bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications for suboptimal low‐dose direct oral anticoagulants for non‐valvular atrial fibrillation patients
Authors: Umei Masahiko , Kishi Mikio , Sato Takahiro , Shindo Akito , Toyoda Masayuki , Yokoyama Masaaki , Matsushita Masashiro , Ohnishi Satoshi , Yamasaki Masao
Published: July 2017

Background

Direct oral anticoagulants (DOACs) have been developed for stroke prevention in patients with non‐valvular atrial fibrillation (NVAF). We conducted a retrospective cohort study of patients with NVAF who were newly treated with DOACs in a real‐world clinical setting.

Methods

We retrospectively analyzed patients with NVAF newly treated with one of three DOACs—dabigatran, rivaroxaban, or apixaban—between January 1, 2013, and December 31, 2015.

Results

A total of 670 patients with NVAF who were newly prescribed one of the three DOACs were analyzed; 74 patients (10.9%) received dabigatran, 290 (43.3%) received rivaroxaban, and 306 (45.8%) received apixaban. Fifteen patients had thromboembolic events, almost half of which were due to discontinuation of DOACs. Six patients had major bleeding, although almost all were discharged with good neurological prognoses. A total of 129 patients were treated with a suboptimal low‐dose DOAC; none experienced a thromboembolic event as long as the DOAC was taken regularly, and none of the patients in any of the three DOAC groups had major bleeding events.

Conclusions

With good adherence, the clinical course associated with DOACs is comparatively good. In the future, suboptimal low‐dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding.
Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein expression predicts disease severity in chronic hepatitis C patients
Authors: Huang Ching‐I , Huang Chung‐Feng , Yeh Ming‐Lun , Lin Yi‐Hung , Liang Po‐Cheng , Hsieh Meng‐Hsuan , Dai Chia‐Yen , Hsieh Ming‐Yen , Lin Zu‐Yau , Chen Shinn‐Cherng , Huang Jee‐Fu , Yu Ming‐Lung , Chuang Wan‐Long
Published: July 2017

Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C (CHC) in Taiwan. The association between WFA+‐M2BP and histological features was evaluated among those CHC patients underwent liver biopsy. We also aimed to clarify the factors determining the performance of WFA+‐M2BP in CHC. A total of 229 CHC patients were consecutively recruited. The mean value of WFA+‐M2BP in patients from F0 to F4 was 1.68, 2.23, 3.45, 3.48, 3.77 respectively (linear trend P = 0.008). Linear regression analysis revealed that alanine aminotransferase (odds ratio [OR]: 0.03, 95% confidence intervals [CI]: 0.02–0.05, P < 0.001), AST (OR: −0.1, 95% CI: −0.02 to −0.01, P < 0.001), and liver fibrosis (OR: 0.30, 95% CI: 0.01–0.59, P = 0.043) were the independent factors correlated to serum WFA+‐M2BP level. The optimal cutoff values of WFA+‐M2BP for fibrosis stages F1, F2, F3, and F4 were 1.42, 1.61, 1.42, and 2.67, respectively. Multivariate analysis revealed that the platelet count (OR/CI: −0.009/0.986–0.996, P = <0.001), r‐glutamyl transferase (OR/CI: 0.007/1.000–1.013, P = 0.036), and WFA+‐M2BP (OR/CI: 0.187/1.057–1.374, P = 0.005). We concluded that WFA+‐M2BP is a competent noninvasive marker for liver fibrosis assessment in CHC patients.
High frequencies of a favorable IL‐28B rs8099917 polymorphism and the clinical implications in patients with HCV in one multiracial area of Taiwan
Authors: Cheng Chun‐Han , Lin Ching‐Chung , Chen Huan‐Lin , Lin I.‐Tsung , Wu Chia‐Hsien , Lee Yuan‐Kai , Wong Ming‐Wun , Bair Ming‐Jong
Published: July 2017

There is a strong association between hepatitis C virus (HCV) treatment efficacy and the interleukin (IL)‐28B gene. However, the IL‐28B variant's distribution and potential role in the therapeutic response are not well established in Taitung, a racially diverse county in Taiwan. Here, we investigated the distribution pattern of IL‐28B rs8099917 and its influence on treatment efficacy. In this retrospective study, we enrolled 180 patients who had been treated with pegylated‐interferon plus ribavirin. Patients' general information, virological characteristics, IL‐28B status, laboratory results, treatment course, and outcome were analyzed. Of the patients enrolled, 56.7% were male, with a mean age of 54.11 years. A total of 24.4% of the population were indigenous people. The majority of patients had the favorable IL‐28B polymorphism (rs8099917 TT/TG/GG: 94.4%/5.6%/0%). The proportion of patients with the TT genotype seemed to be higher in indigenous patients. The rate of sustained virological response (SVR) among included patients was 73.0%. Univariate analysis showed that genotype non‐1, patients achieved rapid virological response (RVR), lower body mass index (BMI), and lower baseline HCV viral load were significantly associated with SVR. Multivariate analysis revealed that BMI <25 and RVR are the independent predictor of success treatment. In conclusion, the favorable IL‐28B rs8099917 polymorphism occurs in high frequency in this multiracial area, which might be important to help guide physicians and patients in their future clinical decisions.
Disposition and clinical implications of protein-bound uremic toxins
Authors: Jansen Jitske , Jankowski Joachim , Gajjala Prathibha R. , Wetzels Jack F.M. , Masereeuw Rosalinde
Published: July 2017

In patients with chronic kidney disease (CKD), adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds with intrinsic biological activities, many of which are too large to be filtered and/or are protein bound. The renal excretion of protein-bound toxins depends largely on active tubular secretion, which shifts the binding and allows for active secretion of the free fraction. To facilitate this process, renal proximal tubule cells are equipped with a range of transporters that co-operate in basolateral uptake and luminal excretion. Many of these transporters have been characterized as mediators of drug disposition, but have recently been recognized for their importance in the proximal renal tubular transport of uremic toxins as well. This also indicates that during uremia, drug disposition may be severely affected as a result of drug–uremic toxin interaction. In addition, CKD patients receive various drugs to treat their complications potentially resulting in drug–drug interactions (DDIs), also for drugs that are non-renally excreted. This review discusses the current knowledge on formation, disposition and removal of protein-bound uremic toxins. Furthermore, implications associated with drug treatment in kidney failure, as well as innovative renal replacement therapies targetting the protein-bound uremic toxins are being discussed. It will become clear that the complex problems associated with uremia warrant a transdisciplinary approach that unites research experts in the area of fundamental biomedical research with their colleagues in clinical nephrology.
Pathogenesis of asthma: implications for precision medicine
Authors: Russell Richard J. , Brightling Christopher
Published: July 2017

The pathogenesis of asthma is complex and multi-faceted. Asthma patients have a diverse range of underlying dominant disease processes and pathways despite apparent similarities in clinical expression. Here, we present the current understanding of asthma pathogenesis. We discuss airway inflammation (both T2HIGH and T2LOW), airway hyperresponsiveness (AHR) and airways remodelling as four key factors in asthma pathogenesis, and also outline other contributory factors such as genetics and co-morbidities. Response to current asthma therapies also varies greatly, which is probably related to the inter-patient differences in pathogenesis. Here, we also summarize how our developing understanding of detailed pathological processes potentially translates into the targeted treatment options we require for optimal asthma management in the future.
MicroRNA in glutamate receptor-dependent neurological diseases
Authors: Alsharafi Walid A. , Luo Zhaohui , Long Xiaoyan , Xie Yuanyuan , Xiao Bo
Published: July 2017

Glutamate-mediated excitotoxicity is the major neuropathological process contributing to numerous neurological diseases. Recently, emerging evidence indicates that microRNAs (miRNAs) play essential roles in the pathophysiology of a wide range of neurological diseases. Notably, there have been significant developments in understanding the biogenesis of miRNAs, their regulatory mechanisms, and their potential as effective biomarkers and therapies. In the present review, we summarize the recent literature that highlights the versatile roles played by miRNAs in glutamate receptor (GluR)-dependent neurological diseases. Based on the reported studies to date, modulation of miRNAs could emerge as a promising therapeutic target for a variety of neurological diseases that were discussed in this review.
Grim news for science and research in Trump budget
Authors: Kramer David
Published: July 2017

Across-the-board cuts to civilian R&D programs would help pay for increased defense spending, but they face an uncertain future in Congress.
Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays
Authors: Brühmann Stefan , Ushakov Dmitry S. , Winterhoff Moritz , Dickinson Richard B. , Curth Ute , Faix Jan
Published: July 2017

Significance

Ena/VASP proteins are tetramers that drive the processive elongation of actin filaments. Because Ena/VASP proteins are implicated in motility, embryogenesis, and cancer, it is mandatory to understand their molecular mechanism. The kinetic model of VASP-mediated filament elongation in solution and on beads revealed that VASP uses one arm for tethering to growing barbed ends while three GABs on other arms are used to capture and deliver actin monomers to growing filament tips. However, the underlying mechanism must be profoundly diverse because only in clustered arrays does VASP-mediated filament elongation become exceptionally processive and resistant against capping protein. Using VASP oligomerization mutants and total internal reflection fluorescence microscopy (TIRFM) imaging, we show now that, in clustered arrays, adjacent VASP tetramers synergize in the elongation of single filaments.
Cardiac Rehabilitation Participation Rates and Outcomes for Patients With Heart Failure
Authors: Rengo Jason L. , Savage Patrick D. , Barrett Trace , Ades Philip A.
Published: July 2017

Purpose:

Exercise training has been shown to reduce combined cardiovascular mortality and hospitalizations in patients with chronic heart failure (CHF) with reduced ejection fraction (HFrEF). Whereas there are extensive data on exercise training for individuals with HFrEF in a research setting, the experience of delivering cardiac rehabilitation (CR) services in the clinical setting has not been well described. With little knowledge regarding the number of qualifying patients with HFrEF in the United States, we described our 18-month experience recruiting hospitalized inpatients and stable outpatients into phase 2 CR.

Methods:

Patients hospitalized with CHF HFrEF were tracked for enrollment in CR. Exercise training response was described for patients identified as inpatients and for stable HFrEF outpatients referred from cardiology clinic or heart failure clinic.

Results:

The cohort included 83 patients hospitalized with CHF and 36 outpatients. Only 17% (14/83) of eligible HFrEF inpatients enrolled in CR following CHF hospitalization compared with 97% (35/36) outpatient referrals. Improvements in aerobic capacity for the total cohort were observed whether expressed as estimated metabolic equivalents (n = 19, 4.6 ± 1.6 to 6.2 ± 2.4, P < .0001) or

JOURNAL/jcprh/04.03/01273116-201801000-00006/6FSM1/v/2023-09-11T232139Z/r/image-gif

o
2peak (n = 14, 14.4 ± 3.5 to 16.4 ± 4.6 mL/kg/min, P = .02) for those who completed CR.

Conclusion:

Significant barriers to recruiting and enrolling patients with HFrEF were observed and only 17% of inpatients attended CR. Systematic in-hospital referral with close followup in the outpatient setting has the potential to capture more eligible patients. The participation of referred stable outpatients with HFrEF was much higher. Regardless of the referral source, patients with HFrEF completing CR can expect improvements in aerobic capacity, muscle strength, and depressive symptoms.
A benchmarking of workflows for detecting differential splicing and differential expression at isoform level in human RNA-seq studies
Authors: Merino Gabriela A. , Conesa Ana , Fernández Elmer A.
Published: July 2017

Over the last few years, RNA-seq has been used to study alterations in alternative splicing related to several diseases. Bioinformatics workflows used to perform these studies can be divided into two groups, those finding changes in the absolute isoform expression and those studying differential splicing. Many computational methods for transcriptomics analysis have been developed, evaluated and compared; however, there are not enough reports of systematic and objective assessment of processing pipelines as a whole. Moreover, comparative studies have been performed considering separately the changes in absolute or relative isoform expression levels. Consequently, no consensus exists about the best practices and appropriate workflows to analyse alternative and differential splicing. To assist the adequate pipeline choice, we present here a benchmarking of nine commonly used workflows to detect differential isoform expression and splicing. We evaluated the workflows performance over three different experimental scenarios where changes in absolute and relative isoform expression occurred simultaneously. In addition, the effect of the number of isoforms per gene, and the magnitude of the expression change over pipeline performances were also evaluated. Our results suggest that workflow performance is influenced by the number of replicates per condition and the conditions heterogeneity. In general, workflows based on DESeq, DEXSeq, Limma and NOISeq performed well over a wide range of transcriptomics experiments. In particular, we suggest the use of workflows based on Limma when high precision is required, and DESeq2 and DEXseq pipelines to prioritize sensitivity. When several replicates per condition are available, NOISeq and Limma pipelines are indicated.
Analysis of theAedes albopictusC6/36 genome provides insight into cell line adaptations toin vitroviral propagation
Authors: Miller Jason R , Koren Sergey , Dilley Kari A , Puri Vinita , Brown David M , Harkins Derek M , Thibaud-Nissen Françoise , Rosen Benjamin , Chen Xiao-Guang , Tu Zhijian , Sharakhov Igor V , Sharakhova Maria V , Sebra Robert , Stockwell Timothy B , Bergman Nicholas H , Sutton Granger G , Phillippy Adam M , Piermarini Peter M , Shabman Reed S
Published: July 2017

Background

The 50-year oldAedes albopictusC6/36 cell line is a resource for the detection, amplification, and analysis of mosquito-borne viruses including Zika, dengue, and chikungunya. The cell line is derived from an unknown number of larvae from an unspecified strain ofAedes albopictusmosquitoes. Toward improved utility of the cell line for research in virus transmission, we present an annotated assembly of the C6/36 genome.

Results

The C6/36 genome assembly has the largest contig N50 (3.3 Mbp) of any mosquito assembly, presents the sequences of both haplotypes for most of the diploid genome, reveals independent null mutations in both alleles of the Dicer locus, and indicates a male-specific genome. Gene annotation was computed with publicly available mosquito transcript sequences. Gene expression data from cell line RNA sequence identified enrichment of growth-related pathways and conspicuous deficiency in aquaporins and inward rectifier K+channels. As a test of utility, RNA sequence data from Zika-infected cells was mapped to the C6/36 genome and transcriptome assemblies. Host subtraction reduced the data set by 89%, enabling faster characterization of non-host reads.

Conclusions

The C6/36 genome sequence and annotation should enable additional uses of the cell line to study arbovirus vector interactions and interventions aimed at restricting the spread of human disease.
TECPR2a positive regulator of autophagy is implicated in healthy brain ageing
Authors: Alexander John , Ströbel Thomas , Georgitsi Marianthi , Schuster Michael , Penz Thomas , Bock Christoph , Hönigschnabl Selma , Reiner Angelika , Fischer Peter , Paschou Peristera , Kovacs Gabor G.
Published: July 2017

Understanding the healthy brain aging process is key to uncovering the mechanisms leading to pathological age-related neurodegeneration, including progression to Alzheimer’s disease (AD). Here, we report the first deep whole genome sequencing study aiming to identify variants that are associated specifically to healthy brain aging defined on both clinical and neuropathological level, thus tacking the issue of pathological heterogeneity that often underlies a clinical AD diagnosis. We studied samples from the VITA brain bank and followed an extreme phenotypic ends study design comparing neuropathologically “healthy” aging individuals above 80 years of age with pure AD patients of the same age. Focusing on the extreme ends of the phenotypic distribution, and potentially functional variants, we discover a single variant(rs10149146)carried by 53.6% of the “healthy” brain elderly individuals in our study (15/28 individuals) and none of the 12 AD cases. This variant lies on the autophagy and cell cycle associatedTECPR2gene. Autophagy dysfunction has been previously implicated in multiple progressive neurodegenerative diseases. An additional non-synonymous variant on theCINPgene (encoding a cell-cycle checkpoint protein) is also found in 46% of healthy controls and absent from all the AD cases.TECPR2andCINPappear to be “partner” genes in terms of regulation and their associated transcription factors have been previously implicated in AD and neurodegeneration. Our study is the first to support the hypothesis that aTECPR2non-synonymous variant carries a significant neuroprotective effect pointing to key molecules for the involvement of autophagy and cell cycle control in protection from neurodegeneration.
Obstruction of pilus retraction stimulates bacterial surface sensing
Authors: Ellison Courtney K. , Kan Jingbo , Dillard Rebecca S. , Kysela David T. , Hampton Cheri M. , Ke Zunlong , Wright Elizabeth R. , Biais Nicolas , Dalia Ankur B. , Brun Yves V.
Published: July 2017

Surface association provides numerous fitness advantages to bacteria. Thus, it is critical for bacteria to recognize surface contact and to consequently initiate physiological changes required for a surface-associated lifestyle (1). Ubiquitous microbial appendages called pili are involved in sensing surfaces and mediating downstream surface-associated behaviors (2–6). The mechanism by which pili mediate surface sensing remains unknown, largely due to the difficulty to visualize their dynamic nature and to directly modulate their activity without genetic modification. Here, we show thatCaulobacter crescentuspili undergo dynamic cycles of extension and retraction that cease within seconds of surface contact, and this arrest of pilus activity coincides with surface-stimulated holdfast synthesis. By physically blocking pili, we show that imposing resistance to pilus retraction is sufficient to stimulate holdfast synthesis in the absence of surface contact. Thus, resistance to type IV pilus retraction upon surface attachment is used for surface sensing.

One Sentence Summary

Bacteria use the tension imparted on retracting pilus fibers upon their binding to a surface for surface sensing.
Two phosphoglucomutase paralogs regulate triggered secretion of theToxoplasmamicronemes
Authors: Saha Sudeshna , Coleman Bradley I. , Sansom Tiffany , Dubey Rashmi , Blader Ira J. , Gubbels Marc-Jan
Published: July 2017

Parafusin is a phosphoglucomutase (PGM) paralog that acts as a signaling scaffold protein in calcium mediated exocytosis across many eukaryotes. InToxoplasma gondiithe parafusin related protein 1 (PRP1) has been associated in indirect and heterologous studies with the regulated exocytosis of the micronemes, which are required for successful host cell invasion and egress. Here we directly assessed the role of PRP1 by deleting the gene from the parasite. We observed a specific defect in microneme secretion in response to high Ca2+fluxes, but not to phosphatidic acid fluxes controlling microneme release. We observed no defect in constitutive microneme secretion which was sufficient to support completion of the lytic cycle. Furthermore, deletion of the other PGM inToxoplasma, PGM2, as well as the double PRP1/PGM2 deletion resulted in a similar phenotype. This suggests a functional interaction between these two genes. Strikingly, tachyzoites without both paralogs are completely viablein vitroand during acute mice infections. This indicates that PGM activity is neither required for glycolysis. In conclusion, the PRP1-PGM2 pair is required for a burst in microneme secretion upon high Ca2+fluxes, but this burst is not essential to complete the lytic cycle of the parasite.

Plain Language Summary

Calcium mediated control of microneme secretion is essential for host cell invasion and egress ofToxoplasma gondii. Here it is shown that the two phosphoglucomutases inToxoplasmaboth function in the translation of a spike in calcium into a burst in microneme secretion.
PHYLOSCANNER: Inferring Transmission from Within‐ and Between-Host Pathogen Genetic Diversity
Authors: Wymant Chris , Hall Matthew , Ratmann Oliver , Bonsall David , Golubchik Tanya , de Cesare Mariateresa , Gall Astrid , Cornelissen Marion , Fraser Christophe
Published: July 2017

A central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbour subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner.
Synthesizing developmental trajectories
Authors: Villoutreix Paul , Andén Joakim , Lim Bomyi , Lu Hang , Kevrekidis Ioannis G. , Singer Amit , Shvartsman Stanislav Y.
Published: July 2017

Dynamical processes in biology are studied using an ever-increasing number of techniques, each of which brings out unique features of the system. One of the current challenges is to develop systematic approaches for fusing heterogeneous datasets into an integrated view of multivariable dynamics. We demonstrate that heterogeneous data fusion can be successfully implemented within a semi-supervised learning framework that exploits the intrinsic geometry of high-dimensional datasets. We illustrate our approach using a dataset from studies of pattern formation in Drosophila. The result is a continuous trajectory that reveals the joint dynamics of gene expression, subcellular protein localization, protein phosphorylation, and tissue morphogenesis. Our approach can be readily adapted to other imaging modalities and forms a starting point for further steps of data analytics and modeling of biological dynamics.
Selfing species exhibit diminished niche breadth over time
Authors: Park Daniel S. , Ellison Aaron M. , Davis Charles C.
Published: July 2017

Self-pollinating plants (“selfers”) have larger geographic ranges and inhabit higher latitudes than their outcrossing relatives. This finding has led to the hypothesis that selfers also have broader climatic niches. It is possible that the increased likelihood of successful colonization into new areas and the initial purging of deleterious mutations may offset selfers’ inability to adapt to new environments due to low heterozygosity. Here, for the first time, we examine the climatic niches and mutation accumulation rates of hundreds of closely related selfing and outcrossing species. Contrary to expectations, selfers do not have wider climatic niche breadths than their outcrossing sister taxa despite selfers’ greatly expanded geographic ranges. Selfing sister pairs also exhibit greater niche overlap than outcrossing sisters, implying that climatic niche expansion becomes limited following the transition to selfing. Further, the niche breadth of selfers is predicted to decrease significantly faster than that of closely-related outcrossers. In support of these findings, selfers also display significantly higher mutation accumulation rates than their outcrossing sisters, implying decreased heterozygosity, effective population size, and adaptive potential. These results collectively suggest that while the release from mate limitation among selfing species may result in initial range expansion, range size and niche breadth are decoupled, and the limitations of an increasingly homogeneous genome will constrict selfers’ climatic niches and over time reduce their geographic ranges.
A systematic survey of regional multitaxon biodiversity: evaluating strategies and coverage
Authors: Brunbjerg Ane Kirstine , Bruun Hans Henrik , Brøndum Lars , Classen Aimée T. , Dalby Lars , Fog Kåre , Frøslev Tobias G. , Goldberg Irina , Hansen Anders Johannes , Hansen Morten D.D. , Høye Toke T. , Illum Anders A. , Læssøe Thomas , Newman Gregory S. , Skipper Lars , Søchting Ulrik , Ejrnæs Rasmus
Published: July 2017

Background

In light of the biodiversity crisis and our limited ability to explain variation in biodiversity, tools to quantify spatial and temporal variation in biodiversity and its underlying drivers are critically needed. Inspired by the recently published ecospace framework, we developed and tested a sampling design for environmental and biotic mapping. We selected 130 study sites (40 × 40 m) across Denmark using stratified random sampling along the major environmental gradients underlying biotic variation. Using standardized methods, we collected site species data on vascular plants, bryophytes, macrofungi, lichens, gastropods and arthropods. To evaluate sampling efficiency, we calculated regional coverage (relative to the known species number per taxonomic group), and site scale coverage (i.e., sample completeness per taxonomic group at each site). To extend taxonomic coverage to organisms that are difficult to sample by classical inventories (e.g., nematodes and non-fruiting fungi), we collected soil for metabarcoding. Finally, to assess site conditions, we mapped abiotic conditions, biotic resources and habitat continuity.

Results

Despite the 130 study sites only covering a minute fraction (0.0005 %) of the total Danish terrestrial area, we found 1774 species of macrofungi (54 % of the Danish fungal species pool), 663 vascular plant species (42 %), 254 bryophyte species (41 %) and 200 lichen species (19 %). For arthropods, we observed 330 spider species (58 %), 123 carabid beetle species (37 %) and 99 hoverfly species (33 %). Correlations among species richness for taxonomic groups were predominantly positive. Overall, sample coverage was remarkably high across taxonomic groups and sufficient to capture substantial spatial variation in biodiversity across Denmark. This inventory is nationally unprecedented in detail and resulted in the discovery of 143 species with no previous record for Denmark. Comparison between plant OTUs detected in soil DNA and observed plant species confirmed the usefulness of carefully curated environmental DNA-data. Species richness did not correlate well among taxa suggesting differential and complex biotic responses to environmental variation.

Conclusions

We successfully and adequately sampled a wide range of diverse taxa along key environmental gradients across Denmark using an approach that includes multi-taxon biodiversity assessment and ecospace mapping. Our approach is applicable to assessments of biodiversity in other regions and biomes where species are structured along environmental gradient.
CD18-mediated adhesion is required for lung inflammation induced by mononuclear cell-derived extracellular vesicles
Authors: Neri Tommaso , Scalise Valentina , Passalacqua Ilaria , Giusti Ilaria , Balia Cristina , D’Alessandro Delfo , Berrettini Stefano , Pedrinelli Roberto , Paggiaro Pierluigi , Dolo Vincenza , Celi Alessandro
Published: July 2017

Extracellular vesicles are submicron vesicles that upregulate the synthesis of proinflammatory mediators by lung epithelial cells.

We investigated whether these structures adhere to lung epithelial cells, and whether adhesion is a prerequisite for their proinflammatory activity.

Extracellular vesicles were generated by stimulation of normal human mononuclear cells with the calcium ionophore A23187, and labelled with carboxyfluorescein diacetate succinimidyl ester. Adhesion of vesicles to monolayers of immortalized bronchial epithelial cells (16HBE) and alveolar cells (A549) was analysed by fluorescence microscopy. The role of candidate adhesion receptors was evaluated with inhibitory monoclonal antibodies and soluble peptides. The synthesis of proinflammatory mediators was assessed by ELISA.

Transmission electron microscopy confirmed the generation of closed vesicles with an approximate size range between 50 and 600 nm. Adhesion of extracellular vesicles to epithelial cells was minimal in baseline conditions and was upregulated upon stimulation of the latter with tumour necrosis factor-α. Adhesion was blocked by an anti-CD18 antibody and by peptides containing the sequence RGD. The same molecules also blocked the upregulation of the synthesis of interleukin-8 and monocyte chemotactic protein-1 induced by extracellular vesicles.

Summary statement

Extracellular vesicles upregulate the synthesis of proinflammatory mediators by lung epithelial cells. CD18-mediated adhesion to target cells is required for this proinflammatory effect and might represent a target for anti-inflammatory therapy.
Unification of Countermanding and Perceptual Decision-making
Authors: Middlebrooks Paul G. , Zandbelt Bram B. , Logan Gordon D. , Palmeri Thomas J. , Schall Jeffrey D.
Published: July 2017

Perceptual decision-making, studied using two-alternative forced-choice tasks, is explained by sequential sampling models of evidence accumulation, which correspond to the dynamics of neurons in sensorimotor structures of the brain1 2. Response inhibition, studied using stop-signal (countermanding) tasks, is explained by a race model of the initiation or canceling of a response, which correspond to the dynamics of neurons in sensorimotor structures3 4. Neither standard model accounts for performance of the other task. Sequential sampling models incorporate response initiation as an uninterrupted non-decision time parameter independent of task-related variables. The countermanding race model does not account for the choice process. Here we show with new behavioral, neural and computational results that perceptual decision making of varying difficulty can be countermanded with invariant efficiency, that single prefrontal neurons instantiate both evidence accumulation and response inhibition, and that an interactive race between two GO and one STOP stochastic accumulator fits countermanding choice behavior. Thus, perceptual decision-making and response control, previously regarded as distinct mechanisms, are actually aspects of more flexible behavior supported by a common neural and computational mechanism. The identification of this aspect of decision-making with response production clarifies the component processes of decision-making.
PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides
Authors: Jacob Laurent , Combes Florence , Burger Thomas
Published: July 2017

We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge, so that they are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via thepepa.testfunction of theDAPARBioconductor R package.
Ribosome profiling reveals post-translational signaling mechanisms drive the retrograde enhancement of presynaptic efficacy
Authors: Chen Xun , Dickman Dion K.
Published: July 2017

Presynaptic efficacy can be modulated by retrograde control mechanisms, but the nature of these complex signaling systems remain obscure. We have developed and optimized a tissue specific ribosome profiling approach inDrosophila.We first demonstrate the ability of this technology to define genome-wide translational regulations. We then leverage this technology to test the relative contributions of transcriptional, translational, and post-translational mechanisms in the postsynaptic muscle that orchestrate the retrograde control of presynaptic function. Surprisingly, we find no changes in transcription or translation are necessary to enable retrograde homeostatic signaling. Rather, post-translational mechanisms appear to ultimately gate instructive retrograde communication. Finally, we find that a global increase in translation induces adaptive responses in both transcription and translation of protein chaperones and degradation factors to promote cellular proteostasis. Together, this demonstrates the power of ribosome profiling to define transcriptional, translational, and post-translational mechanisms driving retrograde signaling during adaptive plasticity.

AUTHOR SUMMARY

Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems. However, transcriptional expression alone does not necessarily report gene translation, the process of ultimate importance in understanding cellular function. To circumvent this limitation, biochemical tagging of ribosomes and isolation of ribosomally-associated mRNA has been developed. However, this approach, called TRAP, has been shown to lack quantitative resolution compared to a superior technology, ribosome profiling, which quantifies the number of ribosomes associated with each mRNA. Ribosome profiling typically requires large quantities of starting material, limiting progress in developing tissue-specific approaches. Here, we have developed the first tissue specific ribosome profiling system inDrosophilato reveal genome-wide changes in translation. We first demonstrate successful ribosome profiling from a specific tissue, muscle, with superior resolution compared to TRAP. We then use transcriptional and ribosome profiling to define transcriptional and translational adaptions necessary for synaptic signaling at the neuromuscular junction. Finally, we utilize ribosome profiling to demonstrate adaptive changes in cellular translation following cellular stress to muscle tissue. Together, this now enables the power ofDrosophilagenetics to be leveraged with translational profiling in specific tissues.
A crush on small fungi: An efficient and quick method for obtainingDNAfrom minute ascomycetes
Authors: Sundberg Henrik , Ekman Stefan , Kruys Åsa
Published: July 2017

We have developed a reliable technique for extractingDNAfrom single microscopic fungal thalli, including efficient cell disruption and transfer of cell content for subsequent polymerase chain reaction (PCR). The technique was primarily developed for members of the ascomycete order Laboulbeniales, which are minute fungi with tough cell walls that are exceedingly difficult to disrupt with standard extraction techniques.

Our method makes routine amplification ofDNAfrom single thalli possible, even from small species or poorly developed individuals.DNArelease is accomplished in an entirely mechanical manner using an arbor press fitted with custom‐made components. This approach has eliminated additional treatment such as laborious freeze‐thaw cycles, enzymes, or lysing agents.

The overallPCRsuccess rate of 89% is comparable to or better than alternative protocols that make use of substantially larger amounts of fungal tissue. From 97% of the successfulPCRs a total of 156 sequences from four gene regions were produced.

Being able to restrictDNAextractions to a single thallus is critical to all genetic studies requiring data at the level of individual, e.g. population genetics. As all researchers working with minute uncultivable organisms in many respects face the same problems (effective handling of the material, small quantities ofDNAetc.), the methodology described here has a potential to be widely applicable. Necessary custom‐made components can be manufactured at fairly low cost by any precision‐tool workshop using our detail drawings.
The relationship between gambling expenditure, socio‐demographics, health‐related correlates and gambling behaviour—a cross‐sectional population‐based survey in Finland
Authors: Castrén Sari , Kontto Jukka , Alho Hannu , Salonen Anne H.
Published: July 2017

Aims

To investigate gambling expenditure and its relationship with socio‐demographics, health‐related correlates and past‐year gambling behaviour.

Design

Cross‐sectional population survey.

Setting

Population‐based survey in Finland.

Participants

Finnish people aged 15–74 years drawn randomly from the Population Information System. The participants in this study were past‐year gamblers with gambling expenditure data available (n = 3251, 1418 women and 1833 men).

Measurements

Expenditure shares, means of weekly gambling expenditure (WGE, €) and monthly gambling expenditure as a percentage of net income (MGE/NI, %) were calculated. The correlates used were perceived health, smoking, mental health [Mental Health Inventory (MHI)‐5], alcohol use [Alcohol Use Disorders Identification Test (AUDIT)‐C], game types, gambling frequency, gambling mode and gambling severity [South Oaks Gambling Screen (SOGS)].

Findings

Gender (men versus women) was found to be associated significantly with gambling expenditure, with exp(β) = 1.40, 95% confidence interval (CI) = 1.29, 1.52 and P < 0.005 for WGE, and exp(β) = 1.39, 95% CI = 1.27, 1.51 and P < 0.005 for MGE/NI. All gambling behaviour correlates were associated significantly with WGE and MGE/NI: gambling frequency (several times a week versus once a month/less than monthly, exp(β) = 30.75, 95% CI = 26.89, 35.17 and P < 0.005 for WGE, and exp(β) = 31.43, 95% CI = 27.41, 36.03 and P < 0.005 for MGE/NI), gambling severity (probable pathological gamblers versus non‐problem gamblers, exp(β) = 2.83, 95% CI = 2.12, 3.77 and P < 0.005 for WGE, and exp(β) = 2.67, 95% CI = 2.00, 3.57 and P < 0.005 for MGE/NI) and on‐line gambling (on‐line and land‐based versus land‐based only, exp(β) = 1.35, 95% CI = 1.24, 1.47 and P < 0.005 for WGE, and exp(β) = 1.35, 95% CI = 1.24, 1.47 and P < 0.005 for MGE/NI).

Conclusions

In Finland, male gender is associated significantly with both weekly gambling expenditure and monthly gambling expenditure related to net income. People in Finland with lower incomes contribute proportionally more of their income to gambling compared with middle‐ and high‐income groups.
The association between personal income and smoking among adolescents: a study in six European cities
Authors: Perelman Julian , Alves Joana , Pfoertner Timo‐Kolja , Moor Irene , Federico Bruno , Kuipers Mirte A. G. , Richter Matthias , Rimpela Arja , Kunst Anton E. , Lorant Vincent
Published: July 2017

Aims

This study investigates the link between personal income and smoking among adolescents, and aims to answer the following questions: (i) to what extent is personal income related to smoking, independent of family socio‐economic status (SES) and (ii) does the association between personal income and smoking apply to different subpopulations?

Design

Cross‐sectional study.

Setting

Six cities from European countries (Amersfoort, the Netherlands; Coimbra, Portugal; Hannover, Germany; Latina, Italy; Namur, Belgium; Tampere, Finland) in 2013.

Participants

A school‐based sample of 10 794 adolescents aged 14–17 years.

Measurements

We modelled smoking experimentation, weekly smoking, daily smoking and (among daily smokers) smoking intensity as function of personal income, adjusting for age, sex, family SES, parental smoking and country. We tested interactions between personal income and covariates. Stratification analyses were performed for the variables for which interactions were significant.

Findings

Adolescents in the highest income quintile were more likely to be smoking experimenters [odds ratio (OR) = 1.87; P < 0.01], weekly smokers (OR = 3.51; P < 0.01) and daily smokers (OR = 4.55; P < 0.01) than those in the lowest quintile. They also consumed more cigarettes per month (β = 0.79; P < 0.01). Adjusting for family SES did not modify the significance of relationships, and increased the magnitude of the association for daily smoking. None of the interactions between covariates and personal income was significant for smoking measures. For the intensity of smoking, the interaction was significant for SES. The stratified analysis showed a non‐significant association between smoking intensity and personal income among the oldest adolescents and those with the lowest SES background, while significant among younger and higher SES backgrounds.

Conclusion

In the Netherlands, Portugal, Germany, Italy, Belgium and Finland, adolescents' personal income is related positively to smoking behaviours independent of family socio‐economic status (SES). However, among low socio‐economic status adolescent daily smokers, the association between the intensity of smoking and personal income is weaker.
Measuring the effects of reduced snow cover on Australia's alpine arthropods
Authors: Slatyer Rachel A. , Nash Michael A. , Hoffmann Ary A.
Published: July 2017

Snow is one of the most important factors in the ecology of alpine ecosystems. In Australia, both the depth and duration of snow cover have declined significantly in recent decades and this trend is projected to continue with global warming. Many small arthropods remain active throughout the winter, within a space beneath the snowpack (subnivean) where the snow's insulation creates a thermally stable environment. Using field surveys and experimental manipulation of snow depth at two locations in the Australian alpine region, we explored the diversity of winter‐active arthropods and their response to reduced snow. Individuals from 18 arthropod Orders were detected beneath the snow during winter, with Collembola, Araneae, Acari and Coleoptera accounting for 95–98% of the individuals collected. The subnivean taxa represented a distinct subset of those active outside the winter months. Removal of the snow layer increased daily temperature fluctuations, increased the number of days below freezing and raised the mean surface temperatures. Community composition was altered by snow removal, driven by changes in the numbers of two abundant springtail taxa at each location. We found a strong reduction in the abundances of both taxa at one study site, and contrasting responses (one strong positive and one strong negative) to snow removal at the second study site. Subnivean arthropod communities in Australia thus appear sensitive to snow conditions at small spatial scales.
Short stature homeobox‐containing gene duplications in 3.7% of girls with tall stature and normal karyotypes
Authors: Upners Emmie N. , Jensen Rikke B. , Rajpert‐De Meyts Ewa , Dunø Morten , Aksglaede Lise , Juul Anders
Published: July 2017

Aim

The short stature homeobox‐containing gene (SHOX) plays an important role in short stature, but has not been explored in detail in a tall stature population before. This study explored the prevalence of SHOX aberrations in girls diagnosed with idiopathic tall stature with a normal karyotype.

Methods

We studied SHOX aberrations in 81 girls with a median age of 10.43 (7.17–12.73) years diagnosed with tall stature who were referred to our clinic at Copenhagen University Hospital, Denmark, between 2003 and 2013. SHOX copy variations were analysed by quantitative polymerase chain reaction, and aberrations were confirmed by multiplex ligation probe‐dependent amplification.

Results

One extra SHOX copy was found in three (3.7%) of the 81 girls with tall stature, and their heights were 2.87, 3.71 and 3.98 standard deviation scores (SDS) and above the median height SDS of the girls with two SHOX copies. Their sitting height/height ratios (−3.08, −2.00 and −2.18 SDS) were all lower than the population mean. Despite these SHOX duplications, the three girls were clinically and biochemically comparable to the 78 girls with two SHOX copies.

Conclusion

This study was the first to demonstrate SHOX duplications in three girls with tall stature and normal karyotypes.
Professionals’ positive perceptions of fathers are associated with more favourable attitudes towards including them in family interventions
Authors: de Montigny Francine , Gervais Christine , Meunier Sophie , Dubeau Diane
Published: July 2017

Aim

This Université du Québec en Outaouais study examined professionals’ attitudes towards fathers, their perceived self‐efficacy when working with them and their perceptions of the importance of including fathers in family interventions.

Methods

Professionals in Québec, Canada, working in childcare fields such as education, social services, health, community services and management answered a self‐report questionnaire between 2013 and 2015. The 296 respondents (90% females) had a mean age of 39 (20–65), were from urban, semi‐urban and rural settings and provided services to families with children up to five years of age.

Results

Social service professionals perceived fathers more negatively than did other professionals. Even though male professionals perceived fathers more negatively, they felt more confident working with them than did their female counterparts. Positive perceptions of fathers were associated with more favourable attitudes towards including them in family interventions, and this association was mediated by the professionals’ perceptions of their own self‐efficacy.

Conclusion

The most negative attitudes were reported by social service professionals. Male professionals viewed fathers more negatively but were more confident working with them than were female colleagues. Improving professionals’ perceptions of fathers could help to promote their inclusion in family interventions.