bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate models of animal sex: breaking binaries leads to a better understanding of ecology and evolution
Authors: McLaughlin J. F. , Brock Kinsey M. , Gates Isabella , Pethkar Anisha , Piattoni Marcus , Rossi Alexis , Lipshutz Sara E. 
Published: January 2023

Abstract‘Sex’ is often used to describe a suite of phenotypic and genotypic traits of an organism related to reproduction. However, these traits – gamete type, chromosomal inheritance, physiology, morphology, behavior, etc. – are not necessarily coupled, and the rhetorical collapse of variation into a single term elides much of the complexity inherent in sexual phenotypes. We argue that consideration of ‘sex’ as a constructed category operating at multiple biological levels opens up new avenues for inquiry in our study of biological variation. We apply this framework to three case studies that illustrate the diversity of sex variation, from decoupling sexual phenotypes to the evolutionary and ecological consequences of intrasexual polymorphisms. We argue that instead of assuming binary sex in these systems, some may be better categorized as multivariate and nonbinary. Finally, we conduct a meta-analysis of terms used to describe diversity in sexual phenotypes in the scientific literature to highlight how a multivariate model of sex can clarify, rather than cloud, studies of sexual diversity within and across species. We argue that such an expanded framework of ‘sex’ better equips us to understand evolutionary processes, and that as biologists it is incumbent upon us to push back against misunderstandings of the biology of sexual phenotypes that enact harm on marginalized communities.
Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10-/-mouse model of inflammatory bowel disease
Authors: Armstrong Heather , Rahbari Mandana , Park Heekuk , Sharon David , Thiesen Aducio , Hotte Naomi , Sun Ning , Syed Hussain , Abofayed Hiatem , Wang Weiwei , Madsen Karen , Wine Eytan , Mason Andrew 
Published: January 2023

AbstractBackgroundFollowing viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-I0-/-) model derived from the SvEv mouse, had evidence of increased mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wildtype. MMTV is endemic in several mouse strains as an endogenously encoded betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10-/-model.ResultsViral preparations extracted from IL-10-/-weanling stomachs revealed augmented MMTV load compared to the SvEv wildtype. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4% - 97.3% identity with themtv-1endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTVsaggene cloned from IL-10-/-spleen encoded the MTV-9 superantigen that preferentially activates T cell receptor Vβ-12 subsets, which were expanded in the IL-10-/-versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10-/-splenocytes with amplified interferon-γ production versus the SvEv wildtype. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12 weeks treatment versus placebo. The combination anti-retroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL10-/-mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis.ConclusionsThis study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis.
Pooled CRISPR screening of high-content cellular phenotypes by ghost cytometry
Authors: Tsubouchi Asako , An Yuri , Kawamura Yoko , Yanagihashi Yuichi , Murata Yuri , Teranishi Kazuki , Ishiguro Soh , Aburatani Hiroyuki , Yachie Nozomu , Ota Sadao 
Published: January 2023

AbstractFast enrichment of cells based on morphological information remains a challenge, limiting genome-wide perturbation screening for diverse high-content phenotypes of cells. Here we show that multi-modal ghost cytometry-based cell sorting is applicable to fast pooled CRISPR screening for both fluorescence and label-free high-content phenotypes of millions of cells. By employing the high-content cell sorter in the fluorescence mode, we enabled the genome-wide CRISPR screening of genes that affect NF-κB nuclear translocation. Furthermore, by employing the multi-parametric, label-free mode, we performed the large-scale screening to identify a gene involved in macrophage polarization. Especially the label-free platform can enrich target phenotypes without invasive staining, preserving untouched cells for downstream assays and unlocking the potential to screen for the cellular phenotypes even when suitable markers are lacking.One-Sentence SummaryMachine vision-based cell sorter enabled genome-wide perturbation screens for high-content cell phenotypes even without labeling
Neural tuning instantiates prior expectations in the human visual system
Authors: Harrison William J , Bays Paul M , Rideaux Reuben 
Published: January 2023

ABSTRACTPerception is often modelled as a process of active inference, whereby prior expectations are combined with noisy sensory measurements to estimate the structure of the world. This mathematical framework has proven critical to understanding perception, cognition, motor control, and social interaction. While theoretical work has shown how priors can be computed from environmental statistics, their neural instantiation could be realised through multiple competing encoding schemes. Using a data-driven approach, here we extract the brain’s representation of visual orientation and compare this with simulations from different sensory coding schemes. We found that the tuning of the human visual system is highly conditional on stimulus-specific variations in a way that is not predicted by previous proposals. We further show that the adopted encoding scheme effectively embeds an environmental prior for natural image statistics within the sensory measurement, providing the functional architecture necessary for optimal inference in the earliest stages of cortical processing.
COVID-19-related burnout reduces COVID-19 vaccination intention in cardiac patients: a cross-sectional study in Greece
Authors: Galanis Petros , Katsiroumpa Aglaia , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Kaitelidou Daphne 
Published: January 2023

AbstractBackgroundNew SARS-CoV-2 variants have emerged and COVID-19 is still a public health issue, especially for vulnerable groups such as people with chronic medical conditions.ObjectiveTo investigate the impact of COVID-19-related burnout on COVID-19 vaccination intention in cardiac patients. Moreover, we investigated other possible demographic and psychological predictors of vaccination intention in cardiac patients.MethodsWe conducted a cross-sectional study in Greece using a convenience sample. Data collection was performed from 20 November 2022 to 10 January 2023. We measured demographic data, COVID-19-related burnout, anxiety, depression, social support, and resilience. We used the following valid tools: COVID-19 burnout scale, Patient Health Questionnaire-4, Multidimensional Scale of Perceived Social Support, and Brief Resilience Scale.ResultsAmong patients, 45.8% were willing to accept a COVID-19 booster dose, 25.3% were hesitant, and 28.9% were unwilling. Patients experienced moderate levels of COVID-19-related burnout. After multivariable linear regression analysis, we found that increased age and decreased emotional exhaustion due to COVID-19 were associated with increased vaccination intention. Moreover, patients who have already received a booster dose had also a greater willingness to accept a new booster dose.ConclusionsIdentification of factors that influence patients’ decision to accept a COVID-19 booster dose is crucial to maintain a high vaccination coverage rate among them in order to avoid COVID-19-related outcomes. Since a COVID-19 booster dose on an annual basis seems to be necessary policy makers should develop and implement vaccination programmes tailored for patients.
Waves in time, but not in space – An analysis of pandemic severity of COVID-19 in Germany based on spatio-temporal clustering
Authors: Kuebart Andreas , Stabler Martin 
Published: January 2023

AbstractWhile pandemic waves are often studied on the national scale, they typically are not distributed evenly within countries. This paper employs a novel approach to analyze the tempo-spatial dynamics of the COVID-19 pandemic in Germany. First, we base the analysis on a composite indicator of pandemic severity to gain a more robust understanding of the temporal dynamics of the pandemic. Second, we subdivide the pandemic during the years 2020 and 2021 into fifteen phases, each with a coherent trend of pandemic severity. Third, we analyze the patterns of spatial association during each phase. Fourth, similar types of trajectories of pandemic severity among all German counties were identified through hierarchical clustering. The results imply that the hotspots and cold spots of the first four waves of the pandemic were relatively stationary in space so that the pandemic moved in time but less in space.
Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD
Authors: Park Se-Hyung , Helsley Robert N. , Fadhul Taghreed , Willoughby Jennifer L.S. , Noetzli Leila , Tu Ho-Chou , Solheim Marie H. , Fujisaka Shiho , Pan Hui , Dreyfuss Jonathan M. , Bons Joanna , Rose Jacob , King Christina D. , Schilling Birgit , Lusis Aldons J. , Pan Calvin , Gupta Manoj , Kulkarni Rohit N. , Fitzgerald Kevin , Kern Philip A. , Divanovic Senad , Kahn C. Ronald , Softic Samir 
Published: January 2023

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform increases endoplasmic reticulum (ER) stress in a dose dependent fashion, so when fructose is coupled with a HFD intake it leads to unresolved ER stress. Conversely, a liver-specific knockdown of KHK in C57BL/6J male mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Overexpression of KHK-C in cultured hepatocytes is sufficient to induce ER stress in fructose free media. Upregulation of KHK-C is also observed in genetically obesity ob/ob, db/db and lipodystrophic FIRKO male mice, whereas KHK knockdown in these mice improves metabolic function. Additionally, in over 100 inbred strains of male or female mice hepatic KHK expression correlates positively with adiposity, insulin resistance, and liver triglycerides. Similarly, in 241 human subjects and their controls, hepaticKhkexpression is upregulated in early, but not late stages of NAFLD. In summary, we describe a novel role of KHK-C in triggering ER stress, which offers a mechanistic understanding of how the combined intake of fructose and a HFD propagates the development of metabolic complications.
Efficient image analysis for large-scale next generation histopathology using pAPRica
Authors: Scholler Jules , Jonsson Joel , Jordá-Siquier Tomás , Gantar Ivana , Batti Laura , Cheeseman Bevan L. , Pagès Stéphane , Sbalzarini Ivo F. , Lamy Christophe M. 
Published: January 2023

AbstractThe large size of imaging datasets generated by next-generation histology methods limits the adoption of those approaches in research and the clinic. We propose pAPRica (pipelines for Adaptive Particle Representation image compositing and analysis), a framework based on the Adaptive Particle Representation (APR) to enable efficient analysis of large microscopy datasets, scalable up to petascale on a regular workstation. pAPRica includes stitching, merging, segmentation, registration, and mapping to an atlas as well as visualization of the large 3D image data, achieving 100+ fold speedup in computation and commensurate data-size reduction.
Iron Regulatory Protein 1 is Required for the Propagation of Inflammation in Inflammatory Bowel Disease
Authors: Fahoum L. , Belisowski S. , Ghatpande N. , Guttmann-Raviv N. , Zhang W. , Li K. , Tong W-H. , Nyska A. , Waterman M. , Weisshof R. , Zuckerman A. , Meyron-Holtz E.G. 
Published: January 2023

AbstractObjectiveInflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation.DesignThis study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD.ResultsWe found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation.ConclusionThese findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.What is already known on this topicInflammatory bowel diseases (IBD) are chronic conditions that cause inflammation in the digestive tract. Iron accumulation is a common feature of IBD, but the mechanism of accumulation and its implications for the course of inflammation are not fully understood.What this study addsThis study reveals an inflammatory intestinal iron distribution-pattern, that has not been described previously involving iron accumulation in immune cells and iron deficiency in epithelial cells. We show that an inflammation mediated activation of the Iron Regulatory Protein (IRP)1 is responsible for this inflammatory iron pattern and that this drives the propagation of the inflammation in IBD. Moreover, targeted deletion of IRP1 completely abolished the intestinal inflammation.How this study might affect research, practice or policyThese findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa in IBD. This might lead to the development of novel treatment approaches for IBD focused on modulating IRP1 activity.
Mitotic heritability of DNA methylation at intermediately methylated sites is imprecise
Authors: Hay Amir D. , Kessler Noah J. , Gebert Daniel , Takahashi Nozomi , Tavares Hugo , Teixeira Felipe K. , Ferguson-Smith Anne C. 
Published: January 2023

AbstractDNA methylation is considered a stable epigenetic mark due to its presumed long-term inheritance through cell divisions. Here, we perform high-throughput bisulfite sequencing on clonally derived cell lines to quantitatively measure mitotic methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity. Moreover, we determine that the probabilistic changes that occur at intermediately methylated sites are due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the concept of DNA methylation as a consistently stable epigenetic mark.
The fission yeast methyl phosphate capping enzyme Bmc1 guides 2’-O-methylation of the U6 snRNA
Authors: Porat Jennifer , Slat Viktor A. , Rader Stephen D. , Bayfield Mark A. 
Published: January 2023

AbstractSplicing requires the tight coordination of dynamic spliceosomal RNAs and proteins. U6 is the only spliceosomal RNA transcribed by RNA Polymerase III and undergoes an extensive maturation process. In humans and fission yeast, this includes addition of a 5’ γ-monomethyl phosphate cap by members of the Bin3/MePCE family. Previously, we have shown that the Bin3/MePCE homolog Bmc1 is recruited to theS. pombetelomerase holoenzyme by the LARP7 family protein Pof8, where it acts in a catalytic-independent manner to protect the telomerase RNA and facilitate holoenzyme assembly. Here, we show that Bmc1 and Pof8 also interact in a U6-containing snRNP. We demonstrate that Bmc1 and Pof8 promote 2’-O-methylation of U6 and identify and characterize a non-canonical snoRNA that guides this methylation. Further, we show that fission yeast strains deleted of Bmc1 or Pof8 show altered U6 snRNP assembly patterns, supporting a more general role for these factors in guiding noncoding RNP assembly beyond the telomerase RNP. These results are thus consistent with a novel role for Bmc1/MePCE family members in stimulating U6 post-transcriptional modifications.
Power Series Template Matching Model for Pitch Perception
Authors: Takahashi Jun-ichi 
Published: January 2023

AbstractThe problem of pitch perception has been the subject of a long debate between place theory and time theory. Here, we propose a Power Series Template (PoST) model to answer the problem of how and why pitch perception comes about. The sensitive measurement of acoustic signals requires efficient Sound Amplification, which inevitably accompanies mode coupling due to the perturbative non-linearities. Under reinforcement learning for Sound Localization with the second- and third-order modes as default teacher signals, a chain of coincidence is generated. After learning in Sound Localization is completed, two power series templates of 2nand 3mare generated, and the 2f1−f2coupling of the elements contained therein fills the blanks of matchable harmonics up to N=10 in the template, providing the well-known harmonic template. When complex tones containing multiple harmonics are input into the trained network, two power series are evoked from each harmonic, and from their intersection, the brain acquires the fundamental of the complex tone as the pitch. Based on this template model, consistent explanations are given for the problems of missing fundamental, pitch shift, pitch and chroma, and resolvability jump without the help of time theory.
Phylogenetics and phylogeography ofEuphorbia canariensisreveal an extreme Canarian-Asian disjunction and limited inter-island colonization
Authors: Coello Alberto J. , Vargas Pablo , Cano Emilio , Riina Ricarda , Fernández-Mazuecos Mario 
Published: January 2023

AbstractEuphorbia canariensisis an iconic endemic species of the Canary Islands and one of the most characteristic species of lowland xerophytic communities known, in Spanish, as ‘cardonal-tabaibal’. This species is widely distributed in the archipelago, which contrasts with the theoretically low dispersal abilities suggested by its unspecialized diasporas. Furthermore, the phylogenetic relationships of this species are unclear, although it is thought to be related to the IndianE. epiphylloidesand not to other cactus-likeEuphorbiaof the Canary Islands (E. handiensis) and Africa. Here we aimed to reconstruct the evolutionary history ofE. canariensisat two levels: (i) a phylogenetic approach aimed at unravelling relationships of this species and large-scale biogeographic patterns, and (ii) a phylogeographic approach focused on the history of colonization between islands of the Canarian archipelago in relation to habitat availability for this species through time. Based on previous phylogenetic studies ofEuphorbia, we sequenced the ITS region forE. canariensisand several potentially related species to build a phylogenetic framework. We also sequenced two cpDNA regions for 92 individuals from 29 populations ofE. canariensisrepresenting its distribution range. We estimated the number of inter-island colonization events using PAICE, a recently developed method that includes a sampling effort correction. Additionally, we used species distribution modelling (SDM) to project current habitat availability forE. canariensisto past periods. Phylogenetic results supported the CanarianE. canariensisas closely related to the Southeast AsianE. epiphylloidesandE. sessiliflora. In the Canarian archipelago,E. canariensisdisplayed a surprising west-to-east colonization pattern. The estimated number of inter-island colonization events was c. 20 – 50, and SDM suggested an increase in habitat availability in recent times. In summary, in this study we confirmed an extreme biogeographic disjunction between Macaronesia and Southeast Asia, described only for a small number of plant species, and estimated relatively low dispersal capabilities forE. canariensis, with a west-to-east colonization pattern in the Canary Islands.HighlightsThe CanarianEuphorbia canariensisis sister to Southeast Asian species.This lineage shows one of the widest disjunctions affecting Macaronesian plants.The lack of intermediate relatives could be the result of extinction events.E. canariensisdisplays low colonization ability in the Canarian archipelago.