bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive assay of social motivation reveals sex-differential roles of ASC-associated genes and oxytocin
Authors: Maloney Susan E. , Sarafinovska Simona , Weichselbaum Claire , McCullough Katherine B. , Swift Raylynn G. , Liu Yating , Dougherty Joseph D. 
Published: May 2022

AbstractSocial motivation is critical to the development of healthy social functioning. Autism spectrum condition (ASC) is characterized in part by challenges with social communication and social interaction. The root of these challenges is hypothesized to be a deficit in social motivation, specifically in one or more subcomponents (e.g. social reward reward seeking or social orienting). Current social behavior assays lack the ability to quantitatively measure both social reward seeking and social orienting simultaneously. We have developed an automated socially-rewarded operant conditioning task coupled with video tracking, to quantify effort to achieve access to a social partner and concurrent social orienting behavior in mice. We established that adult wildtype mice will work for access to a social partner, that male mice exhibit greater social motivation compared to females, and there is high test-retest reliability in the task across multiple days. We then benchmarked the method with two test-case manipulations. We first tested a mouse model of Phelan-McDermid syndrome, a neurodevelopmental disorder associated with ASC. TheseShank3Bmutants failed to show social reward seeking and exhibited reduced social orienting. Next, we demonstrated that oxytocin receptor antagonism decreased social motivation in wildtype mice, consistent with its role in social reward circuitry. Intriguingly, only male mice were vulnerable toShank3Bmutation, while females were more vulnerable to oxytocin blockade, a double dissociation suggesting separate circuits for social motivation in male and female brain. Overall, we believe this method provides a valuable addition to the assessment of social phenotypes in rodent models of ASC and the mapping of potentially sex-specific social motivation circuits in the brain.
UHMK1 is a novel splicing regulatory kinase
Authors: Arfelli Vanessa C. , Chang Yun-Chien , Bagnoli Johannes W. , Kerbs Paul , Ciamponi Felipe E. , Paz Laissa M. S. , Massirer Katlin B. , Enard Wolfgang , Kuster Bernhard , Greif Philipp A. , Archangelo Leticia Fröhlich 
Published: May 2022

AbstractThe U2AF Homology Motif Kinase 1 (UHMK1) is the only kinase that contains the U2AF homology motif (UHM), a common protein interaction domain among splicing factors. Through this motif, UHMK1 interacts with the splicing factors SF1 and SF3B1, known to participate in the 3’ splice site recognition during the early steps of spliceosome assembly. Although UHMK1 phosphorylates these splicing factors in vitro, the involvement of UHMK1 in RNA processing has not previously been demonstrated. Here, we identify novel putative substrates of this kinase and evaluate UHMK1 contribution to overall gene expression and splicing, by integrating global phosphoproteomics, RNA-seq, and bioinformatics approaches. Upon UHMK1 modulation, 163 unique phosphosites were differentially phosphorylated in 117 proteins, of which 106 are novel potential substrates of this kinase. Gene Ontology (GO) analysis showed enrichment of terms previously associated with UHMK1 function, such as mRNA splicing, cell cycle, cell division and microtubule organization. The majority of the annotated RNA-related proteins are components of the spliceosome, but are also involved in several steps of gene expression. Comprehensive analysis of splicing showed that UHMK1 affected over 200 alternative splicing events. Moreover, splicing reporter assay further supported UHMK1 function on splicing. Overall, RNA-seq data demonstrated that UHMK1 knockdown had a minor impact on gene expression and pointed to UHMK1 function in epithelial-mesenchymal transition. Finally, the functional assays demonstrated that UHMK1 modulation affects proliferation, colony formation, and migration of the cells. Taken together, our data implicate UHMK1 as a splicing regulatory kinase, connecting protein regulation through phosphorylation and gene expression in key cellular processes.
Integration of metabolism and regulation reveals rapid adaptability to growth on non-native substrates
Authors: Trivedi Vikas D. , Sullivan Sean F. , Choudhury Debika , Endalur Gopinarayanan Venkatesh , Hart Taylor , Nair Nikhil U. 
Published: May 2022

ABSTRACTEngineering synthetic heterotrophy (i.e., growth on non-native substrates) is key to the efficient bio-based valorization of renewable and waste substrates. Among these, engineering hemicellulosic pentose utilization has been well-explored inSaccharomyces cerevisiae(yeast) over several decades – yet the answer to what makes their utilization inherently recalcitrant remains elusive. Through implementation of a semi-synthetic regulon, we find that harmonizing cellular and engineering objectives are key to obtaining highest growth rates and yields with minimal metabolic engineering effort. Concurrently, results indicate that “extrinsic” factors – specifically, upstream genes that direct flux of pentoses into central carbon metabolism – are rate-limiting. We also reveal that yeast metabolism is innately highly adaptable to rapid growth on non-native substrates and that systems metabolic engineering (i.e., flux balancing, directed evolution, functional genomics, and network modeling) is largely unnecessary. We posit that the need for extensive engineering espoused by prior works is a consequence of unfortunate (albeit avoidable) antagonism between engineering and cellular objectives. We also found that deletion of endogenous genes to promote growth demonstrate inconsistent outcomes that are genetic-context- and condition-dependent. For the most part, these knockouts also lead to deleterious pleiotropic effects that decrease the robustness of strains against inhibitors and stressors associated with bioprocessing. Thus, at best, perturbation of “intrinsic” factors (e.g., native metabolic, regulatory genes) results in incremental and inconsistent benefits. At worst, they are detrimental. Overall, this work provides insight into the limitations and pitfalls to realizing efficient synthetic heterotrophy using traditional/systems metabolic engineering approaches, demonstrates the innate adaptability of yeast for metabolism of non-native substrates, and provides an alternate, novel, holistic (and yet minimalistic) approach based on integrating non-native metabolic genes with a native regulon system.
A survey of mapping algorithms in the long-reads era
Authors: Sahlin Kristoffer , Baudeau Thomas , Cazaux Bastien , Marchet Camille 
Published: May 2022

AbstractIt has been ten years since the first publication of a method dedicated entirely to mapping third-generation sequencing long-reads. The unprecedented characteristics of this new type of sequencing data created a shift, and methods moved on from theseed-and-extendframework previously used for short reads to aseed-and-chainframework due to the abundance of seeds in each read. As a result, the main novelties in proposed long-read mapping algorithms are typically based on alternative seed constructs or chaining formulations. Dozens of tools now exist, whose heuristics have considerably evolved with time. The rapid progress of the field, synchronized with the frequent improvements of data, does not make the literature and implementations easy to keep up with. Therefore, in this survey article, we provide an overview of existing mapping methods for long reads with accessible insights into methods. Since mapping is also very driven by the implementations themselves, we join an original visualization tool to understand the parameter settings (http://bcazaux.polytech-lille.net/Minimap2/) for the chaining part.
Transplantation Elicits a Clonally Diverse CD8+T Cell Response that is Comprised of Potent CD43+Effectors
Authors: Cohen Gregory A. , Kallarakal Melissa A. , Jayaraman Sahana , Ibukun Francis I. , Tong Katherine P. , Orzolek Linda D. , Larman H. Benjamin , Krummey Scott M. 
Published: May 2022

SUMMARYCD8+T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. The factors that govern differentiation of graft-directed effector CD8+T cells could lead to targeted approaches to limit acute rejection. Using MHC Class I tetramers, we found that allogeneic CD8+T cells were present at an elevated precursor frequency in naïve mice, only modestly increased in number after grafting, and maintained high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defined potent effectors after transplantation. Activated CD43+effector T cells maintained high expression of ICOS in the presence of CTLA-4 Ig, and dual CTLA-4 Ig/anti-ICOS treatment prolonged graft survival. These data demonstrate that graft-specific CD8+T cells have a distinct response profile relative to anti-pathogen CD8+T cells, and that CD43 and ICOS are critical surface receptors that define potent effector CD8+T cell populations that form after transplantation.
Trends, changes and determinants of medical attention received before death among deceased adults in India: Evidence from pooled cross-sectional survey data (2004-2018)
Authors: Akhtar Saddaf Naaz , Saikia Nandita 
Published: May 2022

AbstractBackgroundIndia is coping an ageing population without an adequate medical care service. However, trends, changes and factors of receiving medical attention before death remains unknown. Therefore, we intend to examine the trends, changes and determinants of medical attention received before death among the deceased adults in India.MethodsOur study has used a nationally representative pooled-cross-sectional survey data from2004 to 2017-18. We performed univariate, bivariate and multivariate analyses. We have examined the trends from 2004 to 2017-18. Then we estimated the absolute changes in medical attention rate (MAR) received before death by the 45+ deceased adults for the time period between 2004-2005 & 2017-2018 and 2014 & 2017-2018. Lastly, we applied binary logistic regression analysis to identify the effect of significant predictor variables on the medical attention received before death.ResultsOur study has revealed that there has been marginal increase (0.74%) in the overall trend in medical attention received before death among 45+ adults from 2004 to 2017-18. Females, rural residence are showing negative change in receiving medical attention. However, our finding has showed that young-old, middle-old and oldest-old have significantly lower odds of receiving medical attention compared to middle-aged adults. Surprisingly, our result has revealed that Southern and Western regions are found to have significantly less likely to receive medical attention before death among deceased adults which is a striking finding.ConclusionsTherefore, there is an urgent need to establish a primary health center at community level that play an important role in order to meet the comprehensive requirements of middle-aged and older adults in India. It would be helpful to develop and execute the health policies and programs that would enable India to achieve healthy aging in India at national and subnational levels, as it is a key element of public health challenges.
Socio-economic and demographic determinants of all-cause, main-cause and sub-cause mortality among 45+ adults: Evidence from Longitudinal Ageing Study in India
Authors: Akhtar Saddaf Naaz , Saikia Nandita 
Published: May 2022

AbstractBackgroundStudies on cause-specific mortality among 45+ adults remain unknown in Indian settings. However, understanding the epidemiology of this public health problem can guide policy development for premature and old-age mortality prevention. Therefore, we intend to examine the socio-economic and demographic determinants of all-cause, main-cause and sub-cause mortality among 45+ adults in India.MethodsWe adopted the cross-sectional data from the Longitudinal Ageing Study of India (LASI-wave-I) conducted in 2017-18. We performed descriptive, bivariate and multivariate analysis.ResultsFemales, young-old, middle-old, oldest-old showed lower odds of all-cause, main-cause and sub-cause mortality than males and middle-aged adults. Central region showed significantly greater odds of all-cause mortality risks than Northern region. Christians have lower odds of all-cause mortality risk than Hindus. With the increase in household income, the odds of NCD-related mortality risks also increase. Central (OR=1.54; p<0.01), Eastern (OR=1.28; p<0.01) and Western regions (OR=1.18; p<0.1) have greater odds of non-NCD-related mortality-risks than Northern regions. Urban residence (OR=01.34; p<0.05) has significantly higher odds of CVD-related mortality-risk than rural residence. OBC (OR=0.59; p<0.01) has lower odds of cancer-related mortality risks than general caste. North-eastern region (OR=2.00; p<0.01) has significantly greater odds of diabetes-related mortality risks.ConclusionsThe premature and old-age mortality components would help formulate and execute integrated interventions aimed at specific age groups and causes-specific mortality. Medical care, pollution management, environmental control, more involvement in physical activity and a healthy lifestyle could assist in lowering the CVD, cancer & diabetes-related mortality. A new strategy is needed to avoid future deaths and burdens from ageing-related CVD.HighlightsThis is the first-ever study that provides the socio-economic and demographic factors association of all-cause, main-cause and sub-cause mortality by characteristics among 45+ adults in India.Females, young-old, middle-old, and oldest-old showed lower odds of all-cause, main-cause and sub-cause mortality than males and middle-aged adults.With the increase in household income, the odds of NCD-related mortality risks also increase.Urban residents have significantly higher odds of CVD-related mortality risk than rural residents.OBC has lower odds of cancer-related mortality risks than general caste.
An improved TurboID pipeline in C. elegans by biochemical depletion of endogenously biotinylated carboxylases
Authors: Artan Murat , Hartl Markus , Chen Weiqiang , de Bono Mario 
Published: May 2022

AbstractProximity-dependent protein labeling provides a powerful in vivo strategy to characterize the interactomes of specific proteins. We previously optimized a proximity labeling protocol for C. elegans using the highly active biotin ligase TurboID. A significant constraint on the sensitivity of TurboID is the presence of abundant, endogenously biotinylated proteins that take up bandwidth in the mass spectrometer, notably carboxylases that use biotin as a co-factor. In C. elegans, these comprise POD-2/acetyl-CoA carboxylase alpha, PCCA-1/propionyl-CoA carboxylase alpha, PYC-1/pyruvate carboxylase and MCCC-1/methylcrotonyl-CoA carboxylase alpha. We developed ways to remove these carboxylases prior to streptavidin purification and mass spectrometry, by engineering their corresponding genes to add a C-terminal His10 tag. This allows us to deplete them from C. elegans lysates using immobilized metal affinity chromatography (IMAC). To demonstrate the method’s efficacy, we use it to expand the interactome map of the presynaptic active zone protein ELKS-1. We identify many known active zone proteins, as well as previously uncharacterized potentially synaptic proteins. Our approach provides a quick and inexpensive solution to a common contaminant problem in biotin- dependent proximity labeling. The approach may be applicable to other model organisms and will enable deeper and more complete analysis of interactors for proteins of interest.
Molecular evidence of chemical disguise by the socially parasitic spiny ant Polyrhachis lamellidens (Hymenoptera: Formicidae) when invading a host colony
Authors: Iwai Hironori , Mori Masaru , Tomita Masaru , Kono Nobuaki , Arakawa Kazuharu 
Published: May 2022

AbstractWhile most ant species establish a colony independently, some socially parasitic ants build the foundation of their colony by invading other ant (host) colonies and utilizing their labour forces. Many socially parasitic ants disguise their cuticular hydrocarbon (CHC) profile, which is also known as nestmate discrimination pheromones, when invading the host colony. Since the strategy of chemical disguise is widespread in socially parasitic ants, elucidating the mechanism of chemical disguise will promote knowledge on the evolutionary history of social parasitism. However, detailed knowledge is still lacking, as the relevant information has only originated from circumstantial evidence, which was obtained from ecological observations. In this study, we investigated the mechanism of chemical disguise in a new queen of a temporary socially parasitic spiny ant (Polyrhachis lamellidens) by measuring its CHC profile, performing a tracing assay with labelled substances, and analysing gene expression levels. First, after rubbing behaviour was observed against the host workers, the CHC profile in P. lamellidens shifted to pronounced peaks that closely resembling that of the host workers. We also observed a reduction in aggressive behaviours by the host ant against P. lamellidens after rubbing behaviour was performed. In addition, P. lamellidens acquired artificially-applied labelling substances from host workers through their rubbing behaviours, while gene expression profiling showed the expression of CHC synthesis-related genes did not change during this behaviour. These results suggest that P. lamellidens directly obtains host CHCs through rubbing behaviour, and these host CHCs enables P. lamellidens to remain disguised during colony invasion.
Lasting consequences on physiology and social behavior following cesarean delivery in prairie voles
Authors: Kenkel William , Kingsbury Marcy , Reinhart John , Cetinbas Murat , Sadreyev Ruslan I. , Carter C. Sue , Perkeybile Allison 
Published: May 2022

ABSTRACTCesarean delivery is associated with diminished plasma levels of several ‘birth-signaling’ hormones, such as oxytocin and vasopressin. These same hormones have been previously shown to exert organizational effects when acting in early life. For example, our previous work found a broadly gregarious phenotype in prairie voles exposed to oxytocin at birth. Meanwhile, cesarean delivery has been previously associated with changes in social behavior and metabolic processes related to oxytocin and vasopressin. In the present study, we investigated the long-term neurodevelopmental consequences of cesarean delivery in prairie voles. After cross-fostering, vole pups delivered either via cesarean or vaginal delivery were studied throughout development. Cesarean-delivered pups responded to isolation differently in terms of their vocalizations (albeit in opposite directions in the two experiments), huddled in less cohesive groups under warmed conditions, and shed less heat. As young adults, we observed no differences in anxiety-like or alloparental behavior. However, in adulthood, cesarean-delivered voles of both sexes failed to form partner preferences with opposite sex conspecifics. In a follow-up study, we replicated this deficit in partner-preference formation among cesarean-delivered voles and were able to normalize pair-bonding behavior by treating cesarean-delivered vole pups with oxytocin (0.25 mg/kg) at delivery. Finally, we detected minor differences in regional oxytocin receptor expression within the brains of cesarean-delivered voles, as well as microbial composition of the gut. Gene expression changes in the gut epithelium indicated that cesarean-delivered male voles have altered gut development. These results speak to the possibility of unintended developmental consequences of cesarean delivery, which currently accounts for 32.9% of deliveries in the U.S. and suggest that further research should be directed at whether hormone replacement at delivery influences behavioral outcomes in later life.
A Murine Model of Abductor Insufficiency Accelerates the Development of Hip Osteoarthritis
Authors: Geary Michael B. , Orner Caitlin A. , Shammas Helen , Reuter John M. , Loiselle Alayna E. , Wu Chia-Lung , Giordano Brian D. 
Published: May 2022

AbstractOsteoarthritis (OA) of the hip is a common and debilitating painful joint disease. A growing body of evidence suggests that there may be an association between periarticular myotendinous pathology and the development of hip OA. Thus, we hypothesized that a murine model of hip OA could be achieved through selective injury of the abductor complex around the hip. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free, active movement until sacrifice at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining (IHC) of the femoral head articular cartilage were performed, along with μCT analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significant OA severity with loss of Type II Collagen staining compared to sham control mice at 20 weeks post-surgery, comparable MMPI13 expression was observed between injury and sham groups. No significant differences in subchondral bone were found on μCT after 20 weeks following injury. Our study suggests a link between abductor dysfunction and the development of hip OA, which are common pathomorphologies encountered in routine orthopaedic clinical practice. Further, this novel animal model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.
A bifunctional kinase-phosphatase module integrates mitotic checkpoint and error-correction signalling to ensure mitotic fidelity
Authors: Corno Andrea , Cordeiro Marilia H , Allan Lindsey A , Wei Qian , Harrington Elena , Smith Richard J , Saurin Adrian T. 
Published: May 2022

SUMMARYTwo major mechanisms have evolved to safeguard genome stability during mitosis: the mitotic checkpoint delays mitosis until all chromosomes have attached to microtubules, and the kinetochore-microtubule error-correction pathway keeps this attachment process free from errors. We demonstrate here that the optimal strength and dynamics of both processes is set by a kinase-phosphatase pair (PLK1-PP2A) that engage in negative feedback on the BUB complex. Uncoupling this homeostatic feedback to skew the balance towards PLK1 produces a strong checkpoint, weak microtubule attachments, and mitotic delays. Conversely, skewing the balance towards PP2A causes a weak checkpoint, strong microtubule attachments, and chromosome segregation errors. The number of MELT motifs on the KNL1 signalling scaffold sets the optimal levels of each enzyme, because engineering KNL1 to recruit too many BUB complexes increases KNL1-PLK1/PP2A levels, and enhances checkpoint/microtubule attachment strength. In contrast, recruiting too few BUB complexes lowers KNL1-PLK1/PP2A, and decreases checkpoint/microtubule attachment strength. Both of these situations are associated with chromosome segregation errors. Together, these data demonstrate how a single bifunctional kinase-phosphatase module integrates two major mitotic processes to help preserve genome stability.