bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of single-cell and transcriptome based RNA-seq multilayer network and WGCNA for construction and validation of an immune cell-related prognostic model in clear cell renal cell carcinoma
Authors: Wu Guanlin , Guo Weiming , Zhu Shuai , Fan Gang 
Published: October 2021

AbstractClear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer (RCC). The increasing incidence and poor prognosis of ccRCC after tumour metastasis makes the study of its pathogenesis extremely important. Traditional studies mostly focus on the regulation of ccRCC by single gene, while ignoring the impact of tumour heterogeneity on disease progression. The purpose of this study is to construct a prognostic risk model for ccRCC by analysing the differential marker genes related to immune cells in the single-cell database for providing help in clinical diagnosis and targeted therapy. Single-cell data and ligand-receptor relationship pair data were downloaded from related publications, and ccRCC phenotype and expression profile data were downloaded from TCGA and CPTAC. The DEGs and marker genes of the immune cell were combined and then intersected with the ligand-receptor gene data, and the 981 ligand-receptor relationship pairs obtained were intersected with the target gene of the transcription factor afterwards; 7,987 immune cell multilayer network relationship pairs were finally observed. Then, the genes in the network and the genes in TCGA were intersected to obtain 966 genes for constructing a co-expression network. Subsequently, 53 genes in black and magenta modules related to prognosis were screened by WGCNA for subsequent analysis. Whereafter, using the data of TCGA, 28 genes with significant prognostic differences were screened out through univariate Cox regression analysis. After that, LASSO regression analysis of these genes was performed to obtain a prognostic risk scoring model containing 16 genes, and CPTAC data showed that the effectiveness of this model was good. The results of correlation analysis between the risk score and other clinical factors showed that age, grade, M, T, stage and risk score were all significantly different (p < 0.05), and the results of prognostic accuracy also reached the threshold of qualification. Combined with clinical information, univariate and multivariate Cox regression analyses verified that risk score was an independent prognostic factor (p < 0.05). A nomogram constructed based on a predictive model for predicting the overall survival was established, and internal validation performed well. Our findings suggest that the predictive model built based on the immune cells scRNA-seq will enable us to judge the prognosis of patients with ccRCC and provide more accurate directions for basic relevant research and clinical practice.
Speed fluctuations of bacterial replisomes
Authors: Bhat Deepak , Hauf Samuel , Plessy Charles , Yokobayashi Yohei , Pigolotti Simone 
Published: October 2021

AbstractReplisomes are multi-protein complexes that replicate genomes with remarkable speed and accuracy. Despite their importance, their dynamics is poorly characterized, especially in vivo. In this paper, we present an approach to infer the replisome dynamics from the DNA abundance distribution measured in a growing bacterial population. Our method is sensitive enough to detect subtle variations of the replisome speed along the genome. As an application, we experimentally measured the DNA abundance distribution in Escherichia coli populations growing at different temperatures using deep sequencing. We find that the average replisome speed increases nearly five-fold between 17°C and 37°C. Further, we observe wave-like variations of the replisome speed along the genome. These variations correlate with previously observed variations of the mutation rate. We interpret this correlation as a speed–error trade-off in DNA replication. Our approach has the potential to elucidate replication dynamics in E. coli mutants and in other bacterial species.
Discovery of small molecule inhibitors of the PTK7/β-catenin inter-action targeting the Wnt signaling pathway in colorectal cancer
Authors: Ganier Laetitia , Betzi Stéphane , Derviaux Carine , Roche Philippe , Muller Christophe , Hoffer Laurent , Morelli Xavier , Borg Jean-Paul 
Published: October 2021

ABSTRACTSecond cause of death due to cancer worldwide, colorectal cancer (CRC) is a major public health issue. The discovery of new therapeutic targets is thus essential. The pseudokinase PTK7 intervenes in the regulation of the Wnt/β-catenin pathway signaling, in part, through a kinase-domain dependent interaction with the β-catenin protein. PTK7 is overexpressed in CRC; an event associated with metastatic development and reduced survival of non-metastatic patient. In addition, numerous alterations have been identified in CRC inducing constitutive activation of Wnt/β-catenin pathway signaling through β-catenin accumulation. Thus, we thought that targeting PTK7/β-catenin interaction could be of interest for future drug development. In this study, we have developed a NanoBRET™ screening assay recapitulating the interaction between PTK7 and β-catenin to identify compounds able to disrupt this protein-protein interaction. A high-throughput screening allowed us to identify small molecule inhibitors targeting the Wnt pathway signaling and inducing anti-proliferative effect in vitro in CRC cells harboring β-catenin or APC mutations downstream of PTK7. Thus, inhibition of the PTK7/β-catenin interaction could represent, in the future, a new therapeutic strategy to inhibit cell growth dependent on Wnt signaling pathway. Moreover, despite a lack of enzymatic activity of its tyrosine kinase domain, targeting the PTK7 kinase domain-dependent functions appears to be of interest for further therapeutic development.
SustainedRanavirusoutbreak causes mass-mortality and morbidity in imperiled amphibians
Authors: Hartmann Arik M. , Maddox Max L. , Ossiboff Robert J. , Longo Ana V. 
Published: October 2021

AbstractA persistent two-month long outbreak ofRanavirusin a natural community of amphibians contributed to a mass die-off of gopher frog tadpoles(Lithobates capito)and severe disease in striped newts(Notophthalmus perstriatus)in Florida. Ongoing mortality inL. capitoand signs inN. perstriatuscontinued for five weeks after the first observation. Hemorrhagic disease and necrosis were diagnosed from pathological examination ofL. capitotadpoles. We confirmed detection of a Frog Virus 3 (FV3)-likeRanavirusvia quantitative PCR in all species. Our findings highlight the susceptibility of these species toRvand the need for long-term disease surveillance during epizootics.
Association of ocean macroplastic debris with stranded sea turtles in the Central Gulf of Thailand
Authors: Prampramote Jindarha , Boonhoh Worakan , Intongead Sutsiree , Sakornwimol Watchara , Prachamkhai Pimchanok , Sansamur Chalutwan , Hayakijkosol Orachun , Wongtawan Tuempong 
Published: October 2021

ABSTRACTThe impact of macroplastic debris (> 5 mm in size) on marine life is a global concern but is rarely investigated in Thailand. Our objective was to investigate the relationship between stranded sea turtles and macroplastics found in the Central Gulf of Thailand. The turtle (n = 388) stranding record between 2017-2020 was analysed retrospectively to determine their size, species, and interaction with macroplastics. Thereafter, between 2019-2020, macroplastics were collected, from the gastrointestinal (GI) tract of dead turtles and from the beaches where stranded turtles were found. A stereomicroscope was used to visually categorise the macroplastics, and the plastic composition was analysed using a Fourier-transform infrared (FTIR) spectrometer. Green sea turtles (Chelonia mydas) were found to account for the majority of stranded turtles (74%, n = 251), and macroplastics were discovered in 74% of cases of entanglement and ingestion. At the juvenile stage, the stranded turtle was strongly related to macroplastics. Immature turtles were more likely to become entangled than adult turtles. Entangled turtles had a greater survival rate than turtles that had consumed plastic. The plastic fibres were the majority of macroplastics found in the GI tracts (62%, n = 152/244) and on the beach (64%, n = 74/115). Most fibres from GI tracts (83%, n = 126/152) and the beaches (93%, n = 68/74) were identified as the fishing net comprised of polyethylene or polypropylene. We concluded that fishing nets made of polyethylene or polypropylene might be one of the significant causes of sea turtle stranding in the Central Gulf of Thailand, and this issue requires immediate resolution.
Synchronous seasonality in the gut microbiota of wild wood mouse populations
Authors: Marsh K.J. , Raulo A.M. , Brouard M. , Troitsky T. , English H. M. , Allen B. , Raval R. , Webster J.P. , Knowles S. C. L. 
Published: October 2021

AbstractThe gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, what factors drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood.Here, we use a multi-population dataset from a common rodent species (the wood mouse,Apodemus sylvaticus), to test whether a consistent set of ‘core’ gut microbes is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations.Between 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild UK mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species.Although broadly similar at high taxonomic levels and despite being only 50km apart, the two wild populations did not share a single bacterial amplicon sequence variant (ASV). Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite strong taxonomic divergence in the microbiota, the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, seasonal convergence in the gut microbiota among individuals occurred in late winter/early spring.These findings reveal highly repeatable seasonal gut microbiota dynamics across distinct populations of this species, despite divergent taxa being involved. Providing a platform for future work to understand the drivers and functional implications of such predictable seasonal microbiome restructuring, including whether it might provide the host with adaptive seasonal phenotypic plasticity.
Food or physics: plankton communities structured across Gulf of Alaska eddies
Authors: Kroeger Caitlin , Gentemann Chelle , García-Reyes Marisol , Batten Sonia , Sydeman William 
Published: October 2021

AbstractOceanic features, such as mesoscale eddies that entrap and transport water masses, create heterogeneous seascapes to which biological communities may respond. To date, however, our understanding of how internal eddy dynamics influence plankton community structuring is limited by sparse sampling of eddies and their associated biotic communities. In this paper, we used 10 years of archived Continuous Plankton Recorder (CPR) data (2002-2013) associated with 9 mesoscale eddies in the Northeast Pacific/Gulf of Alaska to test the hypothesis that eddy origin and rotational direction determines the structure and dynamics of entrained plankton communities. Using generalized additive models and accounting for confounding factors (e.g., timing of sampling), we found peak diatom abundance within both cyclonic and anticyclonic eddies near the eddy edge. Zooplankton abundances, however, varied with distance to the eddy center/edge by rotational type and eddy life stage, and differed by taxonomic group. For example, the greatest abundance of small copepods was found near the center of anticyclonic eddies during eddy maturation and decay, but near the edge of cyclonic eddies during eddy formation and intensification. Distributions of copepod abundances across eddy surfaces were not mediated by phytoplankton distribution. Our results therefore suggest that physical mechanisms such as internal eddy dynamics exert a direct impact on the structure of zooplankton communities rather than indirect mechanisms involving potential food resources.
Accounting for animal movement improves vaccination strategies against wildlife disease in heterogeneous landscapes
Authors: McClure Katherine M. , Bastille-Rousseau Guillaume , Davis Amy J. , Stengel Carolyn A. , Nelson Kathleen , Chipman Richard B. , Wittemyer George , Abdo Zaid , Gilbert Amy T. , Pepin Kim M. 
Published: October 2021

ABSTRACTOral baiting is used to deliver vaccines to wildlife to prevent, control, and eliminate infectious diseases. A central challenge is how to spatially distribute baits to maximize encounters by target animal populations, particularly in urban and suburban areas where wildlife like raccoons (Procyon lotor) are abundant and baits are delivered along roads. Methods from movement ecology that quantify movement and habitat selection could help to optimize baiting strategies by more effectively targeting wildlife populations across space. We developed a spatially explicit, individual-based model of raccoon movement and oral rabies vaccine seroconversion to examine whether and when baiting strategies that match raccoon movement patterns perform better than currently employed baiting strategies in an oral rabies vaccination zone in greater Burlington, Vermont, USA. Habitat selection patterns estimated from locally radio-collared raccoons were used to parameterize movement simulations. We then used our simulations to estimate raccoon population rabies seroprevalence under currently used baiting strategies (actual baiting) relative to habitat selection-based baiting strategies (habitat baiting). We conducted simulations on the Burlington landscape and artificial landscapes that varied in heterogeneity relative to Burlington in the proportion and patch size of preferred habitats. We found that the benefits of habitat baiting strongly depended on the magnitude and variability of raccoon habitat selection and the degree of landscape heterogeneity within the baiting area. Habitat baiting improved seroprevalence over actual baiting for raccoons characterized as habitat specialists but not for raccoons that displayed weak habitat selection similar to radio-collared individuals—except when baits were delivered off roads where preferred habitat coverage and complexity was more pronounced. In contrast, in artificial landscapes with either more strongly juxtaposed favored habitats and/or higher proportions of favored habitats, habitat baiting performed better than actual baiting, even when raccoons displayed weak habitat preferences and where baiting was constrained to roads. Our results suggest that habitat selection-based baiting could increase raccoon population seroprevalence in urban-suburban areas, where practical, given the heterogeneity and availability of preferred habitat types in those areas. Our novel simulation approach provides a flexible framework to test alternative baiting strategies in multiclass landscapes to optimize bait distribution strategies.
TargetedTshz3deletion in corticostriatal circuit components segregates core autistic behaviors
Authors: Caubit Xavier , Gubellini Paolo , Roubertoux Pierre L. , Carlier Michèle , Molitor Jordan , Chabbert Dorian , Metwaly Mehdi , Salin Pascal , Fatmi Ahmed , Belaidouni Yasmine , Brosse Lucie , Goff Lydia Kerkerian-Le , Fasano Laurent 
Published: October 2021

AbstractWe previously linkedTSHZ3haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatalTshz3deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. We show that in the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABA interneurons, while not in cholinergic interneurons or glial cells. TSHZ3-expressing cells, which are predominantly SCINs in the striatum, represent a low proportion of neurons in the ascending cholinergic projection system. We then characterized two new conditional knockout (cKO) models generated by crossingTshz3flox/floxwithEmx1-Cre(Emx1-cKO) orChat-Cre(Chat-cKO) mice to decipher the respective role of CPNs and SCINs.Emx1-cKOmice show altered excitatory synaptic transmission onto CPNs and plasticity at corticostriatal synapses, with neither cortical neuron loss nor impaired layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior.Chat-cKOmice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.
Enhanced mismatch negativity in harmonic compared to inharmonic sounds
Authors: Quiroga-Martinez D. R. , Basiński K. , Nasielski J. , Tillmann B. , Brattico E. , Cholvy F. , Fornoni L. , Vuust P. , Caclin A 
Published: October 2021

AbstractMany natural sounds have frequency spectra composed of integer multiples of a fundamental frequency. This property, known as harmonicity, plays an important role in auditory information processing. However, the extent to which harmonicity influences the processing of sound features beyond pitch is still unclear. This is interesting because harmonic sounds have lower information entropy than inharmonic sounds. According to predictive processing accounts of perception, this property could produce more salient neural responses due to the brain’s weighting of sensory signals according to their uncertainty. In the present study, we used electroencephalography to investigate brain responses to harmonic and inharmonic sounds commonly occurring in music: piano tones and hi-hat cymbal sounds. In a multi-feature oddball paradigm, we measured mismatch negativity (MMN) and P3a responses to timbre, intensity, and location deviants in listeners with and without congenital amusia—an impairment of pitch processing. As hypothesized, we observed larger amplitudes and earlier latencies (for both MMN and P3a) in harmonic compared to inharmonic sounds. These harmonicity effects were modulated by sound feature. Moreover, the difference in P3a latency between harmonic and inharmonic sounds was larger for controls than amusics. We propose an explanation of these results based on predictive coding and discuss the relationship between harmonicity, information entropy, and precision weighting of prediction errors.
Functional screen of Inflammatory bowel disease genes reveals key epithelial functions
Authors: Ntunzwenimana Jessy Carol , Boucher Gabrielle , Paquette Jean , Gosselin Hugues , Alikashani Azadeh , Morin Nicolas , Beauchamp Claudine , Thauvette Louise , Rivard Marie-Ève , Dupuis Frédérique , Deschenes Sonia , Foisy Sylvain , Latour Frédéric , Lavallée Geneviève , Daly Mark J. , Xavier Ramnik J. ,   the iGenoMed Consortium, Charron Guy , Goyette Philippe , Rioux John D. 
Published: October 2021

ABSTRACTBackgroundGenetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts have been more limited.MethodsWe identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses. Comparing the genes whose expression was modulated by each ORF, as well as the functions enriched within these gene lists, identified ORFs with shared impacts and their putative disease-relevant biological functions.ResultsAnalysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1 and SMAD3 identified functions consistent for what is known for these genes. These analyses also identified two major cluster of genes: Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1 and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses highlight how multiple IBD gene candidates impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota, and demonstrate that DUSP16, acts a regulator of MAPK activity and contributes to mucosal defense, in part via its regulation of the polymeric immunoglobulin receptor, involved in the protection of the intestinal mucosa from enteric microbiota.ConclusionsThis functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell’s transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions. Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology, providing a scientific rationale for a drug development strategy that targets epithelial functions in addition to the current therapies targeting immune functions.