bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exclusion and genomic relatedness methods for assignment of parentage using genotyping-by-sequencing data
Authors: Dodds K. G. , McEwan J. C. , Brauning R. , van Stijn T. C. , Rowe S. J. , McEwan K. M. , Clarke S. M. 
Published: March 2019

SummaryGenotypes are often used to assign parentage in agricultural and ecological settings. Sequencing can be used to obtain genotypes but does not provide unambiguous genotype calls, especially when sequencing depth is low in order to reduce costs. In that case, standard parentage analysis methods no longer apply. A strategy for using low-depth sequencing data for parentage assignment is developed here. It entails the use of relatedness estimates along with a metric termed excess mismatch rate which, for parent-offspring pairs or trios, is the difference between the observed mismatch rate and the rate expected under a model of inheritance and allele reads without error. When more than one putative parent has similar statistics, bootstrapping can provide a measure of the relatedness similarity. Putative parent-offspring trios can be further checked for consistency by comparing the offspring’s estimated inbreeding to half the parent relatedness. Suitable thresholds are required for each metric. These methods were applied to a deer breeding operation consisting of two herds of different breeds. Relatedness estimates were more in line with expectation when the herds were analysed separately than when combined, although this did not alter which parents were the best matches with each offspring. Parentage results were largely consistent with those based on a microsatellite parentage panel with three discordant parent assignments out of 1561. Two models are investigated to allow the parentage metrics to be calculated with non-random selection of alleles. The tools and strategies given here allow parentage to be assigned from low-depth sequencing data.
Cross-transmission is not the source of newMycobacterium abscessusinfections in a multi-centre cohort of cystic fibrosis patients
Authors: Doyle Ronan M. , Rubio Marc , Dixon Garth , Hartley John , Klein Nigel , Coll Pere , Harris Kathryn A. 
Published: March 2019

AbstractBackgroundMycobacterium abscessusis an extensively drug resistant pathogen that causes pulmonary disease particularly in cystic fibrosis (CF) patients. Identifying direct patient-to-patient transmission ofM. abscessusis critically important in directing infection control policy for the management of risk in CF patients. A variety of clinical labs have used molecular epidemiology to investigate transmission. However there is still conflicting evidence as to howM. abscessusis acquired and whether cross-transmission occurs. Recently labs have applied whole-genome sequencing (WGS) to investigate this further and in this study we investigate whether WGS can reliably identify cross-transmission inM. abscessus.MethodsWe retrospectively sequenced the whole genomes of 145M. abscessusisolates from 62 patients seen at four hospitals in two countries over 16 years.ResultsWe have shown that a comparison of a fixed number of core single nucleotide variants (SNVs) alone cannot be used to infer cross-transmission inM. abscessusbut does provide enough information to replace multiple existing molecular assays. We detected one episode of possible direct patient-to-patient transmission in a sibling pair. We found that patients acquired uniqueM. abscessusstrains even after spending considerable time on the same wards with otherM. abscessuspositive patients.ConclusionsThis novel analysis has demonstrated that the majority of patients in this study have not acquiredM. abscessusthrough direct patient-patient transmission or a common reservoir. Tracking transmission using WGS will only realise its full potential with proper environmental screening as well as patient sampling.Key pointsWhole genome sequencing should replace current molecular typing used routinely in clinical microbiology laboratories.Patient-to-patient spread ofM. abscessusis not common.Environmental screening may provide a better understanding acquisition ofM. abscessusinfections.
Non-medical prescribing policy in the United Kingdom National Health Service: systematic review and narrative synthesis
Authors: Graham-Clarke Emma , Rushton Alison , Noblet Timothy , Marriott John 
Published: March 2019

AbstractNon-medical prescribing was introduced into the United Kingdom (UK) to improve patient care, through extending healthcare professionals’ roles. More recent government health service policy focuses on the increased demand and the need for efficiency. This systematic review aimed to describe any changes in government policy position and the role that non-medical prescribing plays in healthcare provision.The systematic review and narrative analysis included policy and consultation documents that describe independent non-medical prescribing. A pre-defined protocol was registered with PROSPERO (CRD42015019786). Professional body websites, other relevant websites and the following databases were searched to identify relevant papers: HMIC, Lexis Nexis, UK Government Web Archive, UKOP, UK Parliamentary Papers and Web of Science. Papers published between 2006 and February 2018 were included.Following exclusions, 45 papers were selected for review; 23 relating to policy or strategy and 22 to consultations. Of the former, 13/23 were published 2006-2010 and the remainder since 2013. Two main themes are identified: chronological aspects and healthcare provision. The impact of government change and associated major healthcare service reorganisation resulted in the publication gap for policy documents. The role of non-medical prescribing has evolved to support efficient service delivery, and cost reduction. For many professions, prescribing appears embedded into practice; however, pharmacy continues to produce policy documents, suggesting that prescribing is not yet perceived as normal practice.Prescribing appears to be more easily adopted into practice where it can form part of the overall care of the patient. Where new roles are required to be established, then prescribing takes longer to be universally adopted. While this research concerns policy and practice in the UK, this aspect of role adoption has wider potential implications.
Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke
Authors: Allegra Mascaro Anna Letizia , Conti Emilia , Lai Stefano , Giovanna Antonino Paolo Di , Spalletti Cristina , Alia Claudia , Panarese Alessandro , Scaglione Alessandro , Sacconi Leonardo , Micera Silvestro , Caleo Matteo , Pavone Francesco Saverio 
Published: March 2019

SummaryRehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor recovery prompted by rehabilitative therapy. Here, we investigated which aspects of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We revealed that the stabilization of peri-infarct synaptic contacts fostered by rehabilitation goes along with increased vascular density induced by angiogenesis. Furthermore, we showed the progressive formation of a new motor representation in the peri-infarct area where temporal and spatial features of cortical activation recovered towards pre-stroke condition. In the same animals we observed the reinforcement of inter-hemispheric connectivity after rehabilitation. The present work provides the first evidences that rehabilitation promotes the combined recovery of structural and functional features distinctive of healthy neuronal networks.
Neuronal histone methyltransferase EZH2 regulates neuronal morphogenesis, synaptic plasticity, and cognitive behavior of mice
Authors: Zhang Mei , Zhang Yong , Xu Qian , Crawford Joshua , Qian Cheng , Wang Guo-Hua , Lewis Eastman , Hall Philip , Dolen Gül , Huganir Richard L. , Qian Jiang , Dong Xin-Zhong , Pletnikov Mikhail V. , Liu Chang-Mei , Zhou Feng-Quan 
Published: March 2019

AbstractRecent studies showed that in the nervous system histone methyltransferase EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) acts to regulate neural stem cell proliferation and fate specificity through silencing different gene sets. Here we explored the function of EZH2 in early post-mitotic excitatory neurons by generating a neuronal specific Ezh2 conditional knockout mouse line. The results showed that lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and significantly increased dendritic spine density. RNA-sequencing (RNA-seq) experiments comparing control and Ezh2 knockout neurons revealed that neuronal EZH2 regulated genes related to neuronal morphogenesis. In particular, Pak3 was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of dominant negative PAK3 reversed Ezh2 knockout-induced higher dendritic spine density. Lastly, lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 played important roles in controlling multiple steps of neuronal morphogenesis during development, which had long-lasting effects on cognitive function in adult mice.
Microfluidic Rapid and Autonomous Analytical Device (microRAAD) to Detect HIV from Whole Blood Samples
Authors: Phillips Elizabeth A. , Moehling Taylor J. , Ejendal Karin F.K. , Hoilett Orlando S. , Byers Kristin M. , Basing Laud Anthony , Jankowski Lauren A. , Bennett Jackson B. , Lin Li-Kai , Stanciu Lia A. , Linnes Jacqueline C. 
Published: March 2019

AbstractEarly Human Immunodeficiency Virus (HIV) testing is critical to preventing transmission and providing treatment to HIV-positive individuals, yet an estimated 30% of HIV-positive individuals do not know their status because of barriers to early diagnosis. Readily accessible, highly sensitive, and rapid diagnostic tests would enable patients’ prompt treatment with anti-retroviral therapies and reduce transmission. However, existing HIV diagnostic technologies either do not detect early stages of infection or require multiple days of laboratory processing, delaying notification of patients’ status.Molecular techniques that amplify HIV RNA can detect the earliest stages of infection, within 8-10 days after transmission. However, most of these molecular assays require cold-chain storage of reagents, significant sample preparation, and extensive laboratory infrastructure. To achieve early detection, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay with a limit of detection of 10 HIV-1 RNA copies visualized by eye using a lateral flow immunoassay. To demonstrate automated sample-to-answer detection of HIV, we incorporate dried amplification reagents and wax valves in low-cost substrates with resistive heating elements and circuitry. By combining controlled heating with paper’s capillary flow, our assembled device automatically isolates viral particles from human blood samples, amplifies HIV-1 RNA, and transports products to a detection zone. We determine that as few as 105HIV-1 viral particles can be separated from whole blood, amplified, and visually detected within 90 minutes of sample addition into our Microfluidic Rapid and Autonomous Analysis Device (microRAAD). The low-cost and automated attributes of microRAAD demonstrate its utility as a point-of-care testing platform.
Mechanosensing by the lamina protects against nuclear rupture, DNA damage, and cell cycle arrest
Authors: Cho Sangkyun , Vashisth Manasvita , Abbas Amal , Majkut Stephanie , Vogel Kenneth , Xia Yuntao , Ivanovska Irena L. , Irianto Jerome , Tewari Manorama , Zhu Kuangzheng , Tichy Elisia D. , Mourkioti Foteini , Tang Hsin-Yao , Greenberg Roger A. , Prosser Benjamin L. , Discher Dennis E. 
Published: March 2019

SummaryWhether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (~1hr) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. Embryonic hearts, differentiated iPS-cells, and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and by contractility modulators in clinical trials. Contractile cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility is seen to minimize DNA damage. Lamin-A is thus stress-stabilized to mechano-protect the genome.
Assessing the role of long-noncoding RNA in nucleus accumbens in subjects with alcohol dependence
Authors: McMichael Gowon O. , Drake John , Vornholt Eric Sean , Cresswell Kellen , Williamson Vernell , Chatzinakos Chris , Mamdani Mohammed , Hariharan Siddharth , Kendler Kenneth S. , Miles Michael F. , Kalsi Gursharan , Riley Brien P. , Dozmorov Mikhail , Bacanu Silviu-Alin , Vladimirov Vladimir I. 
Published: March 2019

AbstractRecently, long noncoding RNA (lncRNA) were implicated in the etiology of alcohol dependence (AD). As lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step towards understanding lncRNA functions in AD. To that end, we profiled the expression of lncRNA and protein coding genes (PCG) in nucleus accumbens (NAc) from 41 subjects with AD and 41 controls. At false discovery rate (FDR) of 5%, we identified 69 and 309 differentially expressed lncRNA and PCG genes, respectively. Using co-expression network analyses, we identified three lncRNA and five PCG modules significantly correlated with AD at Bonferroni adj. p≤0.05. To better understand lncRNA functions, we integrated the lncRNA and PCG hubs from the significant AD modules; at FDR of 5%, we identified 3 151 positive and 2 255 negative correlations supporting the functional role of lncRNA in the development of AD. Gene enrichment analysis revealed that PCG significantly correlated with lncRNA are, among others, enriched for neuronal and immune related processes. To highlight the mechanisms, by which genetic variants contribute to AD, we integrated lncRNA and PCG hubs with genome-wide SNP data. At FDR≤0.3, we identified 276 expression quantitative trait loci (eQTL), affecting the expression of 20 and 256 lncRNA and PCG hubs, respectively. Our study is the first to profile lncRNA expression in nucleus accumbens in a large postmortem alcohol brain sample and our results may provide novel insights into the regulation of the brain transcriptome across disease.
Neutrophil-derived extracellular vesicles: proinflammatory trails and anti-inflammatory microvesicles
Authors: Youn Young-Jin , Shrestha Sanjeeb , Kim Jun-Kyu , Lee Yu-Bin , Lee Jee Hyun , Hur Keun , Mali Nanda Maya , Nam Sung-Wook , Kim Sun-Hwa , Song Dong-Keun , Jin Hee Kyung , Bae Jae-sung , Hong Chang-Won 
Published: March 2019

SUMMARYExtracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we investigated the similarities and differences between neutrophil-derived EV subtypes. Neutrophil-derived EVs shared similar characteristics regarding stimulators, generation mechanisms, and surface marker expression. Both neutrophil-derived EV subtypes exhibited similar functions, such as direct bactericidal activity and induction of monocyte chemotaxis via MCP-1. However, NDTR generation was dependent on the integrin signaling, while NDMV generation was dependent on the PI3K pathway. The CD16 expression level differentiated the neutrophil-derived EV subtypes. Interestingly, both subtypes showed different patterns of miRNA expression and were easily phagocytosed by monocytes. NDTRs induced M1 macrophage polarization, whereas NDMVs induced M2 macrophage polarization. Moreover, NDTRs but not NDMVs exerted protective effects against sepsis-induced lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. These results suggest a new insight into neutrophil-derived EV subtypes: proinflammatory NDTRs and anti-inflammatory NDMVs.Key pointsNeutrophil-derived trails are proinflammatory extracellular vesicles that induce M1 macrophage polarization and protect against inflammationNeutrophil-derived microvesicles are anti-inflammatory extracellular vesicles that induce M2 macrophage polarization
A regulatory RNA is associated to invasive meningococcal disease in Europe
Authors: Karlsson Jens , Eichner Hannes , Jacobsson Susanne , Loh Edmund 
Published: March 2019

AbstractThe strictly human pathogenNeisseria meningitidisis a commensal bacterium but can occasionally turn lethal causing septicaemia and meningitis. The mechanisms of how the meningococcus shifts to invasive infection remain poorly understood. Here we demonstrate that an eight base-pair tandem repeat deletion in the 5’-untranslated region of the polysaccharide capsular biosynthesis operon results in a hypercapsulation phenotype in clinical isolates. The increased capsule production significantly improves the bacterium survival in human serum while impairing its ability to adhere and colonise human pharyngeal cells. Among 4501 reported meningococcal cases in Europe from 2010-2018, the loss of an eight base-pair tandem repeat is three times more prevalent in invasive isolates (16.3%) compared to carrier isolates (5.1%).Combined results indicate that polymorphisms in this regulatory RNA contributes to meningococcal virulence.ImportanceIn this study we report a regulatory RNA to be directly involved in clinical manifestation of meningococcal disease. Using readily accessible WGS of meningococcus, we have now demonstrated that regulatory RNAs directly contribute to the progression of invasive meningococcal infection. We believe this novel combination of molecular and comparative regulatory RNA study could be used for the identification of additional RNAs involved in not only meningococcus but also pave the way for similar studies in other important bacterial pathogens. The identification of specific regulatory RNAs will no doubt facilitate clinicians, microbiologists, and public health practitioners to adjust their diagnostic techniques and treatments to best fit the condition of the patients.
The circadian clock contributes to the long-term water use efficiency of Arabidopsis
Authors: Simon Noriane M. L. , Graham Calum A. , Comben Nicholas E. , Hetherington Alistair M. , Dodd Antony N. 
Published: March 2019

AbstractIn plants, water use efficiency is a complex trait derived from numerous physiological and developmental characteristics. Here, we investigated the involvement of circadian regulation in long-term water use efficiency. Circadian rhythms are generated by the circadian oscillator, which provides a cellular measure of the time of day. In plants, the circadian oscillator contributes to the regulation of many aspects of physiology, including stomatal opening, the rate of photosynthesis, carbohydrate metabolism and developmental processes. We investigated in Arabidopsis the impact of the misregulation of genes encoding a large number of components of the circadian oscillator upon whole plant, long-term water use efficiency. From this, we identified a role for the circadian oscillator in water use efficiency. This appears to be due to contributions of the circadian clock to the control of transpiration and biomass accumulation. We also identified that the circadian oscillator within guard cells can contribute to long-term water use efficiency. Our experiments indicate that knowledge of circadian regulation will be important for developing future crops that use water more efficiently.One-sentence summaryThe circadian clock in Arabidopsis makes an important contribution to long-term water use efficiency.
An evaluation of pool-sequencing transcriptome-based exon capture for population genomics in non-model species
Authors: Deleury Emeline , Guillemaud Thomas , Blin Aurélie , Lombaert Eric 
Published: March 2019

AbstractExon capture coupled to high-throughput sequencing constitutes a cost-effective technical solution for addressing specific questions in evolutionary biology by focusing on expressed regions of the genome preferentially targeted by selection. Transcriptome-based capture, a process that can be used to capture the exons of non-model species, is use in phylogenomics. However, its use in population genomics remains rare due to the high costs of sequencing large numbers of indexed individuals across multiple populations. We evaluated the feasibility of combining transcriptome-based capture and the pooling of tissues from numerous individuals for DNA extraction as a cost-effective, generic and robust approach to estimating the variant allele frequencies of any species at the population level. We designed capture probes for ∼5 Mb of chosende novotranscripts from the Asian ladybirdHarmonia axyridis(5,717 transcripts). We called ∼300,000 bi-allelic SNPs for a pool of 36 non-indexed individuals. Capture efficiency was high, and pool-seq was as effective and accurate as individual-seq for detecting variants and estimating allele frequencies. Finally, we also evaluated an approach for simplifying bioinformatic analyses by mapping genomic reads directly to targeted transcript sequences to obtain coding variants. This approach is effective and does not affect the estimation of SNP allele frequencies, except for a small bias close to some exon ends. We demonstrate that this approach can also be used to predict the intron-exon boundaries of targetedde novotranscripts, making it possible to abolish genotyping biases near exon ends.
Cell cycle inhibitor Whi5 records environmental information to coordinate growth and division in yeast
Authors: Qu Yimiao , Jiang Jun , Liu Xiang , Wei Ping , Yang Xiaojing , Tang Chao 
Published: March 2019

SUMMARYProliferating cells need to evaluate the environment to determine the optimal timing for cell cycle entry, which is essential for coordinating cell division and growth. In the budding yeast Saccharomyces cerevisiae, the commitment to the next round of division is made in G1 at the Start, triggered by the inactivation of the inhibitor Whi5 through multiple mechanisms. However, how a cell reads environmental condition and uses this information to regulate Start is poorly understood. Here, we show that Whi5 is a key environmental indicator and plays a crucial role in coordinating cell growth and division. We found that under a variety of nutrient and stress conditions, the concentration of Whi5 in G1 is proportional to the doubling time in the environment. Thus, under a poorer condition a longer doubling time results in a higher Whi5 concentration, which in turn delays the next cell cycle entry to ensure sufficient cell growth. In addition, the coordination between division and the environment is further fine-tuned in G1 by environmentally dependent G1 cyclin-Cdk1 contribution and Whi5 threshold at Start. Our results show that Whi5 serves as an environmental ‘memory’ and that the cell adopts a simple and elegant mechanism to achieve an adaptive cellular decision making.