bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of nuclear transport factors and surface-conjugated FG nucleoporins: Insights and limitations
Authors: Hayama Ryo , Sorci Mirco , Keating John J. , Hecht Lee M. , Plawsky Joel L. , Belfort Georges , Chait Brian T. , Rout Michael P.
Published: October 2018

Protein-protein interactions are central to biological processes and the methods to thoroughly characterize them are of great interest.In vitromethods to examine protein-protein interactions are generally categorized into two classes: in-solution and surface-based methods. Here, using the multivalent interactions involved in nucleocytoplasmic transport as a model system, we examined the utility of three surface-based methods in characterizing rapid interactions involving intrinsically disordered proteins: atomic force microscopy, quartz crystal microbalance with dissipation, and surface plasmon resonance. Although results were comparable to those of previous reports, the existence of previously overlooked mass transport limitations was revealed. Additional experiments with a loss-of-interaction mutant variant demonstrated the existence of additional physical events and an uncharacterized binding mode. These results suggest the binding events that take place on the surface are more complex than initially assumed, prompting a need for re-interpretation of previous data.
Population receptive field estimates for motion-defined stimuli
Authors: Hughes Anna E. , Greenwood John A. , Finlayson Nonie J. , Schwarzkopf D. Samuel
Published: October 2018

The processing of motion changes throughout the visual hierarchy, from spatially restricted ‘local motion’ in early visual cortex to more complex large-field ‘global motion’ at later stages. Here we used functional magnetic resonance imaging (fMRI) to examine spatially selective responses in these areas related to the processing of random-dot stimuli defined by differences in motion. We used population receptive field (pRF) analyses to map retinotopic cortex using bar stimuli comprising coherently moving dots. In the first experiment, we used three separate background conditions: no background dots (dot-defined bar-only), dots moving coherently in the opposite direction to the bar (kinetic boundary) and dots moving incoherently in random directions (global motion). Clear retinotopic maps were obtained for the bar-only and kinetic-boundary conditions across visual areas V1-V3 and in higher dorsal areas. For the global-motion condition, retinotopic maps were much weaker in early areas and became clear only in higher areas, consistent with the emergence of global-motion processing throughout the visual hierarchy. However, in a second experiment we demonstrate that this pattern is not specific to motion-defined stimuli, with very similar results for a transparent-motion stimulus and a bar defined by a static low-level property (dot size) that should have driven responses particularly in V1. We further exclude explanations based on stimulus visibility by demonstrating that the observed differences in pRF properties do not follow the ability of observers to localise or attend to these bar elements. Rather, our findings indicate that dorsal extrastriate retinotopic maps may primarily be determined by the visibility of the neural responses to the bar relative to the background response (i.e. neural signal-to-noise ratios) and suggests that claims about stimulus selectivity from pRF experiments must be interpreted with caution.
Islet Gene View - a tool to facilitate islet research
Authors: Asplund Olof , Storm Petter , Chandra Vikash , Ottosson-Laakso Emilia , Hatem Gad , Mansour-Aly Dina , Krus Ulrika , Ibrahim Hazem , Ahlqvist Emma , Tuomi Tiinamaija , Renström Erik , Korsgren Olle , Wierup Nils , Wollheim Claes , Artner Isabella , Mulder Hindrik , Hansson Ola , Otonkoski Timo , Groop Leif , Prasad Rashmi B ,   on behalf of the Human Tissue Laboratory at Lund University Diabetes Centre
Published: October 2018

Changes in the hormone-producing pancreatic islets are central culprits in type 2 diabetes (T2D) pathogenesis. Characterization of gene expression in islets how it is altered in T2D are therefore vital in understanding islet function and T2D pathogenesis. We leveraged RNA-sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. The IGW combines expression data for a given gene with phenotypical data such as T2D status, BMI, HbA1c, insulin secretion, purity of islets, etc.), regulation of gene expression by genetic variants e.g., expression quantitative trait loci (eQTLs) and relationship with expression of islet hormones. In IGW, 285 differentially expressed genes (DEGs) were identified in T2D donors islets compared to controls. Forty percent of the DEGs showed cell-type enrichment and a large proportion of them were significantly co-expressed with islet hormone-encoding genes like glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%) and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2 impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model.

Significance Statement

We present Islet Gene View (IGW), a web resource facilitating information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. In IGW, we explored RNA expression from 188 donor-islets and examined their relationship with islet phenotypes including insulin secretion and expression of genes encoding islet hormones. GWAS have shown 403 genetic variants associated with risk of type 2 diabetes (T2D) risk, however, the target genes and function of these variants in islets are largely unknown. By linking T2D risk variants to expression in islets from T2D and non-diabetic donors as well as islet phenotypes, use of IGW provided new insight into mechanisms by which variants in these loci may increase risk of T2D.
Mosquito Transmission and Human Hepatocyte Infections With Plasmodium ovale curtisi and P. ovale wallikeri
Authors: Kristan Mojca , Thorburn Samuel G. , Hafalla Julius , Sutherland Colin J. , Oguike Mary C.
Published: October 2018

Human ovale malaria is caused by the two closely related species Plasmodium ovale curtisi and P. ovale wallikeri. Both species are known to relapse from quiescent hepatic forms months or years after the primary infection occurred. Although some studies have succeeded in establishing mosquito transmission for ovale malaria, none have specifically described transmission and human hepatocyte infection of both sibling species. Here we describe a simplified protocol for successful transmission of both P. ovale curtisi and P. ovale wallikeri to Anopheles coluzzii mosquitoes, and streamlined monitoring of infection using sensitive parasite DNA detection, by loop-activated amplification, in blood-fed mosquitoes. In one experimental infection with P. ovale curtisi and one with P. ovale wallikeri, viable sporozoites were isolated from mosquito salivary glands, and used to successfully infect cultured human hepatocytes. This protocol provides a method for the utilisation of pre-treatment clinical blood samples from ovale malaria patients, collected in EDTA, for mosquito infection studies and generation of the hepatic life cycle stages of P. ovale curtisi and P. ovale wallikeri. We also demonstrate the utility of LAMP as a rapid and sensitive alternative to dissection for estimating the prevalence of infection in Anopheles mosquitoes fed with Plasmodium-infected blood.
Rapid bacterial identification by direct PCR amplification of 16S rRNA genes using the MinIONTMnanopore sequencer
Authors: Kai Shinichi , Matsuo Yoshiyuki , Nakagawa So , Kryukov Kirill , Matsukawa Shino , Tanaka Hiromasa , Iwai Teppei , Imanishi Tadashi , Hirota Kiichi
Published: October 2018

Rapid identification of bacterial pathogens is crucial for appropriate and adequate antibiotic treatment, which significantly improves patient outcomes. 16S ribosomal RNA (rRNA) gene amplicon sequencing has proven to be a powerful strategy for diagnosing bacterial infections. We have recently established a sequencing method and bioinformatics pipeline for 16S rRNA gene analysis utilizing the Oxford Nanopore Technologies MinION™ sequencer. In combination with our taxonomy annotation analysis pipeline, the system enabled the molecular detection of bacterial DNA in a reasonable timeframe for diagnostic purposes. However, purification of bacterial DNA from specimens remains a rate-limiting step in the workflow. To further accelerate the process of sample preparation, we adopted a direct PCR strategy that amplifies 16S rRNA genes from bacterial cell suspensions without DNA purification. Our results indicate that differences in cell wall morphology significantly affect direct PCR efficiency and sequencing data. Notably, mechanical cell disruption preceding direct PCR was indispensable for obtaining an accurate representation of the specimen bacterial composition. Furthermore, 16S rRNA gene analysis of mock polymicrobial samples indicated that primer sequence optimization is required to avoid preferential detection of particular taxa and to cover a broad range of bacterial species. This study establishes a relatively simple workflow for rapid bacterial identification via MinIONTMsequencing, which reduces the turnaround time from sample to result, and provides a reliable method that may be applicable to clinical settings.
16S rRNA:rDNA ratios and cell activity staining reveal consistent patterns of soil microbial activity
Authors: Bowsher Alan W. , Kearns Patrick J. , Shade Ashley
Published: October 2018

Microbial activity plays a major role in the processes that support life on Earth. Nevertheless, across diverse ecosystems many microbes are in a state of dormancy, characterized by strongly reduced metabolic rates. Of the methods used to assess microbial activity-dormancy dynamics, 16S rRNA: rDNA amplicons (“16S ratios”) and active cell staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) are two of the most common, yet each method has its own limitations. To better understand the applicability and potential complementarity of these two methods, we conducted two experiments investigating microbial activity in the rhizosphere. In the first experiment, we treated corn rhizosphere soil with common phytohormones to simulate plant-soil signaling during plant stress, and in the second experiment, we used bean exposed to drought or nutrient enrichment to more directly assess the impacts of plant stress on soil microbial activity. Overall, 16S ratios revealed numerous taxa with detectable RNA but no detectable DNA. However, overarching patterns in percent activity across treatments were unaffected by the method used to account for active taxa, or by the threshold 16S ratio used for taxa to be classified as active. 16S ratio distributions were highly similar across microbial phyla and were only weakly correlated with ribosomal operon number. Lastly, over relatively short time courses, 16S ratios are responsive earlier than CTC staining, a finding potentially related to the temporal sensitivity of activity changes detectable by the two methods. Our results suggest that 16S ratios and CTC staining provide robust and complementary estimates of bulk community activity.

Importance

Although the majority of microorganisms in natural ecosystems are dormant, relatively little is known about the dynamics of the active and dormant microbial pools through both space and time. The limited knowledge of microbial activity-dormancy dynamics is in part due to uncertainty in the methods currently used to quantify active taxa. Here, we directly compared two of the most common methods (16S ratios and active cell staining) for estimating microbial activity in rhizosphere soil, and found that they were largely in agreement in the overarching patterns, suggesting that either method is robust for assessing comparative activity dynamics. Thus, our results suggest that 16S ratios and active cell staining provide robust and complementary information for measuring and interpreting microbial activity-dormancy dynamics in soils. They also support that 16S rRNA:rDNA ratios have comparative value and offer a high-throughput, sequencing-based option for understanding relative changes in microbiome activity.
New insights into the ORF2 capsid protein, a key player of the hepatitis E virus lifecycle
Authors: Ankavay Maliki , Montpellier Claire , Sayed Ibrahim M. , Saliou Jean-Michel , Wychowski Czeslaw , Saas Laure , Duvet Sandrine , Aliouat-Denis Cécile-Marie , Farhat Rayan , de Masson d’Autume Valentin , Meuleman Philip , Dubuisson Jean , Cocquerel Laurence
Published: October 2018

Hepatitis E Virus (HEV) genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Recently, we developed an efficient HEV cell culture system and demonstrated that this virus produces three different forms of its capsid protein: (i) the ORF2i form (infectious/intracellular) which is the form associated with the infectious particles, (ii) the ORF2g (glycosylated ORF2) and ORF2c (cleaved ORF2) forms that are massively secreted glycoproteins not associated with infectious particles, but are the major antigens present in HEV-infected patient sera. The ORF2 protein sequence contains three highly conserved potential N-glycosylation sites (N1, N2 and N3). Although ORF2 protein is the most characterized viral protein, its glycosylation status and the biological relevance of this post-translational modification is still unclear. In the present study, we constructed and extensively characterized a series of ORF2 mutants in which the three N-glycosylation sites were mutated individually or in combination. We demonstrated that the ORF2g/c protein is N-glycosylated on N1 and N3 sites but not on the N2 site. We showed that N-glycosylation of ORF2 protein does not play any role in replication and assembly of infectious HEV particles. We found that glycosylated ORF2g/c forms are very stable proteins which are targeted by patient antibodies. During our study, we also demonstrated that the ORF2i protein is translocated into the nucleus of infected cells. In conclusion, our study led to new insights into the molecular mechanisms of ORF2 expression.
Establishment of murinein vitroblood-brain barrier models using immortalized cell lines: co-cultures of brain endothelial cells, astrocytes, and neurons
Authors: Idris Fakhriedzwan , Hanna Muharram Siti , Zaini Zainun , Diah Suwarni
Published: October 2018

Blood-brain barrier (BBB) is a selective barrier formed by the endothelial cells that line cerebral microvessels. It serves as a physical barrier due to the presence of complex tight junctions between adjacent endothelial cells which limits the paracellular movement of most molecules across the BBB. Manyin vitromodels of the BBB have been established to mimic thesein vivoproperties with limited success. In this study, we described the properties of a cell-based murinein vitroBBB model in five configurations constructed using immortalized cell lines in a 12-well format Transwell system: murine brain endothelial cells (bEnd.3) grown in a monoculture, or as co-culture in contact with astrocytes, or without contact with astrocytes or neurons, and triple co-culture combining the three cell lines. We found that only contact and triple co-culture model closely mimic thein vivoBBB tightness as evaluated by apparent permeability (Papp) of sucrose and albumin producing the lowest Papp values of 0.56 ± 0.16 × 10−6cms−1and 3.30 ± 0.51 × 10−6cms−1, respectively, obtained in triple co-culture model. Co-culturing of bEnd.3 with astrocytes increased the expression of occludin as shown by western blot analysis, and immunohistochemistry showed an increase in peripheral localization of occludin and claudin-5. In addition, we found conditioned media were able to increasein vitroBBB model tightness through the modulation of tight junction proteins localization. We conclude that the presence of astrocytes and neurons in close proximity to brain endothelial cells is essential to produce a tightin vitroBBB model.
Integrating Vectors for Genetic Studies in the Rare ActinomyceteAmycolatopsis marina
Authors: Gao Hong , Murugesan Buvani , Hoßbach Janina , Evans Stephanie K. , Stark W. Marshall , Smith Margaret C.M.
Published: October 2018

Few natural product pathways from rare Actinomycetes have been studied due to the difficulty in applying molecular approaches in these genetically intractable organisms. In this study, we sought to identify integrating vectors, derived using phageint/attPloci, that would efficiently integrate site-specifically in the rare Actinomycete,Amycolatopsis marinaDSM45569. Analysis of the genome of A.marinaDSM45569 indicated the presence ofattB-like sequences for TG1 and R4 integrases. The TG1 and R4attBswere active inin vitrorecombination assays with their cognate purified integrases andattPloci. Integrating vectors containing either the TG1 or R4int/attPloci yielded exconjugants in conjugation assays fromE. colitoA. marinaDSM45569. Site-specific recombination of the plasmids into the host TG1 or R4attBsites was confirmed by sequencing. The presence of homologous TG1 and R4attBsites in other species of this genus indicates that vectors based on TG1 and R4 integrases could be widely applicable.

Importance

Rare Actinomycetes have the same potential of natural product discovery as Streptomyces, but the potential has not been fully explored due to the lack of efficient molecular biology tools. In this study, we identified two serine integrases, TG1 and R4, which could be used in the rare Actinomycetes species,Amycolatopsis marina, as tools for genome integration. The high level of conservation between theattBsites for TG1 and R4 in a number of Amycolatopsis species suggested that plasmids with the integration systems from these phages should be widely useful in this genus.
Comprehensive in silico Analysis of IKBKAP gene that could potentially cause Familial dysautonomia
Authors: Mustafa Mujahed I. , Osman Enas A. , Abdelmoneiom Abdelrahman H. , Hassn Dania M. , Yousif Hadeel M. , Mahgoub Inshrah K. , Badawi Razan M. , Albushra Kutuf A. , Abdelhameed Tebyan A , Hassan Mohamed A.
Published: October 2018

Background

Familial dysautonomia (FD) is a rare neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies. We aimed to identify the pathogenic SNPs in IKBKAP gene by computational analysis software’s, and to determine the structure, function and regulation of their respective proteins.

Materials and Methods

We carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict SNPs influence on protein structure and function.

Result

41 novel mutations out of 973 nsSNPs that are found be deleterious effect on the IKBKAP structure and function.

Conclusion

This is the first in silico analysis in IKBKAP gene to prioritize SNPs for further genetic studies.
Comparison of DNA metabarcoding and morphological identification for stream macroinvertebrate biodiversity assessment and monitoring
Authors: Serrana Joeselle M. , Miyake Yo , Gamboa Maribet , Watanabe Kozo
Published: October 2018

Conventional morphology-based identification is commonly used for routine assessment of freshwater ecosystems. However, cost and time efficient techniques such as high-throughput sequencing (HTS) based approaches may resolve the constraints encountered in conducting morphology-based surveys. Here, we characterized stream macroinvertebrate species diversity and community composition via metabarcoding and morphological analysis from environmental samples collected from the Shigenobu River Basin in Ehime Prefecture, Japan. We compared diversity metrics and assessed both approaches’ ability to evaluate the relationship between macroinvertebrate community and environmental variables. In total, we morphologically identified 45 taxa (3 families, six subfamilies, 31 genera, and five species) from 8,276 collected individuals from ten study sites. We detected 44 species by metabarcoding, with 35 species collapsed into 11 groups matching the morphologically identified taxa. A significant positive correlation between logged depth (number of HTS reads) and abundance of morphological taxa was observed, which implied that quantitative data can be used for subsequent analyses. Relatively higher estimates of alpha diversity were calculated from the metabarcoding data in comparison to morphology-based data. However, beta diversity estimates between metabarcoding and morphology data based on both incidence and abundance-based matrices were correlated proving that community differences between sampling sites were preserved in the molecular data. Also, both models were significant, but metabarcoding data (93%) explained a relatively higher percentage of variation in the relationship between community composition and the environmental variables than morphological data (91%). Overall, we present both the feasibility and limitations of HTS-driven estimations of taxonomic richness, community composition, and diversity metrics, and that metabarcoding was proven comparable and more sensitive against morphology-based analysis for stream macroinvertebrate biodiversity assessment and environmental monitoring.
Empirical noise-mean fitness landscapes and the evolution of gene expression
Authors: Schmiedel Joern M , Carey Lucas B. , Lehner Ben
Published: October 2018

The effects of cell-to-cell variation (noise) in gene expression have proven difficult to quantify, in part due to the mechanistic coupling of noise to mean expression. To independently evaluate the effects of changes in expression mean and noise we determined the fitness landscapes in mean-noise expression space for 33 genes in yeast. The landscapes can be decomposed into two principal topologies: the fitness effects of protein shortage and surplus. For most genes, the fitness impact of sustained (mean) and short-lived (noise) deviations away from the expression optimum are linked and of similar magnitude. Sensitivity to both protein shortage and surplus creates a fitness landscape in which an epistatic ratchet uncouples the evolution of noise from mean expression, promoting noise minimization. These results demonstrate that noise is detrimental for many genes and reveal non-trivial consequences of mean-noise-fitness topologies for the evolution of gene expression systems.
A role for the VPS retromer inBrucellaintracellular replication revealed by genome-wide siRNA screening
Authors: Casanova Alain , Low Shyan Huey , Québatte Maxime , Sedzicki Jaroslaw , Tschon Therese , Ketterer Maren , Smith Kevin , Emmenlauer Mario , Ben-Tekaya Houchaima , Dehio Christoph
Published: October 2018

Brucella,the causing agent of brucellosis, is a major zoonotic pathogen with worldwide distribution.Brucellaresides and replicates inside infected host cells in membrane-bound compartments called BCVs (Brucella-containing vacuoles). Following uptake,Brucellaresides in eBCVs (endosomal BCVs) that gradually mature from early to late endosomal features. Through a poorly understood process that is key to the intracellular lifestyle ofBrucella,the eBCV escapes fusion with lysosomes by transitioning to the rBCV (replicative BCV), a replicative niche directly connected to the endoplasmic reticulum (ER). Despite the notion that this complex intracellular lifestyle must depend on a multitude of host factors, a holistic view on which of these components controlBrucellacell entry, trafficking and replication is still missing. Here we used a systematic cell-based siRNA knockdown screen in HeLa cells infected withBrucella abortusand identified 425 components of the human infectome forBrucellainfection. These include multiple components of pathways involved in central processes such as cell cycle, actin cytoskeleton dynamics or vesicular trafficking. Using assays for pathogen entry, knockdown complementation and co-localization at single-cell resolution, we identified the requirement of the VPS retromer forBrucellato escape the lysosomal degradative pathway and to establish its intracellular replicative niche. We thus validated a component of the VPS retromer as novel host factor critical forBrucellaintracellular trafficking. Further, our genome-wide data shed light on the interplay between central host processes and the biogenesis of theBrucellareplicative niche.

Importance

With >300,000 new cases of human brucellosis annually,Brucellais regarded as one of the most important zoonotic bacterial pathogen worldwide. The causing agent of brucellosis resides inside host cells within vacuoles termedBrucellacontaining vacuoles (BCVs). Although few host components required to escape the degradative lysosomal pathway and to establish the ER-derived replicative BCV (rBCV) have already been identified, the global understanding of this highly coordinated process is still partial and many factors remain unknown. To gain a deeper insight into these fundamental questions we performed a genome-wide RNA interference (RNAi) screen aiming at discovering novel host factors involved in theBrucellaintracellular cycle. We identified 425 host proteins that contribute toBrucellacellular entry, intracellular trafficking, and replication. Together, this study sheds light on previously unknown host pathways required for theBrucellainfection cycle and highlights the VPS retromer components as critical factors for the establishment of theBrucellaintracellular replicative niche.
Children with cystic fibrosis are infected with multiple subpopulations of Mycobacterium abscessus with different antimicrobial resistance profiles
Authors: Shaw Liam P. , Doyle Ronan M. , Kavaliunaite Ema , Spencer Helen , Balloux Francois , Dixon Garth , Harris Kathryn A
Published: October 2018

Background: Children with cystic fibrosis (CF) can develop life-threatening infections of Mycobacterium abscessus. These present a significant clinical challenge, particularly when the strains involved are resistant to antibiotics. Recent evidence of within-patient subclones of M. abscessus in adults with CF suggests the possibility that within-patient diversity may be relevant for the treatment of pediatric CF patients.
Methods: We performed whole genome sequencing (WGS) on 32 isolates of M. abscessus from multiple body sites for two patients with CF undergoing treatment at Great Ormond Street Hospital, UK, in 2015.
Results: We found evidence of extensive diversity within patients over time. Clustering analysis of single nucleotide variants (SNVs) revealed that each patient harboured multiple subpopulations, which were differentially abundant between sputum, lung samples, chest wounds, and pleural fluid. Sputum isolates did not reflect overall within-patient diversity, including failing to detect subclones with mutations previously associated with macrolide resistance (rrl 2058/2059). Some variants were present at intermediate frequencies before lung transplant. The time of transplant coincided with extensive variation, suggesting that this event is particularly disruptive for the microbial community, but transplant did not clear the M. abscessus infection and both patients died as a result of this infection.
Conclusions: Isolates of M. abscessus from sputum do not always reflect the entire diversity present within the patient, which can include subclones with differing AMR profiles. Awareness of this phenotypic variability, with sampling of multiple body sites in conjunction with WGS, may be necessary to ensure the best treatment for this vulnerable patient group.
Insights into the structure-driven protein interactivity of RNA molecules
Authors: de Groot Natalia Sanchez , Armaos Alexandros , Montes Ricardo Graña , Alriquet Marion , Calloni Giulia , Vabulas R. Martin , Tartaglia Gian Gaetano
Published: October 2018

The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet the molecular determinants that govern interactions in protein-RNA networks are poorly known at present. Here we used the most recent experimental data to investigate the relationship between RNA structure and protein interactions. Our results show that, independently of the particular technique, the amount of structure in RNA molecules correlates with the capacity of binding to proteins in vitro and in vivo. To validate this observation, we generated an in vitro network that mimics the composition of phase-separated RNA granules. We observed that RNA, when structured, competes with protein binding and can rearrange the interaction network. The simplicity of the principle bears great potential to boost the understanding and modelling of cellular processes involving RNA-protein interactions.
Experimental evolution of reproductive isolation from a single natural population
Authors: Villa Scott M. , Altuna Juan C. , Ruff James S. , Beach Andrew B. , Mulvey Lane I. , Poole Erik J. , Campbell Heidi E. , Johnson Kevin P. , Shapiro Michael D. , Bush Sarah E. , Clayton Dale H.
Published: October 2018

Ecological speciation occurs when local adaptation generates reproductive isolation as a by-product of natural selection1–3. Although ecological speciation is a fundamental source of diversification, the mechanistic link between natural selection and reproductive isolation remains poorly understood, especially in natural populations2–6. Here we show that experimental evolution of parasite body size over four years (ca. 60 generations) leads to reproductive isolation in natural populations of feather lice on birds. When lice are transferred to pigeons of different sizes they rapidly evolve differences in body size that are correlated with host size. These size differences trigger mechanical mating isolation between lice that are locally adapted to the different sized hosts. Size differences among lice also influence the outcome of competition between males for access to females. Thus, body size directly mediates reproductive isolation through its influence on both inter-sexual compatibility and intra-sexual competition. Our results confirm that divergent natural selection acting on a single phenotypic trait can cause reproductive isolation to emerge from a single natural population in real time.
Would conserving natural land cover in landscapes conserve biodiversity?
Authors: De Camargo Rafael X. , Currie David J.
Published: October 2018

It is generally accepted that protecting natural land cover would protect biodiversity. This would only be true as a general statement if the relationship between richness and natural land cover were monotonic positive and scale- and method-independent. Assertions about habitat loss causing species losses often come from broad-scale assessment of richness (e.g., from range maps) combined with patterns of natural habitat conversion. Yet, the evidence about species loss following habitat loss or fragmentation typically comes from fine-scale experiments. Here, we test whether broad-extent relationships between avian species richness and natural land cover are independent of: 1) whether species distribution data come from systematic censuses (atlases) versus range maps, and 2) the grain size of the analysis. We regressed census-based and range map-based avian species richness against the proportion of natural land cover and temperature. Censused richness at the landscape level was obtained from Breeding Bird Atlases of Ontario and New York State. Range-map richness derived from BirdLife International range maps. Comparisons were made across different spatial grains: 25-km2, 100-km2, and 900-km2. Over regional extents, range-map richness relates strongly to temperature, irrespective of spatial grain. Censused species richness relates to temperature less strongly. Range-map richness is a negative function of the proportion of natural land cover, while realized richness is a peaked function. The two measures of richness are not monotonically related to each other. In conclusion, the data do not indicate that, in practice, landscapes with greater natural land cover in southern Ontario or in New York State have higher species richness. Moreover, different data types can lead to dramatically different relationships between richness and natural land cover. We argue that the argument that habitat loss is the main driver of species loss has become a panchreston. It may be misguiding conservation biology strategies by focusing on a threat that is too general to be usefully predictive.
Drinking motives and alcohol use among college students with the alcohol flush reaction
Authors: Oh Sarah Soyeon , Ju Yeong Jun , Lee San , Jang Sung-in , Park Eun-Cheol
Published: October 2018

Background

This study investigated the relationship between drinking motives and alcohol use among a nationally representative sample of college students with the alcohol flush reaction (AFR). We surveyed and analyzed the data of 2,245 male and 2,326 female college students in a nationally representative sample of 82 colleges in South Korea.

Methods

Of our study population, 725 males (32.3%) and 812 females (34.9%) reported to currently suffering from AFR. Multiple regression analysis was used to identify the association between drinking motives and drinking behavior, measured via the AUDIT.

Results

Relative to drinking because of peer pressure, students drinking for pleasure (males: β = 2.622,p<.0001; females β = 2.769,p<.0001) or stress/depression (males: β = 2.479,p<.0001; females β = 2.489,p<.0001) had higher AUDIT scores. Among students drinking because of stress/depression, seniors (males: β = 3.603,p<.0001; females: β = 3.791,p= 0.000), smokers (males: β = 1.564,p= 0.000; females β = 1.816,p= 0.007) and/or liberal arts students (males: β = 6.1136,p<.0001; females β = 4.2105,p<.0001) consumed more alcohol than their peers. Relative to conformity motives, enhancement and coping motives were found to have a greater influence on alcohol intake among college students with alcohol flush reaction.

Conclusion

Considering that the flush reaction can occur in AFR individuals after just one sip of wine, our results show that educators and policymakers must take action to deal with this problem.
CLEESE: An open-source audio-transformation toolbox for data-driven experiments in speech and music cognition
Authors: Burred Juan José , Ponsot Emmanuel , Goupil Louise , Liuni Marco , Aucouturier JJ
Published: October 2018

Over the past few years, the field of visual social cognition and face processing has been dramatically impacted by a series of data-driven studies employing computer-graphics tools to synthesize arbitrary meaningful facial expressions. In the auditory modality, reverse correlation is traditionally used to characterize sensory processing at the level of spectral or spectro-temporal stimulus properties, but not higher-level cognitive processing of e.g. words, sentences or music, by lack of tools able to manipulate the stimulus dimensions that are relevant for these processes. Here, we present an open-source audio-transformation toolbox, called CLEESE, able to systematically randomize the prosody/melody of existing speech and music recordings. CLEESE works by cutting recordings in small successive time segments (e.g. every successive 100 milliseconds in a spoken utterance), and applying a random parametric transformation of each segment’s pitch, duration or amplitude, using a new Python-language implementation of the phase-vocoder digital audio technique. We present here two applications of the tool to generate stimuli for studying intonation processing of interrogative vs declarative speech, and rhythm processing of sung melodies.
Rabies prevention and control practice and associated factors among dog owners in Aksum town and Laelay-Machew district, north Ethiopia: community based comparative cross-sectional study
Authors: Gebrezgiher Letebrhan , Berhe Gebretsadik , Belay Aregawi Gebreyesus , Adisu Alefech
Published: October 2018

Background

Rabies is nearly 100% fatal zoonotic disease. One thousand seven hundred suspected rabies exposures reported in north Ethiopia, Tigray region in 2017, which has the highest rabies prevalence from Ethiopia. Almost half of them were from Central zone only. Of these 38% were in Aksum town and Laelay-Machew. Though Rabies exposure is prevalent in Tigray, there is scanty information on rabies prevention and control practices among dog owners. Thus, this deals with rabies prevention and control practice and associated factors among dog owners.

Methods and materials

Comparative community based cross-sectional study was conducted in Aksum town and Laelay-Machew district from March 01 to 20, 2018. A multi stage sampling was employed to recruit 558 households. Data were collected via structured and pretested questionnaire. Data were entered into Epi_info_7 and then exported to SPSS_20 for analysis. Both descriptive and inferential analysis was done with 95% confidence intervals at p value of 5% for the final model.

Result

The overall prevalence of poor rabies prevention and control practice was 56% [95%CI (50, 61.9)] in urban and 62% [95% CI (57.2, 67.7)] in rural dog owners. In urban; being government employee [AOR (95%CI) = 0.35 (0.13, 0.94)], private employee [AOR (95%CI) =0.39(0.16, 0.97)] and having poor attitude [(AOR (95%CI) =1.84 (1.04, 3.25)] were significantly associated with outcome variable. Whereas in rural dwellers; having no formal education [AOR (95%CI)=6.41(1.1,38.6)], poor attitude [AOR (95%CI)= 2.19 (1.18,4.05)], having one dog [AOR (95%CI)=3.31(1.34,8.15)], travel ≥30 minute to get vaccine [AOR (95%CI)= 4.26 (2.14,8.47]), no history of dog bite exposure [AOR (95%CI)= 4.16(1.49,11.6)] and neighbors as their source of information [AOR (95%CI) =3.64 (1.31,10.1)] have statistical significance with the outcome variable.

Conclusion and Recommendation

The prevalence of poor rabies prevention and control practice was higher among rural dog owners. Thus; interventions should be implemented both to urban and rural residents based on the identified findings so as to promote effective rabies prevention and control activities.
Evidence for strong fixation bias at 4-fold degenerate sites across genes in the great tit genome
Authors: Gossmann Toni I. , Bockwoldt Mathias , Diringer Lilith , Schwarz Friedrich , Schumann Vic-Fabienne
Published: October 2018

It is well established that GC content varies across the genome in many species and that GC biased gene conversion, one form of meiotic recombination, is likely to contribute to this heterogeneity. Bird genomes provide an extraordinary system to study the impact of GC biased gene conversion owed to their specific genomic features. They are characterised by a high karyotype conservation with substantial heterogeneity in chromosome sizes, with up to a dozen large macrochromosomes and many smaller microchromosomes common across all bird species. This heterogeneity in chromosome morphology is also reflected by other genomic features, such as smaller chromosomes being gene denser, more compact and more GC rich relative to their macrochromosomal counterparts - illustrating that the intensity of GC biased gene conversion varies across the genome. Here we study whether it is possible to infer heterogeneity in GC biased gene conversion rates across the genome using a recently published method that accounts for GC biased gene conversion when estimating branch lengths in a phylogenetic context. To infer the strength of GC biased gene conversion we contrast branch length estimates across the genome both taking and not taking non-stationary GC composition into account. Using simulations we show that this approach works well when GC fixation bias is strong and note that the number of substitutions along a branch is consistently overestimated when GC biased gene conversion is not accounted for. We use this predictable feature to infer the strength of GC dynamics across the great tit genome by applying our new test statistic to data at 4-fold degenerate sites from three bird species - great tit, zebra finch and chicken - three species that are among the best annotated bird genomes to date. We show that using a simple one-dimensional binning we fail to capture a signal of fixation bias as observed in our simulations. However, using a multidimensional binning strategy, we find evidence for heterogeneity in the strength of fixation bias, including AT fixation bias. This highlights the difficulties when combining sequence data across different regions in the genome.
Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor binding head domains
Authors: Turner Hannah L. , Pallesen Jesper , Lang Shanshan , Bangaru Sandhya , Urata Sarah , Li Sheng , Cottrell Christopher A. , Bowman Charles A. , Crowe James E. , Wilson Ian A. , Ward Andrew B.
Published: October 2018

Seasonal influenza virus infections can cause significant morbidity and mortality, but the threat from emergence of a new pandemic influenza strain might have potentially even more devastating consequences. As such, there is intense interest in isolating and characterizing potent neutralizing antibodies that target the hemagglutinin (HA) viral surface glycoprotein. Here, we use cryo-electron microscopy to decipher the mechanism of action of a potent HA head-directed monoclonal antibody bound to an influenza H7 HA. The epitope of the antibody is not solvent accessible in the compact, pre-fusion conformation that typifies all HA structures to date. Instead, the antibody binds between HA head protomers to an epitope that must be partly or transiently exposed in the pre-fusion conformation. The “breathing” of the HA protomers is implied by the exposure of this epitope, which is consistent with metastability of class I fusion proteins. This structure likely therefore represents an early structural intermediate in the viral fusion process. Understanding the extent of transient exposure of conserved neutralizing epitopes also may lead to new opportunities to combat influenza that have not been appreciated previously.

Author Summary

A transiently exposed epitope on influenza H7 hemagglutinin represents a new target for neutralizing antibodies.
Decoding voluntary movements and postural tremor based on thalamic LFPs for closed-loop stimulation for essential tremor
Authors: Tan Huiling , Debarros Jean , Pogosyan Alek , Aziz Tipu Z. , Huang Yongzhi , Wang Shouyan , Timmermann Lars , Visser-Vandewalle Veerle , Pedrosa David J. , Green Alexander L. , Brown Peter
Published: October 2018

High frequency deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET. We recorded LFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements in seven ET patients during temporary lead externalization after the first surgery for DBS when they performed different voluntary upper limb movements and in nine more patients during the surgery, when they were asked to lift their arms to trigger postural tremor. We show that both voluntary movements and postural tremor can be decoded based on features extracted from thalamic LFPs using a machine learning based binary classifier. This information can be used to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes.
Sensory experience controls dendritic structure and behavior by distinct pathways involving degenerins
Authors: Inberg Sharon , Iosilevskii Yael , Calatayud-Sanchez Alba , Setty Hagar , Oren-Suissa Meital , Krieg Michael , Podbilewicz Benjamin
Published: October 2018

Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use theCaenorhabditis elegans’arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity- dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli.

Significance Statement

Little is known about how neuronal activity and sensory experience influence the structure and function of dendritic trees. Furthermore, how dendritic structures affect neuronal functions remains to a large extent a mystery despite their fundamental functions in neuronal sensory and synaptic activities in health and diseases. Here we show that complex dendritic trees of the nociceptive and proprioceptive PVD neuron inC. elegansdisplay a dynamic nature where they undergo pronounced dendritic modifications during adulthood. These modifications are determined by the received sensory signals generated by conspecific worms on the plate or by inert glass beads. We revealed functions for degenerins/Epithelial sodium channels in this phenomenon, using genetic and optogenetic approaches. We found that the degenerin MEC-10 acts cell autonomously to translate environmental mechanical signals into structural and functional modifications in the PVD.
Caring without sharing: Meta-analysis 2.0 for massive genome-wide association studies
Authors: Pourshafeie Armin , Bustamante Carlos D. , Prabhu Snehit
Published: October 2018

Genome-wide association studies have been effective at revealing the genetic architecture of simple traits. Extending this approach to more complex phenotypes has necessitated a massive increase in cohort size. To achieve sufficient power, participants are recruited across multiple collaborating institutions, leaving researchers with two choices: either collect all the raw data at a single institution or rely on meta-analyses to test for association. In this work, we present a third alternative. Here, we implement an entire GWAS workflow (quality control, population structure control, and association) in a fully decentralized setting. Our iterative approach (a) does not rely on consolidating the raw data at a single coordination center, and (b) does not hinge upon large sample size assumptions at each silo. As we show, our approach overcomes challenges faced by meta-studies when it comes to associating rare alleles and when case/control proportions are wildly imbalanced at each silo. We demonstrate the feasibility of our method in cohorts ranging in size from 2K (small) to 500K (large), and recruited across 2 to 10 collaborating institutions.