bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal-neocortical interactions sharpen over time for predictive actions
Authors: Hindy Nicholas C. , Avery Emily W. , Turk-Browne Nicholas B. 
Published: December 2018

AbstractWhen an action is familiar, we are able to anticipate how it will change the state of the world. These expectations can result from retrieval of action-outcome associations in the hippocampus and the reinstatement of anticipated outcomes in visual cortex. How does this role for the hippocampus in action-based prediction change over time? We used high-resolution fMRI and a dual-training behavioral paradigm to examine how the hippocampus interacts with visual cortex during predictive and nonpredictive actions learned either three days earlier or immediately before the scan. Just-learned associations led to comparable background connectivity between the hippocampus and V1/V2, regardless of whether actions predicted outcomes. However, three-day-old associations led to stronger background connectivity and greater differentiation between neural patterns for predictive vs. nonpredictive actions. Hippocampal prediction may initially reflect indiscriminate binding of co-occurring of events, with action information pruning weaker associations and leading to more selective and accurate predictions over time.
Genetic differences in host infectivity affect disease spread and survival in epidemics
Authors: Anacleto Osvaldo , Cabaleiro Santiago , Villanueva Beatriz , Saura María , Houston Ross D. , Woolliams John A. , Doeschl-Wilson Andrea B. 
Published: December 2018

AbstractSurvival during an epidemic is partly determined by host genetics. While quantitative genetic studies typically consider survival as an indicator for disease resistance, mortality rates of populations undergoing an epidemic are also affected by tolerance and infectivity (i.e. the propensity of an infected individual to transmit disease). Few studies have demonstrated genetic variation in disease tolerance, and no study has demonstrated genetic variation in host infectivity, despite strong evidence for considerable phenotypic variation in this trait. Here we propose an experimental design and statistical models for estimating genetic diversity in all three host traits. Using an infection model in fish we provide, for the first time, direct evidence for genetic variation in host infectivity, in addition to variation in resistance and tolerance. We also demonstrate how genetic differences in these three traits contribute to survival. Our results imply that animals can evolve different disease response types affecting epidemic survival rates, with important implications for understanding and controlling epidemics.
How to improve foraging efficiency for restocking measures of juvenile Baltic sturgeon (Acipenser oxyrinchus)
Authors: Cámara-Ruiz Maria , Santo Carlos Espirito , Gessner Joern , Wuertz Sven 
Published: December 2018

ABSTRACTAtlantic sturgeon (Acipenser oxyrinchus), also known as Baltic sturgeon, is considered missing or extinct in German waters. Current conservation efforts focus on re-stocking activities, but classical hatchery rearing may reduce the fitness of the respective juveniles. In this study, we evaluated if foraging efficiency can be improved by short term training. Over a period of 14 d, we kept individuals of the training group in a raceway and fed them chironomids buried in a small sand spot to stimulate benthic feeding behavior while fish of the control group were fed in tanks without substrate. Thereafter, each fish was transferred to a raceway entirely covered with sand. For feeding, chironomids were randomly buried in the sand. During the first 7 days, trained fish recovered the feed significantly faster than untrained fish of the control group. Gene expression revealed an up-regulation in neurod1 in all brain regions after 14 d of training. Thus, this study suggests that foraging efficiency can be improved through short-time training thus improve fitness upon restocking into the wild.
NucMerge: Genome assembly quality improvement assisted by alternative assemblies and paired-end Illumina reads
Authors: Khelik Ksenia , Nederbragt Alexander Johan , Sandve Geir Kjetil , Rognes Torbjørn 
Published: December 2018

AbstractBackgroundIn spite of the major breakthroughs in the second-generation sequencing technologies and the developments of a plethora of assemblers over the last ten years, the resulting genome assemblies may still be fragmented and contain errors. It is typical in genome projects with second-generation reads involved to run multiple assemblers with different parameters and choose the best assembly. However, such an approach is always a trade-off between the strengths and weaknesses of the assemblies. To exploit the advantages of different assemblers, an alternative approach that combines the best parts of several assemblies into one may be applied. The existing tools based on such an approach assist in elongation of assembly fragments and/or improvement of assembly accuracy. Though there has been progress with such a strategy, there is still room for improvement of the existing tools.ResultsWe present NucMerge, a tool for improving genome assembly accuracy by incorporating information derived from an alternative assembly and paired-end Illumina reads from the same genome. The tool corrects insertion, deletion, substitution, and inversion errors and locates different inter- and intra-chromosomal rearrangement errors. NucMerge was compared to two existing alternatives, namely Metassembler and GAM-NGS.ConclusionsThe benchmarking results show that NucMerge has generally better performance than the other tools tested, providing accuracy improvement of more assemblies. NucMerge is freely available at https://github.com/uio-bmi/NucMerge under the MPL license.
A critical role for human ventromedial frontal lobe in value comparison based on multi-attribute configuration
Authors: Pelletier Gabriel , Fellows Lesley K. 
Published: December 2018

ABSTRACTReal-life decisions are often between options with multiple value-relevant attributes. Neuroeconomic models propose that the value associated with each attribute is integrated in a global value for each option. However, evidence from patients with ventromedial frontal (VMF) damage argues against a very general role for this region in value integration, suggesting instead that it contributes critically to specific value inference or comparison processes. Here, we tested value-based decision-making between artificial multi-attribute objects in 12 men and women with focal damage to VMF, compared to a healthy control group (N=24) and a control group with frontal lobe damage sparing VMF (N=12). In a ‘configural’ condition, overall object value was predicted by the conjunction of two attributes, while in an ‘elemental’ condition, object value could be assessed by combining the independent values of individual attributes. Patients with VMF damage were impaired in making choices when value was uniquely predicted by the configuration of attributes, but intact when choosing based on elemental attribute-values. This is evidence that VMF is critical for inferring the value of whole objects in multi-attribute choice. These findings have implications for models of value-based choice, and add to emerging views of how this region may interact with medial temporal lobe systems involved in configural object processing and relational memory.
Nanoparticle-based local translation reveals mRNA as translation-coupled scaffold with anchoring function
Authors: Kashida Shunnichi , Wang Dan Ohtan , Saito Hirohide , Gueroui Zoher 
Published: December 2018

AbstractSpatial regulations of mRNA translation are central to cellular functions and relies on numerous complex processes. Biomimetic approaches could bypass the endogenous complex processes, improve our comprehension, and allow for controlling local translation regulations and functions. However, the causality between localizing translation and nascent protein function remains elusive. Here, we develop a novel nanoparticle-based strategy to magnetically control mRNA spatial patterns in mammalian cell extracts and investigate how local translation impacts nascent protein localization and function. By monitoring translation on magnetically localized mRNAs, we show that mRNA-nanoparticle operates as a source for the continuous production of proteins from defined positions. By applying magnetic localization of mRNAs coding for Actin Binding Proteins, we trigger the local formation of actin cytoskeleton and identify minimal requirements for spatial control of actin filament network. In addition, our bottom-up approach identifies a novel role of mRNA as translation-coupled scaffold for nascent N-terminal protein domain functions. Our approach will serve as a novel platform for regulating mRNA localization and investigating a functional role of nascent protein domains during translation.
Optimal metabolic states in cells
Authors: Liebermeister Wolfram 
Published: December 2018

AbstractCells, in order to thrive, make efficient use of metabolites, proteins, energy, membrane space, and time. How, for example, should they allocate the available amount of protein to different metabolic pathways or cell functions? To model metabolic behaviour as an economic problem, some flux analysis model, kinetic models, and cell models apply optimality principles. However, due to their different assumptions these models are hard to compare and combine. Benefits and costs of metabolic pathways – e.g. favouring high production fluxes and low metabolite and enzyme cost – can be derived from general fitness objectives such as fast cell growth. To define pathway objectives, we may assume “optimistically” that, given a pathway state, any cell variables outside the pathway will be chosen for maximal fitness. The resulting fitness defines an effective pathway objective as a function of the pathway variables. Here I propose a unified theory that considers kinetic models, describes the set of feasible states as a state manifold and score each state by cost and benefit functions for fluxes, metabolite concentrations, and enzyme levels. To screen the state manifold and to find optimal states, the problem can be projected into flux, metabolite, or enzyme space, where effective cost and benefit functions are used. We reobtain existing modelling approaches such as enzyme cost minimisation or nonlinear versions of Flux Balance Analysis. Due to their common origin, the different approaches share mathematical optimality conditions of the same form. A general theory of optimal metabolic states, as proposed here, provides a logical link between existing modelling approaches and can help justify, interconvert, and combine metabolic optimality problems.
Evolution of dispersal can rescue populations from expansion load
Authors: Peischl Stephan , Gilbert Kimberly J. 
Published: December 2018

AbstractUnderstanding the causes and consequences of range expansions or range shifts has a long history in evolutionary biology. Recent theoretical, experimental, and empirical work has identified two particularly interesting phenomena in the context of species range expansions: (i) gene surfing and the relaxation of natural selection, and (ii) spatial sorting. The former can lead to an accumulation of deleterious mutations at range edges, causing an expansion load and slowing down expansion. The latter can create gradients in dispersal-related traits along the expansion axis and cause an acceleration of expansion. We present a theoretical framework that treats spatial sorting and gene surfing as spatial versions of natural selection and genetic drift, respectively. This model allows us to study analytically how gene surfing and spatial sorting interact, and to derive the probability of fixation of pleiotropic mutations at the expansion front. We use our results to predict the co-evolution of mean fitness and dispersal rates, taking into account the effects of random genetic drift, natural selection and spatial sorting, as well as correlations between fitnessand dispersal-related traits. We identify a “rescue effect” of spatial sorting, where the evolution of higher dispersal rates at the leading edge rescues the population from incurring expansion load.
The value structure of metabolic states
Authors: Liebermeister Wolfram 
Published: December 2018

AbstractTo improve their metabolic performance, cells need to find compromises between high metabolic fluxes, low enzyme investments, and well-adapted metabolite concentrations. In mathematical models, such compromises can be described by optimality problems that trade metabolic benefit against enzyme cost. While many such modelling frameworks exist, they are often hard to compare and combine. To unify these modelling approaches, I propose a theory that characterises metabolic systems by a value structure, that is, a pattern of local costs and benefits assigned to all elements in the network. The economic values of metabolites, fluxes, and enzymes are interlinked by local balance equations. Formally defined as shadow values, the economic variables serve as local proxies for benefits that arise anywhere in the network, but are represented as local costs or benefits in the reaction of interest. Here I derive economic variables and their balance equations for kinetic, stoichiometric, and cell models. Metabolic value theory provides a new perspective on biochemical networks, defines concepts for comparing and combining metabolic optimality problems, and is useful for semi-automatic, layered, and modular modelling.
Effects of FLOWERING LOCUS T on FD during the transition to flowering at the shoot apical meristem of Arabidopsis thaliana
Authors: Collani Silvio , Neumann Manuela , Yant Levi , Schmid Markus 
Published: December 2018

ABSTRACTThe transition to flowering is a crucial step in the plant life cycle that is controlled by multiple endogenous and environmental cues, including hormones, sugars, temperature, and photoperiod. Permissive photoperiod induces FLOWERING LOCUS T (FT) in the phloem companion cells of leaves. The FT protein then acts as a florigen that is transported to the shoot apical meristem (SAM) where it physically interacts with the bZIP transcription factor FD and 14-3-3 proteins. However, despite the importance of FD for promoting flowering, its direct transcriptional targets are largely unknown. Here we combined ChIP-seq and RNA-seq to identify targets of FD at the genome-wide scale and assess the contribution of FT to binding DNA. We further investigated the ability of FD to form protein complexes with FT and TFL1 through the interaction with 14-3-3 proteins. Importantly, we observe direct binding of FD to targets involved in several aspects of the plant development not directly related to the regulation of flowering time. Our results confirm FD as central regulator of the floral transition at the shoot meristem and provides evidence for crosstalk between the regulation of flowering and other signaling pathways.Material DistributionThe author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.cell.com/molecular-plant/authors): Markus Schmid (markus.schmid@umu.se).Contact InformationUmeå Plant Science Centre (UPSC), Dept. of Plant Physiology Umeå University, SE-901 87 Umeå, SWEDEN
Expanded genomic analyses for male voice-breaking highlights a shared phenotypic and genetic basis between puberty timing and hair colour
Authors: Hollis Ben , Day Felix R. , Busch Alexander S. , Thompson Deborah J. , Soares Ana Luiza G. , Timmers Paul R.H.J. , Kwong Alex , Easton Doug F. , Joshi Peter K. , Timpson Nicholas J. ,   The PRACTICAL Consortium,   23andMe Research Team, Ong Ken K. , Perry John R.B. 
Published: December 2018

AbstractThe timing of puberty is highly variable and has important consequences for long-term health. Most of our understanding of the genetic control of puberty timing is based on studies in women, as age at menarche is often recorded. Here, we report a multi-trait genome-wide association study for male puberty timing, based on recalled timing of voice breaking and facial hair, with an effective sample size of 205,354 men, nearly four-fold larger than previously reported. We identify 78 independent signals for male puberty timing, including 29 signals not previously associated with puberty in either sex. Novel mechanisms include an unexpected phenotypic and genetic link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and, in Mendelian randomization analyses, shows causal relationships with higher risk of prostate cancer and shorter lifespan. These findings highlight the relationships between puberty timing and later health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.
Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus infection in South Africa
Authors: Mokaya Jolynne , Burn Edward , Tamandjou Cynthia Raissa , Goedhals Dominique , Barnes Eleanor , Andersson Monique , Pinedo-Villanueva Rafael , Matthews Philippa C 
Published: December 2018

ABSTRACTIn light of sustainable development goals for 2030, an important priority for Africa is to have affordable, accessible and sustainable hepatitis B virus (HBV) prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3,940 per infection avoided. S3 led to more infections and higher costs. Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa.
A cell-of-origin epigenetic tracer reveals clinically distinct subtypes of high grade serous ovarian cancer
Authors: Riso Pietro Lo , Villa Carlo Emanuele , Gasparoni Gilles , Luongo Raffaele , Manfredi Anna , Vingiani Andrea , Jungmann Annemarie , Garbi Annalisa , Lupia Michela , Laise Pasquale , Das Vivek , Pruneri Giancarlo , Viale Giuseppe , Colombo Nicoletta , Cavallaro Ugo , Cacchiarelli Davide , Walter Jörn , Testa Giuseppe 
Published: December 2018

AbstractHigh grade serous ovarian cancer (HGSOC) is a major unmet need in oncology. The persistent uncertainty on its originating tissue has contributed to hamper the discovery of oncogenic pathways and effective therapies. Here we define the DNA methylation print that distinguishes the human fimbrial (FI) and ovarian surface epithelia (OSE) and develop a robust epigenetic cell-of-origin tracer that stratifies HGSOC in FI-and OSE-originated tumors across all available cohorts. We translate this origin-based stratification into a clinically actionable transcriptomic signature, demonstrating its prognostic impact on patients’ survival and identifying novel network level dysregulations specific for the two disease subtypes.
QTG-Finder: a machine-learning based algorithm to prioritize causal genes of quantitative trait loci
Authors: Lin Fan , Fan Jue , Rhee Seung Y. 
Published: December 2018

AbstractLinkage mapping is one of the most commonly used methods to identify genetic loci that determine a trait. However, the loci identified by linkage mapping may contain hundreds of candidate genes and require a time-consuming and labor-intensive fine mapping process to find the causal gene controlling the trait. With the availability of a rich assortment of genomic and functional genomic data, it is possible to develop a computational method to facilitate faster identification of causal genes. We developed QTG-Finder, a machine learning based algorithm to prioritize causal genes by ranking genes within a quantitative trait locus (QTL). Two predictive models were trained separately based on known causal genes in Arabidopsis and rice. With an independent validation analysis, we demonstrate the models can correctly prioritize about 65% and 60% of Arabidopsis and rice causal genes when the top 20% ranked genes were considered. The models can prioritize different types of traits though at different efficiency. We also identified several important features of causal genes including paralog copy number, being a transporter, being a transcription factor, and containing SNPs that cause premature stop codon. This work lays the foundation for systematically understanding characteristics of causal genes and establishes a pipeline to predict causal genes based on public data.One sentence summaryWe systematically analyzed the genomic characteristics of causal genes in QTLs and developed a novel computational tool to prioritize causal genes.
A novel photoactivatable tool for intermediate filament disruption indicates a role for keratin filaments in early embryogenesis
Authors: Sanghvi-Shah Rucha , Paranjpe Shalaka , Baek Jiyeon , Dobrowolski Radek , Weber Gregory F. 
Published: December 2018

AbstractThe significance of cytoplasmic intermediate filament proteins has previously been examined largely through various genetic approaches, including knockdown, knockout and transgenic overexpression. Few studies to date have attempted to examine the role of specifically the filamentous intermediate filament network in orchestrating various cell functions. To directly assess the role of the filamentous keratin intermediate filament network in regulation of cellular behavior, we created aPhotoActivatabledisruptor of keratin IntermediateFilaments (PA-dIF). This genetically encoded construct consists of a peptide derived from the 2B2 region of Keratin 8 fused to the photosensitive LOV2 domain fromAvena sativaphototropin-1. Upon 458 nm photoirradiation, PA-dIF disrupts keratin intermediate filaments in multiple species and cell types. Marked remodeling of the keratin intermediate filament network accompanies collective cellular morphogenetic movements that occur during gastrulation and neurulation in theXenopus laevisfrog embryo. Light-based activation of PA-dIF was able to disrupt keratin intermediate filaments inXenopuscells and lead to tissue-specific disruption of morphogenetic processes. Altogether our data show a fundamental requirement for keratin intermediate filaments in orchestrating morphogenetic movements during early embryonic development that have yet to be revealed in other model systems. Moreover, our data validate the utility of a new genetically encoded photoactivatable tool for the disruption and examination of intermediate filaments.