bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiponectin Single Nucleotide Polymorphisms and Serum Levels Are Relevant to Prognosis of Patients With Aneurysmal Subarachnoid Hemorrhages
Authors: Shi Ji-Kui , Yuan Xiao-Chun , Sun Jie , Liu Dong-Hai
Published: January 2016

To investigate the association of adiponectin gene polymorphisms and its levels with aneurysmal subarachnoid hemorrhages (aSAHs) prognosis. This case–control study enrolled 138 patients with aSAH and 102 healthy controls as case group and control group, respectively. Prognosis of case group was evaluated using Glasgow Outcome Scale. Polymerase chain reaction–restriction fragment length polymorphism was used to examine the genotypes of 45T>G and −11377C>G. Enzyme-linked immunosorbent assay was used to detect adiponectin levels. Logistic regression analysis was applied to assess the association of adiponectin gene polymorphism with aSAH prognosis. Case group had increased GG genotype and G allele genotype frequencies of 45T>G and −11377C>G compared with control group (allP< 0.01). In case group, TT genotype had the highest adiponectin level compared with both TG and GC genotypes (bothP< 0.05). As for −11377C>G, GG genotype had the lowest adiponectin levels, followed by CG genotype and CC genotype in both groups (P< 0.05). In general, case group had decreased adiponectin levels compared with control group (P< 0.05). Univariate analysis showed that hypertension, Hunt–Hess grade, aneurysm size, aneurysms multiplicity and −11377C>G were associated with aSAH prognosis, while multivariate logistic regression analysis confirmed that hypertension, Hunt–Hess grade, residual flow in aneurysms and aneurysm size were independent risk factors for aSAH prognosis. Decreased adiponectin levels may be a pathological index for aSAH, which may be explain by the G allele of −11377C>G inadiponectin. Moreover, hypertension, Hunt–Hess grade, residual flow in aneurysms and aneurysm size may be independent risk factors for aSAH prognosis.
Deep genetic structure and ecological divergence in a widespread human commensal toad
Authors: Wogan Guinevere O. U. , Stuart Bryan L. , Iskandar Djoko T. , McGuire Jimmy A.
Published: January 2016

The Asian common toad (Duttaphrynus melanostictus) is a human commensal species that occupies a wide variety of habitats across tropical Southeast Asia. We test the hypothesis that genetic variation inD. melanostictusis weakly associated with geography owing to natural and human-mediated dispersal facilitated by its commensal nature. Phylogenetic and population genetic analyses of mitochondrial and nuclear DNA sequence variation, and predictive species distribution modelling, unexpectedly recovered three distinct evolutionary lineages that differ genetically and ecologically, corresponding to the Asian mainland, coastal Myanmar and the Sundaic islands. The persistence of these three divergent lineages, despite ample opportunities for recent human-mediated and geological dispersal, suggests thatD. melanostictusactually consists of multiple species, each having narrower geographical ranges and ecological niches, and higher conservation value, than is currently recognized. These findings also have implications for the invasion potential of this human commensal elsewhere, such as in its recently introduced ranges on the islands of Borneo, Sulawesi, Seram and Madagascar.
Sexual harassment induces a temporary fitness cost but does not constrain the acquisition of environmental information in fruit flies
Authors: Teseo Serafino , Veerus Liisa , Moreno Céline , Mery Frédéric
Published: January 2016

Across animals, sexual harassment induces fitness costs for females and males. However, little is known about the cognitive costs involved, i.e. whether it constrains learning processes, which could ultimately affect an individual's fitness. Here we evaluate the acquisition of environmental information in groups of fruit flies challenged with various levels of male sexual harassment. We show that, although high sexual harassment induces a temporary fitness cost for females, all fly groups of both sexes exhibit similar levels of learning. This suggests that, in fruit flies, the fitness benefits of acquiring environmental information are not affected by the fitness costs of sexual harassment, and that selection may favour cognition even in unfavourable social contexts. Our study provides novel insights into the relationship between sexual conflicts and cognition and the evolution of female counterstrategies against male sexual harassment.
Bursting noise in gene expression dynamics: linking microscopic and mesoscopic models
Authors: Lin Yen Ting , Galla Tobias
Published: January 2016

The dynamics of short-lived mRNA results in bursts of protein production in gene regulatory networks. We investigate the propagation of bursting noise between different levels of mathematical modelling and demonstrate that conventional approaches based on diffusion approximations can fail to capture bursting noise. An alternative coarse-grained model, the so-called piecewise deterministic Markov process (PDMP), is seen to outperform the diffusion approximation in biologically relevant parameter regimes. We provide a systematic embedding of the PDMP model into the landscape of existing approaches, and we present analytical methods to calculate its stationary distribution and switching frequencies.
Physical limits on bacterial navigation in dynamic environments
Authors: Hein Andrew M. , Brumley Douglas R. , Carrara Francesco , Stocker Roman , Levin Simon A.
Published: January 2016

Many chemotactic bacteria inhabit environments in which chemicals appear as localized pulses and evolve by processes such as diffusion and mixing. We show that, in such environments, physical limits on the accuracy of temporal gradient sensing govern when and where bacteria can accurately measure the cues they use to navigate. Chemical pulses are surrounded by a predictable dynamic region, outside which bacterial cells cannot resolve gradients above noise. The outer boundary of this region initially expands in proportion to the square root of time before rapidly contracting. Our analysis also reveals how chemokinesis—the increase in swimming speed many bacteria exhibit when absolute chemical concentration exceeds a threshold—may serve to enhance chemotactic accuracy and sensitivity when the chemical landscape is dynamic. More generally, our framework provides a rigorous method for partitioning bacteria into populations that are ‘near’ and ‘far’ from chemical hotspots in complex, rapidly evolving environments such as those that dominate aquatic ecosystems.
Do terrestrial hermit crabs sniff? Air flow and odorant capture by flicking antennules
Authors: Waldrop Lindsay D. , Koehl M. A. R.
Published: January 2016

Capture of odorant molecules by olfactory organs from the surrounding fluid is the first step of smelling. Sniffing intermittently moves fluid across sensory surfaces, increasing delivery rates of molecules to chemosensory receptors and providing discrete odour samples. Aquatic malacostracan crustaceans sniff by flicking olfactory antennules bearing arrays of chemosensory hairs (aesthetascs), capturing water in the arrays during downstroke and holding the sample during return stroke. Terrestrial malacostracans also flick antennules, but how their flicking affects odour capture from air is not understood. The terrestrial hermit crab,Coenobita rugosus, uses antennules bearing shingle-shaped aesthetascs to capture odours. We used particle image velocimetry to measure fine-scale fluid flow relative to a dynamically scaled physical model of a flicking antennule, and computational simulations to calculate diffusion to aesthetascs by odorant molecules carried in that flow. Air does not flow into the aesthetasc array during flick downstrokes or recovery strokes. Odorants are captured from air flowing around the outside of the array during flick downstrokes, when aesthetascs face upstream and molecule capture rates are 21% higher than for stationary antennules. Bursts of flicking followed by pauses deliver discrete odour samples to olfactory sensors, causing intermittency in odour capture by a different mechanism than aquatic crustaceans use.
On the organization of human T-cell receptor loci: log-periodic distribution of T-cell receptor gene segments
Authors: Toor Amir A. , Toor Abdullah A. , Rahmani Mohamed , Manjili Masoud H.
Published: January 2016

The human T-cell repertoire is complex and is generated by the rearrangement of variable (V), diversity (D) and joining (J) segments on the T-cell receptor (TCR) loci. The T-cell repertoire demonstrates self-similarity in terms clonal frequencies when defined by V, D and J gene segment usage; therefore to determine whether the structural ordering of these gene segments on the TCR loci contributes to the observed clonal frequencies, the TCR loci were examined for self-similarity and periodicity in terms of gene segment organization. Logarithmic transformation of numeric sequence order demonstrated that the V and J gene segments for both T-cell receptor α (TRA) and β (TRB) loci are arranged in a self-similar manner when the spacing between the adjacent segments was considered as a function of the size of the neighbouring gene segment, with an average fractal dimension of approximately 1.5. Accounting for the gene segments occurring on helical DNA molecules with a logarithmic distribution, sine and cosine functions of the log-transformed angular coordinates of the start and stop nucleotides of successive TCR gene segments showed an ordered progression from the 5′ to the 3′ end of the locus, supporting a log-periodic organization. T-cell clonal frequency estimates, based on V and J segment usage, from normal stem cell donors were plotted against the V and J segment on TRB locus and demonstrated a periodic distribution. We hypothesize that this quasi-periodic variation in gene-segment representation in the T-cell clonal repertoire may be influenced by the location of the gene segments on the periodic-logarithmically scaled TCR loci. Interactions between the two strands of DNA in the double helix may influence the probability of gene segment usage by means of either constructive or destructive interference resulting from the superposition of the two helices.
Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1
Authors: Sitaras Ioannis , Rousou Xanthoula , Kalthoff Donata , Beer Martin , Peeters Ben , de Jong Mart C. M.
Published: January 2016

Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds.
Oxygen depletion in coastal seas and the effective spawning stock biomass of an exploited fish species
Authors: Hinrichsen H.-H. , von Dewitz B. , Dierking J. , Haslob H. , Makarchouk A. , Petereit C. , Voss R.
Published: January 2016

Environmental conditions may have previously underappreciated effects on the reproductive processes of commercially exploited fish populations, for example eastern Baltic cod, that are living at the physiological limits of their distribution. In the Baltic Sea, salinity affects neutral egg buoyancy, which is positively correlated with egg survival, as only water layers away from the oxygen consumption-dominated sea bottom contain sufficient oxygen. Egg buoyancy is positively correlated to female spawner age/size. From observations in the Baltic Sea, a field-based relationship between egg diameter and buoyancy (floating depth) could be established. Hence, based on the age structure of the spawning stock, we quantify the number of effective spawners, which are able to reproduce under ambient hydrographic conditions. For the time period 1993–2010, our results revealed large variations in the horizontal extent of spawning habitat (1000–20 000 km
2
) and oxygen-dependent egg survival (10–80%). The novel concept of an effective spawning stock biomass takes into account offspring that survive depending on the spawning stock age/size structure, if reproductive success is related to egg buoyancy and the extent of hypoxic areas. Effective spawning stock biomass reflected the role of environmental conditions for Baltic cod recruitment better than the spawning stock biomass alone, highlighting the importance of including environmental information in ecosystem-based management approaches.
A stochastic vision-based model inspired by zebrafish collective behaviour in heterogeneous environments
Authors: Collignon Bertrand , Séguret Axel , Halloy José
Published: January 2016

Collective motion is one of the most ubiquitous behaviours displayed by social organisms and has led to the development of numerous models. Recent advances in the understanding of sensory system and information processing by animals impels one to revise classical assumptions made in decisional algorithms. In this context, we present a model describing the three-dimensional visual sensory system of fish that adjust their trajectory according to their perception field. Furthermore, we introduce a stochastic process based on a probability distribution function to move in targeted directions rather than on a summation of influential vectors as is classically assumed by most models. In parallel, we present experimental results of zebrafish (alone or in group of 10) swimming in both homogeneous and heterogeneous environments. We use these experimental data to set the parameter values of our model and show that this perception-based approach can simulate the collective motion of species showing cohesive behaviour in heterogeneous environments. Finally, we discuss the advances of this multilayer model and its possible outcomes in biological, physical and robotic sciences.
Rugged adaptive landscapes shape a complex, sympatric radiation
Authors: Pfaender Jobst , Hadiaty Renny K. , Schliewen Ulrich K. , Herder Fabian
Published: January 2016

Strong disruptive ecological selection can initiate speciation, even in the absence of physical isolation of diverging populations. Species evolving under disruptive ecological selection are expected to be ecologically distinct but, at least initially, genetically weakly differentiated. Strong selection and the associated fitness advantages of narrowly adapted individuals, coupled with assortative mating, are predicted to overcome the homogenizing effects of gene flow. Theoretical plausibility is, however, contrasted by limited evidence for the existence of rugged adaptive landscapes in nature. We found evidence for multiple, disruptive ecological selection regimes that have promoted divergence in the sympatric, incipient radiation of ‘sharpfin’ sailfin silverside fishes in ancient Lake Matano (Sulawesi, Indonesia). Various modes of ecological specialization have led to adaptive morphological differences between the species, and differently adapted morphs display significant but incomplete reproductive isolation. Individual fitness and variation in morphological key characters show that disruptive selection shapes a rugged adaptive landscape in this small but complex incipient lake fish radiation.
Evaluation of the External RNA Controls Consortium (ERCC) reference material using a modified Latin square design
Authors: Pine PS , Munro SA , Parsons JR , McDaniel J , Bergstrom Lucas A , Lozach J , Myers TG , Su Q , Jacobs-Helber SM , Salit M
Published: January 2016

BACKGROUND

Highly multiplexed assays for quantitation of RNA transcripts are being used in many areas of biology and medicine. Using data generated by these transcriptomic assays requires measurement assurance with appropriate controls. Methods to prototype and evaluate multiple RNA controls were developed as part of the External RNA Controls Consortium (ERCC) assessment process. These approaches included a modified Latin square design to provide a broad dynamic range of relative abundance with known differences between four complex pools of ERCC RNA transcripts spiked into a human liver total RNA background.

RESULTS

ERCC pools were analyzed on four different microarray platforms: Agilent 1- and 2-color, Illumina bead, and NIAID lab-made spotted microarrays; and two different second-generation sequencing platforms: the Life Technologies 5500xl and the Illumina HiSeq 2500. Individual ERCCs were assessed for reproducible performance in signal response to concentration among the platforms. Most demonstrated linear behavior if they were not located near one of the extremes of the dynamic range. Performance issues with any individual ERCC transcript could be attributed to detection limitations, platform-specific target probe issues, or potential mixing errors. Collectively, these pools of spike-in RNA controls were evaluated for suitability as surrogates for endogenous transcripts to interrogate the performance of the RNA measurement process of each platform. The controls were useful for establishing the dynamic range of the assay, as well as delineating the useable region of that range where differential expression measurements, expressed as ratios, would be expected to be accurate.

CONCLUSIONS

The modified Latin square design presented here uses a composite testing scheme for the evaluation of multiple performance characteristics: linear performance of individual controls, signal response within dynamic range pools of controls, and ratio detection between pairs of dynamic range pools. This compact design provides an economical sample format for the evaluation of multiple external RNA controls within a single experiment per platform. These results indicate that well-designed pools of RNA controls, spiked-into samples, provide measurement assurance for endogenous gene expression experiments.
Systematic identification of cooperation between DNA binding proteins in 3D space
Authors: Zhang Kai , Li Nan , Wang Wei
Published: January 2016

Cooperation between DNA-binding proteins (DBPs) such as transcription factors and chromatin remodeling enzymes plays a pivotal role in regulating gene expression and other biological processes. Such cooperation is often via interaction between DBPs that bind to loci located distal in the linear genome but close in the 3D space, referred as trans-cooperation. Due to the lack of 3D chromosomal structure, identification of DBP cooperation has been limited to those binding to neighbor regions in the linear genome, referred as cis-cooperation. Here we present the first study that integrates protein ChIP-seq and Hi-C data to systematically identify both cis- and trans-cooperation between DBPs. We developed a new network model that allows identification of cooperation between multiple DBPs and reveals cell type specific or independent regulations. Particularly interesting, we have retrieved many known and previously unknown trans-cooperation between DBPs in the chromosomal loops that may be a key factor for influencing 3D chromosomal structure. The software is available athttp://wanglab.ucsd.edu/star/DBPnet/index.html.
A Probabilistic, Distributed, Recursive Mechanism for Decision-making in the Brain
Authors: Caballero Javier A. , Humphries Mark D. , Gurney Kevin N.
Published: January 2016

Decision formation recruits many brain regions, but the procedure they jointly execute is unknown. Here we characterize its essential composition, using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex (MT). Using it to simulate the random-dot-motion task, we demonstrate it quantitatively replicates the choice behaviour of monkeys, whilst predicting losses of otherwise usable information from MT. Its architecture maps to the recurrent cortico-basal-ganglia-thalamo-cortical loops, whose components are all implicated in decision-making. We show that the dynamics of its mapped computations match those of neural activity in the sensorimotor cortex and striatum during decisions, and forecast those of basal ganglia output and thalamus. This also predicts which aspects of neural dynamics are and are not part of inference. Our single-equation algorithm is probabilistic, distributed, recursive, and parallel. Its success at capturing anatomy, behaviour, and electrophysiology suggests that the mechanism implemented by the brain has these same characteristics.

Author Summary

Decision-making is central to cognition. Abnormally-formed decisions characterize disorders like over-eating, Parkinson’s and Huntington’s diseases, OCD, addiction, and compulsive gambling. Yet, a unified account of decisionmaking has, hitherto, remained elusive. Here we show the essential composition of the brain’s decision mechanism by matching experimental data from monkeys making decisions, to the knowable function of a novel statistical inference algorithm. Our algorithm maps onto the large-scale architecture of decision circuits in the primate brain, replicating the monkeys’ choice behaviour and the dynamics of the neural activity that accompany it. Validated in this way, our algorithm establishes a basic framework for understanding the mechanistic ingredients of decisionmaking in the brain, and thereby, a basic platform for understanding how pathologies arise from abnormal function.
High-quality thermodynamic data on the stability changes of proteins upon single-site mutations
Authors: Pucci Fabrizio , Bourgeas Raphaël , Rooman Marianne
Published: January 2016

We have set up and manually curated a dataset containing experimental information on the impact of amino acid substitutions in a protein on its thermal stability. It consists of a repository of experimentally measured melting temperatures (Tm) and their changes upon point mutations (ΔTm) for proteins having a well-resolved X-ray structure. This high-quality dataset is designed for being used for the training or benchmarking of in silico thermal stability prediction methods. It also reports other experimentally measured thermodynamic quantities when available,i.e. the folding enthalpy (ΔH) and heat capacity (ΔCP) of the wild type proteins and their changes upon mutations (ΔΔHand ΔΔCP), as well as the change in folding free energy (ΔΔG) at a reference temperature. These data are analyzed in view of improving our insights into the correlation between thermal and thermodynamic stabilities, the asymmetry between the number of stabilizing and destabilizing mutations, and the difference in stabilization potential of thermostable versus mesostable proteins.
Statistical evidence for common ancestry: New tests of universal ancestry
Authors: Larget Bret , Ané Cécile , Bontrager Martin , Hunter Steve , Stenz Noah , Baum David A.
Published: January 2016

While there is no doubt among evolutionary biologists that all living species, or merely all living species within a particular group (e.g., animals), share descent from a common ancestor, formal statistical methods for evaluating common ancestry from aligned DNA sequence data have received criticism. One primary criticism is that prior methods take sequence similarity as evidence for common ancestry while ignoring other potential biological causes of similarity, such as functional constraints. We present a new statistical framework to test separate ancestry versus common ancestry that avoids this pitfall. We illustrate the efficacy of our approach using a recently published large molecular alignment to examine common ancestry of all primates (including humans).

We find overwhelming evidence against separate ancestry and in favor of common ancestry for orders and families of primates. We also find overwhelming evidence that humans share a common ancestor with other primate species.

The novel statistical methods presented here provide formal means to test separate ancestry versus common ancestry from aligned DNA sequence data while accounting for functional constraints that limit nucleotide base usage on a site-by-site basis.
ARGON: Fast, Whole-Genome Simulation of the Discrete Time Wright-Fisher Process
Authors: Palamara Pier Francesco
Published: January 2016

Motivation

Simulation under the coalescent model is ubiquitous in the analysis of genetic data. The rapid growth of real data sets from multiple human populations led to increasing interest in simulating very large sample sizes at whole-chromosome scales. When the sample size is large, the coalescent model becomes an increasingly inaccurate approximation of the discrete time Wright-Fisher model (DTWF). Analytical and computational treatment of the DTWF, however, is generally harder.

Results

We present a simulator (ARGON) for the DTWF process that scales up to hundreds of thousands of samples and whole-chromosome lengths, with a time/memory performance comparable or superior to currently available methods for coalescent simulation. The simulator supports arbitrary demographic history, migration, Newick tree output, variable mutation/recombination rates and gene conversion, and efficiently outputs pairwise identical-bydescent (IBD) sharing data.

Availability

ARGON (version 0.1) is written in Java, open source, and freely available athttps://github.com/pierpal/ARGON.

Contact

ppalama@hsph.harvard.edu

Supplementary information

Supplementary data are available online.
The Computational Nature of Memory Modification
Authors: Gershman Samuel J. , Monfils Marie-H , Norman Kenneth A. , Niv Yael
Published: January 2016

Retrieving a memory can modify its influence on subsequent behavior. Whether this phenomenon arises from modification of the contents of the memory trace or its accessibility is a matter of considerable debate. We develop a computational theory that incorporates both mechanisms. Modification of the contents of the memory trace occurs through classical associative learning, but which memory trace is accessed (and thus made eligible for modification) depends on a structure learning mechanism that discovers the units of association by segmenting the stream of experience into statistically distinct clusters (latent causes). New memories are formed when the structure learning mechanism infers that a new latent cause underlies current sensory observations. By the same token, old memories are modified when old and new sensory observations are inferred to have been generated by the same latent cause. We derive this framework from probabilistic principles, and present a computational implementation. Simulations demonstrate that our model can reproduce the major experimental findings from studies of memory modification in the Pavlovian conditioning literature, including dependence on the strength and age of memories, the interval between memory retrieval and extinction, and prediction errors following retrieval.
A performance-optimized model of neural responses across the ventral visual stream
Authors: Seibert Darren , Yamins Daniel , Ardila Diego , Hong Ha , DiCarlo James J. , Gardner Justin L.
Published: January 2016

Human visual object recognition is subserved by a multitude of cortical areas. To make sense of this system, one line of research focused on response properties of primary visual cortex neurons and developed theoretical models of a set of canonical computations such as convolution, thresholding, exponentiating and normalization that could be hierarchically repeated to give rise to more complex representations. Another line or research focused on response properties of high-level visual cortex and linked these to semantic categories useful for object recognition. Here, we hypothesized that the panoply of visual representations in the human ventral stream may be understood as emergent properties of a system constrained both by simple canonical computations and by top-level, object recognition functionality in a single unified framework (Yamins et al., 2014; Khaligh-Razavi and Kriegeskorte, 2014; Güçlü and van Gerven, 2015). We built a deep convolutional neural network model optimized for object recognition and compared representations at various model levels using representational similarity analysis to human functional imaging responses elicited from viewing hundreds of image stimuli. Neural network layers developed representations that corresponded in a hierarchical consistent fashion to visual areas from V1 to LOC. This correspondence increased with optimization of the model’s recognition performance. These findings support a unified view of the ventral stream in which representations from the earliest to the latest stages can be understood as being built from basic computations inspired by modeling of early visual cortex shaped by optimization for high-level object-based performance constraints.

Significance Statement

Prior work has taken two complimentary approaches to understanding the cortical processes underlying our ability to visually recognize objects. One approach identified canonical computations from primary visual cortex that could be hierarchically repeated and give rise to complex representations. Another approach linked later visual area responses to semantic categories useful for object recognition. Here we combined both approaches by optimizing a deep convolution neural network based on canonical computations to preform object recognition. We found that this network developed hierarchically similar response properties to those of visual areas we measured using functional imaging. Thus, we show that object-based performance optimization results in predictive models that not only share similarity with late visual areas, but also intermediate and early visual areas.
Neo-sex chromosomes in the Monarch butterfly,Danaus plexippus
Authors: Mongue Andrew J. , Nguyen Petr , Volenikova Anna , Walters James R.
Published: January 2016

We report the discovery of a neo-sex chromosome in Monarch butterfly,Danaus plexippus, and several of its close relatives. Z-linked scaffolds in theD. plexippusgenome assembly were identified via sex-specific differences in Illumina sequencing coverage. Additionally, a majority of theD. plexippusgenome assembly was assigned to chromosomes based on counts of 1-to-1 orthologs relative to the butterflyMelitaea cinxia(with replication using two other lepidopteran species), in which genome scaffolds have been mapped to linkage groups. Sequencing-coverage based assessments of Z-linkage combined with homology based chromosomal assignments provided strong evidence for a Z-autosome fusion in theDanauslineage, involving the autosome homologous to chromosome 21 inM. cinxia. Coverage analysis also identified three notable assembly errors resulting in chimeric Z-autosome scaffolds. Cytogenetic analysis further revealed a large W-chromosome that is partially euchromatic, consistent with being a neo-W chromosome. The discovery of a neo-Z and the provisional assignment of chromosome linkage for >90% ofD. plexippusgenes lays the foundation for novel insights concerning sex chromosome evolution in this female-heterogametic model species for functional and evolutionary genomics.
Mutation signatures reveal biological processes in human cancer
Authors: R. Covington Kyle , Shinbrot Eve , A. Wheeler David
Published: January 2016

Replication errors in the genome accumulate from a variety of mutational processes, which leave a history of mutations on the affected genome. The relative contribution of each mutational process has been characterized by non-negative matrix factorization and has lead to deeper insight into both mutational and repair processes contributing to cancer. However current implementations of NMF have left unresolved some specific patterns that should be present in the mutation data and have not generated signatures designed for classification. Here, we use a variant of NMF, termed non-smooth NMF, to generate sparse matrix factorizations of somatic mutation profiles present in 7129 tumors. nsNMF factorization revealed 21 mutational signatures. We found three APOBEC mutational processes clearly segregating with the published APOBEC enzymology and trans-lesion repair processes. We discovered several signatures differed between geographic locations even between closely related tissues.
A novel mutation in the nucleoporin NUP35 causes murine degenerative colonic smooth muscle myopathy
Authors: Parish Ian A. , Stamp Lincon A. , Lorenzo Ayla May D. , Fowler Suzanne M. , Sontani Yovina , Miosge Lisa A. , Howard Debbie R. , Goodnow Christopher C. , Young Heather M. , Furness John B.
Published: January 2016

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare, but life-threatening, disease characterized by severe intestinal dysmotility. Histopathological studies of CIPO patients have identified several different mechanisms that appear to be responsible for the dysmotility, including defects in neurons, smooth muscle or interstitial cells of Cajal. Currently there are few mouse models of the various forms of CIPO. We generated a mouse with a point mutation in the RNA Recognition Motif of theNup35gene, which encodes a component of the nuclear pore complex.Nup35mutants developed a severe megacolon and exhibited reduced lifespan. Histopathological examination revealed a degenerative myopathy that developed after birth and specifically affected smooth muscle in the colon; smooth muscle in the small bowel and the bladder were not affected. Furthermore, no defects were found in enteric neurons or interstitial cells of Cajal.Nup35mice are likely to be a valuable model for the sub-type of CIPO characterized by degenerative myopathy. Our study also raises the possibility thatNup35polymorphisms could contribute to some cases of CIPO.

Significance Statement

Chronic Intestinal Pseudo-Obstruction (CIPO) is a disabling bowel disorder in which the symptoms resemble those caused by mechanical obstruction, but no physical obstruction is present. Some patients with CIPO have defects in intestinal neurons while in other CIPO patients the muscle cells in the bowel wall appear to degenerate, but the underlying cause of these defects is unknown in most CIPO patients. We generated a mouse that has a mutation inNup35, which encodes a component of the pores found within the membrane of the cell nucleus. The mutant mice developed intestinal obstruction, which we showed was due to degeneration of the muscle cells in the colon. This mouse is likely to provide new insights into some forms of CIPO.
An Ancestry Based Approach for Detecting Interactions
Authors: Park Danny S. , Eskin Itamar , Kang Eun Yong , Gamazon Eric R. , Eng Celeste , Gignoux Christopher R. , Galanter Joshua M. , Burchard Esteban , Ye Chun J. , Aschard Hugues , Eskin Eleazar , Halperin Eran , Zaitlen Noah
Published: January 2016

I

Background:

Epistasis and gene-environment interactions are known to contribute significantly to variation of complex phenotypes in model organisms. However, their identification in human association studies remains challenging for myriad reasons. In the case of epistatic interactions, the large number of potential interacting sets of genes presents computational, multiple hypothesis correction, and other statistical power issues. In the case of gene-environment interactions, the lack of consistently measured environmental covariates in most disease studies precludes searching for interactions and creates difficulties for replicating studies.

Results:

In this work, we develop a new statistical approach to address these issues that leverages genetic ancestry in admixed populations. We applied our method to gene expression and methylation data from African American and Latino admixed individuals respectively, identifying nine interactions that were significant atp< 5×10−8, we show that two of the interactions in methylation data replicate, and the remaining six are significantly enriched for low p-values (p< 1.8×10−6).

Conclusion:

We show that genetic ancestry can be a useful proxy for unknown and unmeasured covariates in the search for interaction effects. These results have important implications for our understanding of the genetic architecture of complex traits.
Can social networks increase households’ contribution to public-good provision in rural China?
Authors: Cai Qihua , Zhu Yuchun , Chen Qihui
Published: January 2016

Purpose

– The purpose of this paper is to examine the roles social networks play in households’ contribution to the provision of small hydraulic facilities (SHFs) in rural China.

Design/methodology/approach

– This paper adopts a sample-selection ordered probit model (Greene and Hensher, 2010) to estimate the impacts of overall social-network intensity, of the number of strong ties (relatives), and of the number of weak ties (friends), using data on 1,064 representative households collected from three provinces (Inner Mongolia, Ningxia, and Shandong).

Findings

– The numbers of strong ties and weak ties both have significant impacts on households’ willingness to contribute to SHFs provision, but only the latter has a significant impact on their level of contribution. More specifically, a one standard deviation increase in the number of weak ties (i.e. friends) is associated with a 6.6 percent increase in households’ propensity of contributing more than 550 yuan and a 8.2 percent decrease in their propensity of contributing less than 100 yuan.

Originality/value

– This paper is the first to examine the impacts of social networks on households’ contribution to SHFs provision in rural China. Its finding is of great policy relevance-fostering and maintaining social networks (e.g. through rural cooperatives) can significantly increase households’ contribution to public-good provision.
Cash transfers and multiplier effect: lessons from the grain subsidy program in China
Authors: Yi Fujin , Lu Wuyi , Zhou Yingheng
Published: January 2016

Purpose

– The purpose of this paper is to examine the multiplier effects of the grain subsidy program in China, which is a large food self-sufficiency project that is implemented as a cash transfer program. Income multiplier effects have not been empirically examined in the evaluation of the grain subsidy program although increasing the income of farmers is the original goal of this project.

Design/methodology/approach

– A large number of household-level observations are employed to measure the program’s income multiplier. An unrestricted model was first employed to measure the multipliers in a period of two years, and the difference was evaluated. Then, the income promotion effects of grain subsidy on various income sources for each specific subset of the population, such as liquidity conditions and household characteristics, were estimated.

Findings

– The results show that the grain subsidy program has a high income multiplier, and the income promotion effect of the transferred subsidies is from agricultural production derived by intensifying input for each unit of land. The multiplier effect of the grain subsidy program as a cash transfer program can be interpreted as the shadow value of relaxing liquidity constraints and could be particularly utilized by households with more farming land and farmers in less developed regions in China. Hence, to maximize the income multiplier effect, the grain subsidy distribution method should consider these criteria instead of retaining the prevalent standard that is based on contracted land areas.

Originality/value

– This study addresses the gap that the effect of China’s grain subsidy program on income increment has not been empirically examined in nation wide.
Off-farm employments and land rental behavior: evidence from rural China
Authors: Che Yi
Published: January 2016

Purpose

– The purpose of this paper is to examine the impacts of off-farm labor employments on household land rental behavior in rural China.

Design/methodology/approach

– IV-Probit and IV-Tobit model are used to identify the estimate of interest.

Findings

– The results indicate that households with more members participating in either migration or local off-farm work are more/less likely to rent out/in land. Moreover, the effect of migration on household land rental behavior is much larger than the effect of local off-farm work.

Practical implications

– These results suggest that ensuring benefits of migrants in urban cities can automatically promote household land rental behavior in rural China.

Originality/value

– The authors provide a rigorous and careful empirical analysis on the effect of off-farm employment on household land rental behavior and pay special attention to the endogeneity issue tackled using separable instruments.
Applying Lean Six Sigma to improve medication management
Authors: Nayar Preethy , Ojha Diptee , Fetrick Ann , Nguyen Anh T
Published: January 2016

Purpose

– A significant proportion of veterans use dual care or health care services within and outside the Veterans Health Administration (VHA). In this study conducted at a VHA medical center in the USA, the authors used Lean Six Sigma principles to develop recommendations to eliminate wasteful processes and implement a more efficient and effective process to manage medications for dual care veteran patients. The purpose of this study is to: assess compliance with the VHA’s dual care policy; collect data and describe the current process for co-management of dual care veterans’ medications; and draft recommendations to improve the current process for dual care medications co-management.

Design/methodology/approach

– Input was obtained from the VHA patient care team members to draw a process map to describe the current process for filling a non-VHA prescription at a VHA facility. Data were collected through surveys and direct observation to measure the current process and to develop recommendations to redesign and improve the process.

Findings

– A key bottleneck in the process that was identified was the receipt of the non-VHA medical record which resulted in delays in filling prescriptions. The recommendations of this project focus on the four domains of: documentation of dual care; veteran education; process redesign; and outreach to community providers.

Research limitations/implications

– This case study describes the application of Lean Six Sigma principles in one urban Veterans Affairs Medical Center (VAMC) in the Mid-Western USA to solve a specific organizational quality problem. Therefore, the findings may not be generalizable to other organizations.

Practical implications

– The Lean Six Sigma general principles applied in this project to develop recommendations to improve medication management for dual care veterans are applicable to any process improvement or redesign project and has valuable lessons for other VAMCs seeking to improve care for their dual care veteran patients.

Originality/value

– The findings of this project will be of value to VA providers and policy makers and health care managers who plan to apply Lean Six Sigma techniques in their organizations to improve the quality of care for their patients.
Hospital menu interventions: a systematic review of research
Authors: Ottrey Ella , Porter Judi
Published: January 2016

Purpose

– Most patients in developed countries solely depend on the hospital menu to order their food. The provision of menu choices to patients differs between facilities. The purpose of this paper is to determine which strategies that provide menu choices to patients are effective in improving clinical and non-clinical outcomes in hospital.

Design/methodology/approach

– Five databases were searched to identify relevant publications. Prospective research published in English with the menu as the primary intervention was included. Study eligibility was determined and risk of bias assessed. Outcome data were combined narratively due to absence of homogeneous study design and outcomes.

Findings

– Of the 2,201 records screened, six studies met inclusion criteria. Standardised menu formatting and the spoken menu system were found to improve meal tray accuracy. The spoken menu and computerised interactive menu selector system enhanced aspects of patient satisfaction without cost increases. Descriptive menus may increase food consumption. Branding food items was not well supported by patients. One study rated positively for study quality with the remaining five studies receiving neutral quality ratings.

Research limitations/implications

– The small number of studies conducted on each intervention and the quality of the evidence made it difficult to establish a solid evidence base around providing menu choices to patients. Further research is needed on menu ordering systems, including spoken and visual menus, to determine their impact on outcomes in hospital.

Originality/value

– This review is first to examine the effectiveness of menu interventions in hospital. Hospital foodservice departments should consider these findings when reviewing local systems.
The market’s reaction to unexpected, catastrophic events
Authors: Humphrey Phillip , Carter David A. , Simkins Betty
Published: January 2016

Purpose

– The purpose of this paper is to examine the stock market reaction to the Gulf oil spill and determine if the markets exhibited rational pricing. On April 20, 2010, the US Coast Guard received a report of an explosion and fire aboard Transocean’s Deepwater Horizon offshore drilling rig. The resulting spill exceeded the Exxon Valdez oil spill as the worst in US history. With the total cost of the disaster reaching almost $54 billion for British Petroleum, clearly the spill had far-reaching effects on its market value. However, the more interesting question is what valuation effects might exist for other oil and gas firms, due to an increase in perceived risk for all offshore drilling and/or the likelihood of an increase in the regulation of the industry.

Design/methodology/approach

– Because the new information was released piecemeal over time and has the potential to affect a number of firms simultaneously, Gibbon’s (1980) multivariate regression model methodology (MVRM) was used to examine share price reactions of firms in the oil and gas industry in the aftermath of the oil spill. This methodology allows one to test whether significant abnormal returns occur on days where new information is released. Further, one is able to test whether the market reaction was the same for each firm or whether the market differentiated between firms.

Findings

– Evidence of abnormal returns was found for the majority of the information dates in our investigation. Further, the results reject the notion that the market reaction was the same for all oil and gas firms, leading to the conclusion that the market did differentiate between firms.

Originality/value

– This research is important because the results support rational pricing of the US stock markets following this unexpected and catastrophic event. The market was examined over the period following the oil spill on multiple dates when important new information is provided. This study contributes to financial and economic research on market efficiency and reactions to major risk events.