bluuebunny/crossref_metadata_2025 huggingface dataset:
Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1
Authors: Ehlén Åsa , Martin Charlotte , Miron Simona , Julien Manon , Theillet François-Xavier , Ropars Virginie , Sessa Gaetana , Beaurepere Romane , Boucherit Virginie , Duchambon Patricia , El Marjou Ahmed , Zinn-Justin Sophie , Carreira Aura
Published: February 2018

The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identified two highly conserved phosphorylation sites at S193 and T207 of BRCA2. Phosphorylated-T207 is a bona fide docking site for PLK1 as illustrated by the crystal structure of the BRCA2 peptide bound to PLK1 Polo-box domain. We found that BRCA2 bound to PLK1 forms a complex with the phosphatase PP2A and phosphorylated-BUBR1. Reducing BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants S206C and T207A, alters the tetrameric complex resulting in misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a direct role of BRCA2 in the alignment of chromosomes, distinct from its DNA repair function, with important consequences on chromosome stability. These findings may explain in part the aneuploidy observed in BRCA2-mutated tumors.
THEA: A novel approach to gene identification in phage genomes
Authors: McNair Katelyn , Zhou Carol , Souza Brian , Edwards Robert A.
Published: February 2018

Motivation

Currently there are no tools specifically designed for annotating genes in phages. Several tools are available that have been adapted to run on phage genomes, but due to their underlying design they are unable to capture the full complexity of phage genomes. Phages have adapted their genomes to be extremely compact, having adjacent genes that overlap, and genes completely inside of other longer genes. This non-delineated genome structure makes it difficult for gene prediction using the currently available gene annotators. Here we present THEA (The Algorithm), a novel method for gene calling specifically designed for phage genomes. While the compact nature of genes in phages is a problem for current gene annotators, we exploit this property by treating a phage genome as a network of paths: where open reading frames are favorable, and overlaps and gaps are less favorable, but still possible. We represent this network of connections as a weighted graph, and use graph theory to find the optimal path.

Results

We compare THEA to other gene callers by annotating a set of 2,133 complete phage genomes from GenBank, using THEA and the three most popular gene callers. We found that the four programs agree on 82% of the total predicted genes, with THEA predicting significantly more genes than the other three. We searched for these extra genes in both GenBank’s non-redundant protein database and sequence read archive, and found that they are present at levels that suggest that these are functional protein coding genes.

Availability and Implementation

The source code and all files can be found at: https://github.com/deprekate/THEA

Contact

Katelyn McNair: deprekate@gmail.com
Structural variation detection by proximity ligation from FFPE tumor tissue
Authors: Troll Chris , Putnam Nicholas H. , Hartley Paul D. , Rice Brandon , Blanchette Marco , Siddiqui Sameed , Ganbat Javkhlan-Ochir , Powers Martin P. , Kunder Christian A. , Bustamante Carlos D. , Zehnder James L. , Green Richard E. , Costa Helio A.
Published: February 2018

The clinical management and therapy of many solid tumor malignancies is dependent on detection of medically actionable or diagnostically relevant genetic variation. However, a principal challenge for genetic assays from tumors is the fragmented and chemically damaged state of DNA in formalin-fixed paraffin-embedded (FFPE) samples. From highly fragmented DNA and RNA there is no current technology for generating long-range DNA sequence data as is required to detect genomic structural variation or long-range genotype phasing. We have developed a high-throughput chromosome conformation capture approach for FFPE samples that we call “Fix-C”, which is similar in concept to Hi-C. Fix-C enables structural variation detection from fresh and archival FFPE samples. We applied this method to 15 clinical adenocarcinoma and sarcoma specimens spanning a broad range of tumor purities. In this panel, Fix-C analysis achieves a 90% concordance rate with FISH assays – the current clinical gold standard. Additionally, we are able to identify novel structural variation undetected by other methods and recover long-range chromatin configuration information from these FFPE samples harboring highly degraded DNA. This powerful approach will enable detailed resolution of global genome rearrangement events during cancer progression from FFPE material, and inform the development of targeted molecular diagnostic assays for patient care.
Primate MHC class I from Genomes
Authors: Olivieri D.N. , Gambón-Deza F.
Published: February 2018

The major histocompatibility complex (MHC) molecule plays a central role in the adaptive immunity of jawed vertebrates. Allelic variations have been studied extensively in some primate species, however a comprehensive description of the number of genes remains incomplete. Here, a bioinformatics program was developed to identify three MHC Class I exons (EX2, EX3 and EX4) from Whole Genome Sequencing (WGS) datasets. With this algorithm, MHC Class I exons sequences were extracted from 30 WGS datasets of primates, representatives of Apes, Old World and New World monkeys and prosimians. There is a high variability in the number of genes between species. From human WGS, six viable genes (HLA-A, -B, -C, -E, -F, and -G) and four pseudogene sequences (HLA-H, -J, -L, -V) are obtained. These genes serve to identify the phylogenetic clades of MHC-I in primates. The results indicate that human clades of HLA-A -B and -C were generated shortly after the separation of Old World monkeys. The clades pertaining to HLA-E, -H and -F are found in all primate families, except in Prosimians. In the clades defined by HLA-G, -L and -J, there are sequences from Old world monkeys. Specific clades are found in the four primate families. The evolution of these genes is consistent with birth and death processes having a high turnover rates.
ReadFilter - Filtering reads of interest for quicker downstream analysis
Authors: Lee Ng Kim , Johannesen Thor Bech , Østerlund Mark , Kiil Kristoffer , Andersen Paal Skytt , Stegger Marc
Published: February 2018

Whole-genome sequencing is becoming the method of choice but provides redundant data for many tasks. ReadFilter (https://github.com/ssi-dk/serum_readfilter) is offered as a way to improve run time of these tasks by rapidly filtering reads against user-specified sequences in order to work with a small fraction of original reads while maintaining accuracy. This can noticeably reduce mapping time and substantially reduce de novo assembly time.
A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs
Authors: Pflueger Christian , Tan Dennis , Swain Tessa , Nguyen Trung , Pflueger Jahnvi , Nefzger Christian , Polo Jose M. , Ford Ethan , Lister Ryan
Published: February 2018

DNA methylation is a covalent modification of the genome that plays important roles in genome regulation and vertebrate development. Although detection of this modification in the genome has been possible for several decades, the ability to deliberately and specifically manipulate local DNA methylation states in the genome has been extremely limited. Consequently, this has impeded the direct determination of the consequence of DNA methylation on transcriptional regulation and transcription factor binding in the native chromatin context. Thus, highly specific targeted epigenome editing tools are needed to address this outstanding question. Recent adaptations of genome editing technologies, such as the fusion of the DNMT3A methyltransferase catalytic domain to catalytically inactive Cas9 (dC9-D3A), have aimed to provide new tools for altering DNA methylation at desired loci. Here, we performed a deeper analysis of the performance of these tools, revealing consistent off-target binding events and DNA methylation deposition in the genome, limiting the capacity of these tools to unambiguously assess the functional consequences of DNA methylation. To address this, we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA-methylation. dC9Sun-D3A is tunable, specific and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. Importantly, genome-wide characterization of dC9Sun-D3A binding sites and DNA methylation revealed minimal off-target protein binding and induction of DNA methylation with dC9Sun-D3A, compared to pervasive off-target binding and methylation by the dC9-D3A direct fusion construct. Furthermore, we used dC9Sun-D3A to test the impact of DNA methylation upon the DNA binding of CTCF and NRF1 upon targeted methylation of their core binding sites, demonstrating the binding sensitivity of these proteins to DNA methylation in situ. Overall, this modular dC9Sun-D3A system enables precise DNA methylation deposition with the lowest amount of off-target DNA methylation reported to date, allowing accurate functional determination of the role of DNA methylation at single loci.
pyseer: a comprehensive tool for microbial pangenome-wide association studies
Authors: Lees John A , Galardini Marco , Bentley Stephen D , Weiser Jeffrey N , Corander Jukka
Published: February 2018

Genome-wide association studies (GWAS) in microbes face different challenges to eukaryotes and have been addressed by a number of different methods. pyseer brings these techniques together in one package tailored to microbial GWAS, allows greater flexibility of the input data used, and adds new methods to interpret the association results.

Availability and Implementation

pyseer is written in python and is freely available at https://github.com/mgalardini/pyseer, or can be installed through pip. Documentation and a tutorial are available at http://pyseer.readthedocs.io.

Contact

john.lees@nyumc.org and marco@ebi.ac.uk

Supplementary information

Supplementary data are available online.
Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide
Authors: Ruderfer Douglas M. , Walsh Colin G. , Aguirre Matthew W. , Tanigawa Yosuke , Ribeiro Jessica D. , Franklin Joseph C. , Rivas Manuel A.
Published: February 2018

Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype from genotyped samples in the UK Biobank (337,199 participants, 2,433 cases). The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3,250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12×10−4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51×10−2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75×10−5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34 - 0.81) as well as several psychiatric disorders (rg = 0.26 - 0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that improved power for our genetic study.
Biochemical Characterization of RecBCD Enzyme from An AntarcticPseudomonasSpecies and Identification of Its Cognate Chi (χ) Sequence
Authors: Pavankumar Theetha L. , Sinha Anurag Kumar , Ray Malay K.
Published: February 2018

Pseudomonas syringaeLz4W RecBCD enzyme, RecBCDPs, is a trimeric protein complex comprised of RecC, RecB, and RecD subunits. RecBCD enzyme is essential forP. syringaegrowth at low temperature, and it protects cells from low temperature induced replication arrest. In this study, we show that the RecBCDPsenzyme displays distinct biochemical behaviors. UnlikeE. coliRecBCD enzyme, the RecD subunit is indispensable for RecBCDPsfunction. The RecD motor activity is essential for the Chi-like fragments production inP. syringae, highlighting a distinct role forP. syringaeRecD subunit in DNA repair and recombination process. Further, the ssDNA-dependent endonuclease activity is notably absent in RecBCDPsenzyme. Here, we demonstrate that the RecBCDPsenzyme recognizes a unique octameric DNA sequence, 5′-GCTGGCGC-3′ (ChiPs) that attenuates nuclease activity of the enzyme when it enters dsDNA from the 3′-end. We propose that the reduced translocation activities manifested by motor-defective mutants cause cold sensitivity inP. syrinage; emphasizing the importance of DNA processing and recombination functions in rescuing low temperature induced replication fork arrest.

Abbreviations:

ATP

Adenosine triphosphate

DSB

double-strand break

‘Chi

Crossover hotspot instigator

Ni-NTA

Nitrio tri-acetic acid

TLC

thin layer chromatography

MMC

mitomycin C

UV light

Ultra violet

ABM

Antarctic bacterial medium

LB

Luria-Bertani medium
A mechanism for the proliferative control of tissue mechanics in the absence of growth
Authors: Wu Min , Mani Madhav
Published: February 2018

During the development of a multicellular organism, cells coordinate their activities to generate mechanical forces, which in turn drives tissue deformation and eventually defines the shape of the adult tissue. Broadly speaking, it is recognized that mechanical forces can be generated through differential growth and the activity of the cytoskeleton. Based on quantitative analyses of live imaging of theDrosophiladorsal thorax, we suggest a novel mechanism that can generate contractile forces within the plane of an epithelia - via cell proliferation in the absence of growth. Utilizing force inference techniques, we demonstrate that it is not the gradient of junction tension but the divergence of junction-tension associated stresses that induces the area constriction of the proliferating tissue. Using the vertex model simulations, we show that the local averaged stresses can be roughly elevated by a fold ofp2 per cell division without growth. Moreover, this mechanism is robust to disordered cell shapes and the division anisotropy, but can be dominated by growth. In competition with growth, we identify the parameter regime where this mechanism is effective and suggest experiments to test this new mechanism.
Associations between organisational factors, TQM and competitive advantage
Authors: Ferdousi Farhana , Baird Kevin , Munir Rahat , Su Sophia
Published: February 2018

Purpose

The purpose of this paper is to examine the association between the extent of adoption of TQM, using Kaynak’s (2003) core TQM practices (quality data and reporting, supplier quality management, product/service design, process management) model and competitive advantage. In addition, the study examines the antecedent role of organisational-related factors (intensity of market competition, information technology (IT), expert systems and the supplier evaluation programme) in respect to the extent of adoption of TQM.

Design/methodology/approach

A survey was conducted of 673 business units of garment organisations in a developing country, Bangladesh.

Findings

The findings indicate that the extent of adoption of TQM practices was positively associated with competitive advantage. In addition, two organisational-related factors (intensity of market competition and IT) were positively associated with the extent of adoption of TQM.

Practical implications

The findings provide an insight into the ability of TQM to facilitate competitive advantage in developing countries. Practitioners are also provided with an insight into which organisational factors facilitate the adoption of TQM practices.

Originality/value

The findings provide an important insight into the use and value of TQM practices in developing countries.
Project risk analysis based on project characteristics
Authors: Shishodia Anjali , Dixit Vijaya , Verma Priyanka
Published: February 2018

Purpose

The purpose of this paper is to analyze risk profiles of projects based on project characteristics and provide key managerial insights.

Design/methodology/approach

A total of 37 project cases from engineering and construction (E&C), information system/technology (IS/IT), and new product development (NPD) sectors with detailed information on project characteristics and risks were identified from published literature. An integrated framework was developed to analyze the prominent risk categories associated with novelty, technology, complexity, and pace (NTCP) project characteristics.

Findings

Within-sector analysis revealed that schedule, resource, and scope risks are the most prominent risk categories in E&C, IS/IT, and NPD projects, respectively. Similarly, interesting key insights have been drawn from detailed cross-sector analysis, depicting different risk categories based on NTCP project characteristics.

Research limitations/implications

The findings are based on the case studies adopted from the literature that provides details of project characteristics and risk profiles.

Practical implications

Depending upon the risks associated with different project characteristics, an integrated framework developed in the study can be used for the development of highly authentic risk management plans at the onset.

Originality/value

This is one of the earliest studies to provide an integrated risk framework for projects based on their NTCP characteristics. The two contrasting perspectives of within-sector and cross-sector analyses were adopted. Overall, the study will enhance the future preparedness toward risks.
A problem of embeddedness
Authors: Brandl Bernd , Lehr Alex
Published: February 2018

Purpose

The purpose of this paper is to propose a general micro-theoretical framework that helps to understand the embeddedness of trade unions within the European system of industrial relations, and the consequences of this embeddedness for industrial relations outcomes. First, starting from the paradoxical observation of a trend towards homogeneity within a complex, multi-layered European industrial relations system consisting of heterogeneous and autonomous agents, the paper aims to explicate the mechanisms which produce these similarities. Second, the paper seeks to analyse potential mechanisms for transnational trade union cooperation and, third, it concludes by outlining its applicability as the basis for methodological approaches which enable realistic and policy relevant analyses.

Design/methodology/approach

This paper is conceptual and focusses on the development of a general micro-theoretical framework which captures European industrial relations actors’ behaviour and outcomes. It integrates theoretical and empirical accounts from differing social science disciplines and from various methodological starting points on trade union action and interaction into one general micro-theoretical framework.

Findings

Starting from a typology of trade union goals, the authors show how various social mechanisms lead to interdependencies between trade unions and review empirical evidence for their consequences. The authors, then, identify a set of motives for transnational cooperation that would allow outcomes that are in line with trade union objectives.

Originality/value

Against the background that previous studies on trade union action and cross-national interaction have paid less attention to the puzzling stylised fact that industrial relations outcomes are mimicked by heterogeneous and autonomous agents actors in different countries, the authors address this research gap by developing a novel general micro-theoretical framework for the analysis of transnational trade union action and interaction in order to better understand the underlying causal mechanisms for the common behaviour and outcomes of autonomous actors.
Eating and risk: adolescents’ reasoning regarding body and image
Authors: Rendahl Jenny , Korp Peter , Ekström Marianne Pipping , Berg Christina
Published: February 2018

Purpose

The purpose of this paper is to explore and elucidate adolescents’ reasoning about risks related to food and eating.

Design/methodology/approach

Boys and girls aged 15-16 years participated in a focus group interview with role-playing as a stimulus for discussion and reflection. In all, 31 participants took part, divided into five groups. In the role-playing, the participants portrayed agents who they perceived to give messages about food. In the focus group they discussed their experience of carrying out the role-play, and how they usually cope with conflicting messages, preferences and needs regarding food and eating.

Findings

The findings suggested that there were two main themes of risk profiling related to eating. One concerned bodily risk related to the food ingested and included concerns both about not reaching health and performance due to the unfavourable intake of calories, nutrients, additives, bacteria, viruses and parasites, and threats to immediate well-being following consumption. The second main category concerned the risk of being conspicuous, or “sticking out”, which incorporated food-based gender norms and norms related to table manners. In practice, the risk of not displaying an appropriate image of themselves through their food and eating choices was more prominent than risk perceptions related to impacts of food choices on well-being and performance. Difficulties in classifying foods as “good” or “bad” enhanced their uncertainty.

Originality/value

The results suggest that health-promotion activities for young people should focus not only on how to feed their bodies but also on how to avoid feeding their anxieties.
Mystery shopping through the lens of organizational justice
Authors: Pashkina Marina , Plakhotnik Maria S.
Published: February 2018

Purpose

The purpose of this paper is to share how the concept of organizational justice could help to explore employee satisfaction with the mystery shopping appraisal system.

Design/methodology/approach

The research was conducted at a fast-food restaurant chain located in Russia. Data were collected through an online-questionnaire distributed among all 516 chef-cashiers of the 86 restaurants of the chain located in Saint Petersburg. The questionnaire consisted of 17 closed-ended and one open-ended questions.

Findings

Violations of norms of procedural, distributive, and informational justice were identified. The majority of the chief-cashiers thought that the norms of interpersonal justice were met.

Practical implications

The paper also discusses how training and development professionals could use the concept of organizational justice to improve employee satisfaction with a mystery shopping appraisal process. The results collected through the questionnaire can be used in at least two ways: to implement structural changes in the process and to determine and address training needs of three groups of employees.

Originality/value

Perceptions of organizational justice predict employee satisfaction with different aspects of a performance appraisal system. This paper is first to explore how the concept of organizational justice could be useful in evaluating employee satisfaction with such performance appraisal method as mystery shopping.
Spatiotemporal heterogeneity in prey abundance and vulnerability shapes the foraging tactics of an omnivore
Authors: Rayl Nathaniel D. , Bastille‐Rousseau Guillaume , Organ John F. , Mumma Matthew A. , Mahoney Shane P. , Soulliere Colleen E. , Lewis Keith P. , Otto Robert D. , Murray Dennis L. , Waits Lisette P. , Fuller Todd K.
Published: February 2018

Prey abundance and prey vulnerability vary across space and time, but we know little about how they mediate predator–prey interactions and predator foraging tactics. To evaluate the interplay between prey abundance, prey vulnerability and predator space use, we examined patterns of black bear (Ursus americanus) predation of caribou (Rangifer tarandus) neonates in Newfoundland, Canada using data from 317 collared individuals (9 bears, 34 adult female caribou, 274 caribou calves).

During the caribou calving season, we predicted that landscape features would influence calf vulnerability to bear predation, and that bears would actively hunt calves by selecting areas associated with increased calf vulnerability. Further, we hypothesized that bears would dynamically adjust their foraging tactics in response to spatiotemporal changes in calf abundance and vulnerability (collectively, calf availability). Accordingly, we expected bears to actively hunt calves when they were most abundant and vulnerable, but switch to foraging on other resources as calf availability declined.

As predicted, landscape heterogeneity influenced risk of mortality, and bears displayed the strongest selection for areas where they were most likely to kill calves, which suggested they were actively hunting caribou. Initially, the per‐capita rate at which bears killed calves followed a type‐I functional response, but as the calving season progressed and calf vulnerability declined, kill rates dissociated from calf abundance. In support of our hypothesis, bears adjusted their foraging tactics when they were less efficient at catching calves, highlighting the influence that predation phenology may have on predator space use. Contrary to our expectations, however, bears appeared to continue to hunt caribou as calf availability declined, but switched from a tactic of selecting areas of increased calf vulnerability to a tactic that maximized encounter rates with calves.

Our results reveal that generalist predators can dynamically adjust their foraging tactics over short time‐scales in response to changing prey abundance and vulnerability. Further, they demonstrate the utility of integrating temporal dynamics of prey availability into investigations of predator–prey interactions, and move towards a mechanistic understanding of the dynamic foraging tactics of a large omnivore.
Consequences of game bird management for non‐game species in Europe
Authors: Mustin Karen , Arroyo Beatriz , Beja Pedro , Newey Scott , Irivine Robert Justin , Kestler Julia , Redpath Steve M.
Published: February 2018

Game bird management has the potential to benefit conservation, as management practices specifically targeted at reducing the factors limiting game populations may have positive effects on non‐game species. However, such management may also have costs to species.

We review the literature that examines the effect of different forms of game bird management on non‐target species in Europe, including habitat management, predator control, parasite control, provision of water and food and rear and release. We focus on Europe, where these forms of management are common and sometimes intensive.

We identified 35 studies, which recorded 122 individual significant effects. Most studies (80%) focussed on the effects of habitat management and predator control, and >90% were carried out in the UK.

63% of the 122 significant effects on non‐game species were positive. Overall, 85% of the effects of habitat management in agricultural habitats were positive, while in non‐agricultural habitats 65% of effects were negative. Effects of rear and release were mixed (8 positive and 7 negative). Legal predator control was almost always positive (96% of effects), or benign, whereas illegal predator control was always negative (8 effects). This continues to be a major cost to conservation. No studies examined the effects of parasite control on non‐target wildlife. Three of four significant effects of supplementary feeding were negative.

More studies are needed on the impacts of game bird management on non‐game species, and particularly of rear and release, the provision of supplementary food and water, and parasite control. We also found few experimental studies examining the specific effects of management for shooting of game birds, and very few studies overall outside the UK. Future studies should aim to fill these gaps.

Synthesis and applications. The management of game bird populations for shooting is widespread across Europe. Our study shows that effects of such management practices vary between different non‐target species. There is a need to understand these trade‐offs, find effective strategies to limit the damaging aspects of game bird management and work to enhance the benefits for the conservation of biodiversity.
Improving estimation of flight altitude in wildlife telemetry studies
Authors: Poessel Sharon A. , Duerr Adam E. , Hall Jonathan C. , Braham Melissa A. , Katzner Todd E.
Published: February 2018

Altitude measurements from wildlife tracking devices, combined with elevation data, are commonly used to estimate the flight altitude of volant animals. However, these data often include measurement error. Understanding this error may improve estimation of flight altitude and benefit applied ecology.

There are a number of different approaches that have been used to address this measurement error. These include filtering based on GPS data, filtering based on behaviour of the study species, and use of state‐space models to correct measurement error. The effectiveness of these approaches is highly variable.

Recent studies have based inference of flight altitude on misunderstandings about avian natural history and technical or analytical tools. In this Commentary, we discuss these misunderstandings and suggest alternative strategies both to resolve some of these issues and to improve estimation of flight altitude. These strategies also can be applied to other measures derived from telemetry data.

Synthesis and applications. Our Commentary is intended to clarify and improve upon some of the assumptions made when estimating flight altitude and, more broadly, when using GPS telemetry data. We also suggest best practices for identifying flight behaviour, addressing GPS error, and using flight altitudes to estimate collision risk with anthropogenic structures. Addressing the issues we describe would help improve estimates of flight altitude and advance understanding of the treatment of error in wildlife telemetry studies.
Association between famine exposure in early life and type 2 diabetes mellitus and hyperglycemia in adulthood: Results from the China Health And Retirement Longitudinal Study (CHARLS)
Authors: Sun Yanxin , Zhang Longfei , Duan Wenhou , Meng Xin , Jia Chongqi
Published: February 2018

Background

Studies have revealed the association between famine in early life and type 2 diabetes mellitus (T2DM) in adulthood. However, studies on the Great Chinese Famine were not conducted nationwide. Because of regional variations in the severity of this famine, the results of regional studies are limited. This study explored associations between famine and T2DM in adulthood in a nationwide study.

Methods

The present study was performed on 7262 participants who were born between 1 October 1949 and 1 July 1966 using baseline data collected for the China Health And Retirement Longitudinal Study (CHARLS) in 2011. Participants were divided according to birthdate into cohorts with fetal, late, middle, and early childhood exposure and no exposure to famine. Logistic regression models were used to analyze the association between famine exposure in early life and the risk of T2DM and hyperglycemia in adulthood.

Results

For females, the risk of hyperglycemia was higher for famine‐exposed than not exposed cohort (odds ratios [OR] 1.34 and 95% confidence intervals [CIs]: 1.34 [1.04–1.74], 1.48 [1.15–1.90], 1.38 [1.06–1.79], and 1.57 [1.25–1.98] for fetal, early, middle, and late childhood exposure, respectively), and this association was even stronger in female participants who lived in rural areas before the age of 16 years. In males, the risk of T2DM was lower for the early and late childhood exposure than no exposure cohorts (OR [95% CIs]: 0.65 [0.49–0.86] and 0.74 [0.56–0.98], respectively). [Correction added on 23 July 2018, after first online publication: Parts of the above ‘Results’ section have been corrected to interchange the citation of the words ‘late’ and ‘early’.]

Conclusion

Exposure to famine during early life can increase the risk of hyperglycemia in female adults, but may decrease the risk of T2DM in males.
Influence of media coverage and sentiment on seasoned equity offerings
Authors: Sun Ji , Zhou Yi , Wang Jiaguo (George) , Guo Jie (Michael)
Published: February 2018

This article examines the role of media in seasoned equity offerings (SEOs) price and market reactions on SEO announcements. Using a sample of SEO deals in UK, we find that media coverage is significantly and negatively related to SEO price discounts and market returns around SEO announcements. Moreover, we document that more pessimistic media sentiment predicts larger SEO price discounts and more negative market reactions to SEO announcements. In summary, both media coverage and media sentiment influence investor decisions in SEOs, but through different mechanisms.
Feeding patterns of elephants at the Atherstone Collaborative Nature Reserve
Authors: Seloana Makoshane Q. , Jordaan Jorrie J. , Potgieter Martin J. , Kruger Johan W.
Published: February 2018

The African savannah elephant (Loxodonta africana Blumenbach) is a generalist herbivore that relies on widely distributed resources. Vegetation decline, aggravated by these elephants, can compromise local conservation efforts. Thus it imperative to understand the factors that drive them to consume specific plant species and plant parts. The objective of our study was to investigate the feeding patterns of African savannah elephants in the enclosed bushveld savannah at the Atherstone Collaborative Nature Reserve in South Africa. For 1 year, we examined elephant selection of woody versus herbaceous vegetation, and identified which plant species and parts were preferentially consumed. We accomplished this by directly observing feeding elephants, and by utilizing data collected on elephant footprints, dung piles, stripped bark and broken branches. We further conducted vegetation surveys to determine selection frequency relative to species abundance. Elephants showed a preference for different plant parts consumption in the feeding plots. In total, leaves, branches and bark contributed mostly to their diet. Seasonal selection patterns showed an increasing proportion of bark and branch consumption during the dry season.
Leopard abundance, distribution and food habits in the Mt. Rungwe–Kitulo landscape, Southern Tanzania
Authors: De Luca Daniela W. , Mpunga Noah E.
Published: February 2018

Between 2003 and 2010, 2178.5 km of transect was walked and 76 leopard scats counted in the Mt. Rungwe–Kitulo landscape. The number of scats per 10 km ranged between 0 and 0.83 in Mt Rungwe and between 0 and 1.41 in Kitulo. Leopards chiefly selected bamboo forest between 2500 and 2950 m asl. Some 126 interviews revealed that leopards were encountered more in the 1980s than latterly. Leopards used to attack livestock, but in the 1960s and 1970s, were heavily poisoned. We analysed 59 scats for undigested materials and compared them to a hair reference atlas. Some 135 different prey items were found, with an average of 2.3 items per scat. Some 14 samples were identified to species level and four to genus level. The average prey body weight was 5.9 kg. The diet was dominated by small mammals and rodent species up to 5.0 kg (59.57%) of biomass, followed by carnivores (29.14%), primate species (8.91%) and small rodents <1 kg (2.24%). The highest relative biomass consumed was prey classes of 1.1–5.0 kg (61.06%), followed by prey 5.1–50 kg (35.22%) and small rodents <1 kg (2.24%). The total absence of ungulate prey and conservation implications are discussed.
The emergence of a commercial trade in pangolins from Gabon
Authors: Mambeya Meine M. , Baker Francesca , Momboua Brice R. , Koumba Pambo Aurélie Flore , Hega Martin , Okouyi Okouyi Vivien Joseph , Onanga Martial , Challender Daniel W. S. , Ingram Daniel J. , Wang Hongyan , Abernethy Katharine
Published: February 2018

Recent seizures of illegally held wildlife indicate a mounting global trade in pangolins involving all eight species. Seizures of illegally traded African pangolins are increasing as wild populations of Asian species decline. We investigated trade in pangolins and law enforcement efforts in Gabon; a country likely to have intact wild populations of three of the four species of African pangolin. We compared village sales and trade chains between 2002‐2003 and 2014. Hunters reported pangolins to be the most frequently requested species in 2014, and the value of pangolins had increased at every point along their trade chain. In Libreville, giant pangolin prices increased 211% and arboreal pangolin prices 73% whilst inflation rose only 4.6% over the same period. We documented a low rate of interception of illegally traded pangolins despite increased law enforcement. Surveys of potential export routes detected exports across forest borders, in conjunction with ivory, but not through public transport routes. We conclude that whilst there is clear potential and likelihood that a wild pangolin export trade is emerging from Gabon, traditional bushmeat trade chains may not be the primary supply route. We recommend adjusting conservation policies and actions to impede further development of illegal trade within and from Gabon.
Antepartum risk factors for moderate to severe neonatal hypoxic ischemic encephalopathy: a Swedish national cohort study
Authors: Liljestrom Lena , Wikstrom Anna‐Karin , Agren Johan , Jonsson Maria
Published: February 2018

Introduction

Our aim was to identify antepartum risk factors for neonatal hypoxic ischemic encephalopathy, with a focus on maternal body mass index and height.

Material and methods

National population‐based cohort study of 692 428 live‐born infants ≥36 gestational weeks in Sweden, 2009–2015. Data from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register were linked. Short maternal stature was defined as ≤155 cm, and overweight as body mass index ≥25 kg/m2. Therapeutic hypothermia served as surrogate marker of moderate to severe hypoxic ischemic encephalopathy. Associations between maternal and infant characteristics and hypoxic ischemic encephalopathy were calculated with logistic regression analyses, and risks were presented as odds ratios with 95% confidence intervals.

Results

Moderate to severe hypoxic ischemic encephalopathy occurred in 0.67/1000 infants. Nulliparity, previous cesarean delivery, short stature, overweight, gestational age, occiput posterior presentation and birthweight were all independently associated with hypoxic ischemic encephalopathy. The risk of hypoxic ischemic encephalopathy increased with decreasing maternal height and increasing body mass index. Compared with non‐short women (≥156 cm) with normal weight (body mass index <25 kg/m2), those with both short stature and overweight had increased risk of hypoxic ischemic encephalopathy (odds ratio 3.66; 95% confidence intervals 2.41–5.55). Among parous women with both short stature and overweight, the risk was almost sixfold (odds ratio 5.74; 95% confidence intervals 3.41–9.66).

Conclusions

Antepartum risk factors for moderate to severe hypoxic ischemic encephalopathy included nulliparity, previous cesarean delivery, short stature, overweight, gestational age, occiput posterior presentation and birthweight. The combination of maternal short stature and overweight was associated with a more than threefold risk of subsequent hypoxic ischemic encephalopathy.
Intracellular pharmacokinetics of gemcitabine, its deaminated metabolite 2′,2′‐difluorodeoxyuridine and their nucleotides
Authors: Derissen Ellen J. B. , Huitema Alwin D. R. , Rosing Hilde , Schellens Jan H. M. , Beijnen Jos H.
Published: February 2018

Aims

Gemcitabine (2′,2′‐difluoro‐2′‐deoxycytidine; dFdC) is a prodrug that has to be phosphorylated within the tumour cell to become active. Intracellularly formed gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) are considered responsible for the antineoplastic effects of gemcitabine. However, a major part of gemcitabine is converted into 2′,2′‐difluoro‐2′‐deoxyuridine (dFdU) by deamination. In the cell, dFdU can also be phosphorylated to its monophosphate (dFdUMP), diphosphate (dFdUDP) and triphosphate (dFdUTP). In vitro data suggest that these dFdU nucleotides might also contribute to the antitumour effects, although little is known about their intracellular pharmacokinetics (PK). Therefore, the objective of the present study was to gain insight into the intracellular PK of all dFdC and dFdU nucleotides formed during gemcitabine treatment.

Methods

Peripheral blood mononuclear cell (PBMC) samples were collected from 38 patients receiving gemcitabine, at multiple time points after infusion. Gemcitabine, dFdU and their nucleotides were quantified in PBMCs. In addition, gemcitabine and dFdU plasma concentrations were monitored. The individual PK parameters in plasma and in PBMCs were determined.

Results

Both in plasma and in PBMCs, dFdU was present in higher concentrations than gemcitabine [mean intracellular area under the concentration–time curve from time zero to 24 h (AUC0–24 h) 1650 vs. 95 μM*h]. However, the dFdUMP, dFdUDP and dFdUTP concentrations in PBMCs were much lower than the dFdCDP and dFdCTP concentrations. The mean AUC0–24 h for dFdUTP was 312 μM*h vs. 2640 μM*h for dFdCTP.

Conclusions

The study provides the first complete picture of all nucleotides that are formed intracellularly during gemcitabine treatment. Low intracellular dFdU nucleotide concentrations were found, which calls into question the relevance of these nucleotides for the cytotoxic effects of gemcitabine.
Commemoration in crisis: A discursive analysis of who ‘we’ and ‘they’ have been or become in ceremonial political speeches before and during the Greek financial downturn
Authors: Gkinopoulos Theofilos , Hegarty Peter
Published: February 2018

This study analyses the discourse of statements of the leaders of two Greek political parties commemorating the restoration of Greek democracy on 24 July 1974; the ruling party New Democracy and the opposition, Coalition of the Radical Left. We focus on how these leaders act as entrepreneurs of their identities by constructing their ingroups in broad or narrow terms and their outgroups in vague or specific terms. These constructions were ventured during a period of relative political stability (2008) and instability (2012), and we focus on how ingroup prototypes and group boundaries are narrated across Greece's past, present and future in ambiguous or concrete terms. The study aligns the social identity approach to political leadership with studies on political discourse and ‘the rhetoric of we’. We view commemorative statements as historical charters and respond to calls for discourse analysis to take greater account of historical context. The findings suggest concrete hypotheses about how leaders with different amounts of political support might define, as identity entrepreneurs, who ‘we’ are, and who ‘we’ are not in democratic contexts marked by stability or crisis.
Shortcomings in the management of undescended testis: guideline intention vs reality and the underlying causes – insights from the biggest German cohort
Authors: Boehme Philip , Geis Berit , Doerner Johannes , Wirth Stefan , Hensel Kai O.
Published: February 2018

Objectives

To assess the implementation of the current guideline and identify potential underlying causes for late surgery in children with undescended testis (UDT) in Germany. UDT is the most common surgical issue in paediatric urology and to avoid malignant degeneration and subfertility current guidelines recommend orchidopexy during the first year of life; however, this seems not to be implemented in practice.

Patients and Methods

In all, 5 547 patients with cryptorchidism at 16 hospitals nationwide were studied regarding age at orchidopexy between 2003 and 2016. Multivariate analysis was performed to identify factors influencing timing of surgery. Additionally, a survey on knowledge of UDT management was conducted amongst physicians treating boys and final‐year medical students.

Results

Between 2003 and 2008 only 4% of boys with UDT underwent surgery before the age of 1 year. After the guideline update from 2009, this figure was 5% from 2010 to 2012, and 8% from 2013 to 2016. The presence of a specialised department for paediatric surgery, as well as a high UDT case‐to‐year ratio positively influenced the timing of orchidopexy. The survey revealed discipline‐specific differences in the levels of knowledge about UDT management. One‐third of respondents did not know the guideline recommendations and 61% felt insufficiently informed. International comparisons revealed significant differences in the age at surgery of boys with UDT, with Germany and Great Britain ranging in the middle of the field.

Conclusions

Currently, only a small proportion of boys with UDT are operated upon during their first year of life. The level of knowledge in attending physicians remains in need of improvement. This should be actively addressed, i.e. by campaigns and educational programmes. Further studies are needed to investigate the underlying causes of late orchidopexy in UDT.
GPCRs in context: sexual dimorphism in the cardiovascular system
Authors: Mouat Margaret A , Coleman James L J , Smith Nicola J
Published: February 2018

Cardiovascular disease (CVD) remains the largest cause of mortality worldwide, and there is a clear gender gap in disease occurrence, with men being predisposed to earlier onset of CVD, including atherosclerosis and hypertension, relative to women. Oestrogen may be a driving factor for female‐specific cardioprotection, though androgens and sex chromosomes are also likely to contribute to sexual dimorphism in the cardiovascular system (CVS). Many GPCR‐mediated processes are involved in cardiovascular homeostasis, and some exhibit clear sex divergence. Here, we focus on the G protein‐coupled oestrogen receptor, endothelin receptors ETA and ETB and the eicosanoid G protein‐coupled receptors (GPCRs), discussing the evidence and potential mechanisms leading to gender dimorphic responses in the vasculature. The use of animal models and pharmacological tools has been essential to understanding the role of these receptors in the CVS and will be key to further delineating their sex‐specific effects. Ultimately, this may illuminate wider sex differences in cardiovascular pathology and physiology.

Linked Articles

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc