bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIM34 acts with TRIM5 to restrict HIV and SIV capsids
Authors: Ohainle Molly , Kim Kyusik , Keceli Sevnur , Felton Abby , Campbell Ed , Luban Jeremy , Emerman Michael 
Published: October 2019

AbstractThe HIV-1 capsid protein makes up the core of the virion and plays a critical role in early steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a target for host cell factors that act directly to block infection such as TRIM5 and MxB. Several host proteins also play a role in facilitating infection, including in the protection of HIV-1 capsid from recognition by host cell restriction factors. Through an unbiased screening approach, called HIV-CRISPR, we show that the Cyclophilin A-binding deficient P90A HIV-1 capsid mutant becomes highly-sensitized to TRIM5alpha restriction in IFN-treated cells. Further, the CPSF6-binding deficient, N74D HIV-1 capsid mutant is sensitive to restriction mediated by human TRIM34, a close paralog of the well-characterized HIV restriction factor TRIM5. This restriction occurs at the step of reverse transcription, is independent of interferon stimulation and limits HIV-1 infection in key target cells of HIV infection including CD4+ T cells and monocyte-derived dendritic cells. TRIM34 restriction requires TRIM5alpha as knockout or knockdown of TRIM5alpha results in a loss of antiviral activity. TRIM34 can also restrict some SIV capsids. Through immunofluorescence studies, we show that TRIM34 and TRIM5alpha colocalize to cytoplasmic bodies and are more frequently observed to be associated with infecting N74D capsids than with WT capsids. Our results identify TRIM34 as an HIV-1 CA-targeting restriction factor and highlight the potential role for heteromultimeric TRIM interactions in contributing restriction of HIV-1 infection in human cells.
Revisiting australianectocarpus subulatus(phaeophyceae) from the hopkins river: distribution, abiotic environment, and associated microbiota
Authors: Dittami Simon M. , Peters Akira F. , West John , Cariou Thierry , KleinJan Hetty , Burgunter-Delamare Bertille , Prechoux Aurelie , Egan Suhelen , Boyen Catherine 
Published: October 2019

AbstractEctocarpusis a genus of common marine brown algae. In 1995 a strain ofEctocarpuswas isolated from Hopkins River Falls, Victoria, Australia, constituting one of few available freshwater or nearly freshwater brown algae, and the only one belonging toEctocarpus. It has since been used as a model to study acclimation and adaptation to low salinities and the role of its microbiota in these processes. However, little is known about the distribution of this strain or whether it represents a stable population. Furthermore, its microbiota may have been impacted by the long period of cultivation.Twenty-two years after the original finding we searched forEctocarpusin the Hopkins River and surrounding areas. We found individuals with ITS andcox1 sequences identical to the original isolate at three sites upstream of Hopkins River Falls, but none at the original isolation site. The osmolarity of the water at these sites ranged from 74-170 mOsmol, and it was rich in sulfate. The diversity of bacteria associated with the algaein situwas approximately one order of magnitude higher than in previous studies of the original laboratory culture, and 95 alga-associated bacterial strains were isolated fromE. subulatusfilaments on site. In particular,Planctomyceteswere abundantin situbut rare in the laboratory-cultured strain.Our results confirm thatE. subulatushas stably colonized the Hopkins River, and the newly isolated algal and bacterial strains offer new possibilities to study the adaptation ofEctocarpusto low salinity and its interactions with its microbiome.
ZCWPW1 is recruited to recombination hotspots by PRDM9, and is essential for meiotic double strand break repair
Authors: Wells Daniel , Bitoun Emmanuelle , Moralli Daniela , Zhang Gang , Hinch Anjali Gupta , Donnelly Peter , Green Catherine , Myers Simon R 
Published: October 2019

AbstractDuring meiosis, homologous chromosomes pair (synapse) and recombine, enabling balanced segregation and generating genetic diversity. In many vertebrates, recombination initiates with double-strand breaks (DSBs) within hotspots where PRDM9 binds, and deposits H3K4me3 and H3K36me3. However, no protein(s) recognising this unique combination of histone marks have yet been identified.We identifiedZcwpw1, which possesses H3K4me3 and H3K36me3 recognition domains, as highly co-expressed withPrdm9. Here, we show that ZCWPW1 has co-evolved with PRDM9 and, in human cells, is strongly and specifically recruited to PRDM9 binding sites, with higher affinity than sites possessing H3K4me3 alone. Surprisingly, ZCWPW1 also recognizes CpG dinucleotides, including within many Alu transposons.MaleZcwpw1homozygous knockout mice show completely normal DSB positioning, but persistent DMC1 foci at many hotspots, particularly those more strongly bound by PRDM9, severe DSB repair and synapsis defects, and downstream sterility. Our findings suggest a model where ZCWPW1 recognition of PRDM9-bound sites on either the homologous, or broken, chromosome is critical for synapsis, and hence fertility.Graphical Abstract LegendIn humans and other species, recombination is initiated by double strand breaks at sites bound by PRDM9. Upon binding, PRDM9 deposits the histone marks H3K4me3 and H3K36me, but the functional importance of these marks has remained unknown. Here, we show that PRDM9 recruits ZCWPW1, a reader of both these marks, to its binding sites genome-wide. ZCWPW1 does not help position the breaks themselves, but is essential for their downstream repair and chromosome pairing, and ultimately meiotic success and fertility in mice.
A dormant sub-population expressing interleukin-1 receptor characterises anti-estrogen resistant ALDH+ breast cancer stem cells
Authors: Sarmiento-Castro Aida , Caamaño-Gutiérrez Eva , Sims Andrew H. , James Mark I. , Santiago-Gómez Angélica , Eyre Rachel , Clark Christopher , Brown Martha E. , Brooks Michael D. , Hayes Daniel F. , Wicha Max S. , Howell Sacha J. , Clarke Robert B. , Simões Bruno M. 
Published: October 2019

SUMMARYEstrogen receptor-positive (ER+) breast tumours are often treated with anti-estrogen (AE) therapies but frequently develop resistance. Cancer Stem Cells (CSCs) with high aldehyde dehydrogenase (ALDH) activity (ALDH+ cells) are reported to be enriched following AE treatment. Here we perform in vitro and in vivo functional CSC assays and gene expression analysis to characterise the ALDH+ population in AE resistant metastatic patient samples and an ER+ cell line. We show that the IL1β signalling pathway is activated in ALDH+ cells and data from single cells reveals that AE treatment selects for IL1R1-expressing ALDH+ cells. Importantly, we demonstrate that increased expression of IL1R1 is observed in the tumours of patients treated with AE therapy and predicts for treatment failure. Single-cell gene expression analysis revealed that at least 2 sub-populations exist within the ALDH+ population, one proliferative and one quiescent. Following AE therapy, the quiescent ALDH+IL1R1+ population is expanded, which suggests CSC dormancy as an adaptive strategy that facilitates treatment resistance. Supporting this, analysis of AE resistant dormant tumours reveals significantly increased expression of ALDH1A1, ALDH1A3 and IL1R1 genes. Thus, we propose that targeting of ALDH+IL1R1+ cells will reverse AE resistance, including in patients with minimal residual disease.
Mapping sequences can bias population receptive field estimates
Authors: Infanti Elisa , Schwarzkopf D. Samuel 
Published: October 2019

AbstractPopulation receptive field (pRF) modelling is a common technique for estimating the stimulus-selectivity of populations of neurons using neuroimaging. Here, we aimed to address if pRF properties estimated with this method depend on the spatio-temporal structure and the predictability of the mapping stimulus. We mapped the polar angle preference and tuning width of voxels in visual cortex (V1-V4) of healthy, adult volunteers. We compared sequences orderly sweeping through the visual field or jumping from location to location employing stimuli of different width (45° vs 6°) and cycles of variable duration (8s vs 60s). While we did not observe any systematic influence of stimulus predictability, the temporal structure of the sequences significantly affected tuning width estimates. Ordered designs with large wedges and short cycles produced systematically smaller estimates than random sequences. Interestingly, when we used small wedges and long cycles, we obtained larger tuning width estimates for ordered than random sequences. We suggest that, ordered and random mapping protocols show different susceptibility to other design choices such as stimulus type and duration of the mapping cycle and can produce significantly different pRF results.
A complex virome that includes two distinct emaraviruses is associated to virus-like symptoms in Camellia japonica
Authors: Peracchio C. , Forgia M. , Chiapello M. , Vallino M. , Turina M. , Ciuffo M. 
Published: October 2019

SUMMARYCamellia japonica plants manifesting a complex and variable spectrum of viral symptoms like chlorotic ringspots, necrotic rings, yellowing with necrotic rings, yellow mottle, leaves and petals deformations, flower color-breaking were studied since 1940 essentially through electron microscopic analyses; however, a strong correlation between symptoms and one or more well characterized viruses was never verified. In this work samples collected from symptomatic plants were analyzed by NGS technique and a complex virome composed by viruses members of the Betaflexiviridae and Fimoviridae families was identified. In particular, the genomic fragments typical of the emaravirus group were organized in the genomes of two new emaraviruses species, tentatively named Camellia japonica associated emaravirus 1 and 2. They are the first emaraviruses described in camellia plants and were always found solely in symptomatic plants. On the contrary, in both symptomatic and asymptomatic plants, we detected five betaflexiviruses isolates that, based on aa identitiy comparisons, can be classified in two new putative species called Camellia japonica associated betaflexivirus 1 and Camellia japonica associated betaflexivirus 2. Together with other recently identified betaflexiviruses associated to Camellia japonica disease, the betaflexiviruses characterized in this study show an unusual hyper-conservation of the coat protein at aminoacidic level.
Chromatin-based techniques map DNA interaction landscapes in psoriasis susceptibility loci and highlightKLF4as a target gene in 9q31
Authors: Ray-Jones Helen , Duffus Kate , McGovern Amanda , Martin Paul , Shi Chenfu , Hankinson Jenny , Gough Oliver , Yarwood Annie , Morris Andrew P , Adamson Antony , Taylor Christopher , Ding James , Gaddi Vasanthi Priyadarshini , Fu Yao , Gaffney Patrick , Orozco Gisela , Warren Richard B , Eyre Steve 
Published: October 2019

AbstractGenome-wide association studies (GWAS) have uncovered many genetic risk loci for psoriasis, yet many remain uncharacterised in terms of the causal gene and their biological mechanism in disease. Here, we use a disease-focused Capture Hi-C experiment to link psoriasis-associated variants with their target genes in psoriasis-relevant cell lines (HaCaT keratinocytes and My-La CD8+ T cells). We confirm previously assigned genes, suggest novel candidates and provide evidence for complexity at psoriasis GWAS loci. In the 9q31 risk locus we combine further epigenomic evidence to demonstrate how the psoriasis association forms a functional interaction with the distant (>500 kb)KLF4gene. We use CRISPR activation coupled with RNA-seq to demonstrate how activation of psoriasis-associated enhancers upregulatesKLF4in HaCaT cells. Our study design provides a robust pipeline for following up on GWAS disease-associated variants, paving the way for functional translation of genetic findings into clinical benefit.
Tissue- and population-level microbiome analysis of the wasp spiderArgiope bruennichiidentifies a novel dominant bacterial symbiont
Authors: Sheffer Monica M. , Uhl Gabriele , Prost Stefan , Lueders Tillmann , Urich Tim , Bengtsson Mia M. 
Published: October 2019

AbstractMany ecological and evolutionary processes in animals depend upon microbial symbioses. In spiders, the role of the microbiome in these processes remains mostly unknown. We compared the microbiome between populations, individuals, and tissue types of a range-expanding spider, using 16S rRNA gene sequencing. Our study is one of the first to go beyond targeting known endosymbionts in spiders, and characterizes the total microbiome across different body compartments (leg, prosoma, hemolymph, book lungs, ovaries, silk glands, midgut, and fecal pellets). Overall, the microbiome differs significantly between populations and individuals, but not between tissue types. The microbiome of the wasp spiderArgiope bruennichifeatures a novel dominant bacterial symbiont, which is abundant in every tissue type in spiders from geographically distinct populations, and present in offspring. The novel symbiont is affiliated with theTenericutes, but has low sequence identity (<85%) to all previously named taxa, suggesting that the novel symbiont represents a new bacterial clade. Its presence in offspring implies that it is vertically transmitted. Our results shed light on the processes which shape microbiome differentiation in this species, and raise several questions about the implications of the novel dominant bacterial symbiont on the biology and evolution of its host.
mRNA structural dynamics shape Argonaute-target interactions
Authors: Ruijtenberg Suzan , Sonneveld Stijn , Cui Tao Ju , Logister Ive , de Steenwinkel Dion , Xiao Yao , MacRae Ian J. , Joo Chirlmin , Tanenbaum Marvin E. 
Published: October 2019

AbstractSmall RNAs (such as miRNAs, siRNAs and piRNAs) regulate protein expression in a wide variety of biological processes and play an important role in cellular function, development and disease. Association of small RNAs with Argonaute (AGO) family proteins guide AGO to target RNAs, generally resulting in target silencing through transcriptional silencing, translational repression or mRNA degradation. Here we develop a live-cell single-molecule imaging assay to simultaneously visualize translation of individual mRNA molecules and their silencing by human AGO2-siRNA complexes. We find that siRNA target sites are commonly maskedin vivoby RNA secondary structures, which inhibit AGO2-target interactions. Translating ribosomes unmask AGO2 binding sites, stimulating AGO2-target interactions and promoting mRNA degradation. Using a combination of mathematical modeling and experiments, we find that mRNA structures are highly heterogeneous and continuously refolding. We show that structural dynamics of mRNAs shape AGO2-target recognition, which may be a common feature controlling mRNA-protein interactions.
Whole-genome duplication and host genotype affect rhizosphere microbial communities
Authors: Ponsford Julian C. B. , Hubbard Charley J. , Harrison Joshua G. , Maignien Lois , Buerkle C. Alex , Weinig Cynthia 
Published: October 2019

AbstractThe composition of complex microbial communities found in association with plants is influenced in part by host phenotype. Yet, the salient genetic architecture is often unknown. Genome duplication events are common in the evolutionary history of plants, influence many important plant traits, and may affect associated microbial communities. Using experimentally induced whole genome duplication (WGD), we tested the effect of WGD on rhizosphere bacterial communities in Arabidopsis thaliana. Specifically, we performed 16S rRNA amplicon sequencing to characterize differences between microbiomes associated with specific host genotypes (Columbia vs. Landsberg) and ploidy levels (diploid vs. tetraploid). We modeled abundances of individual bacterial taxa by utilizing a hierarchical Bayesian framework, based on the Dirichlet and multinomial distributions. We found that host genotype and host ploidy level affected rhizosphere community composition, for instance, the microbiome of the tetraploid Columbia genotype differed from that of other host genotypes. We then tested to what extent microbiomes derived from a given host genotype or ploidy level affected plant performance by inoculating sterile seedlings of each genotype with microbial communities harvested from a prior generation. We found a negative effect of the tetraploid Columbia microbiome on growth of all four plant genotypes. The findings suggest that while both host genotype and ploidy affect microbial community assembly, bacterial communities found in association with only some host genotypes may affect growth of subsequent plant generations.ImportancePlants influence the composition of their associated microbial communities; yet the underlying host genetic factors are often unknown. Genome duplication events are common in the evolutionary history of plants and affect many plant traits, including the quality and quantity of compounds exuded into the root zone, which can affect root-bound microbes. In Arabidopsis thaliana, we characterized how whole-genome duplication affected the composition of rhizosphere bacterial communities, and how bacterial communities associated with two host plant genotypes and ploidy levels affected subsequent plant growth. We observed an interaction in which ploidy level within one host genotype affected both bacterial community composition and function. This research reveals how genome duplication, a widespread genetic feature of both wild and crop plant species, influences the coexistence of bacterial taxa and affects plant growth.
HD Spot: Interpretable Deep Learning Classification of Single Cell Transcript Data
Authors: Prince Eric , Hankinson Todd C. 
Published: October 2019

ABSTRACTHigh throughput data is commonplace in biomedical research as seen with technologies such as single-cell RNA sequencing (scRNA-seq) and other Next Generation Sequencing technologies. As these techniques continue to be increasingly utilized it is critical to have analysis tools that can identify meaningful complex relationships between variables (i.e., in the case of scRNA-seq: genes) in a way such that human bias is absent. Moreover, it is equally paramount that both linear and non-linear (i.e., one-to-many) variable relationships be considered when contrasting datasets. HD Spot is a deep learning-based framework that generates an optimal interpretable classifier a given high-throughput dataset using a simple genetic algorithm as well as an autoencoder to classifier transfer learning approach. Using four unique publicly available scRNA-seq datasets with published ground truth, we demonstrate the robustness of HD Spot and the ability to identify ontologically accurate gene lists for a given data subset. HD Spot serves as a bioinformatic tool to allow novice and advanced analysts to gain complex insight into their respective datasets enabling novel hypotheses development.
Resveratrol attenuates high-fat diet-induced obesity and the aging-related sarcopenia mitochondrial dysfunction in skeletal muscle
Authors: Bai Chyi-Huey , Alizargar Javad , Wu Jia-Ping 
Published: October 2019

AbstractSarcopenic obesity is a progressive loss of skeletal muscle mass and strength with increases in adiposity. The aim of this study was to investigate the effects of resveratrol on obesity or sarcopenia to potential therapy risk for skeletal muscle declines in physical function. C57BL/6J male mice were fed either a high-fat diet for 4 weeks and resveratrol (low-, middle-, and high-dose) for 8 weeks to express the obesity effect. Samp8 mice sarcopenia skeletal muscle functional deterioration expressed an age-associated decline. Resveratrol (150 mg/Kg BW, daily) was administered by oral gavage two times a week one month of the experimental period. Exercise training based on adaptations in the muscle is training twice a week for 4 weeks. The skeletal muscles from mice in each group were analyzed by H&E staining, TUNEL and western blot analysis to determine mitochondrial function expression, apoptosis and relative fibrosis signaling. Results of the present study indicate that resveratrol in obesity skeletal muscle is linked to an increase in the expression of mitochondrial function involved in Bcl-2 and PI3K/AKT. On the other hand, resveratrol attenuates sarcopenia Samp8 mice, the age-related loss of skeletal muscle mass and mitochondrial function involved in Bad, caspase 3 and IL-6/ERK1. However, exercise training not find a significant difference in sarcopenia skeletal muscles SAMP8 mice. Exercise training didn’t induce sarcopenia skeletal muscle hypertrophy in sarcopenic SAMP8 mice. Therefore, we suggest that resveratrol as a therapeutic potential in the combination of sarcopenia and obesity, the state called sarcopenic obesity.
NHR-8 regulated P-glycoproteins uncouple xenobiotic stress resistance from longevity in chemosensory C. elegans mutants
Authors: Guerrero Gabriel A. , Derisbourg Maxime J. , Wester Laura E. , Gordia Marco , Dinort J. Eike , Alonso María J. , Hartman Matías D. , Schilling Klara , Mayr Felix A.M.C. , Lu Ryan J. , Benayoun Bérénice A. , Denzel Martin S. 
Published: October 2019

AbstractLongevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene osm-3 were significantly protected from tunicamycin-induced ER stress. While osm-3 lifespan extension is dependent on the key longevity factor DAF-16/FOXO, tunicamycin resistance was not. osm-3 mutants are protected from bacterial pathogens, which is pmk-1 p38 MAP kinase dependent while TM resistance was pmk-1 independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated in osm-3 mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptor nhr-8 was necessary to regulate PGPs and tunicamycin resistance in a cholesterol-dependent fashion. We thus identify a cell-nonautonomous regulation of xenobiotic detoxification and show that separate pathways are engaged to mediate longevity, pathogen resistance, and xenobiotic detoxification in osm-3 mutants.
HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells
Authors: Wang Qi , Tsao Li-Chung , Lv Lei , Xu Yanping , Cheng Liang , Yu Haisheng , Zhang Liguo , Xiong Yue , Su Lishan 
Published: October 2019

AbstractPlasmacytoid dendritic cells (pDCs) are the major source of type I interferons (IFN-I) in rapid response to viral infections, with constitutive expression of interferon regulatory factor 7 (IRF7). HIV-1 expresses several accessory proteins to counteract specific IFN-induced host restriction factors. As one abundant virion-associated protein, HIV-1 Vpr remains enigmatic in enhancing HIV-1 infection via unclear mechanisms. Here we report that Vpr impaired IFN-I induction in pDCs to enhance HIV-1 replication in CD4+ T cells. Blockade of IFN-I signaling abrogated the effect of Vpr on HIV-1 replication. Virion-associated Vpr suppressed IFN-I induction in pDC by TLR7 agonists. Modulation of IFN-I induction by Vpr was genetically dependent on its activity of TET2 degradation. We further demonstrate that Vpr-mediated TET2 degradation reduced expression of IRF7 in pDCs. Finally, degradation of TET2 in pDCs by Vpr reduced the demethylation level of the IRF7 promoter via CXXC5-dependent recruitment. We conclude that HIV-1 Vpr functions to promote HIV-1 replication by suppressing TET2-dependent IRF7 expression and IFN-I induction in pDCs. The Vpr-TET2-IRF7 axis provides a novel therapeutic target to control HIV-1 infection.