bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep and the gut microbiota in preschool-aged children
Authors: Wang Yanan , van de Wouw Marcel , Drogos Lauren , Vaghef-Mehrabani Elnaz , Reimer Raylene A , Tomfohr-Madsen Lianne , Giesbrecht Gerald F 
Published: January 2022

Abstract
Sleep plays a significant role in the mental and physical development of children. Emerging evidence in animals and human adults indicates a relationship between sleep and the gut microbiota; however, it is unclear whether the sleep of preschoolers during a key developmental period, associates with features of their gut microbiota. The objective of this study was to assess the relationship between sleep and gut microbiota in preschool-aged children (4.37 ± 0.48 years, n = 143). Sleep measures included total night-time sleep (TST), sleep efficiency (SE), and wake-time after sleep onset (WASO) assessed using actigraphy. Beta-diversity differences between children with low and high TST (p = .048) suggest gut microbiota community differences. Particularly, relative abundance of Bifidobacterium was higher in the high TST group and Bacteroides, was higher in children who had greater SE and less WASO (LDA score &gt;2). In contrast, some Lachnospiraceae members including Blautia and Coprococcus 1 were associated with shorter night-time sleep duration and less efficiency, respectively. We also found a group of fecal metabolites, including specific neuroactive compounds and immunomodulating metabolites were associated with greater sleep efficiency and less time awake at night. Notably, tryptophan and its metabolizing products were higher in children who had higher SE or lower WASO (LDA score &gt;2); concentration of propionate was higher in children with less WASO (p = .036). Overall, our results reveal a novel association between sleep and gut microbiota in preschool-aged children. Longer night-time sleep and greater sleep efficiency were associated with specific commensal bacteria that may regulate sleep through modulating neurotransmitter metabolism and the immune system.
Attitudes towards vaccines, intent to vaccinate and the relationship with COVID-19 vaccination rates in individuals with schizophrenia
Authors: Raffard Stéphane , Bayard Sophie , Eisenblaetter Margot , Attal Jérôme , Andrieu Christelle , Chereau Isabelle , Fond Guillaume , leignier Sylvain , Mallet Jasmina , Tattard Philippe , Urbach Mathieu , Misdrahi David , Laraki Yasmine , Capdevielle Delphine 
Published: January 2022

AbstractBackgroundPeople with schizophrenia are at high risk for developing severe COVID-19 outcomes but recent evidence suggests that this population have lower vaccination rates than the general population. This gap in vaccination rates could be explained by attitudinal and structural barriers.AimsThis study explored the role of potential attitudinal barriers by comparing schizophrenia patients with participants from the general population regarding COVID-19 vaccination rates, general attitudes towards vaccines, and willingness to take a COVID-19 vaccine.MethodWe conducted a cross-sectional study between April 2021 and October 2021. 100 schizophrenia patients and 72 controls were recruited. Attitudes towards vaccines were assessed with the Vaccination Attitudes Examination Scale. COVID-19 vaccination rates, sociodemographic, clinical and health-related variables were also assessed.ResultsIn our study, the proportion of individuals with schizophrenia were under-vaccinated despite similar general attitudes towards vaccination and higher willingness to be vaccinated against COVID-19 compared to the participants from the general population. In patients, negative attitudes toward vaccines was related to higher level of negative psychotic symptoms and higher level of paranoid ideation. As a whole, participants with more negative attitudes towards vaccines were less likely to be vaccinated against COVID-19 and had lower levels of trust in institutions.ConclusionsVaccine hesitancy does not appear to be a major barrier for COVID-19 vaccine uptake amongst people with schizophrenia. This study suggests that disparities in COVID-19 vaccination rates in schizophrenia do not seem related to attitudinal but rather structural barriers.Significant outcomesIn both groups, non-vaccinated individuals had higher general negative attitudes towards vaccines.People with schizophrenia were under-vaccinated (64% versus 77.8%) despite similar general attitudes towards vaccination and higher willingness to be vaccinated in non vaccinated against COVID-19 compared to the controls (41.7% versus 21.5%).General positive attitudes towards vaccines were negatively associated with persecutory ideation and negative symptoms in patients.LimitationsOur two sample groups sere composed exclusively of French individuals, potentially limiting the generalizability of our results.The cross-sectional design of our study.
Naïve arthritogenic SKG T cells have a defect in anergy and a repertoire pruned by superantigen
Authors: Ashouri Judith , McCarthy Elizabeth , Yu Steven , Perlmutter Noah , Lin Charles , DeRisi Joe , Ye Chun Jimmie , Weiss Arthur 
Published: January 2022

AbstractHow autoreactive CD4 T cells develop to cause rheumatoid arthritis remains unknown. We used a reporter for antigen-receptor signaling in the SKG autoimmune arthritis model to profile a T cell subpopulation enriched for arthritogenic naïve CD4 T cells before arthritis onset by bulk and single cell RNA and T cell antigen-receptor (TCR) sequencing. Our analyses reveal that despite their impaired proximal TCR signaling, a subset of SKG naïve CD4 T cells that have recently encountered endogenous antigen upregulate gene programs associated with positive regulation of T cell activation and cytokine signaling at higher levels than wild type cells in the pre-disease state. These arthritogenic cells also induce genes associated with negative regulation of T cell activation but do so less efficiently than wild type cells. Furthermore, their TCR sequences exhibit a previously unrecognized biased peripheral TCR Vβ repertoire likely driven by endogenous viral superantigens. These particular Vβs, known to recognize endogenous mouse mammary tumor virus (MMTV) superantigen, are further expanded in arthritic joints. Our results demonstrate that autoreactive naïve CD4 T cells which recognize endogenous viral superantigens are poised to cause disease by their altered transcriptome.Summary blurbSelf-reactive SKG T cells that escaped negative selection harbor an independent defect in anergy that, together with chronic antigen stimulation, sets the stage for disease. Moreover, we propose a novel role for endogenous mouse mammary tumor virus (MMTV) superantigen in promoting arthritogenic T cell responses.
A candidate gene cluster for the bioactive natural product gyrophoric acid in lichen-forming fungi
Authors: Singh Garima , Calchera Anjuli , Merges Dominik , Otte Jürgen , Schmitt Imke , Grande Francesco Dal 
Published: January 2022

AbstractNatural products of lichen-forming fungi are structurally diverse and have a variety of medicinal properties. Despite this, they a have limited implementation in industry, because the corresponding genes remain unknown for most of the natural products. Here we implement a long-read sequencing and bioinformatic approach to identify the biosynthetic gene cluster of the bioactive natural product gyrophoric acid (GA). Using 15 high-quality genomes representing nine GA-producing species of the lichen-forming fungal genusUmbilicaria, we identify the most likely GA cluster and investigate cluster gene organization and composition across the nine species. Our results show that GA clusters are promiscuous withinUmbilicaria, with only three genes that are conserved across species, including the PKS gene. In addition, our results suggest that the same cluster codes for different but structurally similar NPs, i.e., GA, umbilicaric acid and hiascic acid, bringing new evidence that lichen metabolite diversity is also generated through regulatory mechanisms at the molecular level. Ours is the first study to identify the most likely GA cluster, and thus provides essential information to open new avenues for biotechnological approaches to producing and modifying GA and similar lichen-derived compounds. We show that bioinformatics approaches are useful in linking genes and potentially associated natural products. Genome analyses help unlocking the pharmaceutical potential of organisms such as lichens, which are biosynthetically diverse but slow growing, and difficult to cultivate due to their symbiotic nature.ImportanceThe implementation of natural products in the pharmaceutical industry relies on the possibility of modifying the natural product (NP) pathway to optimize yields and pharmacological effects. Characterization of genes and pathways underlying natural product biosynthesis is a major bottleneck for the use of natural products in the pharmaceutical industry. Genome mining is a promising and relatively cost- and time-effective approach to exploit unexplored NP resources for drug discovery. In this study, we identify the most likely gene cluster for the lichen-forming fungal depside gyrophoric acid in nineUmbilicariaspecies. This compound shows cytotoxic and antiproliferative properties against several cancer cell lines, and is also a broad-spectrum antimicrobial agent. We identify the putative GA cluster from nineUmbilicariaspecies. This information paves the way for generating GA analogs with modified properties by selective activation/deactivation of genes.
Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in an Alzheimer’s disease model
Authors: Zeng Hu , Huang Jiahao , Zhou Haowen , Meilandt William J. , Dejanovic Borislav , Zhou Yiming , Bohlen Christopher J. , Lee Seung-Hye , Ren Jingyi , Liu Albert , Sheng Hao , Liu Jia , Sheng Morgan , Wang Xiao 
Published: January 2022

AbstractAmyloid-β plaques and neurofibrillary tau tangles are the neuropathologic hallmarks of Alzheimer’s disease (AD), but the spatiotemporal cellular responses and molecular mechanisms underlying AD pathophysiology remain poorly understood. Here we introduce STARmap PLUS to simultaneously map single-cell transcriptional states and disease marker proteins in brain tissues of AD mouse models at subcellular resolution (200 nm). This high-resolution spatial transcriptomics map revealed a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocytes (DAA) and oligodendrocyte precursor cells (OPC) are enriched in the outer shells surrounding the plaque- DAM complex. Hyperphosphorylated tau emerged mainly in excitatory neurons in the CA1 region accompanied by the infiltration of oligodendrocyte subtypes into the axon bundles of hippocampal alveus. The integrative STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing an unprecedented roadmap to pinpoint the molecular and cellular mechanisms of AD pathology and neurodegeneration.
NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli
Authors: Wang Andrew G. , Son Minjun , Thom Nicholas , Tay Savaş 
Published: January 2022

AbstractMany scenarios in cellular communication requires cells to interpret multiple dynamic signals. It is unclear how exposure to immune stimuli alters transcriptional responses to subsequent stimulus under inflammatory conditions. Using high-throughput microfluidic live cell analysis, we systematically profiled the NF-κB response to different signal sequences in single cells. We found that NF-κB dynamics stores the history of signals received by cells: depending on the dose and type of prior pathogenic and cytokine signal, the NF-κB response to subsequent stimuli varied widely, from no response to full activation. Using information theory, we revealed that these stimulus-dependent changes in the NF-κB response encode and reflect information about the identity and dose of the prior stimulus. Small-molecule inhibition, computational modeling, and gene expression profiling show that this encoding is driven by stimulus-dependent engagement of negative feedback modules. These results provide a model for how signal transduction networks process sequences of inflammatory stimuli to coordinate cellular responses in complex dynamic environments.
B cells discriminate HIV-1 Envelope protein affinities by sensing antigen binding association rates
Authors: Hossain Md. Alamgir , Anasti Kara , Watts Brian , Cronin Kenneth , Kane Advaiti Pai , Edwards R.J. , Easterhoff David , Zhang Jinsong , Rountree Wes , Ortiz Yaneth , Verkoczy Laurent , Reth Michael , Alam S. Munir 
Published: January 2022

SUMMARYHIV-1 Envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant, KD) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD, and whether B cells discriminate between proteins of similar affinities but that bind with different kinetic rates. Here we used a panel of Env proteins and Ramos B cell lines expressing IgM BCRs with specificity for CD4 binding-site broadly neutralizing (bnAb) or a precursor antibody to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD, but on sensing of association rate and a threshold antigen-BCR half-life.
Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM1
Authors: Grönloh Max L.B. , Arts Janine J.G. , Martínez Sebastián Palacios , van der Veen Amerens A. , Kempers Lanette , van Steen Abraham C.I. , Roelofs Joris J.T.H. , Nolte Martijn A. , Goedhart Joachim , van Buul Jaap D. 
Published: January 2022

AbstractUpon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration ‘hotspot’ regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photo-convertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM-1 determines the location of the transmigration hotspot. Interestingly, loss of ICAM-1 heterogeneity either by CRISPR/Cas9-induced knockout of ICAM-1 or equalizing the distribution of ICAM-1 in all endothelial cells results in loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig-like domains of ICAM-1 are crucial for hotspot recognition. However, the intracellular tail of ICAM-1 and the 4thIg-like dimerization domain are not involved, indicating that intracellular signalling or ICAM-1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation-induced extravasation.
Chemical defense acquired via pharmacophagy can lead to herd protection in a sawfly
Authors: Singh Pragya , Grone Neil , Tewes Lisa Johanna , Müller Caroline 
Published: January 2022

AbstractPredation is an important selection pressure acting on organisms, with organisms evolving diverse anti-predator strategies to combat it. One such widespread strategy is chemical defense in which organisms either synthesize or extrinsically acquire defensive chemicals. Little is known about the intraspecific transfer of such chemicals and if such chemicals acquired from conspecifics can also serve as defense against predation. Here, we used adults of the turnip sawfly, Athalia rosae, which can acquire neo-clerodane diterpenoids (‘clerodanoids’) via pharmacophagy after exposure to the plant, Ajuga reptans. We show that clerodanoid access mediates protection against predation by mantids for the sawflies, both in a no-choice feeding assay and a microcosm setup. Moreover, even indirect access to clerodanoids, via nibbling on conspecifics that had access to the plant, resulted in protection against predation albeit to a much lower degree than direct access. Furthermore, sawflies that had no direct access to clerodanoids were less consumed by mantids when they were grouped with conspecifics that had direct access. Most, but not all, of such initially undefended sawflies could acquire clerodanoids from conspecifics that had direct access to the plant, although in low quantities. Together our results demonstrate that clerodanoids serve as chemical defense that can be intraspecifically transferred. Moreover, the presence of chemically defended individuals in a group can confer protection onto conspecifics that had no direct access to clerodanoids, suggesting a ‘herd-protection’ effect.
Road encroachment mediates species occupancy, trait filtering and dissimilarity of songbird communities
Authors: Ascensão Fernando , D’Amico Marcello , Revilla Eloy , Pereira Henrique M. 
Published: January 2022

AbstractAssessing the road effects on biodiversity is challenging because impacts may depend on both wildlife responses to roads and on the spatial arrangement of roads. We questioned whether an increase in road encroachment i.e., the advancement of roads into non-urban areas, leads to significant changes (positive and negative) in species occurrence, and if so, whether those changes are linked to specific traits related to perturbation sensitiveness, therefore acting as filters that increase the community compositional dissimilarity. Using a large citizen-science dataset of point-counts performed throughout Iberian Peninsula (4,459 unique survey sites), we modelled the effect of road density on the occurrence of common songbirds (n=58), while accounting for potential confounding effects of environment and survey effort. We then tested if species’ occurrence patterns would be linked to specific traits related to the ability to cope with human presence. Finally, we assessed how road density affect the community compositional dissimilarity. We estimated 24 (41%) and 12 (21%) species to be negatively and positively affected by roads, respectively. Increased road encroachment was positively related with a higher prevalence of urban dwellers and negatively related with the occurrence of species nesting and foraging on the ground. Furthermore, increasing road density translated into an increasing community compositional dissimilarity, mostly due to species turnover. Our study support previous research showing that roads have different effects on the occurrence of different species, but we revealed that at least three species' traits have a clear relation with such road responses. Such trait filtering is probably causing a high species turnover between songbird communities occurring in roaded and nearby roadless areas. Overall, we found that different species-specific responses to roads translates into changes at the community level. Landscape and road-network management should be conceived acknowledging that roads are contributing to biodiversity changes. As so, building upon the concepts of Land Sharing / Land Sparing, conservation actions should be tailored according to the different species responses e.g., road verge management targeting species having a positive relation with road density; and compensation actions targeting species showing a negative response toward roads.
Automatic grading of cervical biopsies by combining full and self-supervision
Authors: Lubrano Mélanie , Lazard Tristan , Balezo Guillaume , Bellahsen-Harrar Yaëlle , Badoual Cécile , Berlemont Sylvain , Walter Thomas 
Published: January 2022

AbstractIn computational pathology, predictive models from Whole Slide Images (WSI) mostly rely on Multiple Instance Learning (MIL), where the WSI are represented as a bag of tiles, each of which is encoded by a Neural Network (NN). Slide-level predictions are then achieved by building models on the agglomeration of these tile encodings. The tile encoding strategy thus plays a key role for such models. Current approaches include the use of encodings trained on unrelated data sources, full supervision or self-supervision. While self-supervised learning (SSL) exploits unlabeled data, it often requires large computational resources to train. On the other end of the spectrum, fully-supervised methods make use of valuable prior knowledge about the data but involve a costly amount of expert time. This paper proposes a framework to reconcile SSL and full supervision, showing that a combination of both provides efficient encodings, both in terms of performance and in terms of biological interpretability. On a recently organized challenge on grading Cervical Biopsies, we show that our mixed supervision scheme reaches high performance (weighted accuracy (WA): 0.945), outperforming both SSL (WA: 0.927) and transfer learning from ImageNet (WA: 0.877). We further shed light upon the internal representations that trigger classification results, providing a method to reveal relevant phenotypic patterns for grading cervical biopsies. We expect that the combination of full and self-supervision is an interesting strategy for many tasks in computational pathology and will be widely adopted by the field.
Evolution of assortative mating following selective introgression of pigmentation genes between two Drosophila species
Authors: David Jean R. , Ferreira Erina A. , Jabaud Laure , Ogereau David , Bastide Héloïse , Yassin Amir 
Published: January 2022

AbstractAdaptive introgression is ubiquitous in animals but experimental support for its role in driving speciation remains scarce. In the absence of conscious selection, admixed laboratory strains of Drosophila asymmetrically and progressively lose alleles from one parental species and reproductive isolation against the predominant parent ceases after 10 generations. Here, we selectively introgressed during one year light pigmentation genes of D. santomea into the genome of its dark sibling D. yakuba, and vice versa. We found that the pace of phenotypic change differed between the species and the sexes, and identified through genome sequencing common as well as distinct introgressed loci in each species. Mating assays showed that assortative mating between introgressed flies and both parental species persisted even after four years (∼ 60 generations) from the end of the selection. Those results indicate that selective introgression of as low as 0.5% of the genome can beget morphologically-distinct and reproductively-isolated strains, two prerequisites for the delimitation of new species. Our findings hence represent a significant step towards understanding the genome-wide dynamics of speciation-through-introgression.