bluuebunny/crossref_metadata_2025_split huggingface dataset:
Many options, few solutions: over 60 million years snakes converged on a few optimal venom formulations
Authors: Barua Agneesh , Mikheyev Alexander S. 
Published: November 2018

AbstractGene expression changes contribute to complex trait variations in both individuals and populations. However, how gene expression influences changes of complex traits over macroevolutionary timescales remains poorly understood. Being comprised of proteinaceous cocktails, snake venoms are unique in that the expression of each toxin can be quantified and mapped to a distinct genomic locus and traced for millions of years. Using a phylogenetic generalized linear mixed model, we analysed expression data of toxin genes from 52 snake species spanning the three venomous snake families, and estimated phylogenetic covariance, which acts as a measure of evolutionary constraint. We find that evolution of toxin combinations is not constrained. However, while all combinations are in principle possible, the actual dimensionality of phylomorphic space is low, with envenomation strategies focused around only four major toxins: metalloproteases, three-finger toxins, serine proteases, and phospholipases A2. While most extant snakes prioritize either a single or a combination of major toxins, they are repeatedly recruited and lost. We find that over macroevolutionary timescales the venom phenotypes were not shaped by phylogenetic constraints, which include important microevolutionary constraints such as epistasis and pleiotropy, but more likely by ecological filtering that permits a few optimal solutions. As a result, phenotypic optima were repeatedly attained by distantly related species. These results indicate that venoms evolve by selection on biochemistry of prey envenomation, which permit diversity though parallelism and impose strong limits, since only a few of the theoretically possible strategies seem to work well and are observed in extant snakes.
A multi-year survey of helminths from the gastrointestinal tract of wild saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarins
Authors: Erkenswick Gideon A. , Watsa Mrinalini , Gozalo Alfonso S. , Dudaie Shay , Bailey Lindsey , Muranda Kudakwashe S. , Kuziez Alaa , Parker Patricia G. 
Published: November 2018

AbstractNoninvasive monitoring of gastrointestinal parasites from wild primates demonstrates that parasite-host relationships are altered during habitat or climatic disturbances. Interpreting changes in parasite measures for population health monitoring is problematic, since wild primates are infected with multiple parasites that fluctuate temporally and seasonally. Individual parasite infection data from two wild populations of New World primates, the saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarin, were collected over three years to: 1) establish baseline levels of parasite species richness (PSR) and variation across demography; 2) test for non-random associations of parasite co-occurrence; and 3) test hypothesized relationships between group size and PSR. Ten distinguishable parasite taxa were identified from 288 fecal samples by light microscopy following centrifugation and ethyl-acetate sedimentation. These samples represented 105 unique individuals (71 saddleback and 34 emperor tamarins), across 13 saddleback and seven emperor groups. Of the parasites identified in this study, none were confirmed as host specific, and only two parasites had statistically different prevalence between the host species. With few exceptions, individual infection status remained relatively unchanged over the study period. Considering yearly pair-wise parasite associations, we detected no marked differences between expected and observed levels of co-infection, nor did we detect statistically significant associations between group size and parasite species richness over 30 group-years. Logistic models of individual infection status did not identify a sex bias; however, age or species predicted the presence of four and three parasite taxa, respectively. Our model found higher PSR for saddleback tamarins. Considering the two most common parasites, one is typically pathogenic and the other is not, reinforcing caution when translating clinical findings of pathology to real-world systems. We now have reliable baseline data for future monitoring of these populations. Next steps should involve the molecular characterization of these parasites, and the exploration of linkages with health parameters.
Enhancer redundancy predicts gene pathogenicity and informs complex disease gene discovery
Authors: Wang Xinchen , Goldstein David B. 
Published: November 2018

AbstractNon-coding transcriptional regulatory elements are critical for controlling the spatiotemporal expression of genes. Here, we demonstrate that the number of bases in enhancers linked to a gene reflects its disease pathogenicity. Moreover, genes with redundant enhancer domains are depleted of cis-acting genetic variants that disrupt gene expression, and are buffered against the effects of disruptive non-coding mutations. Our results demonstrate that dosage-sensitive genes have evolved robustness to the disruptive effects of genetic variation by expanding their regulatory domains. This resolves a puzzle in the genetic literature about why disease genes are depleted of cis-eQTLs, suggesting that eQTL information may implicate the wrong genes at genome-wide association study loci, and establishes a framework for identifying non-coding regulatory variation with phenotypic consequences.
CasLocusAnno: a web-based server for annotating Cas loci and their corresponding (sub)types
Authors: Dong Chuan , Zeng Zhi , Wen Qing-Feng , Liu Shuo , Du Meng-Ze , Gao Yi-Zhou , Liao Zhen , Saber Nicholas , Huang Jian , Guo Feng-Biao 
Published: November 2018

ABSTRACTCRISPR-Cas systems are prevalent in bacterial and archaeal genomes, and these systems provide a powerful adaptive immune system against predation by phages and other mobile genetic elements (MGEs). They also contribute to other functions, such as gene regulation in prokaryotic organisms. Determining Cas proteins and Cas loci can help mine Cas proteins and facilitate the identification of Cas-associated accessory proteins. Therefore, the purpose of this work is to develop a web-based server, CasLocusAnno, to annotate Cas proteins and Cas loci and to classify them according to (sub)type based on a previous study. CasLocusAnno can annotate Cas proteins and Cas loci and assign their (sub)types within ∽28 seconds for whole protein sequence submissions, with protein sequence numbers ranging from ∽30 to ∽10500. Comparison with Makarova et al.’s benchmark data demonstrates that CasLocusAnno can accurately identify Cas loci and (sub)types. In addition, CasLocusAnno can identify Cas proteins with higher accuracy and a lower additional prediction rate (APR) than two excellent software programs, CRISPRCasFinder and MacSyFinder. The domain alignment of a Cas protein can be easily browsed in the annotation results. Our server can be freely accessed at http://cefg.uestc.edu.cn/CasLocusAnno/.
Torsional turning motion of chromosomes as an accelerating force to align homolog ous chromosomes during meiosis
Authors: Takao Kazutaka , Takamiya Kazunori , Ding Da-Qiao , Haraguchi Tokuko , Hiraoka Yasushi , Nishimori Hiraku , Awazu Akinori 
Published: November 2018

AbstractHomologous sets of parental chromosomes must pair during meiosis to produce recombined sets of chromosomes for their progeny. This is accompanied by nuclear oscillatory movements. This study aimed to elucidate the significance of these movements with a model, wherein external force was applied to the oscillating nucleus and via hydrodynamic interactions within the nucleus. Simulations revealed that a major force for aligning homologous chromosomes is length-dependent sorting during chromosomal torsional turning, which occur when the nucleus reverses the direction of its movement.
Global biochemical and structural analysis of the type IV pilus from the Gram-positive bacteriumStreptococcus sanguinis
Authors: Berry Jamie-Lee , Gurung Ishwori , Anonsen Jan Haug , Spielman Ingrid , Harper Elliot , Hall Alexander M. J. , Goosens Vivianne J. , Raynaud Claire , Koomey Michael , Biais Nicolas , Matthews Steve , Pelicic Vladimir 
Published: November 2018

AbstractType IV pili (Tfp) are functionally versatile filaments, widespread in prokaryotes, that belong to a large class of filamentous nanomachines known as type IV filaments (Tff). Although Tfp have been extensively studied in several Gram-negative pathogens where they function as key virulence factors, many aspects of their biology remain poorly understood. Here, we performed a global biochemical and structural analysis of Tfp in a recently emerged Gram-positive model,Streptococcus sanguinis. In particular, we focused on the five pilins and pilin-like proteins involved in Tfp biology inS. sanguinis. We found that the two major pilins, PilE1 and PilE2, (i) follow widely conserved principles for processing by the prepilin peptidase PilD and for assembly into filaments; (ii) display only one of the post-translational modifications frequently found in pilins,i.e. a methylated N-terminus; (iii) are found in the same hetero-polymeric filaments; and (iv) are not functionally equivalent. The 3D structure of PilE1, solved by NMR, revealed a classical pilin fold with a highly unusual flexible C-terminus. Intriguingly, PilE1 more closely resembles pseudopilins forming shorter Tff thanbona fideTfp-forming major pilins, underlining the evolutionary relatedness among different Tff. Finally, we show thatS. sanguinisTfp contain a low abundance of three additional proteins processed by PilD, the minor pilins PilA, PilB, and PilC. These findings provide the first global biochemical and structural picture of a Gram-positive Tfp and have fundamental implications for our understanding of a widespread class of filamentous nanomachines.
Homeostatic Inhibitory Control of Cortical Hyperexcitability in Fragile X Syndrome
Authors: Cea-Del Rio C.A. , Nunez-Parra A. , Freedman S. , Restrepo D. , Huntsman M.M. 
Published: November 2018

AbstractIn mouse models of Fragile X Syndrome (FXS), cellular and circuit hyperexcitability are a consequence of altered brain development [reviewed in (Contractor et al., 2015)]. Mechanisms that favor or hinder plasticity of synapses could affect neuronal excitability. This includes inhibitory long term depression (I-LTD) – a heterosynaptic form of plasticity that requires the activation of metabotropic glutamate receptors (mGluRs). Differential circuit maturation leads to shifted time points for critical periods of synaptic plasticity across multiple brain regions (Harlow et al., 2010; He et al., 2014), and disruptions of the development of excitatory and inhibitory synaptic function are also observed both during development and into adulthood (Vislay et al., 2013). However, little is known about how this hyperexcitable environment affects inhibitory synaptic plasticity. Our results demonstrate that the somatosensory cortex of the Fmr1 KO mouse model of FXS exhibits increased GABAergic spontaneous activity, a faulty mGluR-mediated inhibitory input and impaired plasticity processes. We find the overall diminished mGluR activation in the Fmr1 KO mice leads to both a decreased spontaneous inhibitory postsynaptic input to principal cells and also to a disrupted form of inhibitory long term depression (I-LTD). In cortical synapses, this I-LTD is dependent on mGluR activation and the mobilization endocannabinoids (eCBs). Notably, these data suggest enhanced hyperexcitable phenotypes in FXS may be homeostatically counterbalanced by the inhibitory drive of the network and its altered response to mGluR modulation.Significance StatementFragile X Syndrome is a pervasive neurodevelopmental disorder characterized by intellectual disability, autism, epilepsy, anxiety and altered sensory sensitivity. In both in vitro and in vivo recordings in the somatosensory cortex of the Fmr1 knockout mouse model of Fragile X Syndrome we show that hyperexcitable network activity contributes to ineffective synaptic plasticity at inhibitory synapses. This increased excitability prevents cortical circuits from adapting to sensory information via ineffective plasticity mechanisms.
Analysing Patterns in Population Dynamics using Repeated Population Surveys with Three Types of Detection Data
Authors: Péron Guillaume , Garel Mathieu 
Published: November 2018

ABSTRACTWe generalize the distance sampling protocol to accommodate three types of detection data in population surveys (population counts): distance to the observer, multiple observers, and time-to-detection. We also account for the effect of a partially-observed individual covariate, with the aim to account for the non-independence of individuals in groups and the effect of group size on detection probability. Finally, we separate the probability of availability to detection and the probability of detection when available.We compute the statistical power of our new model using simulations and illustrate some of the biases in the simpler alternative analytical procedures that oue new formulation allows to avoid. We discuss issues of weak identifiability (an issue shared with other state-space models) and the bias-precision tradeoff in population survey analyses.We recommend maintaining both simple analyses of population survey data and more complex analyses of the detection process, maybe in a dashboard of indicators. Discrepancies between results from simple and complex analyses can help identify sources of biases and loss of precision.
Minimization of a harmful cross-talk between mitotic checkpoint silencing and error correction
Authors: Roy Babhrubahan , Verma Vikash , Sim Janice , Fontan Adrienne , Joglekar Ajit P. 
Published: November 2018

AbstractAccurate chromosome segregation during cell division requires that the pair of sister kinetochores on each chromosome attach to microtubules originating from opposite spindle poles. This is ensured by the combined action of the Spindle Assembly Checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect attachment of both sister kinetochores to the same spindle pole. These processes are downregulated by Protein Phosphatase 1 (PP1), which both silences the SAC and stabilizes kinetochore-microtubule attachments. We find that this dual PP1 role can be problematic: if PP1 is recruited to the kinetochore for SAC silencing prior to chromosome biorientation, it interferes with error correction. We show that to mitigate this cross-talk, the yeast kinetochore uses independent PP1 sources to stabilize correct attachments and to silence the SAC, and also delays the recruitment of PP1 for SAC silencing. Consequently, chromosome biorientation precedes SAC silencing ensuring accurate chromosome segregation.
Drosophila anion exchanger 2 is required for proper ovary development and oogenesis
Authors: Benitez Marimar , Tatapudy Sumitra , Barber Diane L. , Nystul Todd 
Published: November 2018

AbstractUnderstanding how cell fate decisions are regulated is a central question in stem cell biology. Recent studies have demonstrated that intracellular pH (pHi) dynamics contribute to this process. Indeed, the pHi of cells within a tissue is not simply a consequence of chemical reactions in the cytoplasm and other cellular activity, but is actively maintained at a specific setpoint in each cell type. We found previously that the pHi of cells in the follicle stem cell (FSC) lineage in theDrosophilaovary increases progressively during differentiation from an average of 6.8 in the FSCs, to 7.0 in newly produced daughter cells, to 7.3 in more differentiated cells. Two major regulators of pHi in this lineage areDrosophilasodium-proton exchanger 2 (dNhe2) and a previously uncharacterized gene,CG8177, that is homologous to mammalian anion exchanger 2 (AE2). Based on this homology, we named the geneae2. Here, we generated null alleles ofae2and found that homozygous mutant flies are viable but have severe defects in ovary development and adult oogenesis. Specifically, we find thatae2null flies have smaller ovaries, reduced fertility, and impaired follicle formation. In addition, we find that the follicle formation defect can be suppressed by a decrease indNhe2copy number and enhanced by the overexpression ofdNhe2, suggesting that this phenotype is due to the dysregulation of pHi. These findings support the emerging idea that pHi dynamics regulate cell fate decisions and our studies provide new genetic tools to investigate the mechanisms by which this occurs.
Differences in effective ploidy as drivers of genome-wide endosperm expression asymmetries and seed failure in wild tomato hybrids
Authors: Roth Morgane , Florez-Rueda Ana M. , Städler Thomas 
Published: November 2018

AbstractEndosperm misdevelopment leading to hybrid seed failure is a common cause of postzygotic isolation in angiosperms and is observed in both interploidy and homoploid crosses between closely related lineages. Moreover, parental dosage is critical for successful endosperm and seed development, typically requiring a ratio of two maternal to one paternal genome(s) in within-species crosses. The recently revived concept of ‘effective ploidy’ can largely explain the outcome of experimental crosses that (partly) ameliorate hybrid seed failure by manipulating the actual ploidy in one of the parents. However, genome-wide expression perturbations concomitant with levels of hybrid seed failure have yet to be reported. The tomato clade (SolanumsectionLycopersicon), encompassing closely related diploids with partial-to-complete hybrid seed failure and diverse mating systems, provides outstanding opportunities to study these issues. Here we compared replicated endosperm transcriptomes from six crosses within and among three wild tomato lineages. Strikingly, both strongly inviable hybrid crosses displayed conspicuous, asymmetric expression perturbations with strong signatures of cross direction. In particular,Solanum peruvianum, the species inferred to have evolved higher effective ploidy than the other two, drove hybrid expression landscapes in both maternal and paternal roles. This global expression divergence was mirrored in functionally important gene families such as transcription factors and E3 ubiquitin ligases, and revealed differences in cell-cycle tuning between lineages that match phenotypic differences in developing endosperm and mature seed size between reciprocal crosses. Our work initiates the exploration of links between parental conflict, genomic imprinting, expression dosage and hybrid seed failure in flowering plants.
Challenging times: building a health, housing and social care local workforce strategy
Authors: Dearnaley Patricia , Smith Joanne E. 
Published: November 2018

Purpose
The purpose of this paper is to stimulate a wider debate around the coordination of workforce planning in non-statutory services (in this case, specialist housing for older people or those with long-term health and social care needs, such as learning disabilities). The authors argue that current NHS reforms do not go far enough in that they fail to include specialist housing and its workforce in integration, and by doing so, will be unable to optimise the potential efficiencies and streamlining of service delivery to this group.

Design/methodology/approach
The paper used exploratory study using existing research and data, enhanced by documentary analysis from industry bodies, regulators and policy think tanks.

Findings
That to achieve the greatest operational and fiscal impact upon the health care services, priority must be given to improving the efficiency and coordination of services to older people and those requiring nursing homes or registered care across the public and third sectors through the integration of service delivery and workforce planning.

Research limitations/implications
Whilst generalisable and achievable, the model proposed within the paper cannot be fully tested theoretically and requires further testing the in real health and social care market to evidence its practicality, improved quality of care and financial benefits.

Originality/value
The paper highlights some potential limitations to the current NHS reforms: by integrating non-statutory services, planned efficiency savings may be optimised and service delivery improved.
How face consciousness reverse pro-self-behavior? A study on ecological consumption from the perspective of social value orientation
Authors: Shi Zhuomin , Wu Lufang , Kuang Zaoying 
Published: November 2018

PurposeThe purpose of this paper is to focus on ecological consumption and test the effect of social value orientation on ecological consumption. What is more, this paper explores how Chinese consumers choose between prosocial and non-prosocial products under the influence of Chinese face culture.Design/methodology/approachThe authors assume that social value orientation will change individual’s ecological consumption through the in-group identification, and simultaneously predict that the influence in pro-self and pro-social consumer groups will vary. Furthermore, Chinese face consciousness will moderate the relationship between ecological consumption and social value orientation. Online research and intercept survey are employed to collect data. In total, 600 questionnaires were distributed.FindingsThe results indicate that pro-social individuals prefer sustainable consumption than pro-self-individuals, and in-group identification mediates the effect of social value orientation on ecological consumption. Interestingly, pro-self-individuals’ behaviors have changed dramatically by the influence of face consciousness.Originality/valueThe authors discovered that social value orientation has a deep impact on ecological consumption through in-group identification. The authors tested and verified the dominance of Chinese face culture. Besides, four key elements of China’s “face” construct are proposed, namely, holism, synergy, synchronicity and dynamics, which enlarge the horizon of the theory of face.