bluuebunny/crossref_metadata_2025_split huggingface dataset:
From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left–right patterning
Authors: McDowell Gary , Rajadurai Suvithan , Levin Michael 
Published: November 2016

Consistent left–right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla, and errors of laterality form an important class of human birth defects. Its molecular underpinning was first discovered as a sequential pathway of left- and right-sided gene expression that controlled positioning of the heart and visceral organs. Recent data have revised this picture in two important ways. First, the physical origin of chirality has been identified; cytoskeletal dynamics underlie the asymmetry of single-cell behaviour and patterning of the LR axis. Second, the pathway is not linear: early disruptions that alter the normal sidedness of upstream asymmetric genes do not necessarily induce defects in the laterality of the downstream genes or in organsitus. Thus, the LR pathway is a unique example of two fascinating aspects of biology: the interplay of physics and genetics in establishing large-scale anatomy, and regulative (shape-homeostatic) pathways that correct molecular and anatomical errors over time. Here, we review aspects of asymmetry from its intracellular, cytoplasmic origins to the recently uncovered ability of the LR control circuitry to achieve correct gene expression and morphology despite reversals of key ‘determinant’ genes. We provide novel functional data, inXenopus laevis, on conserved elements of the cytoskeleton that drive asymmetry, and comparatively analyse it together with previously published results in the field. Our new observations and meta-analysis demonstrate that despite aberrant expression of upstream regulatory genes, embryos can progressively normalize transcriptional cascades and anatomical outcomes. LR patterning can thus serve as a paradigm of how subcellular physics and gene expression cooperate to achieve developmental robustness of a body axis.This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.
Structure of theLegionellaDot/Icm type IV secretion systemin situby electron cryotomography
Authors: Ghosal Debnath , Chang Yi-Wei , Jeong Kwangcheol C. , Vogel Joseph P. , Jensen Grant J. 
Published: November 2016

AbstractType IV secretion systems (T4SSs) are large macromolecular machines that translocate protein and DNA and are involved in the pathogenesis of multiple human diseases. Here, using electron cryotomography (ECT), we report thein situstructure of the Dot/Icm type IVB secretion system (T4BSS) utilized by the human pathogenLegionella pneumophila. This is the first structure of a type IVB secretion system, and also the first structure of any T4SSin situ. While the Dot/Icm system shares almost no sequence homology with type IVA secretion systems (T4ASSs), its overall structure shows remarkable similarities to two previously imaged T4ASSs, suggesting shared aspects of mechanism. However, compared to one of these, the negative-stain reconstruction of the purified T4ASS from the R388 plasmid, it is approximately twice as long and wide and exhibits several additional large densities, reflecting type-specific elaborations and potentially better structural preservationin situ.
A Large Scale Joint Analysis of Flowering Time Reveals Independent Temperate Adaptations in Maize
Authors: Swarts Kelly , Bauer Eva , Glaubitz Jeffrey C. , Ho Tiffany , Johnson Lynn , Li Yongxiang , Li Yu , Miller Zachary , Romay Cinta , Schöen Chris-Carolin , Wang Tianyu , Zhang Zhiwu , Buckler Edward S. , Bradbury Peter 
Published: November 2016

AbstractModulating days to flowering is a key mechanism in plants for adapting to new environments, and variation in days to flowering drives population structure by limiting mating. To elucidate the genetic architecture of flowering across maize, a quantitative trait, we mapped flowering in five global populations, a diversity panel (Ames) and four half-sib mapping designs, Chinese (CNNAM), US (USNAM), and European Dent (EUNAM-Dent) and Flint (EUNAM-Flint). Using whole-genome projected SNPs, we tested for joint association using GWAS, resampling GWAS and two regional approaches; Regional Heritability Mapping (RHM) (1,2) and a novel method, Boosted Regional Heritability Mapping (BRHM). Direct overlap in significant regions detected between populations and flowering candidate genes was limited, but whole-genome cross-population predictive abilities were ≤0.78. Poor predictive ability correlated with increased population differentiation (r = 0.41), unless the parents were broadly sampled from across the North American temperate-tropical germplasm gradient; uncorrected GWAS results from populations with broadly sampled parents were well predicted by temperate-tropical FSTs in machine learning. Machine learning between GWAS results also suggested shared architecture between the American panels and, more distantly, the European panels, but not the Chinese panel. Machine learning approaches can reconcile non-linear relationships, but the combined predictive ability of all of the populations did not significantly enhance prediction of physiological candidates. While the North American-European temperate adaption is well studied, this study suggest independent temperate adaptation evolved in the Chinese panel, most likely in China after 1500, a finding supported by differential gene ontology term enrichment between populations.
L-DOPA Reduces Model-Free Control of Behavior by Attenuating the Transfer of Value to Action
Authors: Kroemer Nils B. , Lee Ying , Pooseh Shakoor , Eppinger Ben , Goschke Thomas , Smolka Michael N. 
Published: November 2016

AbstractDopamine is a key neurotransmitter in reinforcement learning and action control. Recent findings suggest that these components are inherently entangled. Here, we tested if increases in dopamine tone by administration of L-DOPA upregulate deliberative “model-based” control of behavior or reflexive “model-free” control as predicted by dual-control reinforcement-learning models. Alternatively, L-DOPA may impair learning as suggested by “value” or “thrift” theories of dopamine. To this end, we employed a two-stage Markov decision-task to investigate the effect of L-DOPA (randomized cross-over) on behavioral control while brain activation was measured using fMRI. L-DOPA led to attenuated model-free control of behavior as indicated by the reduced impact of reward on choice and increased stochasticity of model-free choices. Correspondingly, in the brain, L-DOPA decreased the effect of reward while prediction-error signals were unaffected. Taken together, our results suggest that L-DOPA reduces model-free control of behavior by attenuating the transfer of value to action.
Incomplete Dominance of Deleterious Alleles Contributes Substantially to Trait Variation and Heterosis in Maize
Authors: Yang Jinliang , Mezmouk Sofiane , Baumgarten Andy , Buckler Edward S. , Guill Katherine E. , McMullen Michael D. , Mumm Rita H. , Ross-Ibarra Jeffrey 
Published: November 2016

AbstractDeleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring by crossing two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.Author SummaryA key long-term goal of biology is understanding the genetic basis of phenotypic variation. Although most new mutations are likely disadvantageous, their prevalence and importance in explaining patterns of phenotypic variation is controversial and not well understood. In this study we combine whole genome-sequencing and field evaluation of a maize mapping population to investigate the contribution of deleterious mutations to phenotype. We show thata prioriprediction of deleterious alleles correlates well with effect sizes for grain yield and that variants predicted to be more damaging are on average more recessive. We develop a simple model allowing for variation in the heterozygous effects of deleterious mutations and demonstrate its improved ability to predict both phenotypes and hybrid vigor. Our results help reconcile alternative explanations for hybrid vigor and highlight the use of leveraging evolutionary history to facilitate breeding for crop improvement.
Flowtrace: simple visualization of coherent structures in biological fluid flows
Authors: Gilpin William , Prakash Vivek N. , Prakash Manu 
Published: November 2016

1AbstractWe present a simple, intuitive algorithm for visualizing time-varying flow fields that can reveal complex flow structures with minimal user intervention. We apply this technique to a variety of biological systems, including the swimming currents of invertebrates and the collective motion of swarms of insects. We compare our results to more experimentally-diffcult and mathematically-sophisticated techniques for identifying patterns in fluid flows, and suggest that our tool represents an essential “middle ground” allowing experimentalists to easily determine whether a system exhibits interesting flow patterns and coherent structures without the need to resort to more intensive techniques. In addition to being informative, the visualizations generated by our tool are often striking and elegant, illustrating coherent structures directly from videos without the need for computational overlays. Our tool is available as fully-documented open-source code available for MATLAB, Python, or ImageJ atwww.flowtrace.org.
Evolutionary forces affecting synonymous variations in plant genomes
Authors: Clément Yves , Sarah Gautier , Holtz Yan , Homa Felix , Pointet Stéphanie , Contreras Sandy , Nabholz Benoit , Sabot François , Sauné Laure , Ardisson Morgane , Bacilieri Roberto , Besnard Guillaume , Berger Angélique , Cardi Céline , De Bellis Fabien , Fouet Olivier , Jourda Cyril , Khadari Bouchaib , Lanaud Claire , Leroy Thierry , Pot David , Sauvage Christopher , Scarcelli Nora , Tregear James , Vigouroux Yves , Yahiaoui Nabila , Ruiz Manuel , Santoni Sylvain , Labouisse Jean-Pierre , Pham Jean-Louis , David Jacques , Glémin Sylvain 
Published: November 2016

AbstractBase composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic datasets based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.
Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells
Authors: Lev Shapira , Maya Ralph , Enosh Tomer , Shai Cohen , Oren Kobiler 
Published: November 2016

AbstractAlthough many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1) fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s). Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA), Suberohydroxamic Acid (SBX), Valporic Acid (VPA) and Suberoylanilide Hydoxamic Acid (SAHA). We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the infection. Different cell types (HFF, Vero and U2OS), which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX), which may down regulate the number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in differences in the number of genomes that initiate expression.
Bridging microscopic and macroscopic mechanisms of p53-MDM2 binding using molecular simulations and kinetic network models
Authors: Zhou Guangfeng , Pantelopulos George A. , Mukherjee Sudipto , Voelz Vincent A. 
Published: November 2016

Under normal cellular conditions, the tumor suppressor protein p53 is kept at a low levels in part due to ubiquitination by MDM2, a process initiated by binding of MDM2 to the intrinsically disordered transactivation domain (TAD) of p53. Although many experimental and simulation studies suggest that disordered domains such as p53 TAD bind their targets nonspecifically before folding to a tightly-associated conformation, the molecular details are unclear. Toward a detailed prediction of binding mechanism, pathways and rates, we have performed large-scale unbiased all-atom simulations of p53-MDM2 binding. Markov State Models (MSMs) constructed from the trajectory data predict p53 TAD peptide binding pathways and on-rates in good agreement with experiment. The MSM reveals that two key bound intermediates, each with a non-native arrangement of hydrophobic residues in the MDM2 binding cleft, control the overall on-rate. Using microscopic rate information from the MSM, we parameterize a simple four-state kinetic model to (1) determine that induced-fit pathways dominate the binding flux over a large range of concentrations, and (2) predict how modulation of residual p53 helicity affects binding, in good agreement with experiment. These results suggest new ways in which microscopic models of bound-state ensembles can be used to understand biological function on a macroscopic scale.AUTHOR SUMMARYMany cell signaling pathways involve protein-protein interactions in which an intrinsically disordered peptide folds upon binding its target. Determining the molecular mechanisms that control these binding rates is important for understanding how such systems are regulated. In this paper, we show how extensive all-atom simulations combined with kinetic network models provide a detailed mechanistic understanding of how tumor suppressor protein p53 binds to MDM2, an important target of new cancer therapeutics. A simple four-state model parameterized from the simulations shows a binding-then-folding mechanism, and recapitulates experiments in which residual helicity boosts binding. This work goes beyond previous simulations of small-molecule binding, to achieve pathways and binding rates for a large peptide, in good agreement with experiment.
Odorant cues linked to social immunity induce lateralized antenna stimulation in honey bees (Apis mellifera L.)
Authors: McAfee Alison , Collins Troy F. , Madilao Lufiani L. , Foster Leonard J. 
Published: November 2016

AbstractHygienic behaviour (HB) is a social immunity trait in honey bees (Apis mellifera L.) whereby workers detect, uncap and remove unhealthy brood, improving disease resistance in the colony. This is clearly economically valuable; however, the molecular mechanism behind it is not well understood. The freeze-killed brood (FKB) assay is the conventional method of HB selection, so we compared odour profiles of FKB and live brood. Surprisingly, we found that significantly more brood pheromone (β-ocimene) was released from FKB. β-ocimene abundance also positively correlated with HB, suggesting there could be a brood effect contributing to overall hygiene. We found that &#x03B2; ocimene stimulated worker antennae in a dose-dependent manner, with the left antennae responding significantly stronger than right antennae in hygienic bees, but not in non-hygienic bees. This suggests that HB depends not only on odour detection, but also lateralization of sensitivity. We also compared odour profiles of Varroa-infested brood to healthy brood and found an overall interactive effect between developmental stage and infestation, but specific odours did not drive these differences. Overall, the data we present here is an important foundation on which to build our understanding the molecular mechanism behind this complex behaviour.
Gender bias in household education expenditure: the case of West Bengal
Authors: Majumder Amita , Mitra Chayanika 
Published: November 2016

Purpose
This paper aims to detect gender bias in education expenditure on “students”, who are children and young adults, in a household in the rural and the urban sectors of West Bengal. Outlay equivalent ratios have been calculated using the Engel curve approach, where the budget share function is log quadratic in income, to identify items relating exclusively to education of school/college going students. Heckman’s (1979) two-step procedure is used for estimation to address selection bias The 68th round (July 2011 to June 2012) household level consumption expenditure survey data of the National Sample Survey Organisation have been used for the analysis.

Design/methodology/approach
Engel curve approach is used to capture parental preference for student’s welfare and to find the existence of male student favouritism in the field of education. In case of exclusive adult goods, the addition of a student will reduce the resource allocated for adult goods leading to negative income effect. If a household favours males over females, then that household is likely to sacrifice more for a male student’s education than that for a female student. To address selection bias, Heckman’s two-step procedure has been used.

Findings
The authors find that not all education items relate exclusively to students of a household. Expenditure on books is not exclusively for students, whereas other educational items, such as stationary and photocopy charges, tuition fees and private coaching fees, are found to be students’ items only. Transport cost is found to be an adult good. Further, we find evidence of pro male bias in expenditure on educational items, and the extent of gender bias is more in the urban sectors compared to the rural sectors in West Bengal.

Originality/value
The objective of this paper is to identify the educational items exclusively for “students” and to test the difference in the allocation of resources in education, with respect to these items, between a male student and a female student for both sectors in West Bengal, using the outlay equivalent ratios.
A generalized stochastic production frontier analysis of technical efficiency of rice farming
Authors: Bhattacharyya Aditi , Mandal Raju 
Published: November 2016

Purpose
This paper aims to analyze farm-level technical inefficiency of rice farming in Assam, India, using a multiple-output generalized stochastic frontier framework.

Design/methodology/approach
Primary data for this study were collected in 2009-2010 from 310 farm-households in four non-contiguous districts of Dhubri, Morigaon, Dibrugarh and Cachar that are located in different agro-climatic regions of Assam. Based on a Cobb–Douglas production function for multiple rice varieties, the paper simultaneously estimates the generalized stochastic production frontier and examines effects of exogenous factors on farm-level technical inefficiency.

Findings
Results of this study show that the average technical inefficiency of farms is 8.5 per cent in the sample. Further, inefficiency is lower in the frequently flood prone areas, and availability of government support helps reduce such inefficiency as well. However, technical efficiency is higher for the Muslim farm-households, and it decreases with greater land fragmentation. The study also finds that the use of primitive technology like bullock reduces technical efficiency of rice farming.

Originality/value
This paper is based on a novel data set that has specially been collected to examine productivity and efficiency of rice cultivation in the flood plains of Assam that has not been studied before. Further, to the best of the authors’ knowledge, this paper is the first one to model rice production as a multiple-output stochastic production frontier and analyze technical efficiency of rice production accordingly.