bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric activation dictates PRC2 activity independent of its recruitment to chromatin
Authors: Lee Chul-Hwan , Yu Jia-Ray , Kumar Sunil , Jin Ying , Kaneko Syuzo , Hamilton Andrew D. , Reinberg Danny
Published: October 2017

PRC2 is a therapeutic target for several types of cancers currently undergoing clinical trials. Its activity is regulated by a positive feedback loop whereby its terminal enzymatic product, H3K27me3, is specifically recognized and bound by an aromatic cage present in its EED subunit. The ensuing allosteric activation of the complex stimulates H3K27me3 deposition on chromatin. Here, we report a step-wise feedback mechanism entailing key residues within distinctive interfacing motifs of EZH2 or EED that are found mutated in cancers and/or Weaver syndrome. PRC2 harboring these EZH2 or EED mutants manifest little activity in vivo but, unexpectedly, exhibited similar chromatin association as wild-type PRC2, indicating an uncoupling of PRC2 activity and recruitment. With genetic and chemical tools, we further demonstrated that targeting allosteric activation overrode the gain-of-function effect of EZH2Y646X oncogenic mutations. These results revealed critical implications to the regulation and biology of PRC2 and a novel vulnerability in tackling PRC2-addicted cancers.
An intermittent control model predicts the triphasic muscles activity during hand reaching
Authors: Leib Raz , d’Avella Andrea , Nisky Ilana
Published: October 2017

There are numerous ways to reach for an apple hanging from a tree. Yet, our motor system uses a specific muscle activity pattern to generate reaching movements that have similar characteristics. For many decades, we know that this pattern features activity bursts and silent periods. We suggest that these bursts are a strong evidence against the common view that the brain continuously controls the commands to the muscles. Instead, we suggest a model that changes these commands in a discrete way. We use unsupervised machine learning to identify transitions in the state of the muscles, and show that fitting a discrete model to the kinematics of movement using only one parameter predicts the transitions in the state of the muscles. Such discrete controller suggests that the brain reduces the complexity of the motor control problem as well as the wear-and-tear of the muscles by sending commands to the muscles at sparse times. Identifying this discrete controller can be applied in the control of prostheses and physical human-robot interaction systems such as exoskeletons and assistive devices.
Exploring the single-cell RNA-seq analysis landscape with the scRNA-tools database
Authors: Zappia Luke , Phipson Belinda , Oshlack Alicia
Published: October 2017

As single-cell RNA-sequencing (scRNA-seq) datasets have become more widespread the number of tools designed to analyse these data has dramatically increased. Navigating the vast sea of tools now available is becoming increasingly challenging for researchers. In order to better facilitate selection of appropriate analysis tools we have created the scRNA-tools database (www.scRNA-tools.org) to catalogue and curate analysis tools as they become available. Our database collects a range of information on each scRNA-seq analysis tool and categorises them according to the analysis tasks they perform. Exploration of this database gives insights into the areas of rapid development of analysis methods for scRNA-seq data. We see that many tools perform tasks specific to scRNA-seq analysis, particularly clustering and ordering of cells. We also find that the scRNA-seq community embraces an open-source approach, with most tools available under open-source licenses and preprints being extensively used as a means to describe methods. The scRNA-tools database provides a valuable resource for researchers embarking on scRNA-seq analysis and records of the growth of the field over time.

Author summary

In recent years single-cell RNA-sequeing technologies have emerged that allow scientists to measure the activity of genes in thousands of individual cells simultaneously. This means we can start to look at what each cell in a sample is doing instead of considering an average across all cells in a sample, as was the case with older technologies. However, while access to this kind of data presents a wealth of opportunities it comes with a new set of challenges. Researchers across the world have developed new methods and software tools to make the most of these datasets but the field is moving at such a rapid pace it is difficult to keep up with what is currently available. To make this easier we have developed the scRNA-tools database and website (www.scRNA-tools.org). Our database catalogues analysis tools, recording the tasks they can be used for, where they can be downloaded from and the publications that describe how they work. By looking at this database we can see that developers have focued on methods specific to single-cell data and that they embrace an open-source approach with permissive licensing, sharing of code and preprint publications.
Delirium symptoms are associated with decline in cognitive function between ages 53 to 69: findings from a British birth cohort study
Authors: Tsui A , Kuh D , Richards M , Davis D
Published: October 2017

INTRODUCTION

Few population studies have investigated whether longitudinal decline after delirium in mid-to-late life might affect specific cognitive domains.

METHODS

Participants from a birth cohort completing assessments of search speed, verbal memory and the Addenbrooke’s Cognitive Examination at age 69 were asked about delirium symptoms between ages 60-69. Linear regression models estimated associations between delirium symptoms and cognitive outcomes.

RESULTS

Period prevalence of delirium between 60 and 69 was 4% (95% CI 3.2%,4.9%). Self-reported symptoms of delirium over the seventh decade were associated with worse scores in the Addenbrooke’s Cognitive Examination (−1.7 points, 95% CI −3.2, −0.1, p=0.04). In association with delirium symptoms, verbal memory scores were initially lower, with subsequent decline in search speed by age 69. These effects were independent of other Alzheimer’s risk factors.

DISCUSSION

Delirium symptoms may be common even at relatively younger ages, and their presence may herald cognitive decline, particularly in search speed, over this time period.
Correlation of gene expressions between nucleus and cytoplasm reflects single-cell physiology
Authors: Abdelmoez Mahmoud N. , Iida Kei , Oguchi Yusuke , Nishikii Hidekazu , Yokokawa Ryuji , Kotera Hidetoshi , Uemura Sotaro , Santiago Juan G. , Shintaku Hirofumi
Published: October 2017

Background

Eukaryotes transcribe RNAs in nuclei and transport them to the cytoplasm through multiple steps of post-transcriptional regulation. Existing single-cell sequencing technologies, however, are unable to analyse nuclear (nuc) and cytoplasmic (cyt) RNAs separately and simultaneously. Hence, there remain challenges to discern correlation, localisation, and translocation between them.

Results

Here we report a microfluidic system that physically separates nucRNA and cytRNA from a single cell and enables single-cell integrated nucRNA and cytRNA-sequencing (SINC-seq). SINC-seq constructs two individual RNA-seq libraries, nucRNA and cytRNA per cell, quantifies gene expression in the subcellular compartments and combines them to create a novel single-cell RNA-seq data enabled by our system, which we here term in-silico single cell.

Conclusions

Leveraging SINC-seq, we discovered three distinct natures of correlation among cytRNA and nucRNA that reflected the physiological state of single cells: The cell-cycle-related genes displayed highly correlated expression pattern with minor differences; RNA splicing genes showed lower nucRNA-to-cytRNA correlation, suggesting a retained intron may be implicated in inhibited mRNA transport; A chemical perturbation, sodium butyrate treatment, transiently distorted the correlation along differentiating human leukemic cells to erythroid cells. These data uniquely provide insights into the regulatory network of mRNA from nucleus toward cytoplasm at the single cell level.
Measurements of three-dimensional refractive index tomography and membrane deformability of live erythrocytes fromPelophylax nigromaculatus
Authors: Kim Geon , Lee Moosung , Youn SeongYeon , Lee EuiTae , Kwon Daeheon , Shin Jonghun , Lee SangYun , Lee Youn Sil , Park YongKeun
Published: October 2017

Unlike mammalian erythrocytes, amphibian erythrocytes have distinct morphological features including large cell sizes and the presence of nuclei. The sizes of the cytoplasm and nuclei of erythrocytes vary significantly over different species, their environments, or pathophysiology, which makes hematological studies important for investigating amphibian species. Here, we present a label-free three-dimensional optical quantification of individual amphibian erythrocytes from frogsPelophylax nigromaculatus (Rana nigromaculata). Using optical diffraction tomography, we measured three-dimensional refractive index (RI) tomograms of the cells, which clearly distinguished the cytoplasm and nuclei inside the erythrocytes. From the measured RI tomograms, we extracted the relevant biochemical parameters of the cells, including hemoglobin contents and hemoglobin concentrations. Furthermore, we measured dynamic membrane fluctuations and investigated the mechanical properties of the cell membrane. From the statistical and correlative analysis of these retrieved parameters, we investigated interspecific differences between frogs and previously studied mammals.
Targeted genome fragmentation with CRISPR/Cas9 improves hybridization capture, reduces PCR bias, and enables efficient high-accuracy sequencing of small targets
Authors: Nachmanson Daniela , Lian Shenyi , Schmidt Elizabeth K. , Hipp Michael J. , Baker Kathryn T. , Zhang Yuezheng , Tretiakova Maria , Loubet-Senear Kaitlyn , Kohrn Brendan F. , Salk Jesse J. , Kennedy Scott R. , Risques Rosa Ana
Published: October 2017

Current next-generation sequencing techniques suffer from inefficient target enrichment and frequent errors. To address these issues, we have developed a targeted genome fragmentation approach based on CRISPR/Cas9 digestion. By designing all fragments to similar lengths, regions of interest can be size-selected prior to library preparation, increasing hybridization capture efficiency. Additionally, homogenous length fragments reduce PCR bias and maximize read usability. We combine this novel target enrichment approach with ultra-accurate Duplex Sequencing. The result, termed CRISPR-DS, is a robust targeted sequencing technique that overcomes the inherent challenges of small target enrichment and enables the detection of ultra-low frequency mutations with small DNA inputs.
Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis
Authors: Cozens Christopher , Pinheiro Vitor B.
Published: October 2017

Engineering proteins for designer functions and biotechnological applications almost invariably requires (or at least benefits from) multiple mutations to non-contiguous residues. Several methods for multiple site-directed mutagenesis exist, but there remains a need for fast and simple methods to efficiently introduce such mutations – particularly for generating large, high quality libraries for directed evolution. Here, we present Darwin Assembly, which can deliver high quality libraries of over 108 transformants, targeting multiple (> 10) distal sites with minimal wild-type contamination (lower than 0.25% of total population) and which takes a single working day from purified plasmid to library transformation. Darwin Assembly uses commercially available enzymes, can be readily automated, and offers a cost-effective route to highly complex and customizable library generation.
Integrin alpha 4 / beta 1 (CD49d/CD29) is a component of the murine IgG3 receptor
Authors: Saylor Hawk Carolyn , Coelho Carolina , Lima de Oliveira Diane Sthefany , Paredes Verenice , Albuquerque Patrícia , Lorenzetti Bocca Anamélia , Correa dos Santos Ananésia , Rusakova Victoria , Holemon Heather , Soares Felipe Maria Sueli , Yagita Hideo , Nicola André Moraes , Casadevall Arturo
Published: October 2017

Antibodies exert several of their effector functions by binding to cell surface receptors. For murine IgG3 (mIgG3) the identity of its receptors (and the very existence of a receptor) is still under debate, as not all mIgG3 functions can be explained by interaction with Fcγ-receptor I (FcγRI). This implies the existence of an alternate receptor, whose identity we sought to pinpoint. We found that blockage of the alpha4/beta1 integrin (Itga4/Itgb1) selectively hampered binding of mIgG3 to macrophages and mIgG3-mediated phagocytosis. Manganese, an integrin activator, increased mIgG3 binding to macrophages. Blockage of FcγRI or Itgb1 inhibited binding of different mIgG3 antibodies to variable extents. Our results indicate an integrin component in the mIgG3 receptor. Given the more ancient origin of integrins in comparison with FcγR, this observation could have far ranging implications for our understanding of the evolution of antibody-mediated immunity, as well as in immunity to microorganisms, pathogenesis of autoimmune diseases and antibody engineering.
Interleukins 4 and 13 Induce Exon Skipping of MutantDystrophinPre-mRNA to Restore Dystrophin Production
Authors: Low SiewHui , Fan Chen-Ming
Published: October 2017

Duchenne muscular dystrophy is (DMD) a lethal muscle degenerative disease caused by nonsense or out of frame deletion mutations in theDMDgene1, which encodes Dystrophin2,3. While multiple therapeutic strategies to ameliorate the disease symptoms are under development, there is currently no cure. Here we report an unexpected finding that intramuscular injections of the anti-inflammatory interleukin 4 or 13 (IL4/13) not only reduce inflammation but also restore Dystrophin protein production in themdxmouse model4. IL4/13 restores Dystrophin production by inducing changes in theDmdpre-mRNA splicing pattern that exclude the mutated exon and restore the reading frame. We further show that systemic delivery of IL4-Fc can restore Dystrophin in multiple muscle groups and increase muscle endurance and strength inmdxmice. Importantly, IL4/13 treatment ofmdxmyoblasts is sufficient to induce exon skipping and restoreDmdreading framein vitro. Moreover, IL4-treated DMD patient myoblasts produce Dystrophin-positive myofibers after transplantation. In light of the established clinical safety of IL4 treatment5,6, we recommend IL4 as an agent of immediate consideration for treating Duchenne muscular dystrophy.
Scanning X-ray diffraction on cardiac tissue: automatized data analysis and processing
Authors: Nicolas Jan-David , Bernhardt Marten , Markus Andrea , Alves Frauke , Burghammer Manfred , Salditt Tim
Published: October 2017

A scanning X-ray diffraction study of cardiac tissue has been performed, covering the entire cross section of a mouse heart slice. To this end, moderate focusing by compound refractive lenses to micrometer spot size, continuous scanning, data acquisition by a fast single-photon-counting pixel detector, and fully automated analysis scripts have been combined. It was shown that a surprising amount of structural data can be harvested from such a scan, evaluating the local scattering intensity, interfilament spacing of the muscle tissue, the filament orientation, and the degree of anisotropy. The workflow of data analysis is described and a data analysis toolbox with example data for general use is provided. Since many cardiomyopathies rely on the structural integrity of the sarcomere, the contractile unit of cardiac muscle cells, the present study can be easily extended to characterize tissue from a diseased heart.
Revisiting conditional accounting conservatism in state-controlled firms
Authors: Li Wilson , He Tina , Marshall Andrew , Tang Gordon
Published: October 2017

Purpose

The purpose of this paper is to explore the demand for conditional accounting conservatism from equity shareholders in state-controlled firms.

Design/methodology/approach

This study presents empirical investigation of firms listed on Hong Kong Stock Exchange from 1997 to 2013.

Findings

The first finding is the extent of conditional conservatism in state-controlled firms increases when the leverage ratio decreases. It is also found that the high control rights held by the government in state-controlled firms are associated with high conditional conservatism. In addition, further analyses document the an offsetting effect between high control rights and firm leverage; a reinforcing effect between high control rights and year of incorporation after 1992; and a substituting effect between high control rights and dividend payments.

Originality/value

These findings suggest that the demand from equity shareholders, in addition to the debt demand, can be an important determinant of conditional conservatism and examination of these differing sources of demand can enhance the understanding on accounting conservatism in state-controlled firms.
Positioning ethics and social responsibility as a strategic tool in employees’ affective commitment
Authors: Low Mei Peng , Ong Seng Fook , Tan Pei Meng
Published: October 2017

Purpose

The purpose of this paper is to study the impact of ethics and social responsibility on employees’ affective commitment in the context of small and medium-sized enterprises (SMEs).

Design/methodology/approach

This is a quantitative research. The authors employ multistage sampling technique, non-probability and judgmental sampling method. Data were collected through questionnaire survey to measure the respondents’ perceptions of the ethics and social responsibility, as well as internal corporate social responsibility (CSR) practices. The data obtained were analyzed through variance-based structural equation modeling (SEM), i.e., partial least square SEM.

Findings

The findings reveal that perceived role of ethics and social responsibility (PRESOR) and internal CSR are positively related to employees’ affective commitment. Job satisfaction is found to be mediating the relationship between PRESOR and affective commitment. The result also showed that internal CSR practices mediate the relationship between PRESOR and affective commitment.

Research limitations/implications

There are few limitations in the present research. First, present research merely investigates the practices of ethics and social responsibility by SMEs and did not perform a comparison with larger organizations. Second, the use of non-probability sampling method is unable to generalize results for the entire population. Future research could address the shortcoming of present research in order to further contribute to the academic and business world.

Practical implications

The findings provide insights to entrepreneurs and SMEs on the manifestation of ethics and social responsibility in enhancing employees’ affective commitment. In turn, it reduces employees’ turnover intention and enhances SMEs sustainability to strive in the competitive environment.

Social implications

These findings highlight the positive chain effects of enterprises in discharging their moral obligation as well as their social responsibility. The enterprises are benefited from the good reputation which may act as a magnet to attract talent-employees and also sustaining their enterprises through employees’ retention.

Originality/value

This research paper contributes to current knowledge by painting a better picture on the importance of ethics and social responsibility and internal CSR from the employees’ perception. As to date, employees’ perception of ethics and social responsibility and internal CSR practices are still under-investigated. Moreover, past research often focuses the impact of ethics and social responsibility in the larger corporation but scant research is conducted in the smaller organization such as SMEs.
Resource development conflict: a quantitative approach
Authors: Lytle Murray , Hitch Michael
Published: October 2017

Purpose

The purpose of this paper is to propose the thesis that how an individual views the world – their worldview – is indicative of their acceptance of resource development. A definition of worldview is given and the significance of worldview to cultural and civilizational development is described. A methodology for testing the hypothesis is described and the results of a survey used to collect data are analyzed. At least for the approximately 300 respondents to the survey, there is a correlation between their responses to a series of worldview questions and their acceptance of resource development. Not surprisingly, the correlation becomes stronger as the homogeneity of the respondent group increases. The results of the survey analysis are then compared to a known resource development conflict in a case study to understand the potential significance of the results in a real-world setting.

Design/methodology/approach

A definition of worldview is given and the significance of worldview to cultural and civilizational development is described and evaluated. A methodology for testing the hypothesis is described and the results of a survey used to collect data are analyzed.

Findings

At least for the 300 respondents to the survey, there is a correlation between their responses to a series of worldview questions and their acceptance of resource development. The case study indicates that respondents can hold contradictory views depending upon the level of inquiry.

Research limitations/implications

The sample size is too small to draw any but the most preliminary of conclusions. However, the correlations are high enough to encourage additional work.

Practical implications

The research may point to a relatively simple means of understanding the level of acceptance of resource development among all parties to a development proposal. This will allow proponents to identify issues early enough to address them in the design and negotiation phases of project development.

Social implications

Resource developers and residents local to the proposed development are often talking at cross-purposes because the issues are not understood at a deep enough level. Once issues are understood at the deeper level of worldview opportunities for resolution may be identified.

Originality/value

As far as the researchers are aware this is the only published methodology for quantifying the acceptance of resource development. As identified by the case study, it is possible for a community to reject resource development for reasons that have little to do with resource development either in the particular or in the general.
MHD mixed convection oblique stagnation-point flow on a vertical plate
Authors: Giantesio Giulia , Verna Anna , Roşca Natalia C. , Rosca Alin V. , Pop Ioan
Published: October 2017

Purpose

This paper aims to study the problem of the steady plane oblique stagnation-point flow of an electrically conducting Newtonian fluid impinging on a heated vertical sheet. The temperature of the plate varies linearly with the distance from the stagnation point.

Design/methodology/approach

The governing boundary layer equations are transformed into a system of ordinary differential equations using the similarity transformations. The system is then solved numerically using the “bvp4c” function in MATLAB.

Findings

An exact similarity solution of the magnetohydrodynamic (MHD) Navier–Stokes equations under the Boussinesq approximation is obtained. Numerical solutions of the relevant functions and the structure of the flow field are presented and discussed for several values of the parameters which influence the motion: the Hartmann number, the parameter describing the oblique part of the motion, the Prandtl number (Pr) and the Richardson numbers. Dual solutions exist for several values of the parameters.

Originality value

The present results are original and new for the problem of MHD mixed convection oblique stagnation-point flow of a Newtonian fluid over a vertical flat plate, with the effect of induced magnetic field and temperature.
Openness, productivity and welfare with heterogeneous firms
Authors: Jung Jaewon
Published: October 2017

Purpose

The purpose of this paper is to theoretically examine the effects of outward FDI on domestic aggregate productivity and welfare.

Design/methodology/approach

This paper develops a North-South general equilibrium model in which firms' technology adoption and workers’ skill-technology matching are endogenous. Technologically heterogeneous firms in the North make explicit delocalization decisions to the South through FDI and heterogeneous workers endogenously sort into different technologies according to their respective comparative advantages.

Findings

This paper highlights how globalization-induced technology-upgrading mechanisms of firms and workers increase aggregate productivity and welfare, though at the cost of increased income inequalities. The model shows also that the same technological shock (favoring high-tech firms) leads to different results in closed and open economy: both technology up- and downgrading occur in closed economy, while technology upgrading prevails in open economy.

Originality/value

By modeling and exploring the technology-skill links in a North-South setting, this paper provides richer predictions on the implications of outward FDI. In particular, the model highlights that the initial openness degree of the economy matters: the more open the country initially, the more technology upgrading as globalization proceeds, leading to higher aggregate productivity and welfare gains.
Exploring the decline in trade credit investment
Authors: Harris Chris , Roark Scott
Published: October 2017

Purpose

The purpose of this paper is to identify three factors leading to the observed decline in trade credit offered from publicly traded firms.

Design/methodology/approach

The study conducts firm fixed effect regressions testing the relationship between cash flow volatility and firm investment in trade credit. The relationship is further examined with all firms separated into two groups, based on SIC codes, designating if they are in industries that traditionally offer higher amounts of trade credit.

Findings

The proportion of US firms that has traditionally extended the most trade credit has been decreasing over time, contributing to part of the decline in trade credit offered. Increases in cash flow volatility have also contributed to decreasing investment in trade credit. The negative relationship with cash flow volatility is greatest amongst firms that traditionally place the highest value on trade credit. Firms with access to credit, proxied by investment grade debt ratings, do not experience the same decline in trade credit offered.

Practical implications

Firms that value the ability to extend trade credit may maintain their level of investment in trade credit, even with increased risk of cash flow volatility, by maintaining a comparative advantage in access to credit.

Originality/value

This study extends prior findings by providing three previously unexplored explanations for the decline in offered trade credit seen in the USA. The changing make-up of publicly traded firms, a market-wide increase in cash flow volatility, and access to credit all play an important role in observed declines of trade credit investment.
Stand‐level drivers most important in determining boreal forest response to climate change
Authors: Boulanger Yan , Taylor Anthony R. , Price David T. , Cyr Dominic , Sainte‐Marie Guillaume
Published: October 2017

Forest ecosystems contain several climate‐sensitive drivers that respond differentially to changes in climate and climate variability. For example, growth and regeneration processes are “stand‐scale” drivers, while natural disturbances operate at “landscape scale”. The relative contributions of these different scale drivers of change in ecosystems create great uncertainty when simulating potential responses of a forest to changes in climate.

Here, we assess those contributions, along with harvesting effects, on biomass (both total and of individual species) in the southern boreal forest of Canada under three climate scenarios (RCP2.6,RCP4.5 andRCP8.5).

Projections were performed for three future 30‐year time periods, in four study regions located on an east–west transect, using a forest landscape model (LANDIS‐II), parameterized using a forest patch model (PICUS). Projected future impacts were assessed for each driver of change, and found to vary greatly among regions, species, future period and forcing scenarios. Fire, and stand‐scale climate‐induced impacts, had the strongest effects on forest vegetation, as well as on total and species’ biomass under mostRCPscenarios, but the largest impacts occurred mostly after 2050, particularly with theRCP8.5 scenario.

The relative importance and trends in species‐specific impacts varied, both spatially and according to the differentRCPscenarios. Western regions were generally more sensitive to stand‐scale climate‐induced changes, whereas eastern regions were more sensitive to changes in fire regime. Our study also highlights the importance of considering the prevalence of species‐level functional traits when assessing the sensitivity of forest landscapes to a given driver of change in the context of increasing anthropogenic climate forcing.

Synthesis. Increases in fire activity, and direct impacts of climate change on forest growth and regeneration, will be the most important drivers of future changes in southern boreal forest landscapes.
The Daily Mail and the Stephen Lawrence Murder
Authors: Cathcart Brian
Published: October 2017

The Daily Mail's coverage of the 1993 race murder of Stephen Lawrence has been held up as an example of newspaper journalism at its best. It is a cause of pride to the paper, which has asserted that its 1997 front page accusing five men of the murder, and the comment and reporting that followed, brought about significant social and policy changes and helped achieve justice. The coverage has also been cited by the paper to rebut critics who accuse it of intolerance. Examined in detail here and set in their context, the paper's claims about its role in the case prove to be either exaggerated or not supported by evidence. The Mail's engagement in the Lawrence case involved a famous instance of editorial brilliance, but insofar as its campaign brought about or contributed to changes, they were not usually changes sought by the paper and they were sometimes contrary to its aims.
Suicide by Medication Overdose in Prison: A Study of Three Cases
Authors: Bartoli Christophe , Berland‐Benhaim Caroline , Tuchtan‐Torrents Lucile , Kintz Pascal , Leonetti Georges , Pelissier‐Alicot Anne‐Laure
Published: October 2017

Suicide is one of the principal causes of mortality in a prison environment. Although suicide by medication overdose is less frequent than suicide by hanging, self‐strangulation, or vein cutting, it raises questions as to how the medications are obtained, particularly in view of the specific organization of the medication circuit in prisons. We present three cases of suicide by medication overdose involving different therapeutic classes with different distribution circuits and review the regulatory requirements and the measures that could be taken to prevent such suicides.
Spatiotemporal Evaluation of Simulated Evapotranspiration and Streamflow over Texas Using the WRF‐Hydro‐RAPID Modeling Framework
Authors: Lin Peirong , Rajib Mohammad Adnan , Yang Zong‐Liang , Somos‐Valenzuela Marcelo , Merwade Venkatesh , Maidment David R. , Wang Yan , Chen Li
Published: October 2017

This study assesses a large‐scale hydrologic modeling framework (WRF‐Hydro‐RAPID) in terms of its high‐resolution simulation of evapotranspiration (ET) and streamflow over Texas (drainage area: 464,135 km2). The reference observations used include eight‐day ET data from MODIS and FLUXNET, and daily river discharge data from 271 U.S. Geological Survey gauges located across a climate gradient. A recursive digital filter is applied to decompose the river discharge into surface runoff and base flow for comparison with the model counterparts. While the routing component of the model is pre‐calibrated, the land component is uncalibrated. Results show the model performance for ET and runoff is aridity‐dependent. ET is better predicted in a wet year than in a dry year. Streamflow is better predicted in wet regions with the highest efficiency ~0.7. In comparison, streamflow is most poorly predicted in dry regions with a large positive bias. Modeled ET bias is more strongly correlated with the base flow bias than surface runoff bias. These results complement previous evaluations by incorporating more spatial details. They also help identify potential processes for future model improvements. Indeed, improving the dry region streamflow simulation would require synergistic enhancements of ET, soil moisture and groundwater parameterizations in the current model configuration. Our assessments are important preliminary steps towards accurate large‐scale hydrologic forecasts.
Combining noninvasive genetics and a new mammalian sex‐linked marker provides new tools to investigate population size, structure and individual behaviour: An application to bats
Authors: Zarzoso‐Lacoste Diane , Jan Pierre‐Loup , Lehnen Lisa , Girard Thomas , Besnard Anne‐Laure , Puechmaille Sebastien J. , Petit Eric J.
Published: October 2017

Monitoring wild populations is crucial for their effective management. Noninvasive genetic methods provide robust data from individual free‐ranging animals, which can be used in capture–mark–recapture (CMR) models to estimate demographic parameters without capturing or disturbing them. However, sex‐ and status‐specific behaviour, which may lead to differences in detection probabilities, is rarely considered in monitoring. Here, we investigated population size, sex ratio, sex‐ and status‐related behaviour in 19Rhinolophus hipposiderosmaternity colonies (Northern France) with a noninvasive geneticCMRapproach (using faeces) combined with parentage assignments. The use of theDDX3X/Y‐Mam sexual marker designed in this study, which shows inter‐ and intrachromosomal length polymorphism across placental mammals, together with eight polymorphic microsatellite markers, produced high‐quality genetic data with limited genotyping errors and allowed us to reliably distinguish different categories of individuals (males, reproductive and nonreproductive females) and to estimate population sizes. We showed that visual counts represent well‐adult female numbers and that population composition in maternity colonies changes dynamically during the summer. Before parturition, colonies mainly harbour pregnant and nonpregnant females with a few visiting males, whereas after parturition, colonies are mainly composed of mothers and their offspring with a few visiting nonmothers and males. Our approach gives deeper insight into sex‐ and status‐specific behaviour, a prerequisite for understanding population dynamics and developing effective monitoring and management strategies. Provided sufficient samples can be obtained, this approach can be readily applied to a wide range of species.
International Capacity Cooperation—Financing China's Export of Industrial Overcapacity
Authors: Kenderdine Tristan , Ling Han
Published: October 2017

International capacity cooperation (国际产能合作) exports China's Keynesian project system, offshoring its excess industrial capacity as fixed‐capital investment. Leveraged against foreign exchange reserves, the central policy banks and sovereign wealth funds push credit through a variety of purpose‐built infrastructure investment funds to provincial governments, state‐owned enterprises and ultimately to offshore projects. This paper explores the historical institutional development of funds used to channel central government funds through China's financial bureaucracy into target countries. We explore the export of the policy bank model, provincial implementation and recipient regional industrial policy, and examine the role of international capacity cooperation in China's international trade and investment strategy and its implications for China's domestic industrial policy. We conclude with post‐Keynesian analyses of China's export of industrial overcapacity while maintaining a closed financial model which is likely to introduce excessive risk to the global capital pool.
Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease
Authors: Roy Shubhrajit , Ganguly Kausik , Pal Prosenjit , Ghosh Sampurna , Das Shyamal K , Gangopadhyay Prasanta K. , Bavdekar Ashish , Ray Kunal , Sengupta Mainak , Ray Jharna
Published: October 2017

Wilson disease (WD) is an autosomal‐recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests diverse neurological and hepatic phenotypes and different age of onset, even among the siblings, with same mutational background suggesting complex nature of the disease and involvement of other candidate genes. In that context, Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be potential candidates for modifying the WD phenotype and age of onset. This study aims to identify the contribution of APOE and PRNP polymorphisms on the variable phenotypic expression of Indian WD patients.

A total of 171 WD patients and 291 controls from Indian population were included in this study. Two APOE cSNPs (rs429358 and rs7412) resulting in three isoforms and M129V (rs1799990) polymorphism of PRNP were examined for their association with WD and its clinical phenotypes.

The APOE ԑ4 allele was found to be significantly overrepresented in WD patients compared to controls. However, the frequency of the APOE ԑ3 allele and ԑ3/ԑ3 genotype was significantly higher in WD patients without cognitive behavior impairment compared to the ones with the impairment. On the contrary, the PRNP allele representing Val129 was found to be present in higher proportion in WD patients with cognitive behavioral decline. Our data suggest that the APOE ԑ4 allele could act as a potential risk for the pathogenesis of WD. Also, APOE and PRNP might contribute toward the cognitive behavioral decline in a section of WD patients.
Holocene permafrost history and cryostratigraphy in the High‐Arctic Adventdalen Valley, central Svalbard
Authors: Cable Stefanie , Elberling Bo , Kroon Aart
Published: October 2017

This paper presents the history and cryostratigraphy of the upper permafrost in the High‐Arctic Adventdalen Valley, central Svalbard. Nineteen frozen sediment cores, up to 10.7 m long, obtained at five periglacial landforms, were analysed for cryostructures, ice, carbon and solute contents, and grain‐size distribution, and were 14C‐ and OSL‐dated. Spatial variability in ice and carbon contents is closely related to the sedimentary history and mode of permafrost aggradation. In the valley bottom, saline epigenetic permafrost with pore ice down to depths of 10.7 m depth formed in deltaic sediments since the mid‐Holocene; cryopegs were encountered below 6 m. In the top 1 to 5 m, syngenetic and quasi‐syngenetic permafrost with microlenticular, lenticular, suspended and organic‐matrix cryostructures developed due to loess and alluvial sedimentation since the colder late Holocene, which resulted in the burial of organic material. At the transition between deltaic sediments and loess, massive ice bodies occurred. A pingo developed where the deltaic sediments reached the surface. On hillslopes, suspended cryostructure on solifluction sheets indicates quasi‐syngenetic permafrost aggradation; lobes, in contrast, were ice‐poor. Suspended cryostructure in eluvial deposits reflects epigenetic or quasi‐syngenetic permafrost formation on a weathered bedrock plateau. Landform‐scale spatial variations in ground ice and carbon relate to variations in slope, sedimentation rate, moisture conditions and stratigraphy. Although the study reveals close links between Holocene landscape evolution and permafrost history, our results emphasize a large uncertainty in using terrain surface indicators to infer ground‐ice contents and upscale from core to landform scale in mountainous permafrost landscapes.
5‐HT1F receptor‐mediated mitochondrial biogenesis for the treatment of Parkinson's disease
Authors: Scholpa Natalie E , Lynn Mary K , Corum Daniel , Boger Heather A , Schnellmann Rick G
Published: October 2017

Background and Purpose

Parkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioural abnormalities. Mitochondrial dysfunction, leading to loss of ATP‐dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5‐HT1F receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), we investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron loss in a mouse model of Parkinson's disease.

Experimental Approach

Male C57BL/6 mice underwent bilateral intrastriatal 6‐hydroxydopamine or saline injections and daily treatment with 2 mg·kg−1 LY344864 or vehicle for 14 days beginning 7 days post‐lesion. Tyrosine hydroxylase immunoreactivity (TH‐ir) and MB were assessed in the brains of all groups following treatment, and locomotor activity was evaluated prior to lesioning, 7 days post‐lesion and after treatment.

Key Results

Increased mitochondrial DNA content and nuclear‐ and mitochondrial‐encoded mRNA and protein expression was observed in specific brain regions of LY344864‐treated naïve and lesioned mice, indicating augmented MB. LY344864 attenuated TH‐ir loss in the striatum and substantia nigra compared to vehicle‐treated lesioned animals. LY344864 treatment also increased locomotor activity in 6‐hydroxydopamine lesioned mice, while vehicle treatment had no effect.

Conclusions and Implications

These data revealed that LY344864‐induced MB attenuates dopaminergic neuron loss and improves behavioural endpoints in this model. We suggest that stimulating MB may be beneficial for the treatment of Parkinson's disease and that the 5‐HT1F receptor may be an effective therapeutic target.
Adalimumab and postoperative complications of elective intestinal resections in Crohn's disease: a propensity score case‐matched study
Authors: Kotze P. G. , Magro D. O. , Martinez C. A. R. , Saab B. , Saab M. P. , Pinheiro L. V. , Olandoski M. , Yamamoto T. , Coy C. S. R.
Published: October 2017

Aim

Data are scarce regarding the effect of preoperative adalimumab (ADA) in postoperative complications in Crohn's disease (CD) patients. Our aim was to compare the rates of postoperative complications after intestinal resections in CD, with and without previous exposure to ADA.

Method

This was a case‐matched retrospective observational study of patients submitted to intestinal resections for CD. The patients were allocated to two groups, according to their previous exposure to ADA before surgery. The patients under ADA therapy were matched with controls (patients without previous biologics) with the propensity score method (PSM), according to age at surgery, CD location (Montreal L) and phenotype (Montreal B). Medical and surgical complications were compared.

Results

Initially 123 patients were considered, 71 with previous biologics (32 under ADA therapy) and 52 without. The PSM selected 25 ADA patients to be matched with 25 controls from the non‐biologics group. There was no difference regarding overall surgical complications (40% in the controlvs36% in the ADA group;P = 1.0000) or medical complications (36%vs12% in the control and ADA groups, respectively;P = 0.095). In univariate analysis, previous ADA was not considered a risk factor for higher postoperative complication rates. Stomas were considered a risk factor for surgical complications, and previous steroids were associated with higher medical complication rates.

Conclusions

Preoperative ADA did not influence the rates of medical and surgical complications after elective intestinal resections for CD. This was the first study to include exclusively patients under ADA therapy.
A decrease in serum 1,5‐anhydroglucitol levels is associated with the presence of a first‐degree family history of diabetes in a Chinese population with normal glucose tolerance
Authors: Hu X. , He X. , Ma X. , Su H. , Ying L. , Peng J. , Wang Y. , Bao Y. , Zhou J. , Jia W.
Published: October 2017

Aim

This study aimed to investigate alterations in HbA1c, glycated albumin (GA) and 1,5‐anhydroglucitol (1,5‐AG) in Chinese first‐degree relatives of individuals with diabetes (FDR) in pursuit of an index for early screening of glucose metabolism disturbance.

Methods

A total of 467 participants (age range: 20–78 years) with normal weight and normal glucose tolerance, as determined by a 75‐g oral glucose tolerance test, were enrolled. HbA1c was measured using high‐performance liquid chromatography. Serum GA and 1,5‐AG levels were determined by enzymatic methods. Serum insulin levels were measured using an electrochemiluminescence immunoassay.

Results

The study population included 208 FDR and 259 non‐FDR. Serum 1,5‐AG levels were lower in FDR than that in non‐FDR (20.4 ± 7.5 vs 23.8 ± 8.3 μg/ml, P < 0.001), but HbA1c and GA levels did not differ between them (P = 0.835 and 0.469, respectively). Logistic regression analysis revealed an independent relationship between a first‐degree family history of diabetes and reduced serum 1,5‐AG levels (odds ratio = 0.944, P < 0.001). Multiple regression analysis showed that a first‐degree family history of diabetes (β = –3.041, P < 0.001) and insulinogenic index (β = 0.081, P = 0.001) were independently associated with serum 1,5‐AG levels.

Conclusion

In a Chinese population with normal glucose tolerance, serum 1,5‐AG levels were lower among FDR, and serum 1,5‐AG levels were independently associated with FDR status. For FDR, serum 1,5‐AG levels were more sensitive than HbA1c or GA levels to early‐phase abnormality in glucose metabolism.
Dipeptidyl peptidase‐4 inhibitors moderate the risk of genitourinary tract infections associated with sodium‐glucose co‐transporter‐2 inhibitors
Authors: Fadini Gian Paolo , Bonora Benedetta Maria , Mayur Sarangdhar , Rigato Mauro , Avogaro Angelo
Published: October 2017

Genitourinary tract infections (GUTIs) are the most common adverse event (AE) occurring during therapy with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors. We evaluated whether dipeptidyl peptidase‐4 inhibitors moderate the risk of GUTI during SGLT2 inhibitor therapy, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTIs in patients receiving DPP‐4 inhibitor/SGLT2 inhibitor combination therapy vs those receiving an SGLT2 inhibitor only. In the five trials we retrieved, the pooled risk ratio for genital tract infections (GTIs) in patients on DPP‐4 inhibitor/SGLT2 inhibitor combination therapy vs those on SGLT2 inhibitors alone was 0.51 (95% confidence interval [CI] 0.28‐0.92). Second, we found that within the Food and Drug Administration AE Reporting System, the frequency of GUTIs among reports listing both SGLT2 and DPP‐4 inhibitors as suspect or concomitant drugs was significantly lower than among reports listing SGLT2 inhibitors without DPP‐4 inhibitors, with a proportional reporting ratio of 0.74 (95% CI 0.61‐0.90). In conclusion, in RCTs and in a large pharmacovigilance database, combination therapy with a DPP‐4 inhibitor appears to reduce the frequency of G(U)TIs associated with SGLT2 inhibitors.