continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses. Here we describe the first lytic proteome-wide analysis of CD8+ T cell responses to a gamma1-herpesvirus, Epstein-Barr virus (EBV), and the first such proteome-wide analysis of primary versus memory CD8+ T cell responses to any human herpesvirus. Primary effector preparations were generated directly from activated CD8+ T cells in the blood of infectious mononucleosis (IM) patients by in vitro mitogenic expansion. For memory preparations, EBV-specific cells in the blood of long-term virus carriers were first re-stimulated in vitro by autologous dendritic cells loaded with a lysate of lytically-infected cells, then expanded as for IM cells. Preparations from 7 donors of each type were screened against each of 70 EBV lytic cycle proteins in combination with the donor’s individual HLA class I alleles. Multiple reactivities against immediate early (IE), early (E) and late (L) lytic cycle proteins, including many hitherto unrecognised targets, were detected in both contexts. Interestingly however, the two donor cohorts showed a different balance between IE, E and L reactivities. Primary responses targeted IE and a small group of E proteins preferentially, seemingly in line with their better presentation on the infected cell surface before later-expressed viral evasins take full hold. By contrast, target choice equilibrates in virus carriage with responses to key IE and E antigens still present but with responses to a select subset of L proteins now often prominent. We infer that, for EBV at least, long-term virus carriage with its low level virus replication and lytic antigen release is associated with a re-shaping of the virus-specific response.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 28
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-26
    Description: by Esther S. Oh, Kaj Blennow, George E. Bigelow, Sharon K. Inouye, Edward R. Marcantonio, Karin J. Neufeld, Paul B. Rosenberg, Juan C. Troncoso, Nae-Yuh Wang, Henrik Zetterberg, Frederick E. Sieber, Constantine G. Lyketsos Background There is strong association of Alzheimer’s disease (AD) pathology with gait disorder and falls in older adults without dementia. The goal of the study was to examine the prevalence and severity of AD pathology in older adults without dementia who fall and sustain hip fracture. Methods Cerebrospinal fluid (CSF) was obtained from 168 hip fracture patients. CSF Aβ42/40 ratio, p-tau, and t-tau measures were dichotomized into normal vs. abnormal, and categorized according to the A/T/N classification. Results Among the hip fracture patients, 88.6% of the cognitively normal (Clinical Dementia Rating-CDR 0; n = 70) and 98.8% with mild cognitive impairment (CDR 0.5; n = 81) fell in the abnormal biomarker categories by the A/T/N classification. Conclusions A large proportion of older hip fracture patients have CSF evidence of AD pathology. Preoperative determination of AD biomarkers may play a crucial role in identifying persons without dementia who have underlying AD pathology in perioperative settings.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 29
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-26
    Description: by Steffen D. Kriechbaum, Christoph B. Wiedenroth, Till Keller, Jan Sebastian Wolter, Ruth Ajnwojner, Karina Peters, Moritz A. Haas, Fritz C. Roller, Andreas Breithecker, Andreas J. Rieth, Stefan Guth, Andreas Rolf, Dirk Bandorski, Christian W. Hamm, Eckhard Mayer, Christoph Liebetrau Aims Balloon pulmonary angioplasty (BPA) is an interventional treatment modality for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Therapy monitoring, based on non-invasive biomarkers, is a clinical challenge. This post-hoc study aimed to assess dynamics of high-sensitivity cardiac troponin T (hs-cTnT) as a marker for myocardial damage and its relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker for cardiac wall stress. Methods and results This study included 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between 3/2014 and 3/2017. Biomarker measurement was performed consecutively prior to each BPA and at 6-MFU.In total, the 51 patients underwent an average of 5 BPA procedures. The 6-month survival rate was 96.1%. The baseline (BL) meanPAP (39.5±12.1mmHg) and PVR (515.8±219.2dyn×sec×cm -5 ) decreased significantly within the 6-MFU (meanPAP: 32.6±12.6mmHg, P
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 30
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-26
    Description: by Guangming Ren, Lan Liu, Mingku Feng, Yingji He We introduce a random strategy update rule for the evolutionary public goods game on networks based on survival of the fittest. A survival cost parameter is introduced to public goods game. Players whose payoffs are below the survival cost will be deleted from the network. The same number of new nodes are randomly connected to the network and randomly designated cooperation or defection. Numerical results show that cooperation can flourish if the multiplication factor of the public goods game is greater than the network degree. We present a simple analytical method to explain this result. The fraction of cooperators reaches the maximum for a suitable survival cost. Furthermore, the initial random network has evolved into a heterogeneous network which facilitates the emergence of the cooperation. Our work could be helpful to understand how natural selection favors cooperation. It suggests a new method to investigate the impact of the survival cost on the evolution of cooperation.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 31
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-26
    Description: by Simon Poirier, Olivier Rué, Raphaëlle Peguilhan, Gwendoline Coeuret, Monique Zagorec, Marie-Christine Champomier-Vergès, Valentin Loux, Stéphane Chaillou Meat and seafood spoilage ecosystems harbor extensive bacterial genomic diversity that is mainly found within a small number of species but within a large number of strains with different spoilage metabolic potential. To decipher the intraspecies diversity of such microbiota, traditional metagenetic analysis using the 16S rRNA gene is inadequate. We therefore assessed the potential benefit of an alternative genetic marker, gyrB , which encodes the subunit B of DNA gyrase, a type II DNA topoisomerase. A comparison between 16S rDNA-based (V3-V4) amplicon sequencing and gyrB -based amplicon sequencing was carried out in five types of meat and seafood products, with five mock communities serving as quality controls. Our results revealed that bacterial richness in these mock communities and food samples was estimated with higher accuracy using gyrB than using16S rDNA. However, for Firmicutes species, 35% of putative gyrB reads were actually identified as sequences of a gyrB paralog, parE , which encodes subunit B of topoisomerase IV; we therefore constructed a reference database of published sequences of both gyrB and pare for use in all subsequent analyses. Despite this co-amplification, the deviation between relative sequencing quantification and absolute qPCR quantification was comparable to that observed for 16S rDNA for all the tested species. This confirms that gyrB can be used successfully alongside 16S rDNA to determine the species composition (richness and evenness) of food microbiota. The major benefit of gyrB sequencing is its potential for improving taxonomic assignment and for further investigating OTU richness at the subspecies level, thus allowing more accurate discrimination of samples. Indeed, 80% of the reads of the 16S rDNA dataset were represented by thirteen 16S rDNA-based OTUs that could not be assigned at the species-level. Instead, these same clades corresponded to 44 gyrB -based OTUs, which differentiated various lineages down to the subspecies level. The increased ability of gyrB -based analyses to track and trace phylogenetically different groups of strains will generate improved resolution and more reliable results for studies of the strains implicated in food processes.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 32
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Marie Hoarau, Yannick Malbert, Romain Irague, Christelle Hureau, Peter Faller, Emmanuel Gras, Isabelle André, Magali Remaud-Siméon
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 33
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 34
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Lena Morgon Banks, Hannah Kuper, Sarah Polack
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 35
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-27
    Description: by Lana Hamieh, Toni K. Choueiri, Barbara Ogórek, Damir Khabibullin, Daniel Rosebrock, Dimitri Livitz, Andre Fay, Jean-Christophe Pignon, David F. McDermott, Neeraj Agarwal, Wenhua Gao, Sabina Signoretti, David J. Kwiatkowski The mechanistic target of rapamycin (mTOR) is an established therapeutic target in renal cell carcinoma (RCC). Mechanisms of secondary resistance to rapalog therapy in RCC have not been studied previously. We identified six patients with metastatic RCC who initially responded to mTOR inhibitor therapy and then progressed, and had pre-treatment and post-treatment tumor samples available for analysis. We performed deep whole exome sequencing on the paired tumor samples and a blood sample. Sequence data was analyzed using Mutect, CapSeg, Absolute, and Phylogic to identify mutations, copy number changes, and their changes over time. We also performed in vitro functional assays on PBRM1 in RCC cell lines. Five patients had clear cell and one had chromophobe RCC. 434 somatic mutations in 416 genes were identified in the 12 tumor samples. 201 (46%) of mutations were clonal in both samples while 129 (30%) were acquired in the post-treatment samples. Tumor heterogeneity or sampling issues are likely to account for some mutations that were acquired in the post-treatment samples. Three samples had mutations in TSC1 ; one in PTEN ; and none in MTOR . PBRM1 was the only gene in which mutations were acquired in more than one post-treatment sample. We examined the effect of PBRM1 loss in multiple RCC cell lines, and could not identify any effect on rapalog sensitivity in in vitro culture assays. We conclude that mTOR pathway gene mutations did not contribute to rapalog resistance development in these six patients with advanced RCC. Furthermore, mechanisms of resistance to rapalogs in RCC remain unclear and our results suggest that PBRM1 loss may contribute to sensitivity through complex transcriptional effects.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 36
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Mustafa Mahooti, Parvaneh Vasli, Esmail Asadi Family-centered care is one the most important indicators of high-quality care. The organizational citizenship behavior and commitment can enhance the quality of healthcare. This study aimed to investigate the effect of the organizational citizenship behavior on family-centered care considering the mediating role of multiple commitment. This descriptive study was conducted on 237 nurses working in pediatric and infant units of hospitals in Tehran city, Iran. The subjects were selected using the convenience sampling method. Data collection was performed using the Organizational Citizenship Behavior Scale, Perceived Family-Centered Care Staff Questionnaire, Affective Commitment Scale, and Commitment to the Supervisor Scale. The SPSS v.22 and SEM-PLS v.2 software were used for data analysis. Results were extracted in the form of a standard model and fitted for indices pertaining to the measurement and structural models. Accordingly, the organizational citizenship behavior had a direct effect on family-centered care (β = 0.19, t = 2.39). Moreover, multiple commitment including commitment to the leader and commitment to the organization had indirect weak and moderate effects on the relationship between the organizational citizenship behavior and family-centered care, respectively. An inverse association was reported between commitment to the leader and family-centered care. Furthermore, the organizational citizenship behavior predicted family-centered care by 70% considering the mediating role of multiple commitment. Therefore, family-centered care as an indicator of high-quality care can be improved through enhancing the organizational citizenship behavior and organizational commitment among Iranian nurses working in pediatric wards.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 37
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Masafumi Hayashi, Kenji Keyamura, Takashi Hishida The DNA damage tolerance (DDT) pathway facilitates the bypass of the fork-blocking lesions without removing them through either translesion DNA synthesis or error-free damage bypass mechanism. The Saccharomyces cerevisiae Rad5 is a multi-functional protein involved in the error-free branch of the DDT pathway, and its protein level periodically fluctuates through the cell cycle; however, the mechanistic basis and functional importance of the Rad5 level for the cell cycle regulation remain unclear. Here, we show that Rad5 is predominantly phosphorylated on serine 130 (S130) during S/G2 phase and that this modification depends on the cyclin-dependent kinase Cdc28/CDK1. We also show that the phosphorylated Rad5 species at S130 exhibit a relatively short half-life compared with non-phosphorylated Rad5 moiety, and that the Rad5 protein is partially stabilized in phosphorylation-defective rad5 S130A cells. Importantly, the elimination of this modification results in a defective cell-cycle dependent Rad5 oscillation pattern. Together, our results demonstrate that CDK1 modulates Rad5 stability by phosphorylation during the cell cycle, suggesting a crosstalk between the phosphorylation and degradation of Rad5.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 38
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Javier Carrillo-Campos, Héctor Riveros-Rosas, Rogelio Rodríguez-Sotres, Rosario A. Muñoz-Clares Few land plants can synthesize and accumulate the osmoprotectant glycine betaine (GB) even though this metabolic trait has major adaptive importance given the prevalence of drought, hypersaline soils or cold. GB is synthesized from choline in two reactions catalyzed by choline monooxygenases (CMOs) and enzymes of the family 10 of aldehyde dehydrogenases (ALDH10s) that gained betaine aldehyde dehydrogenase activity (BADH). Homolog genes encoding CMO and ALDH10 enzymes are present in all known land plant genomes, but since GB-non-accumulators plants lack the BADH-type ALDH10 isozyme, they would be expected to also lack the CMO activity to avoid accumulation of the toxic betaine aldehyde. To explore CMOs substrate specificity, we performed amino acid sequence alignments, phylogenetic analysis, homology modeling and docking simulations. We found that plant CMOs form a monophyletic subfamily within the Rieske/mononuclear non-heme oxygenases family with two clades: CMO1 and CMO2, the latter diverging from CMO1 after gene duplication. CMO1 enzymes are present in all plants; CMO2s only in the Amaranthaceae high-GB-accumulators plants. CMO2s, and particularly their mononuclear non-heme iron domain where the active site is located, evolved at a faster rate than CMO1s, which suggests positive selection. The homology model and docking simulations of the spinach CMO2 enzyme showed at the active site three aromatic residues forming a box with which the trimethylammonium group of choline could interact through cation-π interactions, and a glutamate, which also may interact with the trimethylammonium group through a charge-charge interaction. The aromatic box and the carboxylate have been shown to be critical for choline binding in other proteins. Interestingly, these residues are conserved in CMO2 proteins but not in CMO1 proteins, where two of these aromatic residues are leucine and the glutamate is asparagine. These findings reinforce our proposal that the CMO1s physiological substrate is not choline but a still unknown metabolite.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 39
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Zhiming Jia, Hailin Guo, Hua Xie, Xingqi Bao, Yichen Huang, Ganggang Yang, Fang Chen Cell sheet engineering has recently emerged as a promising strategy for scaffold-free tissue engineering. However, the primary method of harvesting cell sheets using temperature-responsive dishes has potential limitations. Here we report a novel cell sheet technology based on a coculture system in which SMCs are cocultured with EPCs on common polystyrene dishes. We found that an intact and highly viable cell sheet could be harvested using mechanical methods when SMCs and EPCs were cocultured on common polystyrene dishes at a ratio of 6:1 for 5 to 6 days; the method is simple, cost-effective and highly repeatable. Moreover, the cocultured cell sheet contained capillary-like networks and could secrete a variety of angiogenic factors. Finally, in vivo studies proved that the cocultured cell sheets were more favorable for the fabrication of vascularized smooth muscle tissues compared to single SMC sheets. This study provides a promising avenue for smooth muscle tissue engineering.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 40
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-09-27
    Description: by Olof Stephansson, Kari Johansson, Jonas Söderling, Ingmar Näslund, Martin Neovius Background Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics. Methods and findings We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year ( N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III–IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m 2 , the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m 2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60–0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31–0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53–0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59–0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30–0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25–0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44–0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching. Conclusions Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births.
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 41
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Tatiane Cargnin Faccin, Juliana Felipetto Cargnelutti, Fernando de Souza Rodrigues, Fernanda Rezer de Menezes, José Vitor Marcon Piazer, Stella Maris Pereira de Melo, Betina Fabis Lautert, Eduardo Furtado Flores, Glaucia Denise Kommers Upper digestive tract (UDT) cancer is rare in cattle, however in Southern Brazil, the UDT squamous cell carcinomas (SCCs) are relatively common and have been associated with bracken fern consumption and the presence of papillomas. Although a theory of pathogenesis considers bovine papillomavirus type 4 (BPV-4) as a cofactor in the development of these SCCs, some aspects of the etiopathogenesis of this disease need to be more investigated. In fact, detection of BPV-4 in UDT papillomas is scarce in other regions of the world and has not been performed in Brazil. Therefore, this study had two aims: 1) to analyze the epidemiological, clinical and pathological aspects of 100 natural cases of SCCs in the UDT of cattle grazing on bracken fern ( Pteridium arachnoideum ) highly contaminated areas, investigating the associations between these parameters; and 2) to investigate the presence of papillomavirus DNA by polymerase chain reaction (PCR) in the UDT papillomas (n = 47) from 30 cattle that also had UDT SCCs. There were statistically significant associations between clinical signs and tumor localization in the UDT; between histological grade of differentiation and tumor localization; and a trend towards significant association between histological grade of differentiation and presence of metastases. The average age of cattle with oropharyngeal SCCs was 7.39 years, with statistically significant difference comparing to cattle with esophageal SCCs (8.6 years). No statistical association was observed among other clinical-pathological parameters (growth pattern and primary site of the tumor) analyzed. No BPV DNA was detected in papillomas by PCR. Therefore, these results suggest the possibility that papillomas of the UDT are not necessarily associated with BPV infection.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 42
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Yasemin Cag, Oguz Karabay, Oguz Resat Sipahi, Firdevs Aksoy, Gul Durmus, Ayse Batirel, Oznur Ak, Zeliha Kocak-Tufan, Aynur Atilla, Nihal Piskin, Turkay Akbas, Serpil Erol, Derya Ozturk-Engin, Hulya Caskurlu, Ugur Onal, Haluk Erdogan, Aslıhan Demirel, Arzu Dogru, Rezan Harman, Aziz Ahmad Hamidi, Derya Karasu, Fatime Korkmaz, Pınar Korkmaz, Fatma Civelek Eser, Yalcin Onem, Sinem Cesur, Musa Salmanoglu, İlknur Erdem, Hüsrev Diktas, Haluk Vahaboglu Sepsis is a severe clinical syndrome owing to its high mortality. Quick Sequential Organ Failure Assessment (qSOFA) score has been proposed for the prediction of fatal outcomes in sepsis syndrome in emergency departments. Due to the low predictive performance of the qSOFA score, we propose a modification to the score by adding age. We conducted a multicenter, retrospective cohort study among regional referral centers from various regions of the country. Participants recruited data of patients admitted to emergency departments and obtained a diagnosis of sepsis syndrome. Crude in-hospital mortality was the primary endpoint. A generalized mixed-effects model with random intercepts produced estimates for adverse outcomes. Model-based recursive partitioning demonstrated the effects and thresholds of significant covariates. Scores were internally validated. The H measure compared performances of scores. A total of 580 patients from 22 centers were included for further analysis. Stages of sepsis, age, time to antibiotics, and administration of carbapenem for empirical treatment were entered the final model. Among these, severe sepsis (OR, 4.40; CIs, 2.35–8.21), septic shock (OR, 8.78; CIs, 4.37–17.66), age (OR, 1.03; CIs, 1.02–1.05) and time to antibiotics (OR, 1.05; CIs, 1.01–1.10) were significantly associated with fatal outcomes. A decision tree demonstrated the thresholds for age. We modified the quick Sequential Organ Failure Assessment (mod-qSOFA) score by adding age (〉 50 years old = one point) and compared this to the conventional score. H -measures for qSOFA and mod-qSOFA were found to be 0.11 and 0.14, respectively, whereas AUCs of both scores were 0.64. We propose the use of the modified qSOFA score for early risk assessment among sepsis patients for improved triage and management of this fatal syndrome.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 43
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by J. C. Noble, Diane Meredith, Robert P. Lane We previously characterized a clonal olfactory placode-derived cell line (OP6) as a model system for studying odorant receptor (OR) choice, where individual OP6 cells, similar to olfactory sensory neurons in vivo , transcribe one allele (“monoallelic”) of one OR gene (“monogenic”). The OP6 cell line provides a unique opportunity to investigate intrinsic properties of OR regulation that cannot easily be investigated in vivo . First, whereas OR-expressing cells in vivo are post-mitotic, OP6 cells are immortalized, raising interesting questions about the stability of epigenetic states associated with OR selection/silencing as OP6 cells progress through the cell cycle. Second, OP6 cells have been isolated away from extrinsic developmental cues, and therefore, any long-term OR selection biases are likely to arise from intrinsic epigenetic states that persist in the absence of developmental context. In this study, we investigated OR re-selection frequency and selection biases within clonal OP6 cell populations. We found no evidence of OR stability through the cell cycle: our results were most consistent with OR re-selection events transpiring at least once per cell division, suggesting that chromatin states associated with OR selection in this system might not be maintained in the subsequent generation. In contrast, we found strong evidence for OR selection biases maintained over prolonged culturing across a diverse set of OP6 cell lineages, suggesting the persistence of intrinsic epigenetic states that advantage some OR loci over others. Together, our data suggest that in the absence of instructive cues, intrinsic epigenetic states influencing OR eligibility, but not those determining OR choice, might persist through the cell cycle.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 44
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Tania Pozzo, Shawn M. Higdon, Sivakumar Pattathil, Michael G. Hahn, Alan B. Bennett An indigenous maize landrace from the Sierra Mixe region of Oaxaca, Mexico exhibits extensive formation of aerial roots which exude large volumes of a polysaccharide-rich gel matrix or “mucilage” that harbors diazotrophic microbiota. We hypothesize that the mucilage associated microbial community carries out multiple functions, including disassembly of the mucilage polysaccharide. In situ , hydrolytic assay of the mucilage revealed endogenous arabinofuranosidase, galactosidase, fucosidase, mannosidase and xylanase activities. Screening the mucilage against plant cell wall glycan-specific monoclonal antibodies recognized the presence of carbohydrate epitopes of hemicellulosic polysaccharides like xyloglucan (both non-fucosylated and fucosylated), xylan (both substituted and unsubstituted xylan domains) and pectic-arabinogalactans, all of which are potential carbon sources for mucilage microbial residents. Mucilage metagenome annotation using MG-RAST identified the members forming the microbial community, and gene fragments with predicted functions associated with carbohydrate disassembly. Data from the in situ hydrolytic activity and monoclonal antibody screening assays were used to guide the selection of five full length genes with predicted glycosyl hydrolase function from the GenBank database that were similar to gene fragments of high relative abundance in the mucilage metagenomes. These five genes were then synthesized for recombinant production in Escherichia coli . Here we report the characterization of an α-N-arabinofuranosidase (GH51) and an oligosaccharide reducing-end xylanase (GH8) from Flavobacterium johnsoniae; an α-L-fucosidase (GH29) and a xylan β-1,4 xylosidase (GH39) from Spirosoma linguale , and a β-mannosidase (GH2) from Agrobacterium fabrum . Biochemical characterization of these enzymes revealed a β-Mannosidase that also exhibits a secondary activity towards the cleavage of galactosyl residues. We also describe two xylanases (GH8 and GH39) from underexplored glycosyl hydrolase families, one thermostable α-L-Fucosidase (GH29) and a thermostable α-N-Arabinofuranosidase (GH51).
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 45
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Qi Chen, Catharina A. Hartman, Jan Haavik, Jaanus Harro, Kari Klungsøyr, Tor-Arne Hegvik, Rob Wanders, Cæcilie Ottosen, Søren Dalsgaard, Stephen V. Faraone, Henrik Larsson Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with other psychiatric conditions in adults. Yet, less is known about its relationship with common metabolic disorders and how sex and ageing affect the overall comorbidity patterns of adult ADHD. We aimed to examine associations of adult ADHD with several common psychiatric and metabolic conditions. Through the linkage of multiple Swedish national registers, 5,551,807 adults aged 18 to 64 years and living in Sweden on December 31, 2013 were identified and assessed for clinical diagnoses of adult ADHD, substance use disorder (SUD), depression, bipolar disorder, anxiety, type 2 diabetes mellitus (T2DM), and hypertension. Logistic regression models and regression standardization method were employed to obtain estimates of prevalence, prevalence difference (PD), and prevalence ratio (PR). All comorbid conditions of interest were more prevalent in adults with ADHD (3.90% to 44.65%) than in those without (0.72% to 4.89%), with the estimated PRs being over nine for psychiatric conditions (p 〈 0.001) and around two for metabolic conditions (p 〈 0.001). Sex differences in the prevalence of comorbidities were observed among adults with ADHD. Effect modification by sex was detected on the additive scale and/or multiplicative scale for the associations of adult ADHD with all comorbidities. ADHD remained associated with all comorbidities in older adults aged 50 to 64 when all conditions were assessed from age 50 onwards. The comorbidity patterns of adult ADHD underscore the severity and clinical complexity of the disorder. Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 46
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-09-27
    Description: by Mikyung Kelly Seo, John Cairns Background Recent advances in targeted therapies have raised expectations that the clinical application of biomarkers would improve patient’s health outcomes and potentially save costs. However, the cost-effectiveness of biomarkers remains unclear irrespective of the cost-effectiveness of corresponding therapies. It is thus important to determine whether biomarkers for targeted therapies provide good value for money. This study systematically reviews economic evaluations of biomarkers for targeted therapies in metastatic colorectal cancer (mCRC) and assesses the cost-effectiveness of predictive biomarkers in mCRC. Methods A literature search was performed using Medline, Embase, EconLit, NHSEED. Papers published from 2000 until June 2018 were searched. All economic evaluations assessing biomarker-guided therapies with companion diagnostics in mCRC were searched. To make studies more comparable, cost-effectiveness results were synthesized as per biomarker tests and corresponding therapies. Methodological quality was assessed using the Quality of Health Economic Studies (QHES) instrument. Results Forty-six studies were included in this review. Of these, 17 studies evaluated the intrinsic value of cancer biomarkers, whereas the remaining studies focused on assessing the cost-effectiveness of corresponding drugs. Most studies indicated favourable cost-effectiveness of biomarkers for targeted therapies in mCRC. Some studies reported that biomarkers were cost-effective, while their corresponding therapies were not cost-effective. A considerable number of economic evaluations were conducted in pre-defined genetic populations and thus, often failed to fully capture the biomarker’s clinical and economic values. The average QHES score was 73.6. Conclusion Cancer biomarkers for targeted therapies in mCRC were mostly found to be cost-effective; otherwise, they at least improved the cost-effectiveness of targeted therapies by saving some costs. However, this did not necessarily make their corresponding therapies cost-effective. While companion biomarkers reduced therapy costs, the savings were not sufficient to make the corresponding agents cost-effective. Evaluation of biomarkers was often restricted to the cost of tests and did not consider their clinical values or biomarker prevalence.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 47
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Patou Masika Musumari, Arunrat Tangmunkongvorakul, Kriengkrai Srithanaviboonchai, Teeranee Techasrivichien, S. Pilar Suguimoto, Masako Ono-Kihara, Masahiro Kihara Background Depression and anxiety symptoms are prevalent among university students in both developed and developing settings. Recently, grit, defined as perseverance and passion for long-term goals, has emerged as an indicator of success and well-being. However, the relationship between grit and poor mental health outcomes among university students is largely unknown. The current study investigates the relationship of grit with depression and anxiety among university students in Chiang Mai, Thailand. Methods This cross-sectional study was conducted from January to March 2018 among university students aged 18–24 years from Chiang Mai University, the first largest university in Chiang Mai Province. Depression and anxiety were assessed with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) Scales, respectively. Grit was measured using the 8-item Short Grit Scale (GRIT-S). Grit scores were grouped into three categories: low (below the 25 th percentile); average (from the 25 th to the 75 th percentiles); and high (above the 75 th percentile). The other covariates included variables such self-esteem and socio-demographic variables. Results Of the 800 participants included in the study, 405 (50.6%) were female and 395 (49.4%) were male. Respectively 21.4% and 7.8% of the participants had depression and clinical symptoms of GAD. Increasing levels of grit negatively correlated with PHQ-9 and GAD-7 scores. Participants with high level of grit scored respectively 1.69 points ( P
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 48
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Nathalie van den Tempel, Kishan A. T. Naipal, Anja Raams, Dik C. van Gent, Martine Franckena, Joost L. Boormans, Roland Kanaar Introduction Bladder cancer (urothelial carcinoma) is a common malignancy characterized by high recurrence rates and intense clinical follow-up, indicating the necessity for more effective therapies. Current treatment regimens include intra-vesical administration of mitomycin C (MMC) for non-muscle invasive disease and systemic cisplatin for muscle-invasive or metastatic disease. Hyperthermia, heating a tumor to 40–44°C, enhances the efficacy of these chemotherapeutics by various modes of action, one of which is inhibition of DNA repair via homologous recombination. Here, we explore whether ex vivo assays on freshly obtained bladder tumors can be applied to predict the response towards hyperthermia. Material and methods The cytochrome C release assay (apoptosis) and the RAD51 focus formation assay (DNA repair) were first established in the bladder cancer cell lines RT112 and T24 as measurements for hyperthermia efficiency, and subsequently tested in freshly obtained bladder tumors (n = 59). Results Hyperthermia significantly increased the fraction of apoptotic cells after cisplatin or MMC treatment in both RT112 and T24 cells and in most of the bladder tumors (8/10). The RAD51 focus formation assay detected both morphological and numerical changes of RAD51 foci upon hyperthermia in the RT112 and T24 cell lines. In 64% of 37 analyzed primary bladder tumor samples, hyperthermia induced similar morphological changes in RAD51 foci. Conclusion The cytochrome C assay and the RAD51 focus formation assay are both feasible on freshly obtained bladder tumors, and could serve to predict the efficacy of hyperthermia together with cytotoxic agents, such as MMC or cisplatin.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 49
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Jared A. Mereness, Soumyaroop Bhattacharya, Qian Wang, Yue Ren, Gloria S. Pryhuber, Thomas J. Mariani Basement membrane (BM) is an essential part of the extracellular matrix (ECM) that plays a crucial role in mechanical support and signaling to epithelial cells during lung development, homeostasis and repair. Abnormal composition and remodeling of the lung ECM have been associated with developmental abnormalities observed in multiple pediatric and adult respiratory diseases. Collagen VI (COL6) is a well-studied muscle BM component, but its role in the lung and its effect on pulmonary epithelium is largely undetermined. We report the presence of COLVI immediately subjacent to human airway and alveolar epithelium in the pediatric lung, in a location where it is likely to interact with epithelial cells. In vitro, both primary human lung epithelial cells and human lung epithelial cell lines displayed an increased rate of “wound healing” in response to a scratch injury when plated on COL6 as compared to other matrices. For the 16HBE cell line, wounds remained 〉5-fold larger for cells on COL1 (p 6-fold larger on matrigel (p 96% closure at 10 hr). The effect of COL6 upon lung epithelial cell phenotype was associated with an increase in cell spreading. Three hours after initial plating, 16HBE cells showed 〉7-fold less spreading on matrigel (p 4-fold less spreading on COL1 (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 50
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Jae Yeong Cho, Kye Hun Kim, Hyun-Jai Cho, Hae-Young Lee, Jin-Oh Choi, Eun-Seok Jeon, Sang Eun Lee, Min-Seok Kim, Jae-Joong Kim, Kyung-Kuk Hwang, Shung Chull Chae, Sang Hong Baek, Seok-Min Kang, Dong-Ju Choi, Byung-Su Yoo, Youngkeun Ahn, Hyun-Young Park, Myeong-Chan Cho, Byung-Hee Oh Background We investigated the role of nutritional risk index (NRI) in predicting 1-year mortality in patients with acute decompensated heart failure (ADHF). Methods Among 5,625 cohort patients enrolled in Korean Acute Heart Failure (KorAHF) Registry, a total of 5,265 patients who were possible to calculate NRI [NRI = (1.519 x serum albumin [g/dl]) + (41.7 x weight [kg]/ideal body weight [kg])] were enrolled. The patients were divided into 4 groups according to the NRI quartile; Q1 100 (n = 1711, 65.6 ± 14.5 years, 779 males). Primary end-point was all-cause mortality at 1-year clinical follow-up. Results The 1-year mortality was significantly increased as the NRI quartile decreased, and the lowest NRI quartile was associated with the highest 1-year mortality (Q1: 27.5% vs. Q2: 20.9% vs. Q3: 12.9% vs. Q4: 8.7%, linear p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 51
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Arne Sinnesael, Sharon Eeckhout, Steven B. Janssens, Erik Smets, Bart Panis, Olivier Leroux, Brecht Verstraete Background and aims The bacterial leaf nodule symbiosis is a close interaction between endophytes and their plant hosts, mainly within the coffee family. The interaction between Rubiaceae species and Burkholderia bacteria is unique due to its obligate nature, high specificity, and predominantly vertical transmission of the endophytes to the next generation of host plants. This vertical transmission is intriguing since it is the basis for the uniqueness of the symbiosis. However, unequivocal evidence of the location of the endophytes in the seeds is lacking. The aim of this paper is therefore to demonstrate the presence of the host specific endophyte in the seeds of Psychotria punctata and confirm its precise location. In addition, the suggested location of the endophyte in other parts of the host plant is investigated. Methods To identify and locate the endophyte in Psychotria punctata , a two-level approach was adopted using both a molecular screening method and fluorescent in situ hybridisation microscopy. Key results The endophytes, molecularly identified as Candidatus Burkholderia kirkii, were detected in the leaves, vegetative and flower buds, anthers, gynoecium, embryos, and young twigs. In addition, they were in situ localised in leaves, flowers and shoot apical meristems, and, for the first time, in between the cotyledons of the embryos. Conclusions Both independent techniques detected the host specific endophyte in close proximity to the shoot apical meristem of the embryo, which confirms for the first time the exact location of the endophytes in the seeds. This study provides reliable proof that the endophytes are maintained throughout the growth and development of the host plant and are transmitted vertically to the offspring.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 52
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Hyung-Chul Lee, Ho-Geol Ryu, Hyung-Jun Kim, Yoonsang Park, Soo Bin Yoon, Seong Mi Yang, Hye-Won Oh, Chul-Woo Jung The widespread use of remifentanil during total intravenous anesthesia (TIVA) has raised concerns about the risk of postoperative remifentanil-associated pain. Although a recent meta-analysis suggests that remifentanil-associated pain is unlikely to occur in patients with TIVA because of the protective effect of co-administered propofol, the evidence is not conclusive. We retrospectively assessed 635 patients who received robotic thyroid surgery under TIVA to evaluate the risk of remifentanil-associated pain. Postoperative pain was evaluated using 11-point numeric rating scale (NRS). Time dependent Cox proportional hazards regression analysis was used to determine the risk factors of treatment-requiring pain (NRS 〉 4) during the first 48 postoperative hours. Postoperative pain rapidly decreased, and treatment-requiring pain remained in 12.8% (81 out of 635) of patients at 48 hours postoperatively. After adjusting for the time-dependent analgesic consumption, intraoperative use of remifentanil 〉 0.2 mcg/kg/min was a positive predictor of postoperative pain with a hazard ratio of 1.296 (95% C.I., 1.014–1.656, P = 0.039) during 48 hours after surgery. In conclusion, excessive use of remifentanil during TIVA was associated with increased risk of pain after robotic thyroid surgery. Prospective trials are required to confirm these results and determine whether decreasing remifentanil consumption below the threshold can reduce postoperative pain.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 53
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Győző László Kaján, Agnieszka Lipiec, Dániel Bartha, Annika Allard, Niklas Arnberg Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal, urogenital, and ocular infections. They are divided into seven species containing 85 genotypes. Straightforward typing systems might help epidemiological investigations. As homologous recombination frequently shapes the evolution of HAdVs, information on a single gene is seldom sufficient to allow accurate and precise typing, and complete genome-based methods are recommended. Even so, complete genome analyses are not always easy to perform for practical reasons, and in such cases a multigene system can provide considerably more information about the strain under investigation than single-gene-based methods. Here we present a rapid, generic, multigene typing system for HAdVs based on three main deterministic regions of these viruses. Three PCR systems were used to amplify the genes encoding the DNA polymerase, the penton base hypervariable Arg-Gly-Asp-containing loop, and the hexon loop 1 (hypervariable region 1–6). Using this system, we typed 281 clinical isolates, detected members of six out of seven HAdV species ( Human mastadenovirus A – F ), and could also detect not only divergent strains of established types but also a new recombinant strain with a previously unpublished combination of adenovirus genomes. This strain was accepted by the Human Adenovirus Working Group as a novel genotype: HAdV-86. Seven strains that could not be typed with sufficient accuracy were also investigated using a PCR based on part of the fiber gene. By analysis of corresponding sequences of the 86 known HAdV genotypes, we determined that the proposed typing system should be able to distinguish all non-recombinant types, and with additional fiber information, all known HAdV genotypes.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 54
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Marta Morais Oliveira, Christophe Marti, Majd Ramlawi, François P. Sarasin, Olivier Grosgurin, Pierre-Alexandre Poletti, Frédéric Rouyer, Olivier T. Rutschmann Objective Overcrowding is common in most emergency departments (ED). Despite the use of validated triage systems, some patients are at risk of delayed medical evaluation. The objective of this study was to assess the impact of a patient-flow physician coordinator (PFPC) on the proportion of patients offered medical evaluation within time limits imposed by the Swiss Emergency Triage Scale (SETS) and on patient flow within the emergency department of a teaching urban hospital. Methods In this before-after retrospective cohort study, we compared the proportions of patients who received their first medical contact within SETS-imposed time limits, mean waiting times before first medical consultation, mean length of stay, and number of patients who left without being seen by a physician, between two periods before and after introducing a PFPC. The PFPC was a senior physician charged with quickly assessing in the waiting area patients who could not immediately be seen and managing patient flow within the department. Results Before introducing the PFPC position, 33,605 patients were admitted, versus 36,288 after. Introducing a PFPC enabled the department to increase the proportion of patients seen within the SETS-imposed time limits from 60.1% to 69.0% (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 55
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Kristin D. Morgan, Brian Noehren Patellofemoral pain (PFP) is one of the most common overuse injuries of the knee. Previous research has found that individuals with PFP exhibit differences in peak hip kinematics; however, differences in peak knee kinematics, where the pain originates, are difficult to elucidate. To better understand the mechanism behind PFP, we sought to characterize differences in knee gait kinematic waveform patterns in individuals with PFP compared to healthy individuals using fast Fourier transform (FFT). Sixteen control and sixteen individuals with PFP participated in a fast walk protocol. FFT was used to decompose the sagittal, frontal and transverse plane knee gait waveforms into sinusoidal signals. A two-way ANOVA and Bonferroni post hoc analysis compared group, limb and interaction effects on sagittal, frontal and transverse amplitude, frequency and phase components between control and PFP individuals gait waveforms. Differences in frequency and phase values were found in the sagittal and frontal plane knee waveforms between the control and PFP groups. The signal-to-noise ratio also reported significant differences between the PFP and control limbs in the sagittal (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 56
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-15
    Description: by Alexandra Lezkan, Knut Drewing Although the natural haptic perception of textures includes active finger movements, it is unclear how closely perception and movements are linked. Here we investigated this question using oriented textures. Textures that are composed of periodically repeating grooves have a clear orientation defined by the grooves. The direction of finger movement relative to texture orientation determines the availability of temporal cues to the spatial period of the texture. These cues are absent during movements directed in line with texture orientation, whereas movements orthogonal to texture orientation maximize the temporal frequency of stimulation. This may optimize temporal cues. In Experiment 1 we tested whether texture perception gets more precise the more orthogonal the movement direction is to the texture. We systematically varied the movement direction within a 2IFC spatial period discrimination task. As expected, perception was more precise (lower discrimination thresholds) when finger movements were directed closer towards the texture orthogonal as compared to in parallel to the texture. In Experiment 2 we investigated whether people adjust movement directions to the texture orthogonal in free exploration. We recorded movement directions during free exploration of standard and comparison gratings. The standard gratings were clearly oriented. The comparison gratings did not have a clear orientation defined by grooves. Participants adjusted movement directions to the texture orthogonal only for clearly oriented textures (standards). The adjustment to texture orthogonal was present in the final movement but not in the first movement. This suggests that movement adjustment is based on sensory signals for texture orientation that were gathered over the course of exploration. In Experiment 3 we assessed whether the perception of texture orientation and movement adjustments are based on shared sensory signals. We determined perceptual thresholds for orientation discrimination and computed ‘movometric’ thresholds from the stroke-by-stroke adjustment of movement direction. Perception and movements were influenced by a common factor, the spatial period, suggesting that the same sensory signals for texture orientation contribute to both. We conclude that people optimize texture perception by adjusting their movements in directions that maximize temporal cue frequency. Adjustments are performed on the basis of sensory signals that are also used for perception.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 57
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-15
    Description: by Katrina B. Velle, Kenneth G. Campellone Enteropathogenic and enterohemorrhagic E . coli (EPEC and EHEC) are closely related extracellular pathogens that reorganize host cell actin into “pedestals” beneath the tightly adherent bacteria. This pedestal-forming activity is both a critical step in pathogenesis, and it makes EPEC and EHEC useful models for studying the actin rearrangements that underlie membrane protrusions. To generate pedestals, EPEC relies on the tyrosine phosphorylated bacterial effector protein Tir to bind host adaptor proteins that recruit N-WASP, a nucleation-promoting factor that activates the Arp2/3 complex to drive actin polymerization. In contrast, EHEC depends on the effector EspF U to multimerize N-WASP and promote Arp2/3 activation. Although these core pathways of pedestal assembly are well-characterized, the contributions of additional actin nucleation factors are unknown. We investigated potential cooperation between the Arp2/3 complex and other classes of nucleators using chemical inhibitors, siRNAs, and knockout cell lines. We found that inhibition of formins impairs actin pedestal assembly, motility, and cellular colonization for bacteria using the EPEC, but not the EHEC, pathway of actin polymerization. We also identified mDia1 as the formin contributing to EPEC pedestal assembly, as its expression level positively correlates with the efficiency of pedestal formation, and it localizes to the base of pedestals both during their initiation and once they have reached steady state. Collectively, our data suggest that mDia1 enhances EPEC pedestal biogenesis and maintenance by generating seed filaments to be used by the N-WASP/Arp2/3-dependent actin nucleation machinery and by sustaining Src-mediated phosphorylation of Tir.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 58
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Wojciech Potrzebowski, Jill Trewhella, Ingemar Andre Many proteins consist of folded domains connected by regions with higher flexibility. The details of the resulting conformational ensemble play a central role in controlling interactions between domains and with binding partners. Small-Angle Scattering (SAS) is well-suited to study the conformational states adopted by proteins in solution. However, analysis is complicated by the limited information content in SAS data and care must be taken to avoid constructing overly complex ensemble models and fitting to noise in the experimental data. To address these challenges, we developed a method based on Bayesian statistics that infers conformational ensembles from a structural library generated by all-atom Monte Carlo simulations. The first stage of the method involves a fast model selection based on variational Bayesian inference that maximizes the model evidence of the selected ensemble. This is followed by a complete Bayesian inference of population weights in the selected ensemble. Experiments with simulated ensembles demonstrate that model evidence is capable of identifying the correct ensemble and that correct number of ensemble members can be recovered up to high level of noise. Using experimental data, we demonstrate how the method can be extended to include data from Nuclear Magnetic Resonance (NMR) and structural energies of conformers extracted from the all-atom energy functions. We show that the data from SAXS, NMR chemical shifts and energies calculated from conformers can work synergistically to improve the definition of the conformational ensemble.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 59
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Joel Atallah, Susan E. Lott The earliest stage of animal development is controlled by maternally deposited mRNA transcripts and proteins. Once the zygote is able to transcribe its own genome, maternal transcripts are degraded, in a tightly regulated process known as the maternal to zygotic transition (MZT). While this process has been well-studied within model species, we have little knowledge of how the pools of maternal and zygotic transcripts evolve. To characterize the evolutionary dynamics and functional constraints on early embryonic expression, we created a transcriptomic dataset for 14 Drosophila species spanning over 50 million years of evolution, at developmental stages before and after the MZT, and compared our results with a previously published Aedes aegypti developmental time course. We found deep conservation over 250 million years of a core set of genes transcribed only by the zygote. This select group is highly enriched in transcription factors that play critical roles in early development. However, we also identify a surprisingly high level of change in the transcripts represented at both stages over the phylogeny. While mRNA levels of genes with maternally deposited transcripts are more highly conserved than zygotic genes, those maternal transcripts that are completely degraded at the MZT vary dramatically between species. We also show that hundreds of genes have different isoform usage between the maternal and zygotic genomes. Our work suggests that maternal transcript deposition and early zygotic transcription are remarkably dynamic over evolutionary time, despite the widespread conservation of early developmental processes.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 60
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Peng Gao, Huan Wang, Jiarui Yu, Jie Zhang, Zhao Yang, Meiyue Liu, Yi Niu, Xiaomei Wei, Wei Wang, Hongmin Li, Yadi Wang, Guogui Sun Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro . Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 61
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by María Gabriela Blanco, María Soledad Vela Gurovic, Gustavo Fabián Silbestri, Andrés Garelli, Sebastián Giunti, Diego Rayes, María José De Rosa Nematode parasites cause substantial morbidity to billions of people and considerable losses in livestock and food crops. The repertoire of effective anthelmintic compounds for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance has become a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system, we here screened the nematicidal potential of novel imidazolium and imidazole derivatives. One of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C . elegans at both mature and immature stages. This lethal effect appears to be specific because DII concentrations which prove to be toxic to C . elegans do not induce significant lethality on bacteria, Drosophila melanogaster , and HEK-293 cells. Our analysis of DII action on C . elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 has been largely reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously unidentified UNC-29-containing muscle AChR, different from the classical L-AChR. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. Its lethality on C . elegans , its harmlessness in non-nematode species and its novel and dual mechanism of action make DII a promising candidate compound for anthelmintic therapy.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 62
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Heather Friberg, Coreen M. Beaumier, Sangshin Park, Pamela Pazoles, Timothy P. Endy, Anuja Mathew, Jeffrey R. Currier, Richard G. Jarman, Kathryn B. Anderson, Steven Hatch, Stephen J. Thomas, Alan L. Rothman Background Hyperendemic circulation of all four types of dengue virus (DENV-1-4) has expanded globally, fueling concern for increased incidence of severe dengue. While the majority of DENV infections are subclinical, epidemiologic studies suggest that type-cross-reactive immunity can influence disease outcome in subsequent infections. The mechanisms controlling these differential clinical outcomes remain poorly defined. Methodology/Principal findings Blood samples were collected from a cohort of school-aged Thai children who subsequently experienced a subclinical DENV infection or developed dengue illness. PBMC collected prior to infection were stimulated in vitro with DENV and the secretion of 30 cytokines was measured using a multiplexed, bead-based array. Significant differences were found in cytokine production based on both the type of DENV used for stimulation and the occurrence of clinical illness. Secretion of IL-15 and MCP-1 was significantly higher by PBMC of subjects who later developed symptomatic DENV infection. In addition, IL-6 was produced by PBMC from all subjects who subsequently developed symptomatic infection, versus 59% of subjects who had subclinical infection. Secretion of IL-12, IL-2R, MIP-1α, RANTES, GM-CSF, and TNFα was significantly lower by PBMC from subjects with symptomatic infection. Conclusions/Significance These data demonstrate significant differences in pre-existing immune responses to DENV associated with the clinical outcome of subsequent infection. The finding of higher levels of some cytokines in subjects with symptomatic infection and higher levels of other cytokines in subjects with subclinical infection supports the existence of both protective and pathologic immune profiles. Clinical-immunological correlations identified in the context of natural DENV infection may be useful for evaluating immune responses to dengue vaccines.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 63
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Maribel Barriopedro, Cristina López de Subijana, Carlos Muniesa The aims of this study were: i) to examine if Dual Career (DC) pathways are independent of gender, ii) to evaluate whether those athletes who followed a DC experienced less difficulty in their integration into the labor force than the athletes devoted entirely to sport regardless of gender, as well as iii) to analyze whether the type of career path chosen was related with the current labor status, and if differences exist between men and women athletes. A quantitative, cross-sectional, and descriptive study was used based on an ad hoc questionnaire. Two-hundred and twenty-eight retired Olympic athletes completed a questionnaire. The response rate was 28.3%. Athletes who followed a DC with studies had a higher educational level at retirement than those devoted solely to sport and those who followed a DC with work, (χ 2 (6) = 38.76; P 〈 .001), but no differences were found between men and women (χ 2 (3) = 3.23; P = .358). Athletes who followed a DC path (with studies or with work) perceived the transition out of sport more positively than those who focused solely on sport ( χ 2 (2) = 7.79; P = .020). Regarding the type of job, more women attained a part-time job (20.9%) than men (3.1%; χ 2 (5) = 21.83; P = .001). The athletes who followed a DC with studies achieved higher monthly incomes than the other two groups ( χ 2 (2) = 9.08; P = .011). Men athletes achieved higher incomes than women (Z = 5.45; P 〈 .001), but the gender wage gap was apparent for those Olympian athletes considered as the qualified group, probably due to a higher presence of part-time women workers. The findings of this study suggest that future professional opportunities and the transition to the labor market could be made easier by following a DC during the mastery stage. Regardless of career path, women experienced more difficulties in their integration into the job market and there is a wage penalty for highly-qualified women.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 64
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Byung Kook Lee, In Soo Cho, Joo Suk Oh, Wook Jin Choi, Jung Hee Wee, Chang Sun Kim, Won Young Kim, Chun Song Youn Introduction The aim of this trial was to investigate the effect of a continuous infusion of a neuromuscular blockade (NMB) in comatose out-of-hospital cardiac arrest (OHCA) subjects who underwent targeted temperature management (TTM). Methods In this open-label, multicenter trial, subjects resuscitated from OHCA were randomly assigned to receive either NMB (38 subjects) or placebo (43 subjects) for 24 hours. Sedatives and analgesics were given according to the protocol of each hospital during TTM. The primary outcome was serum lactate levels at 24 hours after drug infusion. The secondary outcomes included in-hospital mortality, a poor neurological outcome at hospital discharge, changes in lactate levels, changes in the PaO 2 :FiO 2 ratio over time and muscle weakness as assessed by the Medical Research Council (MRC) scale. Results Eighty-one subjects (NMB group: median age, 65.5 years, 30 male patients; placebo group: median age, 61.0 years, 29 male patients) were enrolled in this trial. No difference in the serum lactate level at 24 hours was observed between the NMB (2.8 [1.2–4.0]) and placebo (3.6 [1.8–5.2]) groups ( p = 0.238). In-hospital mortality and a poor neurologic outcome at discharge did not differ between the two groups. No significant difference in the PaO 2 :FiO 2 ratio over time ( p = 0.321) nor the MRC score ( p = 0.474) was demonstrated. Conclusions In OHCA subjects who underwent TTM, a continuous infusion of NMB did not reduce lactate levels and did not improve survival or neurological outcome at hospital discharge. Our results indicated a limited potential for the routine use of NMB during early TTM. However, this trial may be underpowered to detect clinical differences, and future research should be conducted.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 65
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Eri Saeki, Shinji Yasuhira, Masahiko Shibazaki, Hiroshi Tada, Minoru Doita, Tomoyuki Masuda, Chihaya Maesawa Cultured cells easily develop resistance to kinesin-5 inhibitors (K5Is) often by overexpressing a related motor protein, kinesin-12/KIF15, or by acquiring mutations in the N-terminal motor domain of kinesin-5/KIF11 itself. We aimed to identify novel mechanisms responsible for resistance to S-trityl L-cysteine (STLC), one of the K5Is, using human osteosarcoma cell lines. Among six lines examined, U-2OS and HOS survived chronic STLC treatment and gave rise to resistant cells with IC 50 s at least 10-fold higher than those of the respective parental lines. Depletion of KIF15 largely eliminated the acquired K5I resistance in both cases, consistent with the proposed notion that KIF15 is indispensable for it. In contrast to the KIF11-independent property of the cells derived from HOS, those derived from U-2OS still required KIF11 for their growth and, intriguingly, expressed a C-terminal truncated variant of KIF11 resulting from a frame shift mutation (S1017fs). All of the isolated clones harbored the same mutation, suggesting its clonal expansion in the cell population due to the growth advantage during chronic STLC treatment. Transgenic expression of KIF11 S1017fs in the parental U-2OS cells, as well as in HeLa cells, conferred a moderate but reproducible STLC resistance, probably owing to STLC-resistant localization of the mutant KIF11 on mitotic spindle. Our observations indicate that both KIF15 and the C-terminal-truncated KIF11 contributes to the STLC resistance of the U-2OS derived cells.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 66
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Nina Paul, Sara C. Novais, Marco F. L. Lemos, Andreas Kunzmann In nature, a multitude of both abiotic and biotic stressors influence organisms with regard to their overall fitness. Stress responses that finally impair normal biological functions may ultimately result in consequences for whole populations. This study focused on the metabolic response of the intertidal rock pool fish Gobius paganellus towards simulated predation risk. Individuals were exposed to a mixture of skin extracts from conspecifics and chemical alarm cues from a top predator, Octopus vulgaris . Oxygen consumption rates of single fish were measured to establish standard (SMR) and routine metabolic rates (RMR) of G . paganellus , and to address the direct response towards simulated predation risk, compared to handling and light stress. The SMR of G . paganellus (0.0301 ± 0.0081 mg O 2 h -1 g -1 WW) was significantly lower than the RMR (0.0409 ± 0.0078 mg O 2 h -1 g -1 WW). In contrast to increased respiration due to handling and light stress, the exposure to chemical predation cues induced a significant reduction in oxygen consumption rates (0.0297 ± 0.0077 mg O 2 h -1 g -1 WW). This metabolic suppression was interpreted as a result of the stereotypic freezing behaviour as antipredator response of gobiid fish. Results underline the importance of biotic interactions in environmental stress assessments and predation as a biotic factor that will provide more realistic scenarios when addressing stress impacts in tidal rock pool organisms.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 67
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Robin Simsa, Arvind Manikantan Padma, Philipp Heher, Mats Hellström, Andreas Teuschl, Lachmi Jenndahl, Niklas Bergh, Per Fogelstrand Decellularization of native blood vessels is a promising technology to generate 3D biological scaffolds for vascular grafting. Blood vessel decellularization has been performed in previous studies under various experimental conditions, that complicates comparison and optimization of suitable protocols. The goal of this work was to systematically compare the decellularization and recellularization efficacy of 5 different protocols utilizing the detergents sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), CHAPS and TritonX-100 together with DNA-removing enzymes on porcine vena cava in a perfusion bioreactor setup. Additionally, we tested the effect of DNase on the extracellular matrix (ECM) properties. We found that all protocols could efficiently decellularize blood vessels. Mechanical strength, collagen preservation and ECM integrity were similar among all tested detergents, yet TritonX protocols required long-term DNase application for complete decellularization. However, TritonX-based protocols showed the greatest recellularization efficacy with HUVECs in vitro . Furthermore, we developed a novel protocol for TritonX which improved recellularization and reduced total process time and ECM stiffness compared to previous protocols. SDS, SDC and CHAPS based protocols had a lower recellularization potential. In conclusion, decellularization of blood vessels can be achieved with all tested reagents, but TritonX treated ECM can be most efficiently recellularized with endothelial cells.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 68
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Paolo Durandetto, Andrea Sosso This paper presents an open-source package developed in Python that controls and drives a programmable Josephson array to synthesize dc and ac quantum-accurate voltages. Programmable arrays are devices subdivided into independent subsections, each counting a number of series connected Josephson junctions that follows a binary sequence (1, 2, 4, 8, …) to control the output voltage. Our software allows to independently measure the current-voltage characteristics of each subsection by means of a set of arbitrary waveform generators and a nanovoltmeter that measures the voltage across the whole array with high sensitivity. A quantization test tool is also provided to check with sub-microvolt resolution whether the array is operating on its quantum margins. The code is modular and easily expandable with the support of many libraries, allowing prompt reconfiguration for different calibration and testing purposes. It is aimed at being a starting point for cooperation between National Metrology Institutes towards the realization of a shared quantum voltage calibration infrastructure.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 69
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Daniel S. Marchuk, Kristy Crooks, Natasha Strande, Kathleen Kaiser-Rogers, Laura V. Milko, Alicia Brandt, Alexandra Arreola, Christian R. Tilley, Chris Bizon, Neeta L. Vora, Kirk C. Wilhelmsen, James P. Evans, Jonathan S. Berg As whole exome sequencing (WES) becomes more widely used in the clinical realm, a wealth of unanalyzed information will be routinely generated. Using WES read depth data to predict copy number variation (CNV) could extend the diagnostic utility of this previously underutilized data by providing clinically important information such as previously unsuspected deletions or duplications. We evaluated ExomeDepth, a free R package, in addition to an aneuploidy prediction method, to detect CNVs in WES data. First, in a blinded pilot study, five out of five genomic alterations were correctly identified from clinical samples with previously defined chromosomal gains or losses, including submicroscopic deletions, duplications, and chromosomal trisomy. We then examined CNV calls among 53 patients participating in the NCGENES research study and undergoing WES, who had existing clinical chromosomal microarray (CMA) data that could be used for validation. For unique CNVs that overlap well with WES coverage regions, sensitivity was 89% for deletions and 65% for duplications. While specificity of the algorithm calls remains a concern, this is less of an issue at high threshold filtering levels. When applied to all 672 patients from the exome sequencing study, ExomeDepth identified eleven diagnostically relevant CNVs ranging in size from a two exon deletion to whole chromosome duplications, as well as numerous other CNVs with varying clinical significance. This opportunistic analysis of WES data yields an additional 1.6% of patients in this study with pathogenic or likely pathogenic CNVs that are clinically relevant to their phenotype as well as clinically relevant secondary findings. Finally, we demonstrate the potential value of copy number analysis in cases where a single heterozygous likely or known pathogenic single nucleotide alteration is identified in a gene associated with an autosomal recessive condition.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 70
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Kenichi Arai, Daiki Murata, Ana Raquel Verissimo, Yosuke Mukae, Manabu Itoh, Anna Nakamura, Shigeki Morita, Koichi Nakayama A major challenge in cardiac tissue engineering is the host’s immune response to artificial materials. To overcome this problem, we established a scaffold-free system for assembling cell constructs using an automated Bio-3D printer. This printer has previously been used to fabricate other three-dimensional (3D) constructs, including liver, blood vessels, and cartilage. In the present study, we tested the function in vivo of scaffold-free cardiac tubular construct fabricated using this system. Cardiomyocytes derived from induced pluripotent stem cells (iCells), endothelial cells, and fibroblasts were combined to make the spheroids. Subsequently, tubular cardiac constructs were fabricated by Bio-3D printer placing the spheroids on a needle array. Notably, the spheroid fusion and beat rate in the constructs were observed while still on the needle array. After removal from the needle array, electrical stimulation was used to test responsiveness of the constructs. An increased beat rate was observed during stimulation. Importantly, the constructs returned to their initial beat rate after stimulation was stopped. In addition, histological analysis shows cellular reorganization occurring in the cardiac constructs, which may mimic that observed during organ transplantation. Taken together, our results indicate that these engineered cardiac tubular constructs, which address both the limited supply of donor tissues as well as the immune-induced transplant rejection, has potential to be used for both clinical and drug testing applications. To our knowledge, this is the first time that cardiac tubular constructs have been produced using optimized Bio-3D printing technique and subsequently tested for their use as cardiac pumps.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 71
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Tomáš Dostálek, Maan Bahadur Rokaya, Zuzana Münzbergová Insects represent one of the most abundant groups of herbivores, and many of them have significant impacts on the dynamics of plant populations. As insects are very sensitive to changes in climatic conditions, we hypothesize that their effects on plant population dynamics will depend on climatic conditions. Knowledge of the variation in herbivore effects on plant population dynamics is, however, still rather sparse. We studied population dynamics and herbivore damage at the individual plant level of Salvia nubicola along a wide altitudinal gradient representing a range of climatic conditions. Using integral projection models, we estimated the effect of changes in herbivore pressure on plant populations in different climates and habitat types. Since we recorded large differences in the extent of herbivore damage along the altitudinal gradient, we expected that the performance of plants from different altitudes would be affected to different degrees by herbivores. Indeed, we found that populations from low altitudes were better able to withstand increased herbivore damage, while populations from high altitudes were suppressed by herbivores. However, the pattern described above was evident only in populations from open habitats. In forest habitats, the differences in population dynamics between low and high altitudes were largely diminished. The effects of herbivores on plants from different altitudes were thus largely habitat specific. Our results indicate potential problems for plant populations from high altitudes in open habitats because of increased herbivore damage. However, forest habitats may provide refuges for the plants at these high altitudes.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 72
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-12-18
    Description: by Aaron M. Dickey, Gennie Schuller, J. Dustin Loy, Michael L. Clawson Moraxella bovoculi is frequently cultured from the ocular secretions and conjunctiva of cattle with Infectious Bovine Keratoconjunctivitis (IBK). Previous work has shown that single nucleotide polymorphism (SNP) diversity in this species is quite high with 81,284 SNPs identified in eight genomes representing two distinct genotypes isolated from IBK affected eyes (genotype 1) and the nasopharynx of cattle without clinical IBK signs (genotype 2), respectively. The goals of this study were to identify SNPs from a collection of geographically diverse and epidemiologically unlinked M . bovoculi strains from the eyes of IBK positive cattle (n = 183) and another from the eyes of cattle (most from a single population at a single time-point) without signs of IBK (n = 63) and to characterize the genetic diversity. Strains of both genotypes were identified from the eyes of cattle without IBK signs. Only genotype 1 strains were identified from IBK affected eyes, however, these strains were isolated before the discovery of genotype 2, and the protocol for their isolation would have preferentially selected genotype 1 M . bovoculi . The core genome comprised ~74% of the whole and contained 〉127,000 filtered SNPs. More than 80% of these characterize diversity within genotype 1 while 23,611 SNPs (~18%) delimit the two major genotypes. Genotype 2 strains lacked a repeats-in-toxin (RTX) putative pathogenesis factor and any of ten putative antibiotic resistance genes carried within a genomic island. Within genotype 1, prevalence of these elements was 0.85 and 0.12 respectively in strains from eyes that were IBK positive. Recombination appears to be an important source of genetic diversity for genotype 1 and undermines the utility of ribosomal-locus-based species identification. The extremely high genetic diversity in genotype 1 presents a challenge to the development of an efficacious vaccine directed against them, however, several low-diversity pilin-like genes were identified. Finally, the genotype-defining SNPs described in this study are a resource that can facilitate the development of more accurate M . bovoculi diagnostic tests.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 73
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-12-18
    Description: by Timothy M. Rose, A. Gregory Bruce, Serge Barcy, Matt Fitzgibbon, Lisa R. Matsumoto, Minako Ikoma, Corey Casper, Jackson Orem, Warren Phipps KSHV is endemic in Uganda and the HIV epidemic has dramatically increased the incidence of Kaposi sarcoma (KS). To investigate the role of KSHV in the development of KS, we obtained KS biopsies from ART-naïve, HIV-positive individuals in Uganda and analyzed the tumors using RNAseq to globally characterize the KSHV transcriptome. Phylogenetic analysis of ORF75 sequences from 23 tumors revealed 6 distinct genetic clusters with KSHV strains exhibiting M, N or P alleles. RNA reads mapping to specific unique coding sequence (UCDS) features were quantitated using a gene feature file previously developed to globally analyze and quantitate KSHV transcription in infected endothelial cells. A pattern of high level expression was detected in the KSHV latency region that was common to all KS tumors. The clear majority of transcription was derived from the downstream latency transcript promoter P3(LTd) flanking ORF72, with little evidence of transcription from the P1(LTc) latency promoter, which is constitutive in KSHV-infected lymphomas and tissue-culture cells. RNAseq data provided evidence of alternate P3(LTd) transcript editing, splicing and termination resulting in multiple gene products, with 90% of the P3(LTd) transcripts spliced to release the intronic source of the microRNAs K1-9 and 11. The spliced transcripts encode a regulatory uORF upstream of Kaposin A with alterations in intervening repeat sequences yielding novel or deleted Kaposin B/C-like sequences. Hierarchical clustering and PCA analysis of KSHV transcripts revealed three clusters of tumors with different latent and lytic gene expression profiles. Paradoxically, tumors with a latent phenotype had high levels of total KSHV transcription, while tumors with a lytic phenotype had low levels of total KSHV transcription. Morphologically distinct KS tumors from the same individual showed similar KSHV gene expression profiles suggesting that the tumor microenvironment and host response play important roles in the activation level of KSHV within the infected tumor cells.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 74
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-01-03
    Description: by Shayna Stein, Rui Zhao, Hiroshi Haeno, Igor Vivanco, Franziska Michor Human primary glioblastomas (GBM) often harbor mutations within the epidermal growth factor receptor (EGFR). Treatment of EGFR-mutant GBM cell lines with the EGFR/HER2 tyrosine kinase inhibitor lapatinib can effectively induce cell death in these models. However, EGFR inhibitors have shown little efficacy in the clinic, partly because of inappropriate dosing. Here, we developed a computational approach to model the in vitro cellular dynamics of the EGFR-mutant cell line SF268 in response to different lapatinib concentrations and dosing schedules. We then used this approach to identify an effective treatment strategy within the clinical toxicity limits of lapatinib, and developed a partial differential equation modeling approach to study the in vivo GBM treatment response by taking into account the heterogeneous and diffusive nature of the disease. Despite the inability of lapatinib to induce tumor regressions with a continuous daily schedule, our modeling approach consistently predicts that continuous dosing remains the best clinically feasible strategy for slowing down tumor growth and lowering overall tumor burden, compared to pulsatile schedules currently known to be tolerated, even when considering drug resistance, reduced lapatinib tumor concentrations due to the blood brain barrier, and the phenotypic switch from proliferative to migratory cell phenotypes that occurs in hypoxic microenvironments. Our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment schedules in search for optimal dosing strategies for glioblastoma and other cancer types.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 75
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-01-03
    Description: by Chloé Bessière, May Taha, Florent Petitprez, Jimmy Vandel, Jean-Michel Marin, Laurent Bréhélin, Sophie Lèbre, Charles-Henri Lecellier Gene expression is orchestrated by distinct regulatory regions to ensure a wide variety of cell types and functions. A challenge is to identify which regulatory regions are active, what are their associated features and how they work together in each cell type. Several approaches have tackled this problem by modeling gene expression based on epigenetic marks, with the ultimate goal of identifying driving regions and associated genomic variations that are clinically relevant in particular in precision medicine. However, these models rely on experimental data, which are limited to specific samples (even often to cell lines) and cannot be generated for all regulators and all patients. In addition, we show here that, although these approaches are accurate in predicting gene expression, inference of TF combinations from this type of models is not straightforward. Furthermore these methods are not designed to capture regulation instructions present at the sequence level, before the binding of regulators or the opening of the chromatin. Here, we probe sequence-level instructions for gene expression and develop a method to explain mRNA levels based solely on nucleotide features. Our method positions nucleotide composition as a critical component of gene expression. Moreover, our approach, able to rank regulatory regions according to their contribution, unveils a strong influence of the gene body sequence, in particular introns. We further provide evidence that the contribution of nucleotide content can be linked to co-regulations associated with genome 3D architecture and to associations of genes within topologically associated domains.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 76
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    Publication Date: 2018-01-03
    Description: by Igor Marín de Mas, Esther Aguilar, Erika Zodda, Cristina Balcells, Silvia Marin, Guido Dallmann, Timothy M. Thomson, Balázs Papp, Marta Cascante Epithelial-mesenchymal-transition promotes intra-tumoral heterogeneity, by enhancing tumor cell invasiveness and promoting drug resistance. We integrated transcriptomic data for two clonal subpopulations from a prostate cancer cell line (PC-3) into a genome-scale metabolic network model to explore their metabolic differences and potential vulnerabilities. In this dual cell model, PC-3/S cells express Epithelial-mesenchymal-transition markers and display high invasiveness and low metastatic potential, while PC-3/M cells present the opposite phenotype and higher proliferative rate. Model-driven analysis and experimental validations unveiled a marked metabolic reprogramming in long-chain fatty acids metabolism. While PC-3/M cells showed an enhanced entry of long-chain fatty acids into the mitochondria, PC-3/S cells used long-chain fatty acids as precursors of eicosanoid metabolism. We suggest that this metabolic reprogramming endows PC-3/M cells with augmented energy metabolism for fast proliferation and PC-3/S cells with increased eicosanoid production impacting angiogenesis, cell adhesion and invasion. PC-3/S metabolism also promotes the accumulation of docosahexaenoic acid, a long-chain fatty acid with antiproliferative effects. The potential therapeutic significance of our model was supported by a differential sensitivity of PC-3/M cells to etomoxir, an inhibitor of long-chain fatty acid transport to the mitochondria.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 77
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by Mostafa Abdelrahman, Magdi El-Sayed, Shusei Sato, Hideki Hirakawa, Shin-ichi Ito, Keisuke Tanaka, Yoko Mine, Nobuo Sugiyama, Yutaka Suzuki, Naoki Yamauchi, Masayoshi Shigyo
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 78
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by Joanne Canonne, Daniel Marino, Laurent D. Noël, Ignacio Arechaga, Carole Pichereaux, Michel Rossignol, Dominique Roby, Susana Rivas
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 79
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by Michele Pohlen, Nils H. Thoennissen, Jan Braess, Johannes Thudium, Christoph Schmid, Matthias Kochanek, Karl-Anton Kreuzer, Pia Lebiedz, Dennis Görlich, Hans U. Gerth, Christian Rohde, Torsten Kessler, Carsten Müller-Tidow, Matthias Stelljes, Carsten Hullerman, Thomas Büchner, Günter Schlimok, Michael Hallek, Johannes Waltenberger, Wolfgang Hiddemann, Wolfgang E. Berdel, Bernhard Heilmeier, Utz Krug
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 80
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by Loreta A. Kondili, Giovanni Battista Gaeta, Donatella Ieluzzi, Anna Linda Zignego, Monica Monti, Andrea Gori, Alessandro Soria, Giovanni Raimondo, Roberto Filomia, Alfredo Di Leo, Andrea Iannone, Marco Massari, Romina Corsini, Roberto Gulminetti, Alberto Gatti Comini, Pierluigi Toniutto, Denis Dissegna, Francesco Paolo Russo, Alberto Zanetto, Maria Grazia Rumi, Giuseppina Brancaccio, Elena Danieli, Maurizia Rossana Brunetto, Liliana Elena Weimer, Maria Giovanna Quaranta, Stefano Vella, Massimo Puoti
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 81
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by The PLOS ONE Editors
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 82
    facet.materialart.
    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2018-01-03
    Description: by Clifford G. Clark, Chih-yu Chen, Chrystal Berry, Matthew Walker, Stuart J. McCorrister, Patrick M. Chong, Garrett R. Westmacott Whole genome sequencing (WGS) has been used to assess the phylogenetic relationships, virulence and metabolic differences, and the relationship between gene carriage and host or niche differentiation among populations of C . jejuni isolates. We previously characterized the presence and expression of CJIE4 prophage proteins in four C . jejuni isolates using WGS and comparative proteomics analysis, but the isolates were not assessed further. In this study we compare the closed, finished genome sequences of these isolates to the total proteome. Genomes of the four isolates differ in phage content and location, plasmid content, capsular polysaccharide biosynthesis loci, a type VI secretion system, orientation of the ~92 kb invertible element, and allelic differences. Proteins with 99% sequence identity can be differentiated using isobaric tags for relative and absolute quantification (iTRAQ) comparative proteomic methods. GO enrichment analysis and the type of artefacts produced in comparative proteomic analysis depend on whether proteins are encoded in only one isolate or common to all isolates, whether different isolates have different alleles of the proteins analyzed, whether conserved and variable regions are both present in the protein group analyzed, and on how the analysis is done. Several proteins encoded by genes with very high levels of sequence identity in all four isolates exhibited preferentially higher protein expression in only one of the four isolates, suggesting differential regulation among the isolates. It is possible to analyze comparative protein expression in more distantly related isolates in the context of WGS data, though the results are more complex to interpret than when isolates are clonal or very closely related. Comparative proteomic analysis produced log 2 fold expression data suggestive of regulatory differences among isolates, indicating that it may be useful as a hypothesis generation exercise to identify regulated proteins and regulatory pathways for more detailed analysis.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...