bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent remodelling of nucleolar 60S subunit precursors by the Rea1 ATPase and Spb4 RNA helicase
Authors: Mitterer Valentin , Thoms Matthias , Buschauer Robert , Berninghausen Otto , Hurt Ed , Beckmann Roland 
Published: November 2022

AbstractBiogenesis intermediates of nucleolar ribosomal 60S precursor particles undergo a number of structural maturation steps before they transit to the nucleoplasm and are finally exported into the cytoplasm. The AAA+-ATPase Rea1 participates in the nucleolar exit by releasing the Ytm1–Erb1 heterodimer from the evolving pre-60S particle. Here, we show that the DEAD-box RNA helicase Spb4 with its interacting partner Rrp17 is further integrated into this maturation event. Spb4 binds to a specific class of late nucleolar pre-60S intermediates, whose cryo-EM structure revealed how its helicase activity facilitates melting and restructuring of 25S rRNA helices H62 and H63/H63a prior to Ytm1–Erb1 release.In vitromaturation of such Spb4-enriched pre-60S particles, incubated with purified Rea1 and its associated pentameric Rix1-complex in the presence of ATP, combined with cryo-EM analysis depicted the details of the Rea1-dependent large-scale pre-ribosomal remodelling. Our structural insights unveil how the Rea1 ATPase and Spb4 helicase remodel late nucleolar pre-60S particles by rRNA restructuring and dismantling of a network of several ribosomal assembly factors.
Structure of theSaccharolobus solfataricustype III-D CRISPR effector
Authors: Cannone Giuseppe , Kompaniiets Dmytro , Graham Shirley , White Malcolm F , Spagnolo Laura 
Published: November 2022

AbstractCRISPR-Cas is a prokaryotic adaptive immune system, classified into six different types, each characterised by a signature protein. Type III systems, classified based on the presence of a Cas10 subunit, are rather diverse multi-subunit assemblies with a range of enzymatic activities and downstream ancillary effectors. The broad array of current biotechnological CRISPR applications is mainly based on proteins classified as Type II, however recent developments established the feasibility and efficacy of multi-protein Type III CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes. The crenarchaeonSaccharolobus solfataricushas two type III system subtypes (III-B and III-D). Here, we report the cryo-EM structure of the Csm Type III-D complex fromS. solfataricus(SsoCsm), which uses CRISPR RNA to bind target RNA molecules, activating the Cas10 subunit for antiviral defence. The structure reveals the complex organisation, subunit/subunit connectivity and protein/guide RNA interactions of the SsoCsm complex, one of the largest CRISPR effectors known.
Forgetting Dynamics For Items of Different Categories
Authors: Georgiou Antonios , Katkov Mikhail , Tsodyks Misha 
Published: November 2022

AbstractHow the dynamic evolution of forgetting changes for different materials is unexplored. By using a common experimental paradigm with stimuli of different types, we were able to directly cross-examine the emerging dynamics and we found that even though the presentation sets differ minimally by design, the obtained curves appear to fall on a discrete spectrum. Furthermore, we have previously proposed a model of forgetting based on the notion of retrograde interference with a single integer parameter. All measured curves were compatible with the model with different values of the parameter, hinting to a potential common underlying mechanism of forgetting.
Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain
Authors: Newman Benjamin T. , Danoff Joshua S. , Lynch Morgan E. , Giamberardino Stephanie N. , Gregory Simon G. , Connelly Jessica J. , Druzgal T. Jason , Morris James P. 
Published: November 2022

AbstractEpigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. Given the blood plasma correlations used to develop GrimAge, a specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual’s brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions ‘lesioned’ by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.
Circuit-specific selective vulnerability in the DMN persists in the face of widespread amyloid burden
Authors: Brunwasser Samuel J. , Farris Clayton , Elmore Halla , Dyer Eva L. , Nair Kiran Bhaskaran , Whitesell Jennifer D. , Harris Julie A. , Hengen Keith B. 
Published: November 2022

ABSTRACTThe relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the default mode network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. Here we directly test this hypothesis using long-term recordings of the spiking activity of ensembles of single units in freely behaving mice characterized by global cortical and hippocampal Aβ burden (APP/PS1). Specifically, we track the interactions of a population of neurons within a DMN region and two additional populations that comprise monosynaptic targets, one within and the other outside the DMN. In addition, we record single neurons in hippocampus and examine interactions between in-DMN and out-DMN cortical circuits triggered on hippocampal sharp-wave ripples, stereotyped hippocampal events that contribute to memory consolidation in the cortex. We examine the statistics of local activity as well as inter-regional communication in a region, genotype, and brain-state dependent manner. Our data reveal dysfunction restricted to in-DMN projecting circuits. In contrast, communication along neuronal projections that originate in the DMN but target out-DMN populations are equivalent in APP/PS1 and WT mice. Circuit dysfunction is most evident throughout sleep as well as within sharp-wave ripples. Our results indicate that cells in the DMN exhibit differential intrinsic vulnerability to amyloid injury dependent on their projection targets.
Interpreting transient interactions of intrinsically disordered proteins
Authors: Wohl Samuel , Zheng Wenwei 
Published: November 2022

AbstractThe flexible nature of intrinsically disordered proteins (IDPs) gives rise to a conformational ensemble with a diverse set of conformations. The simplest way to describe this ensemble is through a homopolymer model without any specific interactions. However, there has been growing evidence that the conformational properties of IDPs and their relevant functions can be affected by transient interactions between specific and non-local pairs of amino acids. Interpreting these interactions from experimental methods, each of which is most sensitive to a different distance regime referred to as probing length, remains a challenging and unsolved problem. Here, we first show that transient interactions can be realized between short fragments of charged amino acids by generating conformational ensembles using model disordered peptides and coarse-grained simulations. Using these ensembles, we investigate how sensitive different types of experimental measurements are to the presence of transient interactions. We find methods with shorter probing lengths to be more appropriate to detect these transient interactions, but one experimental method is not sufficient due to the existence of other weak interactions typically seen in IDPs. Finally, we develop an adjusted polymer model with an additional short-distance peak which can robustly reproduce the distance distribution function from two experimental measurements with complementary short and long probing lengths. This new model can suggest whether a homopolymer model is insufficient for describing a specific IDP, and meet the challenge of quantitatively identifying specific transient interactions from a background of nonspecific weak interactions.
Promoter-adjacent DNA hypermethylation can downmodulate gene expression:TBX15in the muscle lineage
Authors: Ehrlich Kenneth C. , Lacey Michelle , Baribault Carl , Sen Sagnik , Esteve Pierre Olivier , Pradhan Sriharsa , Ehrlich Melanie 
Published: November 2022

AbstractTBX15, which encodes a differentiation-related transcription factor, displays promoter-adjacent DNA hypermethylation in myoblasts and skeletal muscle (psoas) that is absent from non-expressing cells in other lineages. By whole-genome bisulfite sequencing (WGBS) and enzymatic methyl-seq (EM-seq), these hypermethylated regions were found to border both sides of a constitutively unmethylated promoter. To understand the functionality of this DNA hypermethylation, we cloned the differentially methylated sequences (DMRs) in CpG-free reporter vectors and tested them for promoter or enhancer activity upon transient transfection. These cloned regions exhibited strong promoter activity and, when placed upstream of a weak promoter, strong enhancer activity specifically in myoblast host cells.In vitroCpG methylation targeted to the DMR sequences in the plasmids resulted in 86 - 100% loss of promoter or enhancer activity, depending on the insert sequence. These results as well as chromatin epigenetic and transcription profiles for this gene in various cell types support the hypothesis that DNA hypermethylation immediately upstream and downstream of the unmethylated promoter region suppresses enhancer/extended promoter activity, thereby downmodulating, but not silencing, expression in myoblasts and certain kinds of skeletal muscle. This promoter-border hypermethylation is not found in cell types with a silentTBX15gene probably because they have no transcription to modulate.TBX18, TBX2, TBX3andTBX1displayTBX15-like hypermethylated DMRs at their promoter borders and preferential expression in myoblasts. Therefore, promoter-adjacent DNA hypermethylation for downmodulating transcription to prevent overexpression may be used more frequently for transcription regulation than currently appreciated.
Mutations inrpoBthat confer rifampicin resistance can alter levels of peptidoglycan precursors and affect β-lactam susceptibility
Authors: Patel Yesha , Soni Vijay , Rhee Kyu Y. , Helmann John D. 
Published: November 2022

AbstractBacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance determining region (RRDR) ofrpoBthat reduce antibiotic binding. These changes can also alter transcription and thereby have pleiotropic effects on bacterial fitness. Here, we studied the evolution of resistance inBacillus subtilisto the synergistic combination of RIF and the β-lactam cefuroxime (CEF). Two independent evolution experiments led to the recovery of a singlerpoBallele (S487L) that was able to confer resistance to RIF and CEF through a single mutation. Two other common RRDR mutations made the cells 32x more sensitive to CEF (H482Y) or led to only modest CEF resistance (Q469R). The diverse effects of these three mutations on CEF resistance are correlated with differences in the expression of peptidoglycan (PG) synthesis genes and in the levels of two metabolites crucial in regulating PG synthesis, glucosamine-6-phosphate (GlcN-6-P) and UDP-N-acetylglucosamine (UDP-GlcNAc). We conclude that RRDR mutations can have widely varying effects on pathways important for cell wall biosynthesis, and this may restrict the spectrum of mutations that arise during combination therapy.ImportanceRifampicin (RIF) is one of the most valued drugs in the treatment of tuberculosis. TB treatment relies on a combination therapy, and for multidrug resistant strains may include β-lactams. Mutations inrpoBpresent a common route for emergence of resistance to RIF. In this study, usingB. subtilisas a model, we evaluate the emergence of resistance for the synergistic combination of RIF and the β-lactam cefuroxime (CEF). One clinically-relevantrpoBmutation conferred resistance to both RIF and CEF, whereas two others increased CEF sensitivity. We were able to link these phenotypes to accumulation of specific PG precursors. Mainly, UDP-GlcNAc through its GlmR mediated influence on GlmS activity has a strong impact on CEF resistance. Since these mutations are clinically relevant, these effects on CEF sensitivity may help refine the use of β-lactams in TB therapy.
Social visibility and substance in corporate social sustainability disclosures
Authors: Pollach Irene , Schaper Stefan 
Published: November 2022

PurposeSocial and environmental reports have become an increasingly regulated area of corporate reporting and communication. Nevertheless, the substance and level of detail present in such disclosures is largely at the discretion of companies, which has implications for the value of such disclosures to stakeholders. The purpose of this study is to shed light on social visibility as a determinant of the variation in substance found in social disclosures in order to understand underlying reasons for why some firms offer more substance than others in their social disclosures.Design/methodology/approachBased on a number of hypotheses, which are combined into social visibility, the paper investigates whether a firm's social visibility is a determinant of substance in social disclosures. To this end, the case of modern slavery statements is used as a recently introduced and legally mandated form of social sustainability disclosures.FindingsThe findings suggest that social visibility can explain part of the variation in the substance of social disclosures. However, for the remaining part, it is argued that substance in social disclosures can also be driven by institutional logics, which shape organizational outcomes in specific contexts, but are largely unobservable.Originality/valueThis article contributes new insights to the literature on the relationship between corporate social visibility and the substance of social disclosures.
Health status and elderly care: theory and evidence from a randomized trial with COPD patients in China
Authors: ZONG Qingqing , ZHANG Yi , CHEN Yuyu 
Published: November 2022

PurposeThis paper theoretically and empirically analyzes the effects of the elderly’s physical health status on their need for care and the choice of care models in China.Design/methodology/approachEmpirically, the estimation results of a large-sample randomized intervention trial with chronic obstructive pulmonary disease (COPD) patients through the difference-in-difference method indicated the following: (1) After the COPD intervention trial, the physical health status of the elderly in the treatment group improved significantly, the need for care was substantially reduced and the health improvement led to a 35.5% reduction in the probability of using elderly care. (2) The reduction in the need for care regarding the treatment group occurred mainly in social care. The probability of using social care decreased by 67.8% due to the elderly’s health improvement, while that of home care remained unchanged generally. (3) Further heterogeneity tests suggested that families with fewer potential internal resources for caregiving had a more pronounced decline in the need for social care.FindingsTheoretically, these empirical results support the existence of the “pecking order” theory in the family’s choice of elderly care model, that is, families tend to employ all internal resources for caregiving before resorting to social care, resulting in a higher sensitivity of social care to health.Originality/valueThe main policy implication of this paper is that ex ante preventive health intervention policies can significantly alleviate the burden of care, especially social care, on families. And preventive health intervention policies are particularly effective in reducing the burden of the families with relatively few resources for informal internal care.
Two dimensional MHD nanofluid flow analysis of fractional dual-phase-lag heat conduction between inclined cylinders with variable thickness
Authors: Jiang Jinxia , Zhao Haojie , Zhang Yan 
Published: November 2022

Purpose
This study aims to investigate the two-dimensional magnetohydrodynamic flow and heat transfer of a fractional Maxwell nanofluid between inclined cylinders with variable thickness. Considering the cylindrical coordinate system, the constitutive relation of the fractional viscoelastic fluid and the fractional dual-phase-lag (DPL) heat conduction model, the boundary layer governing equations are first formulated and derived.

Design/methodology/approach
The newly developed finite difference scheme combined with the L1 algorithm is used to numerically solve nonlinear fractional differential equations. Furthermore, the effectiveness of the algorithm is verified by a numerical example.

Findings
Based on numerical analysis, the effects of parameters on velocity and temperature are revealed. Specifically, the velocity decreases with the increase of the fractional derivative parameter α owing to memory characteristics. The temperature increase with the increase of fractional derivative parameter ß due to a decrease in thermal resistance. From a physical perspective, the phase lag of the heat flux vector and temperature gradients τq and τT exhibit opposite trends to the temperature. The ratio τT/τq plays an important role in controlling different heat conduction behaviors. Increasing the inclination angle θ, the types and volume fractions of nanoparticles Φ can increase velocity and temperature, respectively.

Originality/value
Fractional Maxwell nanofluid flows from a fixed-thickness pipe to an inclined variable-thickness pipe, and the fractional DPL heat conduction model based on materials is considered, which provides a basis for the safe and efficient transportation of high-viscosity and condensable fluids in industrial production.
Examining prison entrepreneurship programs, self-efficacy and entrepreneurial resilience as drivers for prisoners' entrepreneurial intentions
Authors: Ciptono Wakhid Slamet , Anggadwita Grisna , Indarti Nurul 
Published: November 2022

PurposeEx-prisoners often experience negative stigma from society, making it difficult to find employment upon release. Prison institutions play an active role in building character and improving prisoners' skills by providing various empowerment programs to increase opportunities for their economic potential. However, these programs are considered not optimal in increasing the entrepreneurial intentions of prisoners. This study aims to identify the effects of prison entrepreneurship programs, entrepreneurial resilience and self-efficacy as drivers in increasing prisoners' entrepreneurial intentions. This study also examines the effect of these variables focusing on prisoners with neither entrepreneurial experience nor entrepreneurial training.Design/methodology/approachThis study deployed a quantitative method by distributing a questionnaire to prisoners involved in talent and skill development activities (called BIMKER, an abbreviation in Indonesian, which means Work Guidance), a compulsory program provided by prison institutions. A total of 204 prisoners, including 70 with no entrepreneurial experience, completed the research questionnaire in one of the prison institutions in Indonesia. Partial least sequential-structural equation modeling (PLS-SEM) was used as the analytical technique.FindingsThe study findings show that the prison entrepreneurship program has not been able to influence prisoners' entrepreneurial intentions directly. However, the prison entrepreneurship program has a positive and significant effect on increasing prisoners' self-efficacy and entrepreneurial resilience that ultimately encourages the emergence of entrepreneurial intentions. Entrepreneurial resilience was found not to affect entrepreneurial intentions for prisoners with no entrepreneurial experience and who have never attended entrepreneurship training.Originality/valueThis study identifies the drivers of prisoners' entrepreneurial intentions, including prison entrepreneurship programs, self-efficacy and entrepreneurial resilience. These can be used as references to build understanding at the theoretical level and can be adopted practically. This study expands the social cognitive theory (SCT) and entrepreneurial intention models (EIMs) by adding new insights into the context of prison entrepreneurship that underline the potential of prisoners engaging in entrepreneurship, once released, to expand opportunities, learning and employment. This study highlights the importance of implementing prison entrepreneurship programs to reduce crime, recidivism rates, poverty and inequality.
Post-COVID-19 poverty in France: magnitude, manifestations and actors from nine case studies
Authors: Bouchet Célia , Duvoux Nicolas 
Published: November 2022

PurposeDrawing on the French case, this article examines the size and scope of poverty resulting from the coronavirus disease 2019 (COVID-19) pandemic, the diversity of poverty's manifestations and the role of public action (among other actors) in addressing the poverty. This reflection unfolds at the confluence between the international literature on the economic effects of COVID-19 around the world and the methodological and conceptual issues on poverty.Design/methodology/approachFollowing a research report to the French Government in 2021, a new academic collaboration is initiated to assess the conceptual issues underlying the report's nine quantitative, qualitative and participatory studies. A thematic analysis is used to elaborate on an original framework.FindingsCOVID-19 not only had detrimental economic effects on specific groups, such as precarious workers and students, but also serious effects on social isolation, mental health, access to welfare and public services. Together with assessing the consequences of the COVID-19 pandemic on poverty in France, this paper highlights the lack of recognition of community support in the face of hard times.Originality/valueThe COVID-19 outbreak has not only deteriorated socioeconomic situations in France, but has also unmasked structural, long-term components of poverty. The paper discusses three policy implications of these revelations, concerning (1) the monitoring of non-monetary dimensions of poverty, (2) the needs of various groups under a welfare state with a dual structure and (3) the role of communities in public policy schemes.