bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive coping supports children’s emotional wellness: Behavioral evidence and neuroendocrine mechanisms
Authors: Tian Ting , Chen Boxuan , Zhao Yuyao , Gao Hongyao , Chen Menglu , He Ying , Xu Jiahua , Jiang Min , Xiong Bingsen , Qin Shaozheng 
Published: February 2023

AbstractA positive coping style is recognized as a stable disposition to foster emotional wellness and resilience, enabling an adaptive process of assessing and dealing with environmental challenges. Such an adaptive process is believed to rely on a nuanced interplay of the hippocampal system and the primary stress hormone cortisol activity. As a hallmark of diurnal cortisol rhythm, cortisol awakening response (CAR) is sensitive to upcoming stress and subserves the preparation of the hippocampal system for rapid behavioral adaption. Yet, little is known about how the hippocampal system and CAR contribute to the merit of positive coping on emotional wellness. By two studies, we investigate the effects of positive coping on children’s emotional wellness and CAR, as well as longitudinal changes in hippocampal-neocortical functional systems involved in emotional processing. Behaviorally, positive coping predicted better emotional regulation ability, but lower anxiety and lower response caution in emotional decision-making. At the endocrine and neurocognitive level, positive coping was associated with greater CAR, which further predicted higher connectivity of the hippocampus with ventrolateral prefrontal cortex (vlPFC) and stimulus-sensitive neocortex one year later. Furthermore, CAR mediated an indirect association between positive coping and longitudinal increases in hippocampal-neocortical connectivity. Positive coping and CAR together could account for the maturity of vlPFC through longitudinal changes in hippocampal-neocortical connectivity. Overall, our findings suggest a cognitive-neuroendocrinal framework in which positive coping shapes hippocampal-neocortical maturation via stress hormone response to support emotional wellness.SignificanceThe role of the hippocampal system in regulating stress response is well recognized, but its contribution to emotional well-being is not yet understood. Here we show that the protective effects of positive coping on emotional well-being are contingent on two factors: the cortisol awakening response (CAR), which is sensitive to upcoming stress, and hippocampal development. We found that positive coping practices promoted emotional wellness, enhanced emotional decision-making and increased CAR in young children. Longitudinal neuroimaging analysis revealed that positive coping-related CAR predicted greater hippocampal connectivity with stimulus-sensitive neocortex one year later. Importantly, CAR acted as a mediator of the promotive influence of positive coping on the longitudinal development of hippocampal-neocortical connectivity, which contributed to the maturity of prefrontal control systems. Our findings emphasize the importance of hippocampal-neocortical development in resilient coping and emotional wellness.
Priors for natural image statistics inform confidence in perceptual decisions
Authors: West Rebecca K , A-Izzeddin Emily J , Sewell David K , Harrison William J 
Published: February 2023

AbstractDecision confidence plays a critical role in humans’ ability to make adaptive decisions in a noisy perceptual world. Despite its importance, there is currently little consensus about the computations underlying confidence judgements in perceptual decisions. In order to better understand these mechanisms, in this study we sought to address the extent to which confidence is informed by a naturalistic prior probability distribution. Contrary to previous research, we did not require participants to internalise the parameters of an arbitrary prior distribution. Instead we used a novel psychophysical paradigm which allowed us to capitalise on probability distributions of low-level image features in natural scenes, which are well-known to influence perception. Participants reported the subjective upright of naturalistic image target patches, and then reported their confidence in their orientation responses. We used computational modelling to relate the statistics of the low-level features in the targets to the distribution of these features across many natural images. As expected, we found that participants used an internalised prior of the regularities of low-level natural image statistics to inform their perceptual judgements. Critically, we also show that the same low-level image statistics predict participants’ confidence judgements. Overall, our study highlights the importance of using naturalistic task designs that capitalise on existing, long-term priors to further our understanding of the computational basis of confidence.
Pressure-driven membrane inflation through nanopores on the cell wall
Authors: Zhong Qi , Wu Chen-Xu , Ma Rui 
Published: February 2023

AbstractWalled cells, such as plants and fungi, compose an important part of the model systems in biology. The cell wall primarily functions to prevent the cell from over-expansion when exposed to water, and is a porous material distributed with nanosized pores on it. In this paper, we study the deformation of a membrane patch by an osmotic pressure through a nanopore on the cell wall. We find that there exists a critical pore size beyond which the membrane cannot stand against the pressure and would inflate out through the pore. The critical pore size scales exponentially with the membrane tension and the spontaneous curvature, and exhibits a power law dependence on the osmotic pressure. Our results also show that the liquid membrane expansion by pressure is mechanically different from the solid balloon expansion, and predict that the bending rigidity of the membrane in walled cells should be larger than that of the mammalian cells so as to prevent inflation through the pores on the cell wall.
Alternative splicing of its 5’-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies
Authors: Ang Zhiwei , Paruzzo Luca , Hayer Katharina E. , Schmidt Carolin , Torres Diz Manuel , Xu Feng , Zankharia Urvi , Zhang Yunlin , Soldan Samantha , Zheng Sisi , Falkenstein Catherine D. , Loftus Joseph P. , Yang Scarlett Y. , Asnani Mukta , King Sainos Patricia , Pillai Vinodh , Chong Emeline , Li Marilyn M. , Tasian Sarah K. , Barash Yoseph , Lieberman Paul M. , Ruella Marco , Schuster Stephen J. , Thomas-Tikhonenko Andrei 
Published: February 2023

ABSTRACTAberrant skipping of coding exons in CD19 and CD22 compromises responses to immunotherapy for B-cell malignancies. Here, we show that theMS4A1gene encoding human CD20 also produces several mRNA isoforms with distinct 5’ untranslated regions (5’-UTR). Four variants (V1-4) were detectable by RNA-seq in distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant by far. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform was found to contain upstream open reading frames (uORFs) and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching Morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, while V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly,in vitroCD20-directed CAR T cells were able to kill both V3- and V1-expressing cells, but the bispecific T cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on four post-mosunetuzumab follicular lymphoma relapses and discovered that in two of them downregulation of CD20 was accompanied by the V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies.Key PointsIn normal & malignant human B cells, CD20 mRNA is alternatively spliced into four 5’-UTR isoforms, some of which are translation-deficient.The balance between translation-deficient and -competent isoforms modulates CD20 protein levels & responses to CD20-directed immunotherapiesExplanation of NoveltyWe discovered that in normal and malignant B-cells, CD20 mRNA is alternatively spliced to generate four distinct 5’-UTRs, including the longer translation-deficient V1 variant. Cells predominantly expressing V1 were still sensitive to CD20-targeting chimeric antigen receptor T-cells. However, they were resistant to the bispecific anti-CD3/CD20 antibody mosunetuzumab, and the shift to V1 were observed in CD20-negative post-mosunetuzumab relapses of follicular lymphoma.
A robust Platform for Integrative Spatial Multi-omics Analysis to Map Immune Responses to SARS-CoV-2 infection in Lung Tissues
Authors: Tan Xiao , Grice Laura F. , Tran Minh , Mulay Onkar , Monkman James , Blick Tony , Vo Tuan , Almeida Ana Clara Simões Flórido , Junior Jarbas da Silva Motta , de Moura Karen Fernandes , Machado-Souza Cleber , Souza-Fonseca-Guimaraes Paulo , Baena Cristina Pellegrino , de Noronha Lucia , Guimaraes Fernanda Simoes Fortes , Luu Hung N. , Drennon Tingsheng , Williams Stephen , Stern Jacob , Uytingco Cedric , Pan Liuliu , Nam Andy , Cooper Caroline , Short Kirsty , Belz Gabrielle T. , Souza-Fonseca-Guimaraes Fernando , Kulasinghe Arutha , Nguyen Quan 
Published: February 2023

AbstractThe SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid, and similar, but a robust platform for deep tissue characterisation of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterise and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.
DAISIEprep: an R package for the extraction and formatting of data for the island biogeography model DAISIE
Authors: Lambert Joshua W. , Roeble Lizzie , Pannetier Théo , Etienne Rampal S. , Valente Luis 
Published: February 2023

AbstractPhylogenetic trees are commonly used to answer questions on biogeographical and diversification histories of different groups.Recently, new approaches have been developed that use community phylogenetic trees requiring a data structure distinct from the single phylogenetic trees that are commonly used, which may be a barrier to the utilisation of these approaches.DAISIE (Dynamic Assembly of Islands through Speciation, Immigration and Extinction) is an island biogeography model that can estimate rates of colonisation, speciation and extinction from phylogenetic data across insular communities, as well as simulate islands under those rates.Here we describe theDAISIEprepR package, a set of pre-processing tools to aid the extraction of data from one or many phylogenetic trees to generate data in a format interpretable by DAISIE for the application of island biogeography inference models. We present examples to illustrate the various data types that can be used.The package includes simple algorithms to extract data on island colonists and account for bio-geographical, topological and taxonomic uncertainty. It also allows flexible incorporation of either missing species or entire insular lineages when phylogenetic data are not available.DAISIEprepenables reproducible and user-friendly data extraction and formatting, and will facili-tate addressing questions about island biogeography, diversification and anthropogenic impacts in insular systems.
Multiple forms of neural processing when repeating voluntary thumb flexions
Authors: Kock Ruchella , Ghosh Arko 
Published: February 2023

AbstractThere is considerable trial-to-trial variability in single cortical neurons when performing the same action repeatedly. One possibility is that neural populations are more stable in representing actions; alternatively, they too may be distinctly engaged from trial-to-trial. To address the nature of variability in large neural populations, we captured the EEG signals time-locked to repeated voluntary thumb flexion movements (∼500 repetitions, 23 subjects). By using non-negative matrix factorization on the low-frequency sensorimotor cortical signals, we quantified the trial-to-trial motor-related potentials (MRPs) in terms of prototypical signals (meta-MRPs) and their corresponding prominence at each trial (meta-trials). Clustering the meta-MRPs across the sampled population revealed 5 distinct signal patterns. There were brain-wide correlates of these meta-MRP clusters. Cortical hemispheres were distinctly recruited from trial-to-trial as certain clusters were accompanied by bilateral motor negativity while others were characterized by ipsilateral motor negativity. The sensory feedback too was distinctly processed from trial-to-trial as the central post-movement positivity was present only for certain clusters. A poorly understood pre-motor positivity accompanied all clusters albeit varying in their timing from trial-to-trial. These patterns – including the time-varying positivity preceding the movement – were rendered invisible by the traditional averaging of the signals. We suggest that the variability in EEG signals is not just noise but a consequence of distinct activation patterns deployed by the cortex. We support the idea that the cortex flexibly switches between distinct forms of neural processing to achieve the same behavioral goals.
Peptide ligands for the affinity purification of adeno-associated viruses from HEK 293 cell lysates
Authors: Chu Wenning , Shastry Shriarjun , Barbieri Eduardo , Prodromou Raphael , Greback-Clarke Paul , Smith Will , Moore Brandyn , Kilgore Ryan , Cummings Christopher , Pancorbo Jennifer , Gilleskie Gary , Daniele Michael A. , Menegatti Stefano 
Published: February 2023

AbstractAdeno-associated viruses (AAVs) are the vector of choice for delivering gene therapies that can cure inherited and acquired diseases. Clinical research on various AAV serotypes significantly increased in recent years alongside regulatory approvals of AAV-based therapies. The current AAV purification platform hinges on the capture step, for which several affinity resins are commercially available. These adsorbents rely on protein ligands – typically camelid antibodies – that provide high binding capacity and selectivity, but suffer from low biochemical stability and high cost, and impose harsh elution conditions (pH < 3) that can harm the transduction activity of recovered AAVs. Addressing these challenges, this study introduces peptide ligands that selectively capture AAVs and release them under mild conditions (pH 6.0). The peptide sequences were identified by screening a focused library and modeledin silicoagainst AAV serotypes 2 and 9 (AAV2 and AAV9) to select candidate ligands that target homologous sites at the interface of the VP1-VP2 and VP2-VP3 virion proteins with mild binding strength (KD∼ 10-5-10-6M). Selected peptides were conjugated to Toyopearl resin and evaluated via binding studies against AAV2 and AAV9, demonstrating the ability to target both serotypes with values of dynamic binding capacity (DBC10%> 1013vp per mL of resin) and product yields (∼50-80%) on par with commercial adsorbents. The peptide-based adsorbents were finally utilized to purify AAV2 from a HEK 293 cell lysate, affording high recovery (50-80%), 80-to-400-fold reduction of host cell proteins (HCPs), and high transduction activity (up to 80%) of the purified viruses.
Distinct mobility patterns of BRCA2 molecules at DNA damage sites
Authors: Paul Maarten W. , Aaron Jesse , Wait Eric , Van Genderen Romano M. , Tyagi Arti , Kabbech Hélène , Smal Ihor , Chew Teng-Leong , Kanaar Roland , Wyman Claire 
Published: February 2023

ABSTRACTBRCA2 is an essential tumor suppressor protein involved in promoting faithful repair of DNA lesions. The activity of BRCA2 needs to be tuned precisely to be active when and where it is needed. Here, we quantified the spatio-temporal dynamics of BRCA2 in living cells using aberration-corrected multifocal microscopy (acMFM). Using multicolor imaging to identify DNA damage sites, we were able to quantify its dynamic motion patterns in the nucleus and at DNA damage sites. While a large fraction of BRCA2 molecules localized near DNA damage sites appear immobile, an additional fraction of molecules exhibits subdiffusive motion, providing a potential mechanism to retain an increased number of molecules at DNA lesions. Super-resolution microscopy revealed inhomogeneous localization of BRCA2 relative to other DNA repair factors at sites of DNA damage. This suggests the presence of multiple nanoscale compartments in the chromatin surrounding the DNA lesion, which could play an important role in the contribution of BRCA2 to the regulation of the repair process.
Selective targeting of α4β7/MAdCAM-1 axis suppresses liver fibrosis by reducing proinflammatory T cell recruitment to the liver
Authors: Gupta Biki , Rai Ravi Prakash , Pal Pabitra B. , Chaudhary Sudrishti , Chiaro Anna , Seaman Shannon , Singhi Aatur D. , Monga Satdarshan P. , Iyer Smita S. , Raeman Reben 
Published: February 2023

ABSTRACTIntegrin α4β7+ T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here we report increased accumulation of α4β7+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl4-induced liver fibrosis was associated with enrichment of intrahepatic α4β7+ CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of α4β7or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl4treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of α4β7+ CD4 and CD8 T cells suggesting that α4β7/MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and α4β7+ T cells promote hepatic fibrosis progression. Analysis of hepatic α4β7+ and α4β7-CD4 T cells revealed that α4β7+ CD4 T cells enriched for markers of activation and proliferation demonstrating an effector phenotype. Notably, blockade of α4β7or MAdCAM-1 did not affect the recruitment of Foxp3+ regulatory T cells, demonstrating the specificity of α4β7/MAdCAM-1 axis in regulating effector T cell recruitment to the liver. The findings suggest that α4β7+ T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of α4β7or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.
Human Arm Redundancy - A New Approach for the Inverse Kinematics Problem
Authors: Barliya Avi , Krausz Nili , Naaman Hila , Chiovetto Enrico , Giese Martin , Flash Tamar 
Published: February 2023

AbstractThe inverse kinematics problem deals with the question of how the nervous system coordinates movement to resolve redundancy, such as in the case of arm reaching movements where more degrees of freedom are available at the joint versus hand level. In particular, this work focuses on determining which coordinate frames can best represent human movements, allowing the motor system to solve the inverse kinematics problem in the presence of kinematic redundancies. In particular, in this work we used a multi-dimensional sparse source separation method called FADA to derive sets of basis functions (here called sources) for both the task and joint spaces, with joint space being represented in terms of either the absolute or anatomical joint angles. We assessed the similarities between the joint and task sources in each of these joint representations. We found that the time-dependent profiles of the absolute reference frame’s sources show greater similarity to those of the corresponding sources in the task space. This result was found to be statistically significant. Hence, our analysis suggests that the nervous system represents multi-joint arm movements using a limited number of basis functions, to allow for simple transformations between task and joint spaces. Importantly, joint space seems to be represented in terms of an absolute reference frame to achieve successful performance and simplify inverse kinematics transformations in the face of the existing kinematic redundancies. Further studies will be needed to determine the generalizability of this finding and its implications for neural control of movement.
The cytidine deaminase APOBEC3A is required for large ribosomal subunit biogenesis
Authors: McCool Mason A. , Bryant Carson J. , Abriola Laura , Surovtseva Yulia V. , Baserga Susan J. 
Published: February 2023

AbstractCancer initiates as a consequence of genomic mutations, and its subsequent progression relies on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. To form more established connections between these two cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory’s established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. We show that APOBEC3A is required for cell cycle progression and global protein synthesis. More specifically, we highlight APOBEC3A’s role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. Through an innovative nuclear RNA sequencing methodology, we identify candidate APOBEC3A C-to-U editing sites on the pre-rRNA and pre-mRNAs for the first time. Our work reveals the exciting possibility that the pre-rRNA can be edited during its maturation. More broadly, we found an additional function of APOBEC3A in cancer pathology, expanding its relevance as a target for cancer therapeutics.