bluuebunny/crossref_metadata_2025_split huggingface dataset:
The amount of nitrogen used for photosynthesis governs molecular evolution in plants
Authors: Kelly Steven 
Published: July 2017

AbstractBackgroundGenome and transcript sequences are composed of long strings of nucleotide monomers (A, C, G and T/U) that require different quantities of nitrogen atoms for biosynthesis.ResultsHere it is shown that the strength of selection acting on transcript nitrogen content is determined by the amount of nitrogen plants require to conduct photosynthesis. Specifically, plants that require more nitrogen to conduct photosynthesis experience stronger selection on transcript sequences to use synonymous codons that cost less nitrogen to biosynthesise. It is further shown that the strength of selection acting on transcript nitrogen cost constrains molecular sequence evolution such that genes experiencing stronger selection evolve at a slower rate.ConclusionsTogether these findings reveal that the plant molecular clock is set by photosynthetic efficiency, and provide a mechanistic explanation for changes in plant speciation rates that occur concomitant with improvements in photosynthetic efficiency and changes in the environment such as light, temperature, and atmospheric CO2concentration.
Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation
Authors: Reagh Zachariah M. , Noche Jessica A. , Tustison Nicholas J. , Delisle Derek , Murray Elizabeth A. , Yassa Michael A. 
Published: July 2017

AbstractThe entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer’s disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally link this condition to previously reported dentate/CA3 hyperactivity, both of which were associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.
A Radically New Theory of how the Brain Represents and Computes with Probabilities
Authors: Rinkus Gerard (Rod) 
Published: July 2017

AbstractMany believe that the brain implements probabilistic reasoning and that it represents information via some form of population (distributed) code. Most prior probabilistic population coding (PPC) theories share basic properties: 1) continuous-valued units; 2) fully/densely distributed codes; 3) graded synap-ses; 4) rate coding; 5) units have innate low-complexity, usually unimodal, tuning functions (TFs); and 6) units are intrinsically noisy and noise is generally considered harmful. I describe a radically different theory that assumes: 1) binary units; 2) sparse distributed codes (SDC); 3)functionallybinary synapses; 4) a novel,atemporal, combinatorial spike code; 5) units initially have flat TFs (all weights zero); and 6) noise is a resource generated/used, normatively, to cause similar inputs to map to similar codes. The theory, Sparsey, was introduced 25+ years ago as: a) an explanation of the physical/computational relationship of episodic and semantic memory for the spatiotemporal (sequential) pattern domain; and b) a canonical, mesoscale cortical probabilistic circuit/algorithm possessing fixed-time, unsupervised, single-trial, non-optimization-based, unsupervised learning and fixed-time best-match (approximate) retrieval; but was not described as an alternative to PPC-type theories. Here, we show that: a) the active SDC in a Sparsey coding field (CF) simultaneously represents not only the likelihood of the single most likely input but the likelihoods of all hypotheses stored in the CF; and b) the whole explicit distribution can be sent, e.g., to a downstream CF, via a set of simultaneous single spikes from the neurons comprising the active SDC.
A comprehensive map of genetic variation in the world’s largest ethnic group - Han Chinese
Authors: Chiang Charleston W. K. , Mangul Serghei , Robles Christopher R. , Kretzschmar Warren W. , Cai Na , Kendler Kenneth S. , Sankararam Sriram , Flint Jonathan 
Published: July 2017

AbstractAs are most non-European populations around the globe, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our dataset. Individuals from our study come from 19 out of 22 provinces across China, allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identify previously unrecognized population structure along the East-West axis of China and report unique signals of admixture across geographical space, such as European influences among the Northwestern provinces of China. Finally, we identified a number of highly differentiated loci, indicative of local adaptation in the Han Chinese. In particular, we detected extreme differentiation among the Han Chinese at MTHFR, ADH7, and FADS loci, suggesting that these loci may not be specifically selected in Tibetan and Inuit populations as previously suggested. On the other hand, we find that Neandertal ancestry does not vary significantly across the provinces, consistent with admixture prior to the dispersal of modern Han Chinese. Furthermore, contrary to a previous report, Neandertal ancestry does not explain a significant amount of heritability in depression. Our findings provide the largest genetic data set so far made available for Han Chinese and provide insights into the history and population structure of the world’s largest ethnic group.
The Detection of Phase Amplitude Coupling During Sensory Processing
Authors: Seymour R.A , Rippon G. , Kessler K. 
Published: July 2017

1.AbstractThere is increasing interest in understanding how the phase and amplitude of distinct neural oscillations might interact to support dynamic communication within the brain. In particular, previous work has demonstrated a coupling between the phase of low frequency oscillations and the amplitude (or power) of high frequency oscillations during certain tasks, termed phase amplitude coupling (PAC). For instance, during visual processing in humans, PAC has been reliably observed between ongoing alpha (8-13Hz) and gamma-band (>40Hz) activity. However, the application of PAC metrics to electrophysiological data can be challenging due to numerous methodological issues and lack of coherent approaches within the field. Therefore, in this article we outline the various analysis steps involved in detecting PAC, using an openly available MEG dataset from 16 participants performing an interactive visual task. Firstly, we localised gamma and alpha-band power using the Fieldtrip toolbox, and extracted time courses from area V1, defined using a multimodal parcellation scheme. These V1 responses were analysed for changes in alpha-gamma PAC, using four common algorithms. Results showed an increase in gamma (40-100Hz) - alpha (7-13Hz) PAC in response to the visual grating stimulus, though specific patterns of coupling were somewhat dependent upon the algorithm employed. Additionally, post-hoc analyses showed that these results were not driven by the presence of non-sinusoidal oscillations, and that trial length was sufficient to obtain reliable PAC estimates. Finally, throughout the article, methodological issues and practical guidelines for ongoing PAC research will be discussed.
Phylogenomics of the olive tree (Olea europaea) disentangles ancient allo- and autopolyploidizations in Lamiales
Authors: Julca Irene , Marcet-Houben Marina , Vargas Pablo , Gabaldón Toni 
Published: July 2017

AbstractBackgroundPolyploidization is one of the major evolutionary processes that shape eukaryotic genomes, being particularly common in plants. Polyploids can arise through direct genome doubling within a species (autopolyploidization) or through the merging of genomes from distinct species after hybridization (allopolyploidization). The relative contribution of either mechanism in plant evolution is debated. Here we used phylogenomics to dissect the tempo and mode of duplications in the genome of the olive tree (Olea europaea), one of the first domesticated Mediterranean fruit trees.ResultsOur results depict a complex scenario involving at least three past polyploidization events, of which two -at the bases of the family Oleaceae and the tribe Oleeae, respectively- are likely to be the result of ancient allopolyploidization. A more recent polyploidization involves specifically the olive tree and relatives.ConclusionOur results show the power of phylogenomics to distinguish between allo- and auto- polyplodization events and clarify the conundrum of past duplications in the olive tree lineage.
Resequencing theEscherichia coligenome by GenoCare single molecule sequencing platform
Authors: Zhao Luyang , Deng Liwei , Li Gailing , Jin Huan , Cai Jinsen , Shang Huan , Li Yan , Yang Andrew X. , Chen Fang , Zhao Zhi , Xu Guanjie , Liu Wuxing , Liu Siyu , Xiang Guobing , Liu Bin , Xu Weibin , Zeng Lidong , Zhang Renli , Zhao Huan , Wu Ping , Zhou Zhiliang , Zheng Jiao , Ezanno Pierre , Chen Weiyue , Yan Qin , Deem Michael W. , Yu Jun , He Jiankui 
Published: July 2017

ABSTRACTNext generation sequencing (NGS) has revolutionized life sciences research. Recently, a new class of third-generation sequencing platforms has arrived to meet increasing demands in the clinic, capable of directly measuring DNA and RNA sequences at the single-molecule level without amplification. Here, we use the new GenoCare single molecule sequencing platform from Direct Genomics to resequence theE. coligenome and show comparable performance to the Illumina MiSeq system. Our platform detects single-molecule fluorescence by total internal reflection microscopy, with sequencing-by-synthesis chemistry. With a consensus sequence of 99.71% nucleotide identity to that of the Illumina MiSeq system’s, GenoCare was determined to be a reliable platform for single-molecule sequencing, with strong potential for clinical applications.
Wide sampling of natural diversity identifies novel molecular signatures of C4photosynthesis
Authors: Kelly Steven , Covshoff Sarah , Wanchana Samart , Thakur Vivek , Quick W. Paul , Wang Yu , Ludwig Martha , Bruskiewich Richard , Fernie Alisdair R. , Sage Rowan F. , Tian Zhijian , Yan Zixian , Wang Jun , Zhang Yong , Zhu Xin-Guang , Ka-Shu Wong Gane , Hibberd Julian M. 
Published: July 2017

Introductory paragraphMuch of biology is associated with convergent traits, and it is challenging to determine the extent to which underlying molecular mechanisms are shared across phylogeny. By analyzing plants representing eighteen independent origins of C4photosynthesis, we quantified the extent to which this convergent trait utilises identical molecular mechanisms. We demonstrate that biochemical changes that characterise C4species are recovered by this process, and expand the paradigm by four metabolic pathways not previously associated with C4photosynthesis. Furthermore, we show that expression of many genes that distinguish C3and C4species respond to low CO2, providing molecular evidence that reduction in atmospheric CO2was a driver for C4evolution. Thus the origin and architecture of complex traits can be derived from transcriptome comparisons across natural diversity.
TriPoly: a haplotype estimation approach for polyploids using sequencing data of related individuals
Authors: Motazedi Ehsan , Ridder Dick de , Finkers Richard , Maliepaard Chris 
Published: July 2017

Knowledge of “haplotypes”, i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci (QTL).We propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of short- read sequencing data for potato (Solanum tuberosum) and banana (Musa acuminata) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to the existing methods that work on single individuals.
Qinichelins, novel catecholate-hydroxamate siderophores synthesized via a multiplexed convergent biosynthesis pathway
Authors: Gubbens Jacob , Wu Changsheng , Zhu Hua , Filippov Dmitri V. , Florea Bogdan I. , Rigali Sébastien , Overkleeft Herman S. , van Wezel Gilles P. 
Published: July 2017

ABSTRACTThe explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate-hydroxamate siderophores termed qinichelins (2–5) fromStreptomycessp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (BGC; namedqch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry and NMR. Synthesis of the qinichelins requires the interplay between four gene clusters, for its synthesis and for precursor supply. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.Pride repository reviewer account details:URL:https://www.ebi.ac.uk/pride/archive/loginProject accession: PXD006577Username: reviewer35793@ebi.ac.ukPassword: 3H0iM1FK
Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane
Authors: Pak Alexander J. , Grime John M. A. , Sengupta Prabuddha , Chen Antony K. , Durumeric Aleksander E. P. , Srivastava Anand , Yeager Mark , Briggs John A. G. , Lippincott-Schwartz Jennifer , Voth Gregory A. 
Published: July 2017

ABSTRACTThe packaging and budding of Gag polyprotein and viral ribonucleic acid (RNA) is a critical step in the human immunodeficiency virus-1 (HIV-1) lifecycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from sub-nanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA-SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while over-expression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.SIGNIFICANCE STATEMENTIn order for human immunodeficiency virus to proliferate, viral proteins and genomic dimers are assembled at host cell membranes and released as immature virions. Disrupting this key intermediate step in viral replication is a potential target for treatment. However, a detailed molecular view of this process remains lacking. Here, we elucidate a network of constitutive interactions that regulate viral assembly dynamics through a combined computational and experimental approach. Specifically, our analysis reveals the active roles of nucleic acid and the membrane as scaffolds that promote the multimerization of Gag polyprotein which proceeds through multi-step and self-correcting nucleation. Our findings also illustrate the functional importance of the N-terminal, C-terminal, and spacer peptide 1 protein domains.
Glycan Clock Forecasts Human Influenza A Virus Hemagglutinin Evolution
Authors: Altman Meghan O. , Angel Matthew , Košík Ivan , Trovão Nídia S. , Zost Seth J. , Gibbs James S. , Hensley Scott E. , Nelson Martha I. , Yewdell Jonathan W. 
Published: July 2017

ABSTRACTAdaptive immunity to influenza A virus is limited by frequent mutations in the immunodominant head of hemagglutinin (HA). Over the last century, the upward trend in HA-head glycosylation indicates glycan addition can increase fitness, but its role in viral evolution remains unclear. Here, we report glycan evolution follows a clock-like rhythm, pacing the timeline, trajectory, and replacement of HA. Following pandemic introduction, glycans are added to HA at 4- to 6-year intervals, until a functional glycan limit is reached, after which, at 9- to 12-year intervals, glycans are either swapped between different sites, or the HA is replaced by a novel pandemic virus. Using this, we predicted the appearance of the newest glycan on pH1N1 HA. Phylogeographic reconstruction suggests these highly fit strains originated in the Middle East, before rapidly replacing all strains globally. Going forward, we can use this simple algorithm to forecast future glycan evolution and identify seasons with higher pandemic potential.
Asleep at the Wheel: Forward Genetic ENU Mutagenesis Screen for Mouse Models of Chronic Fatigue Identifies a Mutation inSlc2a4(GLUT4)
Authors: de Groot Marleen H. M. , Castorena Carlos M. , Kumar Vivek , Mohawk Jennifer A. , Ahmed Newaz I. , Takahashi Joseph S. 
Published: July 2017

ABSTRACTIn a screen of voluntary wheel-running behavior designed to identify genetic mouse models of chronic fatigue in ENU mutagenized C57BL/6J mice, we discovered two lines that showed aberrant wheel-running patterns. These lines both stem from a single original founder identified as a low body-weight candidate in a recessive screen. Progeny from both of these lines showed the abnormal wheel-running behavior, with affected mice showing significantly lower daily activity levels than unaffected mice. They also exhibited low amplitude circadian rhythms, consisting of lower activity levels during the normal active phase, and increased levels of activity during the rest or light phase, but only a modest alteration in free-running period. Their activity is not consolidated into longer bouts, but is frequently interrupted with periods of inactivity throughout the dark phase of the light-dark (LD) cycle. As seen with the low body weight, expression of the behavioral phenotypes in offspring of strategic crosses was consistent with a recessive heritance pattern. Mapping of these phenotypic abnormalities showed linkage to a single locus on chromosome 11, and whole exome sequencing (WES) identified a single point mutation in theSlc2a4gene encoding the GLUT4 insulin-responsive glucose transporter. The single nucleotide change (A to T) was found in the distal end of exon 10, and results in a premature stop (Y440*). To our knowledge, this is the first time a mutation in this gene has been shown to result in extensive changes in general behavioral patterns.SIGNIFICANCE STATEMENTChronic fatigue is a debilitating and devastating disorder with widespread consequences for both the patient and the persons around them, but effective treatment strategies are lacking. The identification of novel genetic mouse models of chronic fatigue may prove invaluable for the study of its underlying physiological mechanisms and for the testing of treatments and interventions. A novel mutation inSlc2a4(GLUT4) was identified in a forward mutagenesis screen because affected mice showed abnormal daily patterns and levels of wheel running consistent with chronic fatigue. This new mouse model may shed light on the pathophysiology of chronic fatigue.
Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age
Authors: Mann Mati , Mehta Arnav , de Boer Carl , Kowalczyk Monika S. , Lee Kevin , Rogel Noga , Knecht Abigail R. , Farouq Daneyal , Regev Aviv , Baltimore David 
Published: July 2017

SummaryLong-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. With age, however, they produce a myeloid-biased output that may lead to poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Using single-cell RNA-seq, we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is much more common amongst aged LT-HSCs and is uniquely primed to respond to acute inflammatory challenge. We predict several transcription factors to regulate differentially expressed genes between mLT-HSCs and other LT-HSC subsets. Among these, we show thatKlf5,Ikzf1andStat3play important roles in age-related inflammatory myeloid bias. These factors may regulate myeloid versus lymphoid balance with age, and can potentially mitigate the long-term deleterious effects of inflammation that lead to hematopoietic pathologies.HighlightsLT-HSCs from young and aged mice have differential responses to acute inflammatory challenge.HSPCs directly sense inflammatory stimuliin vitroand have a robust transcriptional response.Aged LT-HSCs demonstrate a cell-intrinsic myeloid bias during inflammatory challenge.Single-cell RNA-seq unmasked the existence of two subsets within the LT-HSC population that was apparent upon stimulation but not steady-state. One of the LT-HSC subsets is more prevalent in young and the other in aged mice.Klf5,Ikzf1andStat3regulate age‐ and inflammation-related LT-HSC myeloid-bias.One sentence summaryMurine hematopoietic stem cells display transcriptional heterogeneity that is quantitatively altered with age and leads to the age-dependent myeloid bias evident after inflammatory challenge.