bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackgroundThe 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.ResultsThe 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.ConclusionsThe 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

ABSTRACTUnderstanding 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

AbstractSurface 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 SummaryBacteria 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

AbstractParafusin 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 SummaryCalcium 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

AbstractA 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.
Selfing species exhibit diminished niche breadth over time
Authors: Park Daniel S. , Ellison Aaron M. , Davis Charles C. 
Published: July 2017

AbstractSelf-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

AbstractBackgroundIn 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.ResultsDespite 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.ConclusionsWe 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

AbstractExtracellular 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 statementExtracellular 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.
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

AbstractWe 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

ABSTRACTPresynaptic 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 SUMMARYRecent 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

AbstractWe 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

AbstractAimsTo investigate gambling expenditure and its relationship with socio‐demographics, health‐related correlates and past‐year gambling behaviour.DesignCross‐sectional population survey.SettingPopulation‐based survey in Finland.ParticipantsFinnish 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).MeasurementsExpenditure 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)].FindingsGender (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).ConclusionsIn 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.