bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social stressors associated with age-related T lymphocyte percentages in older US adults: Evidence from the Health and Retirement Study
Authors: Klopack Eric T. , Crimmins Eileen M. , Cole Steve W. , Seeman Teresa E. , Carroll Judith E. 
Published: March 2022

AbstractExposure to stress is a well-established risk factor of poor health and accelerated aging. Immune aging, including declines in naive and increases in late memory and terminally differentiated T cells, plays an important role in immune health and tissue specific aging, and may contribute to the observed elevated risk for poor health among those who experience high psychosocial stress. However, past data have been limited in estimating the contribution of life stress to the development of accelerated immune aging and investigating mediators such as lifestyle and CMV infection, that might be useful points of intervention. The current study utilizes a national sample of 5744 US adults over the age of 50 to assess the relationship of social stress (viz., everyday discrimination, stressful life events, lifetime discrimination, life trauma, and chronic stress) with flow cytometric estimates of immune aging, including naive and terminally differentiated T cell percentages and the ratio of CD4+to CD8+T cells. Experiencing life trauma and chronic stress was related to a lower percentage of CD4+naive T cells. Higher everyday discrimination, lifetime discrimination, and chronic stress were each associated with a greater percentage of terminally differentiated CD4+T cells. Stressful life events, high lifetime discrimination, and life trauma were related to a lower percentage of CD8+naive T cells. Stressful life events, high lifetime discrimination and chronic stress were associated with a higher percentage terminally differentiated CD8+T cells. High lifetime discrimination and chronic stress was related to a lower CD4+:CD8+ratio. Lifestyle factors and cytomegalovirus (CMV) seropositivity partially reduced these effects. Results identify psychosocial stress as a contributor to accelerating immune aging by decreasing naive and increasing senescent T cells.
Clinical and Computational Speech Measures are Associated with Social Cognition in Schizophrenia Spectrum Disorders
Authors: Tang Sunny X. , Cong Yan , Nikzad Amir H. , Mehta Aarush , Cho Sunghye , Hänsel Katrin , Berretta Sarah , Kane John , Malhotra Anil K 
Published: March 2022

AbstractIn this study, we compared three domains of social cognition (emotion processing, mentalization, and attribution bias) to clinical and computational language measures in 63 participants with schizophrenia spectrum disorders. Based on the active inference model for discourse, we hypothesized that emotion processing and mentalization, but not attribution bias, would be related to language disturbances. Clinical ratings for speech disturbance assessed disorganized and underproductive dimensions. Computational features included speech graph metrics, use of modal verbs, use of first-person pronouns, cosine similarity of adjacent utterances, and measures of sentiment; these were represented by four principal components characterizing content-rich speech, insular speech, local coherence, and affirmative speech. We found that higher clinical ratings for disorganized speech predicted greater impairments in both emotion processing and mentalization, and that these relationships remained significant when accounting for demographic variables, overall psychosis symptoms, and verbal ability. Similarly, computational features reflecting insular speech also consistently predicted greater impairment in emotion processing. There were notable trends for underproductive speech and decreased content-rich speech predicting mentalization ability. Exploratory longitudinal analyses in a small subset of participants (n=17) found that improvements in both emotion processing and mentalization were predicted by improvements in disorganized speech. Attribution bias did not demonstrate strong relationships with language measures. Altogether, our findings are consistent with the active inference model of discourse and suggest greater emphasis on treatments that target social cognitive and language systems.
Investigating the temporal pattern of neuroimaging-based brain age estimation as a biomarker for Alzheimer’s Disease related neurodegeneration
Authors: Taylor Alexei , Zhang Fengqing , Niu Xin , Heywood Ashley , Stocks Jane , Feng Gangyi , Popuri Karteek , Beg Mirza Faisal , Wang Lei ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

ABSTRACTNeuroimaging-based brain-age estimation via machine learning has emerged as an important new approach for studying brain aging. The difference between one’s estimated brain age and chronological age, the brain age gap (BAG), has been proposed as an Alzheimer’s Disease (AD) biomarker. However, most past studies on the BAG have been cross-sectional. Identifying how an individual’s BAG temporal pattern changes over time would enable improved prediction of clinical outcome based on neurophysiological changes and better understanding of AD progression. To fill this gap, our study conducted predictive modeling using large neuroimaging data with up to 8 years of follow-up to examine the temporal patterns of the BAG’s trajectory and how it varies by subject-level characteristics and disease status. To the best of our knowledge, this is the first effort to take a longitudinal approach to investigate the pattern and rate of change in BAG over time in individuals who progress from mild cognitive impairment (MCI) to clinical AD. Combining multimodal imaging data in a support vector regression model to estimate brain age yielded improved performance than single modality. Multilevel modeling results showed the BAG followed a linear increasing trajectory with a significantly faster rate in individuals with MCI who progressed to AD compared to cognitively normal or MCI individuals who did not progress. The dynamic changes in the BAG during AD progression were further moderated by gender and APOε4 carriership. Findings demonstrate the BAG as a potential biomarker for understanding individual specific temporal patterns related to AD progression.
Task feedback suggests a post-perceptual component to serial dependence
Authors: Fulvio Jacqueline M. , Rokers Bas , Samaha Jason 
Published: March 2022

AbstractDecisions across a range of perceptual tasks are biased toward past stimuli. Such serial dependence is thought to be an adaptive low-level mechanism that promotes perceptual stability across time. However, recent studies suggest post-perceptual mechanisms may also contribute to serially-biased responses, calling into question a single locus of serial dependence and the nature of integration of past and present sensory inputs. We measured serial dependence in the context of a 3D motion perception task where uncertainty in the sensory information varied substantially from trial to trial. We found that serial dependence varied with stimulus properties that impact sensory uncertainty on the current trial. Reduced stimulus contrast was associated with an increased bias toward the previous trial’s stimulus direction. Critically, performance feedback, which reduced sensory uncertainty, abolished serial dependence. These results provide clear evidence for a post-perceptual locus of serial dependence in 3D motion perception and support the role of serial dependence as a response strategy in the face of substantial sensory uncertainty.
No evidence for asymmetric sperm deposition in a species with asymmetric male genitalia
Authors: van Gammeren Sanne , Lang Michael , Rücklin Martin , Schilthuizen Menno 
Published: March 2022

AbstractBackgroundAsymmetric genitalia have repeatedly evolved in animals, yet the underlying causes for their evolution are mostly unknown. The fruitfly Drosophila pachea has asymmetric external genitalia and an asymmetric phallus with a right-sided gonopore. The complex of female and male genitalia is asymmetrically twisted during copulation and males adopt a right-sided copulation posture on top of the female. We wished to investigate if asymmetric male genital morphology and a twisted gentitalia complex may be associated with differential allocation of sperm into female sperm storage organs.MethodsWe examined the internal complex of female and male reproductive organs by micro-computed tomography using Synchrotron X-rays before, during and after copulation. In additon, we monitored sperm aggregation states and timing of sperm transfer during copulation by premature interruption of copulation at different time-points.ResultsThe asymmetric phallus is located at the most caudal end of the female abdomen during copulation. The female reproductive tract, in particular the oviduct, re-arranges during copulation. It is narrow in virgin females and forms a broad vesicle at 20 min after the start of copulation. Sperm transfer into female sperm storage organs (spermathecae) was only in a minority of examined copulation trials (13 / 64). Also, we found that sperm was mainly transferred early, at 2 - 4 min after the start of copulation. We did not detect a particular pattern of sperm allocation in the left or right spermathecae. Sperm adopted a granular or filamentous aggregation state in the female uterus and spermathecae, respectively.DiscussionNo evidence for asymmetric sperm deposition was identified that could be associated with asymmetric genital morphology or twisted complexing of genitalia. Male genital asymmetry may potentially have evolved as a consequence of a complex internal alignment of reproductive organs during copulation in order to optimize low sperm transfer rates.
Discovering dynamical models of human behavior
Authors: Jaffe Paul I. , Poldrack Russell A. , Schafer Robert J. , Bissett Patrick G. 
Published: March 2022

AbstractResponse time (RT) data collected from cognitive tasks are a cornerstone of psychology and neuroscience research, yet existing models of these data either make strong assumptions about the data generating process or are limited to modeling single trials. We introduce task-DyVA, a deep learning framework in which expressive dynamical systems are trained to reproduce sequences of RTs observed in data from individual human subjects. Models fitted to a large task-switching dataset captured subject-specific behavioral differences with high temporal precision, including task-switching costs. Through perturbation experiments and analyses of the models’ latent dynamics, we find support for a rational account of switch costs in terms of a stability-flexibility tradeoff. Thus, our framework can be used to discover interpretable cognitive theories that explain how the brain dynamically gives rise to behavior.
Exploring links between climatic predictability and the evolution of within- and transgenerational plasticity
Authors: Halali Sridhar , Saastamoinen Marjo 
Published: March 2022

ABSTRACTIn variable environments, phenotypic plasticity can increase fitness by providing tight environment-phenotype matching. However, adaptive plasticity is expected to evolve only when the future selective environment can be predicted based on the prevailing conditions. That is, the juvenile environment should be predictive of the adult environment (within-generation plasticity) or the parental environment should be predictive of the offspring environment (transgenerational plasticity). Here, we test links between environmental predictability and evolution of adaptive plasticity by combining time series analyses and a common garden experiment using temperature as a stressor in a temperate butterfly (Melitaea cinxia). Time series analyses revealed that across season fluctuations in temperature over 48 years is overall predictable. However, within the growing season, temperature fluctuations showed high heterogeneity across years with low autocorrelations and timing of temperature peaks were asynchronous. Most life-history traits showed strong within-generation plasticity for temperature and traits such as body size and growth rate broke the temperature-size rule. Evidence for transgenerational plasticity, however, was weak and detected for only two traits each in an adaptive and non-adaptive direction. We suggest that low predictability of temperature fluctuations within the growing season likely disfavours the evolution of adaptive transgenerational plasticity but instead favours strong within-generation plasticity.
Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients
Authors: Shi Zhi-Hong , Zhao Zhong , Liu Ling-Zhen , Bian Xian-Ling , Zhang Yun 
Published: March 2022

AbstractDuring animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, βγ-CAT is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and fatty acids, called nutrisomes, were released in the presence of βγ-CAT. These specific nutrient vesicles were readily taken by starved muscle cells to support their survival. The results uncovered that pore-forming protein βγ-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.
Single-cell RNA-sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the development of osteoarthritis
Authors: Hu Yan , Cui Jin , Liu Han , Wang Sicheng , Zhou Qirong , Zhang Hao , Guo Jiawei , Cao Liehu , Chen Xiao , Xu Ke , Su Jiacan 
Published: March 2022

AbstractThe cellular composition and underlying spatiotemporal transformation processes of subchondral bone in osteoarthritis (OA) remain unknown. Herein, various cell subsets from tibial plateau of OA patients are identified, and the mechanism of subchondral microstructure alteration is elaborated using single-cell RNA sequencing technique. We identified two novel endothelial cell (EC) populations characterized by either exosome synthesis and inflammation response, or vascular function and angiogenesis. Three osteoblast (OB) subtypes are introduced, separately related to vascularization, matrix manufacturing and matrix mineralization. The distinct roles and functions of these novel phenotypes in OA development are further discussed, as well as interaction network between these subpopulations. The variation tendency of each population is testified in a DMM mouse model. The identification of cell types demonstrates a novel taxonomy and mechanism for ECs and OBs inside subchondral bone area, provides new insights into the physiological and pathological behaviors of subchondral bone in OA pathogenesis.
Genome mining, phylogenetic, and functional analysis of arsenic (As) resistance operons in Bacillus strains, isolated from As-rich hot spring microbial mats
Authors: Flores Aurora , Valencia-Marín María F. , Chávez-Avila Salvador , Ramírez-Díaz Martha I. , de los Santos-Villalobos Sergio , Meza-Carmen Victor , del Carmen Orozco-Mosqueda Ma. , Santoyo Gustavo 
Published: March 2022

AbstractThe geothermal zone of Araró, México, is located within the trans-Mexican volcanic belt, an area with numerous arsenic (As)-rich hot springs. In this study, the draft genome sequence of two endemic Bacillus strains (ZAP17 and ZAP62) from Araró microbial mat hot springs was determined, which were able to grow on arsenate (up to 64 mM) and arsenite (up to 32 mM). Phylogenetic analysis based on 16S rRNA and gyrB sequences, as well as genome sequence analysis based on average nucleotide identity (>96%) and digital DNA–DNA hybridization (>70%), indicated that these strains belong to the Bacillus paralicheniformis ZAP17 and Bacillus altitudinis ZAP62. Furthermore, through genome mining, it was identified two arsenic resistance operons, arsRBC, and arsRBCDA in both strains as potential determinants of arsenic (As) resistance. Predicted ArsA (arsenial pump-driving ATPase), ArsB (Arsenical efflux pump protein), ArsC (Arsenate reductase), ArsD (Arsenical efflux pump protein) and ArsR (Metalloregulator/ars operon repressor) proteins, clearly grouped with their respective clades corresponding to other characterized bacterial species, mainly Firmicutes. To further evaluate the functionality of the ars operons in ZAP17 and ZAP62 strains, our results showed that arsRBC and arsRBCDA genes were expressed in the presence of arsenite (III). Finally, the presence of ars operons in the genome of Bacillus species residing in As-rich environments, such as the Araró hot springs, might be a potential mechanism to survive under such harsh conditions, as well as to design sustainable bioremediation strategies.
PrrA modulates Mycobacterium tuberculosis response to multiple environmental cues and is critically regulated by serine/threonine protein kinases
Authors: Giacalone David , Yap Rochelle E. , Ecker Alwyn M. V. , Tan Shumin 
Published: March 2022

ABSTRACTThe ability of Mycobacterium tuberculosis (Mtb) to adapt to its surrounding environment is critical for the bacterium to successfully colonize its host. Transcriptional changes are a vital mechanism by which Mtb responds to key environmental signals experienced, such as pH, chloride (Cl-), nitric oxide (NO), and hypoxia. However, much remains unknown regarding how Mtb coordinates its response to the disparate signals seen during infection. Utilizing a transcription factor (TF) overexpression plasmid library in combination with a pH/Cl--responsive luciferase reporter, we identified the essential TF, PrrA, part of the PrrAB two-component system, as a TF involved in modulation of Mtb response to pH and Cl-. Further studies revealed that PrrA also affected Mtb response to NO and hypoxia, with prrA overexpression dampening induction of NO and hypoxia- responsive genes. PrrA is phosphorylated not just by its cognate sensor histidine kinase PrrB, but also by serine/threonine protein kinases (STPKs) at a second distinct site. Strikingly, a STPK phosphoablative PrrA variant was significantly dampened in its response to NO versus wild type Mtb, disrupted in its ability to adaptively enter a non-replicative state upon extended NO exposure, and attenuated for in vivo colonization. Together, our results reveal PrrA as an important regulator of Mtb response to multiple environmental signals, and uncover a critical role of STPK regulation of PrrA in its function.
Screening of hydrocarbon-stapled peptides for inhibition of calcium-triggered exocytosis
Authors: Lai Ying , Tuvim Michael J. , Leitz Jeremy , Peters John , Pfuetzner Richard A. , Esquivies Luis , Zhou Qiangjun , Czako Barbara , Cross Jason B. , Jones Philip , Dickey Burton F. , Brunger Axel T. 
Published: March 2022

AbstractThe so-called primary interface between the SNARE complex and synaptotagmin-1 (Syt1) is essential for Ca2+-triggered neurotransmitter release in neuronal synapses. The interacting residues of the primary interface are conserved across different species for synaptotagmins (Syt1, Syt2, Syt9), SNAP-25, and syntaxin-1A homologs involved in fast synchronous release. This Ca2+-independent interface forms prior to Ca2+-triggering and plays a role in synaptic vesicle priming. This primary interface is also conserved in the fusion machinery that is responsible for mucin granule membrane fusion. Ca2+ stimulated mucin secretion is mediated by the SNAREs syntaxin-3, SNAP-23, VAMP8, synaptotagmin-2, and other proteins. Here, we designed and screened a series of hydrocarbon-stapled peptides consisting of SNAP-25 fragments that included some of the key residues involved in the primary interface as observed in high-resolution crystal structures. We selected a subset of four stapled peptides that were highly α-helical as assessed by circular dichroism and that inhibited both Ca2+-independent and Ca2+- triggered ensemble lipid-mixing with neuronal SNAREs and Syt1. In a single-vesicle content-mixing assay with reconstituted neuronal SNAREs and synaptotagmin-1 or with reconstituted airway SNAREs and synaptotagmin-2, the selected peptides also suppressed Ca2+-triggered fusion. Taken together, hydrocarbon-stapled peptides that interfere with the primary interface consequently inhibit Ca2+-triggered exocytosis. Our inhibitor screen suggests that these compounds may be useful to combat mucus hypersecretion that is a major cause of airway obstruction in the pathophysiology of COPD, asthma and cystic fibrosis.
Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis
Authors: An Seong J. , Anneken Alexander , Xi Zhiqun , Choi Changseon , Schlessinger Joseph , Toomre Derek 
Published: March 2022

AbstractThe phosphoinositide-3 kinase (PI-3K)/AKT cell survival pathway is an important pathway activated by EGFR signaling. Here we show, that in addition to previously described critical components of this pathway, i.e., the docking protein Gab1, the PI-3K/AKT pathway in epithelial cells is regulated by the exocyst complex, which is a vesicle tether that is essential for exocytosis. Using live-cell imaging, we demonstrate that PI(3,4,5)P3 levels fluctuate at the membrane on a minutes time scale and that these fluctuations are associated with local PI(3,4,5)P3 increases at sites where recycling vesicles undergo exocytic fusion. Supporting a role for exocytosis in PI(3,4,5)P3 generation, acute promotion of exocytosis by optogenetically driving exocyst-mediated vesicle tethering upregulates PI(3,4,5)P3 production and AKT activation. Conversely, acute inhibition of exocytosis using Endosidin2, a small-molecule inhibitor of the exocyst subunit Exo70, impairs PI(3,4,5)P3 production and AKT activation induced by EGF stimulation of epithelial cells. Moreover, prolonged inhibition of EGF signaling by EGFR tyrosine kinase inhibitors results in spontaneous reactivation of AKT without a concomitant relief of EGFR inhibition. However, this reactivation can be negated by acutely inhibiting the exocyst. These experiments demonstrate that exocyst-mediated exocytosis – by regulating PI(3,4,5)P3 levels at the plasma membrane – subserves activation of the PI-3K/AKT pathway by EGFR in epithelial cells.