bluuebunny/crossref_metadata_2025 huggingface dataset:
Competency to Stand Trial in the American Legal System
Authors: Roesch Ronald
Published: December 2016

Competency to stand trial is a long-established legal principle in the U.S. criminal justice system that ensures that a criminal defendant’s right to a fair trial is protected. Fundamental justice requires that criminal defendants should be able to understand the charges against them, appreciate the nature and range of penalties, and communicate with their attorney. If they do not have the capacity in any of these areas, they may be found incompetent to proceed and the judicial proceedings are suspended until they are treated and competency is restored.

While competency to stand trial is the most commonly used term, competency in the criminal trial process encompasses all stages of participation in the legal process, including pretrial, trial, sentencing, and appeals. It is also a consideration if a defendant chooses to represent him or herself. Indeed, the term itself is misleading because few defendants actually go to trial, as the vast majority of cases are resolved through plea bargaining. The competency issue is raised when an officer of the court (defense, prosecution, or judge) has reason to believe there is a bona fide doubt as to a defendant’s competence. Once raised, defendants are typically referred for an evaluation by a mental health professional. Legal precedence has established that the basis of a finding of incompetency must be the presence of a major mental illness or substantial cognitive deficit. However, the mere presence of either of these conditions is not sufficient, as a functional approach to assessing competency dictates that the mental illness or cognitive deficit must be shown to affect the defendant’s specific legal competencies. It is entirely possible, for example, that some defendants with a psychosis or other severe mental illness may nevertheless be able to proceed with their case if the mental illness does not impair the legal abilities necessary to go forward.
Surveys and the Study of Crime, Mass Media, and Popular Culture
Authors: Dennis Jeffery
Published: December 2016

The survey, a research methodology in which variables are measured through the answers to questions on a data collection tool called a “survey questionnaire,” has been used to investigate several potential relationships between mass media and crime. In almost all studies, the relationship hypothesized is media influence, in which the media images change the consumer’s attitudes, beliefs, and behavior. Most commonly the hypothesized change is behavioral: individuals who consume violent, sexual, or otherwise suspect media images purportedly have a heightened risk of engaging in criminal acts. Other hypothesized effects of media consumption that are studied frequently include racist or otherwise biased attitudes, which could impact decision making during the criminal justice process; inaccurate beliefs about crime, with an impact on fear of crime and resultant changes in public policy; and the CSI Effect, an exaggerated belief in the efficiency of forensic science in identifying criminal offenders, which could sway jury decisions.

Survey-based research studies have rarely found that mass media consumption has a significant impact on criminal behavior or biased attitude, and its impact on beliefs about crime are contingent on many more significant factors. While these poor results may suggest that there is indeed minimal impact, the problem may lie within the methodology itself, in the ability of survey-based questions and answers to adequately measure the independent variable (media consumption) and the various dependent variables. Additionally, the problem may lie within the essential premise of media influence, with its passive, naive viewer and a radical disjunction between media and real life.
Relational Pedagogy
Authors: Hinsdale Mary Jo , Ljungblad Ann-Louise
Published: December 2016

One could easily argue that the pedagogy of relation is not new: a genealogy of the approach would send us back to the ancient Greek philosophers. However, in recent years relational pedagogy has been taken up in novel and ever-deepening ways. It is a response to ongoing efforts at school reform that center on teacher and administrator accountability, based on a constraining view of education as the effective teaching of content. In this view, methods, curricula, and high-stakes testing overshadow the human relationship between teacher and student that relational pedagogy theorists place at the center of educational exchanges. When relationships are secondary to content, the result can be disinterested or alienated students and teachers who feel powerless to step outside the mandated curriculum of their school district.

Contemporary relational theorists offer an alternative vision of pedagogy in a concerning era of teacher accountability. Internationally, teachers experience challenging educational environments that reflect troubled social histories across differences of socioeconomic class, race and ethnicity, gender, and ability status. Climate change, civil and economic instability, and war add global pressures that bring immigrant and refugee students into classrooms around the world. In the United States, histories of slavery, genocide, and indigenous removal continue to resound through all levels of education. Putting the teacher-student relationship at the heart of education offers a way to serve all students, allowing them to flourish in spite of the many challenges we face in the 21st century.

Relational pedagogy is inspired by a range of philosophical writings: this article focuses on theorists whose work is informed by the concept of caring, as developed by Nel Noddings, with the critical perspective of Paulo Freire, or the ethics of Emmanuel Levinas. Although these approaches to ethical educational relations do not necessarily mesh together easily, the tensions among them can bear fruit that informs our pedagogy. After outlining the theoretical contours of relational pedagogy, we will turn to more recent empirical work in the field. New studies help us understand how to turn theory into classroom practices that will benefit all students.
Ships and Shipping in Southeast Asia
Authors: Manguin Pierre-Yves
Published: December 2016

Southeast Asian polities were destined to play an active role in the world economy because of their location at the crossroads of East Asian maritime routes and their richness in commodities that were in demand in the whole of Eurasia. For a long time, historians restricted their role to examination of regional peddling trade carried out in small ships. Research on ships and trade networks in the past few decades, however, has returned considerable agency to local societies, particularly to Austronesian speakers of insular Southeast Asia, from proto-historic to early modern times. As far in the past as two thousand years ago, following locally developed shipbuilding technologies and navigational practices, they built large and sophisticated ships that plied South China Sea and Indian Ocean routes, as documented by 1st-millennium Chinese and later Portuguese sources and now confirmed by nautical archaeology. Textual sources also confirm that local shipmasters played a prominent part in locally and internationally run trade networks, which firmly places their operations into the mainstream of Asian global maritime history.
Long-Term Exposure to NO2 and Ozone and Hypertension Incidence in the Black Women’s Health Study
Authors: Coogan Patricia F. , White Laura F. , Yu Jeffrey , Brook Robert D. , Burnett Richard T. , Marshall Julian D. , Bethea Traci N. , Rosenberg Lynn , Jerrett Michael
Published: December 2016

BACKGROUND

Evidence shows that exposure to air pollutants can increase blood pressure in the short and long term. Some studies show higher levels of hypertension prevalence in areas of high pollution. Few data exist on the association of air pollution with hypertension incidence. The purpose of the present study was to prospectively assess the associations of the traffic-related nitrogen dioxide (NO2) and of ozone with the incidence of hypertension in the Black Women’s Health Study (BWHS), a large cohort study of African American women.

METHODS

We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension associated with exposure to NO2 and ozone among 33,771 BWHS participants. NO2 and ozone levels at participant residential locations were estimated with validated models.

RESULTS

From 1995 to 2011, 9,570 incident cases of hypertension occurred in a total of 348,154 person-years (median follow-up time, 11 years). The multivariable HRs per interquartile range of NO2 (9.7 ppb) and ozone (6.7 ppb) were 0.92 (95% CI = 0.86, 0.98) and 1.09 (95% CI = 1.00, 1.18).

CONCLUSIONS

In this large cohort of African American women, higher ozone levels were associated with an increase in hypertension incidence. Higher NO2 levels were not associated with greater hypertension incidence; indeed, incidence was lower at higher NO2 levels.
Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score–Matched Analysis From 130 US Hospitals
Authors: Kadri Sameer S. , Swihart Bruce J. , Bonne Stephanie L. , Hohmann Samuel F. , Hennessy Laura V. , Louras Peter , Evans Heather L. , Rhee Chanu , Suffredini Anthony F. , Hooper David C. , Follmann Dean A. , Bulger Eileen M. , Danner Robert L.
Published: December 2016

Background.

Shock frequently complicates necrotizing fasciitis (NF) caused by group A Streptococcus (GAS) or Staphylococcus aureus. Intravenous immunoglobulin (IVIG) is sometimes administered for presumptive toxic shock syndrome (TSS), but its frequency of use and efficacy are unclear.

Methods.

Adult patients with NF and vasopressor-dependent shock undergoing surgical debridement from 2010 to 2014 were identified at 130 US hospitals. IVIG cases were propensity-matched and risk-adjusted. The primary outcome was in-hospital mortality and the secondary outcome was median length of stay (LOS).

Results.

Of 4127 cases of debrided NF with shock at 121 centers, only 164 patients (4%) at 61 centers received IVIG. IVIG subjects were younger with lower comorbidity indices, but higher illness severity. Clindamycin and vasopressor intensity were higher among IVIG cases, as was coding for TSS and GAS. In-hospital mortality did not differ between matched IVIG and non-IVIG groups (crude mortality, 27.3% vs 23.6%; adjusted odds ratio, 1.00 [95% confidence interval, .55–1.83]; P = .99). Early IVIG (≤2 days) did not alter this effect (P = .99). Among patients coded for TSS, GAS, and/or S. aureus, IVIG use was still unusual (59/868 [6.8%]) and lacked benefit (P = .63). Median LOS was similar between IVIG and non-IVIG groups (26 [13–49] vs 26 [11–43]; P = .84). Positive predictive values for identifying true NF and debridement among IVIG cases using our algorithms were 97% and 89%, respectively, based on records review at 4 hospitals.

Conclusions.

Adjunctive IVIG was administered infrequently in NF with shock and had no apparent impact on mortality or hospital LOS beyond that achieved with debridement and antibiotics.
Perspectives on the history of evo-devo and the contemporary research landscape in the genomics era
Authors: Tickle Cheryll , Urrutia Araxi O.
Published: December 2016

A fundamental question in biology is how the extraordinary range of living organisms arose. In this theme issue, we celebrate how evolutionary studies on the origins of morphological diversity have changed over the past 350 years since the first publication of thePhilosophical Transactions of The Royal Society. Current understanding of this topic is enriched by many disciplines, including anatomy, palaeontology, developmental biology, genetics and genomics. Development is central because it is the means by which genetic information of an organism is translated into morphology. The discovery of the genetic basis of development has revealed how changes in form can be inherited, leading to the emergence of the field known as evolutionary developmental biology (evo-devo). Recent approaches include imaging, quantitative morphometrics and, in particular, genomics, which brings a new dimension. Articles in this issue illustrate the contemporary evo-devo field by considering general principles emerging from genomics and how this and other approaches are applied to specific questions about the evolution of major transitions and innovations in morphology, diversification and modification of structures, intraspecific morphological variation and developmental plasticity. Current approaches enable a much broader range of organisms to be studied, thus building a better appreciation of the origins of morphological diversity.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
Alternative splicing and the evolution of phenotypic novelty
Authors: Bush Stephen J. , Chen Lu , Tovar-Corona Jaime M. , Urrutia Araxi O.
Published: December 2016

Alternative splicing, a mechanism of post-transcriptional RNA processing whereby a single gene can encode multiple distinct transcripts, has been proposed to underlie morphological innovations in multicellular organisms. Genes with developmental functions are enriched for alternative splicing events, suggestive of a contribution of alternative splicing to developmental programmes. The role of alternative splicing as a source of transcript diversification has previously been compared to that of gene duplication, with the relationship between the two extensively explored. Alternative splicing is reduced following gene duplication with the retention of duplicate copies higher for genes which were alternatively spliced prior to duplication. Furthermore, and unlike the case for overall gene number, the proportion of alternatively spliced genes has also increased in line with the evolutionary diversification of cell types, suggesting alternative splicing may contribute to the complexity of developmental programmes. Together these observations suggest a prominent role for alternative splicing as a source of functional innovation. However, it is unknown whether the proliferation of alternative splicing events indeed reflects a functional expansion of the transcriptome or instead results from weaker selection acting on larger species, which tend to have a higher number of cell types and lower population sizes.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
Phylogenetic evidence for the modular evolution of metazoan signalling pathways
Authors: Babonis Leslie S. , Martindale Mark Q.
Published: December 2016

Communication among cells was paramount to the evolutionary increase in cell type diversity and, ultimately, the origin of large body size. Across the diversity of Metazoa, there are only few conserved cell signalling pathways known to orchestrate the complex cell and tissue interactions regulating development; thus, modification to these few pathways has been responsible for generating diversity during the evolution of animals. Here, we summarize evidence for the origin and putative function of the intracellular, membrane-bound and secreted components of seven metazoan cell signalling pathways with a special focus on early branching metazoans (ctenophores, poriferans, placozoans and cnidarians) and basal unikonts (amoebozoans, fungi, filastereans and choanoflagellates). We highlight the modular incorporation of intra- and extracellular components in each signalling pathway and suggest that increases in the complexity of the extracellular matrix may have further promoted the modulation of cell signalling during metazoan evolution. Most importantly, this updated view of metazoan signalling pathways highlights the need for explicit study of canonical signalling pathway components in taxa that do not operate a complete signalling pathway. Studies like these are critical for developing a deeper understanding of the evolution of cell signalling.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
The origins, scaling and loss of tetrapod digits
Authors: Saxena Aditya , Towers Matthew , Cooper Kimberly L.
Published: December 2016

Many of the great morphologists of the nineteenth century marvelled at similarities between the limbs of diverse species, and Charles Darwin noted these homologies as significant supporting evidence for descent with modification from a common ancestor. Sir Richard Owen also took great care to highlight each of the elements of the forelimb and hindlimb in a multitude of species with focused attention on the homology between the hoof of the horse and the middle digit of man. The ensuing decades brought about a convergence of palaeontology, experimental embryology and molecular biology to lend further support to the homologies of tetrapod limbs and their developmental origins. However, for all that we now understand about the conserved mechanisms of limb development and the development of gross morphological disturbances, little of what is presented in the experimental or medical literature reflects the remarkable diversity resulting from the 450 million year experiment of natural selection. An understanding of conserved and divergent limb morphologies in this new age of genomics and genome engineering promises to reveal more of the developmental potential residing in all limbs and to unravel the mechanisms of evolutionary variation in limb size and shape. In this review, we present the current state of our rapidly advancing understanding of the evolutionary origin of hands and feet and highlight what is known about the mechanisms that shape diverse limbs.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
The bald and the beautiful: hairlessness in domestic dog breeds
Authors: Parker Heidi G. , Harris Alexander , Dreger Dayna L. , Davis Brian W. , Ostrander Elaine A.
Published: December 2016

An extraordinary amount of genomic variation is contained within the chromosomes of domestic dogs, manifesting as dramatic differences in morphology, behaviour and disease susceptibility. Morphology, in particular, has been a topic of enormous interest as biologists struggle to understand the small window of dog domestication from wolves, and the division of dogs into pure breeding, closed populations termed breeds. Many traits related to morphology, including body size, leg length and skull shape, have been under selection as part of the standard descriptions for the nearly 400 breeds recognized worldwide. Just as important, however, are the minor traits that have undergone selection by fanciers and breeders to define dogs of a particular appearance, such as tail length, ear position, back arch and variation in fur (pelage) growth patterns. In this paper, we both review and present new data for traits associated with pelage including fur length, curl, growth, shedding and even the presence or absence of fur. Finally, we report the discovery of a new gene associated with the absence of coat in the American Hairless Terrier breed.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
Insulin receptors and wing dimorphism in rice planthoppers
Authors: Xu Hai-Jun , Zhang Chuan-Xi
Published: December 2016

Wing polymorphism contributes significantly to the success of a wide variety of insects. However, its underlying molecular mechanism is less well understood. The migratory planthopper (BPH),Nilaparvata lugens, is one of the most extensively studied insects for wing polymorphism, due to its natural features of short- and long-winged morphs. Using the BPH as an example, we first surveyed the environmental cues that possibly influence wing developmental plasticity. Second, we explained the molecular basis by which two insulin receptors (InR1 and InR2) act as switches to determine alternative wing morphs in the BPH. This finding provides an additional layer of regulatory mechanism underlying wing polymorphism in insects in addition to juvenile hormones. Further, based on a discrete domain structure between InR1 and InR2 across insect species, we discussed the potential roles by which they might contribute to insect polymorphism. Last, we concluded with future directions of disentangling the insulin signalling pathway in the BPH, which serves as an ideal model for studying wing developmental plasticity in insects.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
Evolution of floral diversity: genomics, genes andgamma
Authors: Chanderbali Andre S. , Berger Brent A. , Howarth Dianella G. , Soltis Douglas E. , Soltis Pamela S.
Published: December 2016

A salient feature of flowering plant diversification is the emergence of a novel suite of floral features coinciding with the origin of the most species-rich lineage, Pentapetalae. Advances in phylogenetics, developmental genetics and genomics, including new analyses presented here, are helping to reconstruct the specific evolutionary steps involved in the evolution of this clade. The enormous floral diversity among Pentapetalae appears to be built on a highly conserved ground plan of five-parted (pentamerous) flowers with whorled phyllotaxis. By contrast, lability in the number and arrangement of component parts of the flower characterize the early-diverging eudicot lineages subtending Pentapetalae. The diversification of Pentapetalae also coincides closely with ancient hexaploidy, referred to as thegammawhole-genome triplication, for which the phylogenetic timing, mechanistic details and molecular evolutionary consequences are as yet not fully resolved. Transcription factors regulating floral development often persist in duplicate or triplicate ingamma-derived genomes, and both individual genes and whole transcriptional programmes exhibit a shift from broadly overlapping to tightly defined expression domains in Pentapetalae flowers. Investigations of these changes associated with the origin of Pentapetalae can lead to a more comprehensive understanding of what is arguably one of the most important evolutionary diversification events within terrestrial plants.

This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
AspWood: High-spatial-resolution transcriptome profiles reveal uncharacterized modularity of wood formation inPopulus tremula
Authors: Sundell David , Street Nathaniel R. , Kumar Manoj , Mellerowicz Ewa J. , Kucukoglu Melis , Johnsson Christoffer , Kumar Vikash , Mannapperuma Chanaka , Delhomme Nicolas , Nilsson Ove , Tuominen Hannele , Pesquet Edouard , Fischer Urs , Niittylä Totte , Sundberg Bjöern , Hvidsten Torgeir R.
Published: December 2016

Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, and efforts to engineer new, elite varieties will benefit from an improved understanding of the transcriptional network underlying cambial growth and wood formation. We generated high-spatial-resolution RNA Sequencing data spanning the secondary phloem, vascular cambium and wood forming tissues. The transcriptome comprised 28,294 expressed, previously annotated genes, 78 novel protein-coding genes and 567 long intergenic non-coding RNAs. Most paralogs originating from theSalicaceaewhole genome duplication were found to have diverged expression, with the notable exception of those with high expression during secondary cell wall deposition. Co-expression network analysis revealed that the regulation of the transcriptome underlying cambial growth and wood formation comprises numerous modules forming a continuum of active processes across the tissues. The high spatial resolution enabled identification of novel roles for characterised genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and lignification. The associated web resource (AspWood,http://aspwood.popgenie.org) integrates the data within a set of interactive tools for exploring the expression profiles and co-expression network.
Histone gene expression is regulated by histone H2B ubiquitylation in fission yeast
Authors: Pagé Viviane , Grabowski David , Allis C. David , Tanny Jason C.
Published: December 2016

Cell cycle-regulated expression of histone genes is vital for coordination of DNA replication with chromatin assembly. In yeast, histone genes are regulated by transcriptional activation in S phase and transcriptional repression in other phases of the cell cycle, although the mechanisms are poorly understood. Here we describe a role for histone H2B monoubiquitylation (H2Bub1), a histone mark that is linked to RNA polymerase II transcription elongation, in the activation of replication-dependent histone genes in the fission yeastSchizosaccharomyces pombe. Loss of H2Bub1 is also associated with a delay in S phase progression and reduced expression of the replication initiation factor Cdc18 (ortholog of Cdc6). We provide evidence that H2Bub1 impacts histone gene transcription and acts through a mechanism that involves the 3’UTR. Consistent with our previous finding that H2Bub1 is functionally opposed to the elongation factor Cdk9, we also find that the effects of H2Bub1 on histone genes are suppressed by reduction in the activity of Cdk9. Our data suggest that H2Bub1 promotes cell growth by activating cell cycle-regulated genes.
Variable penetrance of the 15q11.2 BP1–BP2 microduplication in a family with cognitive and language impairment
Authors: Benítez-Burraco Antonio , Barcos-Martínez Montserrat , Espejo-Portero Isabel , Jiménez-Romero Ma Salud
Published: December 2016

The 15q11.2 BP1–BP2 region is found duplicated or deleted in people with cognitive, language, and behavioral impairment.Case presentation. We report on a family (the father and three male twin siblings) who presents with a duplication of the 15q11.2 BP1-BP2 region and a variable phenotype: whereas the father and the fraternal twin are normal carriers, the monozygotic twins exhibit severe language and cognitive delay and behavioral disturbances. The genes located within the duplicated region are involved in brain development and function, and some of them are related to language processing.Conclusions. The probands’ phenotype may result from changes in the expression level of some of these genes important for cognitive development.
Sex matters in Massive Parallel Sequencing: Evidence for biases in genetic parameter estimation and investigation of sex determination systems
Authors: Benestan Laura , Moore Jean-Sébastien , Sutherland Ben J. G. , Le Luyer Jérémy , Maaroufi Halim , Rougeux Clément , Normandeau Eric , Rycroft Nathan , Atema Jelle , Harris Les N. , Tallman Ross F. , Greenwood Spencer J. , Clark K. Fraser , Bernatchez Louis
Published: December 2016

Using massively parallel sequencing data from two species with different life history traits -- American lobster (Homarus americanus) and Arctic Char (Salvelinus alpinus) -- we highlighted how an unbalanced sex ratio in the samples combined with a few sex-linked markers may lead to false interpretations of population structure and thus to potentially erroneous management recommendations. Multivariate analyses revealed two genetic clusters that separated males and females instead of showing the expected pattern of genetic differentiation among ecologically divergent (inshore vs. offshore in lobster) or geographically distant (east vs. west in Arctic Char) sampling locations. We created several subsamples artificially varying the sex ratio in the inshore/offshore and east/west groups, and then demonstrated that significant genetic differentiation could be observed despite panmixia for lobster, and that Fstvalues were overestimated for Arctic Char. This pattern was due to 12 and 94 sex-linked markers driving differentiation for lobster and Arctic Char, respectively. Removing sex-linked markers led to nonsignificant genetic structure (lobster) and a more accurate estimation of Fst(Arctic Char). We further characterized the putative functions of sex-linked markers. Given that only 9.6% of all marine/diadromous population genomic studies to date reported sex information, we urge researchers to collect and consider individual sex information. In summary, we argue that sex information is useful to (i) control sex ratio in sampling, (ii) overcome “sex-ratio bias” that can lead to spurious genetic differentiation signals and (iii) fill knowledge gaps regarding sex determining systems.
Looking at my own Face: Visual Processing Strategies in Physical Self-representation
Authors: Chakraborty Anya , Chakrabarti Bhismadev
Published: December 2016

We live in an age of ‘selfies’. Yet, how we look at our own faces has seldom been systematically investigated. In this study we test if visual processing of self-faces is different from other faces, using psychophysics and eye-tracking. Specifically, the association between the psychophysical properties of self-face representation and visual processing strategies involved in self-face recognition was tested. Thirty-three adults performed a self-face recognition task from a series of self-other face morphs with simultaneous eye-tracking. Participants were found to look at lower part of the face for longer duration for self-face compared to other-face. Participants with a reduced overlap between self and other face representations, as indexed by a steeper slope of the psychometric response curve for self-face recognition, spent a greater proportion of time looking at the upper regions of faces identified as self. Additionally, the association of autism-related traits with self-face processing metrics was tested, since autism has previously been associated with atypical self-processing, particularly in the psychological domain. Autistic traits were associated with reduced looking time to both self and other faces. However, no self-face specific association was noted with autistic traits, suggesting that autism-related features may be related to self-processing in a domain specific manner.
Associations of coffee genetic risk scores with coffee, tea and other beverages in the UK Biobank
Authors: Taylor Amy E. , Munafò Marcus R.
Published: December 2016

Background

Genetic variants which determine amount of coffee consumed have been identified in genome-wide association studies (GWAS) of coffee consumption; these may help to further understanding of the effects of coffee on health outcomes. However, there is limited information about how these variants relate to caffeinated beverage consumption more generally.

Aims

To improve phenotype definition for coffee consumption related genetic risk scores by testing their association with coffee, tea and other beverages.

Methods

We tested the associations of genetic risk scores for coffee consumption with beverage consumption in 114,316 individuals of European ancestry from the UK Biobank. Drinks were self-reported in a baseline questionnaire and in detailed 24 dietary recall questionnaires in a subset.

Results

Genetic risk scores including two and eight single nucleotide polymorphisms (SNPs) explained up to 0.39%, 0.19% and 0.77% of the variance in coffee, tea and combined coffee and tea consumption respectively. A one standard deviation increase in the 8 SNP genetic risk score was associated with a 0.13 cup per day (95% CI: 0.12, 0.14), 0.12 cup per day (95%CI: 0.11, 0.14) and 0.25 cup per day (95% CI: 0.24, 0.27) increase in coffee, tea and combined tea and coffee consumption, respectively. Genetic risk scores also demonstrated positive associations with both caffeinated and decaffeinated coffee and tea consumption. In 48,692 individuals with dietary recall data, the genetic risk scores were positively associated with coffee and tea, (apart from herbal teas) consumption, but did not show clear evidence for positive associations with other beverages. However, there was evidence that the genetic risk scores were associated with lower daily water consumption and lower overall drink consumption.

Conclusions

Genetic risk scores created from variants identified in coffee consumption GWAS associate more broadly with caffeinated beverage consumption and also with decaffeinated coffee and tea consumption.
ASAP: A web-based platform for the analysis and interactive visualization of single-cell RNA-seq data
Authors: Gardeux Vincent , David Fabrice , Shajkofci Adrian , Schwalie Petra C , Deplancke Bart
Published: December 2016

Motivation

Single-cell RNA-sequencing (scRNA-seq) allows whole transcriptome profiling of thousands of individual cells, enabling the molecular exploration of tissues at the cellular level. Such analytical capacity is of great interest to many research groups in the world, yet, these groups often lack the expertise to handle complex scRNA-seq data sets.

Results

We developed a fully integrated, web-based platform aimed at the complete analysis of scRNA-seq data post genome alignment: from the parsing, filtering, and normalization of the input count data files, to the visual representation of the data, identification of cell clusters, differentially expressed genes (including cluster-specific marker genes), and functional gene set enrichment. This Automated Single-cell Analysis Pipeline (ASAP) combines a wide range of commonly used algorithms with sophisticated visualization tools. Compared with existing scRNA-seq analysis platforms, researchers (including those lacking computational expertise) are able to interact with the data in a straightforward fashion and in real time. Furthermore, given the overlap between scRNA-seq and bulk RNA-seq analysis workflows, ASAP should conceptually be broadly applicable to any RNA-seq dataset. As a validation, we demonstrate how we can use ASAP to simply reproduce the results from a single-cell study of 91 mouse cells involving five distinct cell types.

Availability

The tool is freely available athttp://asap.epfl.ch

Contact

bart.deplancke@epfl.ch
Sequence and structural diversity of mouse Y chromosomes
Authors: Morgan Andrew P , de Villena Fernando Pardo-Manuel
Published: December 2016

Over the 180 million years since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes characterized to date in that it is large, gene-rich and euchromatic. Yet little is known about its diversity in natural populations. Here we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number of sex-linked genes in three subspecies of house mice. Copy number of genes on the repetitive long arm of both sex chromosomes is highly variable, but sequence diversity in non-repetitive regions is decreased relative to expectations based on autosomes. We use simulations and theory to show that this reduction in sex-linked diversity is incompatible with neutral demographic processes alone, but is consistent with recent positive selection on genes active during spermatogenesis. Our results support the hypothesis that the mouse sex chromosomes are engaged in ongoing intragenomic conflict.
Quantification of subclonal selection in cancer from bulk sequencing data
Authors: Williams Marc J. , Werner Benjamin , Curtis Christina , Barnes Chris P , Sottoriva Andrea , Graham Trevor A
Published: December 2016

Recent studies have identified prevalent subclonal architectures within many cancer types. However, the temporal evolutionary dynamics that produce these subclonal architectures remain unknown. Here we measure evolutionary dynamics in primary human cancers using computational modelling of clonal selection applied to high throughput sequencing data. Our approach simultaneously determines the subclonal architecture of a tumour sample, and measures the mutation rate, the selective advantage, and the time of appearance of subclones. Simulations demonstrate the accuracy of the method, and revealed the degree to which evolutionary dynamics are recorded in the genome. Application of our method to high-depth sequencing data from gastric and lung cancers revealed that detectable subclones consistently emerged early during tumour growth and had considerably large fitness advantages (>20% growth advantage). Our quantitative platform provides new insight into the evolutionary history of cancers by facilitating the measurement of fundamental evolutionary parameters in individual patients.
The DOE Systems Biology Knowledgebase (KBase)
Authors: Arkin Adam P , Stevens Rick L , Cottingham Robert W , Maslov Sergei , Henry Christopher S , Dehal Paramvir , Ware Doreen , Perez Fernando , Harris Nomi L , Canon Shane , Sneddon Michael W , Henderson Matthew L , Riehl William J , Gunter Dan , Murphy-Olson Dan , Chan Stephen , Kamimura Roy T , Brettin Thomas S , Meyer Folker , Chivian Dylan , Weston David J , Glass Elizabeth M , Davison Brian H , Kumari Sunita , Allen Benjamin H , Baumohl Jason , Best Aaron A , Bowen Ben , Brenner Steven E , Bun Christopher C , Chandonia John-Marc , Chia Jer-Ming , Colasanti Ric , Conrad Neal , Davis James J , DeJongh Matthew , Devoid Scott , Dietrich Emily , Drake Meghan M , Dubchak Inna , Edirisinghe Janaka N , Fang Gang , Faria José P , Frybarger Paul M , Gerlach Wolfgang , Gerstein Mark , Gurtowski James , Haun Holly L , He Fei , Jain Rashmi , Joachimiak Marcin P , Keegan Kevin P , Kondo Shinnosuke , Kumar Vivek , Land Miriam L , Mills Marissa , Novichkov Pavel , Oh Taeyun , Olsen Gary J , Olson Bob , Parrello Bruce , Pasternak Shiran , Pearson Erik , Poon Sarah S , Price Gavin A , Ramakrishnan Srividya , Ranjan Priya , Ronald Pamela C , Schatz Michael C , Seaver Samuel M D , Shukla Maulik , Sutormin Roman A , Syed Mustafa H , Thomason James , Tintle Nathan L , Wang Daifeng , Xia Fangfang , Yoo Hyunseung , Yoo Shinjae
Published: December 2016

The U.S. Department of Energy Systems Biology Knowledgebase (KBase) is an open-source software and data platform designed to meet the grand challenge of systems biology — predicting and designing biological function from the biomolecular (small scale) to the ecological (large scale). KBase is available for anyone to use, and enables researchers to collaboratively generate, test, compare, and share hypotheses about biological functions; perform large-scale analyses on scalable computing infrastructure; and combine experimental evidence and conclusions that lead to accurate models of plant and microbial physiology and community dynamics. The KBase platform has (1) extensible analytical capabilities that currently include genome assembly, annotation, ontology assignment, comparative genomics, transcriptomics, and metabolic modeling; (2) a web-browser-based user interface that supports building, sharing, and publishing reproducible and well-annotated analyses with integrated data; (3) access to extensive computational resources; and (4) a software development kit allowing the community to add functionality to the system.
Quantitative mRNA Imaging Throughout the EntireDrosophilaBrain
Authors: Long Xi , Colonell Jennifer , Wong Allan M , Singer Robert H , Lionnet Timothée
Published: December 2016

We describe a fluorescence in situ hybridization method that permits detection of the localization and abundance of single mRNAs (smFISH) in cleared whole-mount adultDrosophilabrains. The approach is rapid, multiplexable and does not require molecular amplification; it allows facile mRNA expression quantification with subcellular resolution on a standard confocal microscope. Using a custom Bessel Beam-Structured Illumination microscope (BB-SIM), we further demonstrate single-mRNA detection across the entire brain sample.
A practical local tomography reconstruction algorithm based on a known sub-region
Authors: Paleo Pierre , Desvignes Michel , Mirone Alessandro
Published: December 2016

A new method to reconstruct data acquired in a local tomography setup is proposed. This method uses an initial reconstruction and refines it by correcting the low-frequency artifacts, known as the cupping effect. A basis of Gaussian functions is used to correct the initial reconstruction. The coefficients of this basis are found by optimizing iteratively a fidelity term under the constraint of a known sub-region. Using a coarse basis reduces the degrees of freedom of the problem while actually correcting the cupping effect. Simulations show that the known region constraint yields an unbiased reconstruction, in accordance with uniqueness theorems stated in local tomography.
X-ray radiation damage to biological macromolecules: further insights
Authors: Garman Elspeth F. , Weik Martin
Published: December 2016

Despite significant progress made over more than 15 years of research, structural biologists are still grappling with the issue of radiation damage suffered by macromolecular crystals which is induced by the resultant radiation chemistry occurring during X-ray diffraction experiments. Further insights into these effects and the possible mitigation strategies for use in both diffraction and SAXS experiments are given in eight papers in this volume. In particular, damage during experimental phasing is addressed, scavengers for SAXS experiments are investigated, microcrystals are imaged, data collection strategies are optimized, specific damage to tyrosine residues is reexamined, and room temperature conformational heterogeneity as a function of dose is explored. The brief summary below puts these papers into perspective relative to other ongoing radiation damage research on macromolecules.
Crystal structure of a putrescine aminotransferase fromPseudomonassp. strain AAC
Authors: Wilding Matthew , Scott Colin , Newman Janet , Peat Thomas S.
Published: December 2016

The putrescine aminotransferase KES24511 fromPseudomonassp. strain AAC was previously identified as an industrially relevant enzyme based on the discovery that it is able to promiscuously catalyse the transamination of 12-aminododecanoic acid. Here, the cloning, heterologous expression, purification and successful crystallization of the KES24511 protein are reported, which ultimately generated crystals adopting space groupI2. The crystals diffracted X-rays to 2.07 Å resolution and data were collected using the microfocus beamline of the Australian Synchrotron. The structure was solved using molecular replacement, with a monomer from PDB entry 4a6t as the search model.
X-ray crystal structure of a malonate-semialdehyde dehydrogenase fromPseudomonassp. strain AAC
Authors: Wilding Matthew , Scott Colin , Peat Thomas S. , Newman Janet
Published: December 2016

The NAD-dependent malonate-semialdehyde dehydrogenase KES23460 fromPseudomonassp. strain AAC makes up half of a bicistronic operon responsible for β-alanine catabolism to produce acetyl-CoA. The KES23460 protein has been heterologously expressed, purified and used to generate crystals suitable for X-ray diffraction studies. The crystals belonged to space groupP212121and diffracted X-rays to beyond 3 Å resolution using the microfocus beamline of the Australian Synchrotron. The structure was solved using molecular replacement, with a monomer from PDB entry 4zz7 as the search model.
Recombinant hepatocyte growth factor activator inhibitor 1: expression inDrosophilaS2 cells, purification and crystallization
Authors: Liu Min , Yuan Cai , Jiang Yunbin , Jiang Longguang , Huang Mingdong
Published: December 2016

Hepatocyte growth factor activator inhibitor 1 (HAI-1) is a multi-domain membrane-associated protease inhibitor that potently inhibits a variety of serine proteases such as hepatocyte growth factor activator and matriptase. Different truncates of HAI-1 show varying potencies for inhibition of target proteases, suggesting that the domain organization of HAI-1 plays a critical role in its function. Here, the soluble full-length extracellular part of HAI-1 (sHAI-1) was expressed using theDrosophilaS2 insect-cell expression system. Diffraction-quality crystals of sHAI-1 were produced using ammonium sulfate as precipitant. The crystal diffracted to 3.8 Å resolution and belonged to space groupP41212, with unit-cell parametersa=b= 95.42,c= 124.50 Å. The asymmetric unit contains one sHAI-1 molecule.
Expression, purification and crystallization of a protein resulting from the inversion of the amino-acid sequence of a helical bundle
Authors: Kefala Aikaterini , Kotsifaki Dina , Providaki Mary , Amprazi Maria , Kokkinidis Michael
Published: December 2016

Earlier studies have found that the occurrence of inverse sequence identity in proteins is not indicative of three-dimensional similarity, but rather leads to different folds or unfolded proteins. Short helices, however, frequently keep their conformations when their sequences are inverted. To explore the impact of sequence inversion on long helices, revRM6, with the inverse amino-acid sequence relative to RM6, a highly stable variant of the ColE1 Rop protein, was engineered. RM6 is a highly regular four-α-helical bundle that serves as a model system for protein-folding studies. Here, the crystallization and preliminary crystallographic characterization of revRM6 are reported. The protein was overexpressed inEscherichia coli, purified to homogeneity and crystallized. The crystals belonged to space groupP41212, with unit-cell parametersa=b= 44.98,c= 159.74 Å, and diffracted to a resolution of 3.45 Å.
Isotopic niches support the resource breadth hypothesis
Authors: Rader Jonathan A. , Newsome Seth D. , Sabat Pablo , Chesser R. Terry , Dillon Michael E. , Martínez del Rio Carlos
Published: December 2016

Because a broad spectrum of resource use allows species to persist in a wide range of habitat types, and thus permits them to occupy large geographical areas, and because broadly distributed species have access to more diverse resource bases, the resource breadth hypothesis posits that the diversity of resources used by organisms should be positively related with the extent of their geographic ranges.

We investigated isotopic niche width in a small radiation of South American birds in the genusCinclodes. We analysed feathers of 12 species ofCinclodesto test the isotopic version of the resource breadth hypothesis and to examine the correlation between isotopic niche breadth and morphology.

We found a positive correlation between the widths of hydrogen and oxygen isotopic niches (which estimate breadth of elevational range) and widths of the carbon and nitrogen isotopic niches (which estimates the diversity of resources consumed, and hence of habitats used). We also found a positive correlation between broad isotopic niches and wing morphology.

Our study not only supports the resource breadth hypothesis but it also highlights the usefulness of stable isotope analyses as tools in the exploration of ecological niches. It is an example of a macroecological application of stable isotopes. It also illustrates the importance of scientific collections in ecological studies.