bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling the Rate of GWAS False Discoveries
Authors: Brzyski Damian , Peterson Christine B. , Sobczyk Piotr , Candés Emmanuel J. , Bogdan Malgorzata , Sabatti Chiara 
Published: June 2016

AbstractWith the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. While a number of robust FDR controlling strategies exist, the nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on pre-screening to identify the level of resolution of distinct hypotheses. We show how FDR controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS. We demonstrate that our approach is versatile and useful when the data are analyzed using both tests based on single marker and multivariate regression. We provide an R package that allows practitioners to apply our procedure on standard GWAS format data, and illustrate its performance on lipid traits in the NFBC66 cohort study.
Thanatotranscriptome: genes actively expressed after organismal death
Authors: Pozhitkov Alex E. , Neme Rafik , Domazet-Lošo Tomislav , Leroux Brian G. , Soni Shivani , Tautz Diethard , Noble Peter A. 
Published: June 2016

AbstractA continuing enigma in the study of biological systems is what happens to highly ordered structures, far from equilibrium, when their regulatory systems suddenly become disabled. In life, genetic and epigenetic networks precisely coordinate the expression of genes -- but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes are involved. We investigated the unwinding of the clock by identifying upregulated genes, assessing their functions, and comparing their transcriptional profiles through postmortem time in two species, mouse and zebrafish. We found transcriptional abundance profiles of 1,063 genes were significantly changed after death of healthy adult animals in a time series spanning from life to 48 or 96 h postmortem. Ordination plots revealed non-random patterns in profiles by time. While most thanatotranscriptome (thanatos-, Greekdefn. death) transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h. Functional characterization of the most abundant transcripts revealed the following categories: stress, immunity, inflammation, apoptosis, transport, development, epigenetic regulation, and cancer. The increase of transcript abundance was presumably due to thermodynamic and kinetic controls encountered such as the activation of epigenetic modification genes responsible for unraveling the nucleosomes, which enabled transcription of previously silenced genes (e.g., development genes). The fact that new molecules were synthesized at 48 to 96 h postmortem suggests sufficient energy and resources to maintain self-organizing processes. A step-wise shutdown occurs in organismal death that is manifested by the apparent upregulation of genes with various abundance maxima and durations. The results are of significance to transplantology and molecular biology.
Temporal development and spatial scale of coastal fish indicators in reference ecosystems: hydroclimate and anthropogenic drivers
Authors: Östman Örjan , Lingman Anna , Bergström Lena , Olsson Jens 
Published: June 2016

Summary

Indicators of ecosystem status are of increasing importance for management. Many studies infer associations between the environment and fish communities, but little is known about how fish community indicators are related to temporal variation in anthropogenic and hydroclimate drivers, and on what geographical scale, these indicators are representative.

Here, we investigate the spatial synchrony of seven indicators of coastal fish community status among eleven reference sites 2002–2014 in the Baltic Sea. At three of these sites, we study the temporal covariation between indicators and anthropogenic and hydroclimate drivers over 25 years.

The indicators (abundance of) – Perch, Large Piscivores and Non‐perch Piscivores – showed spatial synchrony over the study scale (100–1000 km), whereas temporal dynamics of other indicators reflected changes at scales <100 km.

At the studied reference sites, temporal changes of indicators were mainly associated with climate‐related hydrological variables, but nutrient‐related variables were important in the northern Baltic Sea. Landings showed no associations with any indicator. Four of the indicators showed evident temporal autocorrelation reflecting an influence of internal population/community processes.

Synthesis and applications. Environmental status of coastal fish communities in the Baltic Sea should be assessed and managed at a local scale. The main drivers of fish community indicators of ecosystem status tend to differ between coastal areas, but among the reference sites assessed in this study, hydroclimatic variation and internal processes seem to be of greater importance for the temporal development of indicators than anthropogenic pressures. Therefore, when assessing the status of coastal fish communities and evaluating management measures in areas impacted by anthropogenic activities, it is important to account for variation in salinity, temperature and time lags.
Decomposing trends in Swedish bird populations using generalized additive mixed models
Authors: Knape Jonas 
Published: June 2016

Summary

Estimating trends of populations distributed across wide areas is important for conservation and management of animals. Surveys in the form of annually repeated counts across a number of sites are used in many monitoring programmes, and from these, nonlinear trends may be estimated using generalized additive models (GAM).

I use generalized additive mixed models (GAMM) to decompose population change into a long‐term, smooth, trend component and a component for short‐term fluctuations. The long‐term population trend is modelled as a smooth function of time and short‐term fluctuations as temporal random effects. The methods are applied to analyse trends in goldcrest and greenfinch populations in Sweden using data from the Swedish Breeding Bird Survey. I use simulations to investigate statistical properties of the model.

The model separates short‐term fluctuations from longer term population change. Depending on the amount of noise in the population fluctuations, estimated long‐term trends can differ markedly from estimates based on standard GAMs. For the goldcrest with wide among‐year fluctuations, trends estimated with GAMs suggest that the population has in recent years recovered from a decline. When filtering out, short‐term fluctuations analyses suggest that the population has been in steady decline since the beginning of the survey.

Simulations suggest that trend estimation using the GAMM model reduces spurious detection of long‐term population change found with estimates from a GAM model, but gives similar mean square errors. The simulations therefore suggest that the GAMM model, which decomposes population change, estimates uncertainty of long‐term trends more accurately at little cost in detecting them.

Policy implications. Filtering out short‐term fluctuations in the estimation of long‐term smooth trends using temporal random effects in a generalized additive mixed model provides more robust inference about the long‐term trends compared to when such random effects are not used. This can have profound effects on management decisions, as illustrated in an example for goldcrest in the Swedish breeding bird survey. In the example, if temporal random effects were not used, red listing would be highly influenced by the specific year in which it was done. When temporal random effects are used, red listing is stable over time. The methods are available in an R‐package, poptrend.
Quercus suber dieback alters soil respiration and nutrient availability in Mediterranean forests
Authors: Avila José M. , Gallardo Antonio , Ibáñez Beatriz , Gómez‐Aparicio Lorena 
Published: June 2016

Summary

An increase in tree mortality rates has been recently detected in forests world‐wide. However, few works have focused on the potential consequences of forest dieback for ecosystem functioning.

Here we assessed the effect of Quercus suber dieback on carbon, nitrogen and phosphorus cycles in two types of Mediterranean forests (woodlands and closed forests) affected by the aggressive pathogen Phytophthora cinnamomi. We used a spatially explicit neighbourhood approach to analyse the direct effects of Q. suber dieback on soil variables, comparing the impact of Q. suber trees with different health status, as well as its potential long‐term indirect effects, comparing the impact of non‐declining coexistent species.

Quercus suber dieback translated into lower soil respiration rates and phosphorus availability, whereas its effects on nitrogen varied depending on forest type. Coexistent species differed strongly from Q. suber in their effects on nutrient availability, but not on soil respiration rates. Our models showed low interannual but high intra‐annual variation in the ecosystem impacts of tree dieback.

Synthesis. Our results support that tree dieback might have important short‐ and long‐term impacts on ecosystem processes in Mediterranean forests. With this work, we provide valuable insights to fill the existent gap in knowledge on the ecosystem‐level impacts of forest dieback in general and P. cinnamomi‐driven mortality in particular. Because the activity and range of this pathogen is predicted to increase due to climate warming, these impacts could also increase in the near future altering ecosystem functioning world‐wide.
ddradseqtools: a software package for in silico simulation and testing of double‐digest RADseq experiments
Authors: Mora‐Márquez F. , García‐Olivares V. , Emerson B. C. , López de Heredia U. 
Published: June 2016

AbstractDouble‐digested RADseq (ddRADseq) is a NGS methodology that generates reads from thousands of loci targeted by restriction enzyme cut sites, across multiple individuals. To be statistically sound and economically optimal, a ddRADseq experiment has a preliminary design stage that needs to consider issues related to the selection of enzymes, particular features of the genome of the focal species, possible modifications to the library construction protocol, coverage needed to minimize missing data, and the potential sources of error that may impact upon the coverage. We present ddradseqtools, a software package to help ddRADseq experimental design by (i) the generation of in silico double‐digested fragments; (ii) the construction of modified ddRADseq libraries using adapters with either one or two indexes and degenerate base regions (DBRs) to quantify PCR duplicates; and (iii) the initial steps of the bioinformatics preprocessing of reads. ddradseqtools generates single‐end (SE) or paired‐end (PE) reads that may bear SNPs and/or indels. The effect of allele dropout and PCR duplicates on coverage is also simulated. The resulting output files can be submitted to pipelines of alignment and variant calling, to allow the fine‐tuning of parameters. The software was validated with specific tests for the correct operability of the program. The correspondence between in silico settings and parameters from ddRADseq in vitro experiments was assessed to provide guidelines for the reliable performance of the software. ddradseqtools is cost‐efficient in terms of execution time, and can be run on computers with standard CPU and RAM configuration.
Identification and qualification of 500 nuclear, single‐copy, orthologous genes for the Eupulmonata (Gastropoda) using transcriptome sequencing and exon capture
Authors: Teasdale Luisa C. , Köhler Frank , Murray Kevin D. , O'Hara Tim , Moussalli Adnan 
Published: June 2016

AbstractThe qualification of orthology is a significant challenge when developing large, multiloci phylogenetic data sets from assembled transcripts. Transcriptome assemblies have various attributes, such as fragmentation, frameshifts and mis‐indexing, which pose problems to automated methods of orthology assessment. Here, we identify a set of orthologous single‐copy genes from transcriptome assemblies for the land snails and slugs (Eupulmonata) using a thorough approach to orthology determination involving manual alignment curation, gene tree assessment and sequencing from genomic DNA. We qualified the orthology of 500 nuclear, protein‐coding genes from the transcriptome assemblies of 21 eupulmonate species to produce the most complete phylogenetic data matrix for a major molluscan lineage to date, both in terms of taxon and character completeness. Exon capture targeting 490 of the 500 genes (those with at least one exon >120 bp) from 22 species of Australian Camaenidae successfully captured sequences of 2825 exons (representing all targeted genes), with only a 3.7% reduction in the data matrix due to the presence of putative paralogs or pseudogenes. The automated pipeline Agalma retrieved the majority of the manually qualified 500 single‐copy gene set and identified a further 375 putative single‐copy genes, although it failed to account for fragmented transcripts resulting in lower data matrix completeness when considering the original 500 genes. This could potentially explain the minor inconsistencies we observed in the supported topologies for the 21 eupulmonate species between the manually curated and ‘Agalma‐equivalent’ data set (sharing 458 genes). Overall, our study confirms the utility of the 500 gene set to resolve phylogenetic relationships at a range of evolutionary depths and highlights the importance of addressing fragmentation at the homolog alignment stage for probe design.
Testis‐specific RNA‐Seq of Calligrapha (Chrysomelidae) as a transcriptomic resource for male‐biased gene inquiry in Coleoptera
Authors: Vizán‐Rico Helena I. , Gómez‐Zurita Jesús 
Published: June 2016

AbstractWe report the architecture of testis transcriptomes of four closely related species of Calligrapha (Chrysomelidae) beetles, which diverged during the last 3 million years. Five cDNA libraries were sequenced using Illumina HiSeq technology, retrieving 102 884–176 514 assembled contigs, of which ~33–45% of these longer than 499 nt were functionally annotated. Annotation and sequence similarity comparisons of these libraries revealed high homogeneity in gene composition and the presence of several functional candidates related to reproduction or reproductive processes (0.72–1.08% of annotated sequences). Stringent sequence similarity analyses of these transcriptomes against empirically demonstrated male‐biased genes in Drosophila melanogaster and Tribolium castaneum allowed the identification of 77 homologues in Calligrapha, possible candidates of male‐biased expression. Some of these genes – including CG9313, Tektin‐A or tomboy40 – were confirmed as orthologs of these male‐biased genes using phylogenetic inference and available model insect data, increasing our confidence that they represent functional homologues too. Our transcriptomes are a valuable transcriptomic resource for the analysis of male‐biased genes in Calligrapha, which has the added interest of including several female‐only species. But it simultaneously represents a landmark for similar studies in Coleoptera, broadening the taxonomic diversity currently represented by the model species T. castaneum, and incipient genomic data in other herbivorous lineages, including weevils, longhorn beetles and leaf beetles.
The Role of United Nations Secretary‐General in the Climate Change Process
Authors: Pasztor Janos 
Published: June 2016

AbstractBan Ki‐moon, the UN Secretary‐General (SG) has been visibly engaged throughout the year on preparations for and during the Paris Conference, but his role in contributing to achieving this agreement has been little understood. The SG has no specific mandate to deal with climate change issues. Yet without his intensive engagement it would not have been possible to reach the agreement we had in Paris. The role played by the SG and its outcomes will be the focus of this paper. Particular attention will be paid to events in 2015, but the paper also looks at some earlier events during the entire mandate of this Secretary‐General, covering 2007–2016.
Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?
Authors: Limkakeng Alexander T. , Monte Andrew A. , Kabrhel Christopher , Puskarich Michael , Heitsch Laura , Tsalik Ephraim L. , Shapiro Nathan I. 
Published: June 2016

AbstractPrecision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department (ED). While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the ED will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end‐users.
Pregnancy outcomes following maternal kidney transplantation: a national cohort study
Authors: Majak Guri B. , Sandven Irene , Lorentzen Bjørg , Vangen Siri , Reisæter Anna V. , Henriksen Tore , Michelsen Trond M. 
Published: June 2016

AbstractIntroductionInternal design flaws in previous reports of pregnancies following kidney transplantation have been outlined, and the need for a validation has been stated. The aim of this study was to collect information about obstetrical and neonatal outcomes in all Norwegian pregnancies following maternal kidney transplantation, and to compare these data with the general Norwegian population.Material and methodsA retrospective cohort study based on 1 272 000 deliveries in Norway between 1969 and 2013. All data were collected from medical records. From the source population, we compared 119 first deliveries in kidney transplanted women with 238 first deliveries in nontransplanted women. An explanatory strategy was used in the analysis.ResultsThe risk of preeclampsia was significantly increased in kidney‐transplanted women compared with nontransplanted women (adjusted incidence rate ratio: 6.06, 95% confidence interval 3.18–11.55). Additionally, preeclampsia in kidney‐transplanted women was early onset (diagnosed <34 gestational weeks) in half of the cases. There were also persistent risks of cesarean delivery (adjusted incidence rate ratio 4.14, 95% confidence interval 2.56–6.66), preterm delivery (adjusted incidence rate ratio 4.45, 95% confidence interval 2.13–9.30) and a birthweight below the 10th centile (22.7% vs. 9.7%) in the kidney‐transplanted group. A high proportion (63%) of the kidney‐transplanted women with chronic hypertension developed preeclampsia.ConclusionsUsing consistent diagnostic criteria, this study shows high rates of maternal and neonatal complications in pregnancies following kidney transplantation. In particular, we reveal a high rate of early‐onset preeclampsia requiring operative preterm delivery, conferring long‐term risks on both the mother and child.
Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress
Authors: Karlsson Markus , Kurz Tino 
Published: June 2016

AbstractPurposeOxidative stress‐related damage to retinal pigment epithelial (RPE) cells is an important feature in the development of age‐related macular degeneration. Iron‐catalysed intralysosomal production of hydroxyl radicals is considered a major pathogenic factor, leading to lipofuscin formation with ensuing depressed cellular autophagic capacity, lysosomal membrane permeabilization and apoptosis. Previously, we have shown that cultured immortalized human RPE (ARPE‐19) cells are extremely resistant to exposure to bolus doses of hydrogen peroxide and contain considerable amounts of the iron‐binding proteins metallothionein (MT), heat‐shock protein 70 (HSP70) and ferritin (FT). According to previous findings, autophagy of these proteins depresses lysosomal redox‐active iron. The aim of this study was to investigate whether up‐ or downregulation of these proteins would affect the resistance of ARPE‐19 cells to oxidative stress.MethodsThe sensitivity of ARPE‐19 cells to H2O2 exposure was tested following upregulation of MT, HSP70 and/or FT by pretreatment with ZnSO4, heat shock or FeCl3, as well as siRNA‐mediated downregulation of the same proteins.ResultsUpregulation of MT, HSP70 and FT did not improve survival following exposure to H2O2. This was interpreted as existence of an already maximal protection. Combined siRNA‐mediated attenuation of both FT chains (H and L), or simultaneous downregulation of all three proteins, made the cells significantly more susceptible to oxidative stress confirming the importance of iron‐binding proteins.ConclusionThe findings support our hypothesis that the oxidative stress resistance exhibited by RPE cells may be explained by a high autophagic influx of iron‐binding proteins that would keep levels of redox‐active lysosomal iron low.