bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chunking sequence information by mutually predicting recurrent neural networks
Authors: Asabuki Toshitake , Hiratani Naoki , Fukai Tomoki 
Published: November 2017

AbstractInterpretation and execution of complex sequences is crucial for various cognitive tasks such as language processing and motor control. The brain solves this problem arguably by dividing a sequence into discrete chunks of contiguous items. While chunking has been accounted for by predictive uncertainty, alternative mechanisms have also been suggested, and the mechanism underlying chunking is poorly understood. Here, we propose a class of unsupervised neural networks for learning and identifying repeated patterns in sequence input with various degrees of complexity. In this model, a pair of reservoir computing modules, each of which comprises a recurrent neural network and readout units, supervise each other to consistently predict others’ responses to frequently recurring segments. Interestingly, this system generates neural responses similar to those formed in the basal ganglia during habit formation. Our model extends reservoir computing to higher cognitive function and demonstrates its resemblance to sequence processing by cortico-basal ganglia loops.
Paternal grandparental exposure to crop failure or surfeit during a childhood slow growth period: Epigenetic marks on grandchildren’s growth, glucoregulatory and stress genes
Authors: Olov Bygren Lars , Müller Patrick , Brodin David , Kaati Gunnar , Gustafsson Jan-Åke , Kral John G. 
Published: November 2017

ABSTRACTThis latest in our series of papers describes transgenerational methylation related to midchildhood food availability in 19th century Överkalix, Sweden. Failed vs. bountiful crops differentially influenced methylation in grandchildren of paternal grandparents exposed to feast or famine during their Slow Growth Period (SGP), a sensitive period preceding the pre-pubertal growth spurt. In this case-study of 8 tracked 75-year old progeny with differential ancestral exposure, we found, in 40 posited gene ontology pathways, 39 differentially methylated CpG regions (DMRs) related to famine, excess food and food-insecurity stress, 9 of which with DMRs above 5%. Three gene ontology terms (GOs) “insulin processing”, “adipose development” and “hypothalamus development” were key, with DMRs >14%. An unbiased test of known pathways revealed four nuclear transcription factors upstream of promotors repressing the pathway following paternal grandparental famine experience, as well as 4 upregulated GOs with average DMRs >20%. We conclude that this is the first demonstration of human transgenerational inheritance of epigenetic marks following ancestral childhood exposure to variable food availability inducing early developmental origins of adult disease.
Weak spatiotemporal response of prey to predation risk in a freely interacting system
Authors: Cusack Jeremy J. , Kohl Michel T. , Metz Matthew C. , Coulson Tim , Stahler Daniel R. , Smith Douglas W. , MacNulty Daniel R. 
Published: November 2017

AbstractThe extent to which prey space use actively minimises predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured, and lack of robust null expectations.We addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by grey wolves (Canis lupus) during winter in northern Yellowstone, USA.We quantified spatial overlap between the winter home ranges of GPS-collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf-killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterised by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach.Although a small proportion of elk did show a tendency to minimise use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone.Our results suggest that predator-prey interactions may not always result in strong spatiotemporal patterns of avoidance.
Accurate detection of HIV transmission clusters from phylogenetic trees using a multi-state birth-death model
Authors: Barido-Sottani Joëlle , Stadler Tanja 
Published: November 2017

AbstractHIV transmission networks are highly clustered, and accurate identification of these clusters is essential for effective targeting of public health interventions. This clustering affects the transmission dynamics of the HIV epidemic, which affects the pathogen phylogenies reconstructed from patient samples. We present a new method for identifying transmission clusters by detecting the changes in transmission rate provoked by the introduction of the epidemic into a new cluster. The method employs a multi-state birth-death (MSBD) model where each state represents a cluster. Transmission rates in each cluster decrease exponentially over time, simulating susceptible depletion in the cluster. This model is fitted to the pathogen phylogeny using a Maximum Likelihood approach. Using simulated datasets we show that the MSBD method is able to reliably infer both the cluster repartition and the transmission parameters from a pathogen phylogeny. In contrast to existing cutpoint-based methods for cluster identification, which are dependent on a parameter set by the user, the MSBD method is consistently reliable. It also performs better on phylogenies containing nested clusters. We present an application of our method to the inference of transmission clusters using sequences obtained from the Swiss HIV Cohort Study. The MSBD method is available as an R package.
Acute memory deficits in chemotherapy-treated adults
Authors: Lindner Oana C. , Mayes Andrew , McCabe Martin G. , Talmi Deborah 
Published: November 2017

AbstractData from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory-Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients’ first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically-relevant implications.
PKD2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium
Authors: Liu Xiaowen , Vien Thuy , Duan Jingjing , Sheu Shu-Hsien , DeCaen Paul G. , Clapham David E. 
Published: November 2017

ABSTRACTMutations in eitherPkd1orPkd2result in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although PKD2 is proposed to be an ion channel subunit, recordings of PKD2 ion channels conflict in their properties. Using a new ADPKD mouse model, we observe primary cilia are abnormally long in cells associated with cysts. Using primary cultures of collecting duct epithelial cells, we show that PKD2, but not PKD1, is a required subunit for primary cilia ion channel. The ciliary PKD2 channel conducts potassium and sodium ions, but little calcium. We also demonstrate that PKD2 is not constitutively active in the plasma membrane, but PKD2 channels are functional in primary cilia and are sensitized by high cilioplasmic [Ca2+]. We introduce a novel method for measuring PKD2 channels heterologously expressed in primary cilia of HEK-293 cells, which will have utility characterizingPkd2variants that cause ADPKD in their native ciliary membrane.
Lack of insurance is associated with lower probability of diagnostic imaging use among US trauma patients: An instrumental variable analysis and simulation
Authors: Renson Audrey , Schubert Finn D. , Bjurlin Marc A. 
Published: November 2017

ABSTRACTBackgroundUninsured trauma patients have higher mortality than their insured counterparts. One possible reason is disparities in utilization of appropriate diagnostic imaging, including computed tomography (CT), X-ray, ultrasound (US), and magnetic resonance imaging (MRI). We examined the association between lack of insurance and use of diagnostic imaging.MethodsData come from the National Trauma Databank 2010-2015. Patients were determined uninsured if payment mode was self-pay or missing. The primary outcome was any diagnostic imaging procedure, and secondary outcomes included CT, X-ray, US, or MRI. Risk ratios (RRs) were adjusted for demographics, comorbidities, injury characteristics, facility characteristics. We also used the 2010 Patient Protection and Affordable Care Act as an instrumental variable (IV), with linear terms for year to account for annual trends in imaging use. Monte carlo simulations to test effect of hypothetical violations to IV assumptions of relevance, no direct effect, and no confounding.ResultsOf 4,373,554 patients, 953,281 (21.8%) were uninsured. After adjusting, uninsured patients had lower chance of any imaging (RR 0.98, 95% CI 0.98 to 0.98), x-ray (RR 0.99, 95% CI 0.99 to 1.00), and MRI (RR 0.82, 95% CI 0.81 to 0.83), and higher chance of ultrasound (RR 1.01, 95% CI 1.01 to 1.02). In IV analysis, uninsured status was associated with reduction in any imaging (RR 0.60, 95% CI 0.52 to 0.70), tomography (RR 0.52, 95% CI 0.44 to 0.62) ultrasound (RR 0.46, 95% CI 0.32 to 0.65), and MRI (RR 0.19, 95% CI 0.10 to 0.37) and increased likelihood of x-ray use (RR 1.74, 95% CI 1.31 to 2.32). Simulations indicated that a direct effect RD of −0.02 would be necessary to produce observed results under the null hypothesis.DiscussionOur study suggests an association between insurance status and use of imaging that is unlikely to be driven by confounding or violations of IV assumptions. Mechanisms for this remain unclear, but could include unconscious provider bias or institutional financial constraints. Further research is warranted to elucidate mechanisms and assess whether differences in diagnostic imaging use mediate the association between insurance and mortality.
Needle in a haystack? A comparison of eDNA metabarcoding and targeted qPCR for detection of the great crested newt (Triturus cristatus)
Authors: Harper Lynsey R. , Handley Lori Lawson , Hahn Christoph , Boonham Neil , Rees Helen C. , Gough Kevin C. , Lewis Erin , Adams Ian P. , Brotherton Peter , Phillips Susanna , Hänfling Bernd 
Published: November 2017

SummaryEnvironmental DNA (eDNA) analysis is a rapid, cost-effective, non-invasive biodiversity monitoring tool which utilises DNA left behind in the environment by organisms for species detection. The method is used as a species specific survey tool for rare or invasive species across a broad range of ecosystems. Recently, eDNA and ‘metabarcoding’ have been combined to describe whole communities rather than focusing on single target species. However, whether metabarcoding is as sensitive as targeted approaches for rare species detection remains to be evaluated. The great crested newt Triturus cristatus is a flagship pond species of international conservation concern and the first UK species to be routinely monitored using eDNA. We evaluate whether eDNA metabarcoding has comparable sensitivity to targeted real-time quantitative PCR (qPCR) for T. cristatus detection. Extracted eDNA samples (N = 532) were screened for T. cristatus by qPCR and analysed for all vertebrate species using High-Throughput Sequencing technology. With qPCR and a detection threshold of 1/12 positive qPCR replicates, newts were detected in 50% of ponds. Detection decreased to 32% when the threshold was increased to 4/12 positive qPCR replicates. With metabarcoding, newts were detected in 34% of ponds without a detection threshold, and in 28% of ponds when a threshold (0.028%) was applied. Therefore, qPCR provided greater detection than metabarcoding but metabarcoding detection with no threshold was equivalent to qPCR with a stringent detection threshold. The proportion of T. cristatus sequences in each sample was positively associated with the number of positive qPCR replicates (qPCR score) suggesting eDNA metabarcoding may be indicative of eDNA concentration. eDNA metabarcoding holds enormous potential for holistic biodiversity assessment and routine freshwater monitoring. We advocate this community approach to freshwater monitoring to guide management and conservation, whereby entire communities can be initially surveyed to best inform use of funding and time for species-specific surveys.
Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer’s disease
Authors: Liu Hongde , Luo Kun 
Published: November 2017

AbstractAlzheimer’s disease (AD) is a severe neurodegenerative disorder. Identification of differentially expressed genes in AD would help to find biomarker and therapeutic target. Here, we carried out an analysis to identify the age-independent and AD-specific genes. We found that genes MET, WIF1 and NPTX2 are down regulated in AD. WIF1 and MET are in signaling of WNT and MET, regulating the activity of GSK3β, thus in AD. Importantly, we found gene GMPR shows a gradual increase in AD progress. A logistic model based on GMPR exhibits a good capacity in classifying AD cases. GMPR’s product GMPR1 links with AMPK and adenosine receptor pathways, thus associating phosphorylation of Tau in AD. This allows GMPR1 to be a therapeutic target. Therefore, we screened five possible inhibitors to GMPR1 by docking GMPR1 with 1174 approved drugs. Among them, lumacaftor is ideal due to its high affinity and light molecular weight. We then tested the effect of lumacaftor on AD model mice. After twenty days of oral administration, β-Amyloid accumulation is slowed down and phosphorylation of Tau is almost eliminated in the treated mice, showing a satisfying effect. In conclusion, the elevated expression level of GMPR tightly associates with AD progress and leads to AD phenotype probably through AMPK and adenosine receptor pathways; and one of therapeutic strategies is to inhibit GMPR’s product with lumacaftor.Significance StatementWe found the elevated expression level of GMPR tightly associates with AD progress and leads to AD phenotype probably through AMPK and adenosine receptor pathways; and the therapeutic strategy targeting GMPR1 with lumacaftor shows a satisfying result.
Genome scan identifies flowering-independent effects of barley HsDry2.2 locus on yield traits under water deficit
Authors: Merchuk-Ovnat Lianne , Silberman Roi , Laiba Efrat , Maurer Andreas , Pillen Klaus , Faigenboim Adi , Fridman Eyal 
Published: November 2017

AbstractIncreasing crop productivity under climate change requires the identification, selection and utilization of novel alleles for breeding. We analyzed the genotype and field phenotype of the barley HEB-25 multi-parent mapping population under well-watered and water-limited (WW and WL) environments for two years. A genome-wide association study (GWAS) for genotype by-environment interactions was performed for ten traits including flowering time (HEA), plant grain yield (PGY). Comparison of the GWAS for traits per-se to that for QTL-by-environment interactions (QxE), indicates the prevalence of QxE mostly for reproductive traits. One QxE locus on chromosome 2, Hordeum spontaneum Dry2.2 (HsDry2.2), showed a positive and conditional effect on PGY and grain number (GN). The wild allele significantly reduced HEA, however this earliness was not conditioned by water deficit. Furthermore, BC2F1 lines segregating for the HsDry2.2 showed the wild allele confers an advantage over the cultivated in PGY, GN and harvest index as well as modified shoot morphology, longer grain filling period and reduced senescence (only under drought), therefore suggesting adaptation mechanism against water deficit other than escape. This study highlights the value of evaluating wild relatives in search of novel alleles and clues to resilience mechanism underlying crop adaptation to abiotic stress.HighlightA flowering-time independent reproductive advantage of wild over cultivated allele under drought identified in a barley GWAS for genotype-by-environment interactions, with modified shoot morphology, reduced senescence and longer grain filling
TraRECo: A Greedy Approach based de novo Transcriptome Assembler with Read Error Correction using Consensus Matrix
Authors: Yoon Seokhyun , Kim Daeseung , Kang Keunsoo , Park Woong June 
Published: November 2017

AbstractBackgroundChallenges in developing a good de novo transcriptome assembler include how to deal with read errors and sequence repeats. Almost all de novo assemblers utilize de Bruijn graph, which has a complexity linearly growing with data size while suffers from errors and repeat. Although one can correct errors by inspecting topological structure of the graph, it is an uneasy task when there are too many branches. There are two research directions: improving either graph reliability or path search precision. We focused on improving the reliability.ResultsWe present TraRECo, a greedy approach to de novo assembly employing error-aware graph construction. The idea is similar to overlap-layout-consensus approach used for genome assembly, but is different in that consensus is made through the entire graph construction step. Basically, we built contigs by direct read alignment within a distance margin and performed junction search to construct splicing graphs. While doing so, however, a contig of length l was represented by 4×1 matrix (called consensus matrix), of which each element was the base count of aligned reads so far. A representative sequence is obtained, by taking majority in each column of the consensus matrix, to be used for further read alignment. Once splicing graphs were obtained, we used IsoLasso to find paths with noticeable read depth. The experiments using real and simulated reads showed that the method provides considerable improvements in sensitivity and reasonably better performances when comparing both sensitivity and precision. This could be achieved by making more erroneous reads to be participated in graph construction, which, in turn, improved the depth information quality used for the subsequent path search step. The results for simulated reads showed also challenges are still remaining since non-negligible percentage of transcripts with high abundance were not recovered by the assemblers we considered.Conclusionde novo assembly is mainly to explore not-yet-discovered isoforms and must be able to represent as much reads as possible in an efficient way. In this sense, TraRECo provides us a potential alternative to improve graph reliability, even though the computational burden can be much higher than single k-mer de Bruijn graph approach.
Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription
Authors: Sharma Priyanka , Lioutas Antonios , Fernandez-Fuentes Narcis , Quilez Javier , Carbonell-Caballero José , Wright Roni H.G. , Di Vona Chiara , Le Dily François , Schüller Roland , Eick Dirk , Oliva Baldomero , Beato Miguel 
Published: November 2017

HighlightsPeptidyl arginine deiminase 2 (PADI2) citrullinates arginine1810 (cit1810) present at carboxy-terminal domain of RNA polymerase II (RNAP2-CTD).PADI2 and R1810 of RNAP2-CTD regulate transcription and proliferation of breast cancer cells.Absence of cit1810 at RNAP2-CTD leads to RNAP2 accumulation at proximal promoter regions.Cit1810 at RNAP2-CTD facilitate interaction with P-TFEb complex.SUMMARYThe post-translational modification of key residues at the carboxy-terminal domain of RNA polymerase II (RNAP2-CTD), coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases including cancer. We show that among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 result in accumulation of RNAP2 at transcription start sites, reduced gene expression and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells.
A biophysical dynamic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN)
Authors: Hernández-Hernández Valeria , Barrio Rafael A. , Benítez Mariana , Nakayama Naomi , Romero-Arias José Roberto , Villarreal Carlos 
Published: November 2017

ABSTRACTIntracellular polarisation of auxin efflux carriers is crucial for understanding how auxin gradients form in plants. The polarisation dynamics of auxin efflux carriers PIN-FORMED (PIN) depends on both biomechanical forces as well as chemical, molecular and genetic factors. Biomechanical forces have shown to affect the localisation of PIN transporters to the plasma membrane. We proposed a biophysical module of PIN polarisation that integrates biomechanical, molecular, and cellular processes as well as their non-linear interactions. The module was implemented as a discrete Boolean model and then approximated to a continuous dynamic system, in order to explore the relative contribution of the factors mediating PIN polarisation at the scale of single cell. Our models recovered qualitative behaviours that have been experimentally observed and enabled us to postulate that, in the context of PIN polarisation, the effects of the mechanical forces can predominate over the activity of molecular factors such as the GTPase ROP6 and the CRIB-motif CRIB-motif RIC1.