bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Reinforcement Impairs Cognitive Flexibility by Inhibiting Striatal Cholinergic Neurons
Authors: Gangal Himanshu , Xie Xueyi , Cheng Yifeng , Wang Xuehua , Lu Jiayi , Zhuang Xiaowen , Essoh Amanda , Huang Yufei , Smith Laura N. , Smith Rachel J. , Wang Jun 
Published: October 2022

ABSTRACTThe mechanisms underlying the reduction in cognitive flexibility associated with reinforcement of addictive substance use are unknown. This reinforcement is mediated by substance-induced synaptic plasticity in direct-pathway medium spiny neurons (dMSNs) that project to the substantia nigra (SNr). Cognitive flexibility is mediated by cholinergic interneurons (CINs), which receive extensive local inhibition from the striatum. Here, we report that cocaine or alcohol administration caused a long-lasting potentiation of local inhibitory dMSN→CIN transmission in the dorsomedial striatum (DMS), a brain region critical for goal-directed behavior and cognitive flexibility. This dMSN→CIN potentiation reduced CIN firing activity. Furthermore, chemogenetic and time-locked optogenetic inhibition of DMS CINs suppressed cognitive flexibility in an instrumental reversal learning task. Importantly, rabies-mediated tracing and physiological studies revealed that SNr-projecting dMSNs, which mediate reinforcement, sent axonal collaterals to inhibit DMS CINs, which mediate flexibility. Our findings demonstrate that the local inhibitory dMSN→CIN circuit mediates a reinforcement-induced reduction in cognitive flexibility.HIGHLIGHTSCocaine reinforcement inhibits striatal cholinergic interneurons (CINs) and impairs cognitive flexibility.Optogenetic and chemogenetic CIN inhibition impairs cognitive flexibility.Reinforcement behaviors potentiate inhibitory transmission from direct-pathway medium spiny neurons (dMSNs) to CINs.Substantia nigra-projecting dMSNs mediate reinforcement and also send collaterals that inhibit CINs.
Bacterial Strategies for Damage Management
Authors: Joshi Kunaal , Gandhi Rhea , Krakauer David C. , Iyer-Biswas Srividya , Kempes Christopher P. 
Published: October 2022

ABSTRACTOrganisms are able to partition resources adaptively between growth and repair. The precise nature of optimal partitioning and how this emerges from cellular dynamics including insurmountable trade-offs remains an open question. We construct a mathematical framework to estimate optimal partitioning and the corresponding maximal growth rate constrained by empirical scaling laws. We model a biosynthesis tradeoff governing the partitioning of the ribosome economy between replicating functional proteins and replicating the ribosome pool, and also an energy tradeoff arising from the finite energy budget of the cell. Through exact analytic calculations we predict limits on the range of values partitioning ratios take while sustaining growth. We calculate how partitioning and cellular composition scale with protein and ribosome degradation rates and organism size. These results reveal different classes of optimizing strategies corresponding to phenotypically distinct bacterial lifestyles. We summarize these findings in a quadrant-based taxonomy including: a “greedy” strategy maximally prioritizing growth, a “prudent” strategy maximally prioritizing the management of damaged pools, and “strategically limited” intermediates.
High air humidity dampens salicylic acid pathway and plant resistance via targeting of NPR1
Authors: Yao Lingya , Jiang Zeyu , Wang Yiping , Wan Shiwei , Xin Xiu-Fang 
Published: October 2022

AbstractThe occurrence of plant disease is determined by interactions among host, pathogen and climate conditions. Air humidity has long been recognized to profoundly influence diseases in the phyllosphere and high air humidity (e.g., after rain falls) is known as a prerequisite for numerous disease outbreaks in the field1–3. However, the molecular basis of how high humidity interferes with plant resistance mechanisms to favor disease remained elusive. Here we show that high humidity is associated with an “immune-compromised” status of plants, revealed by lower expression of defense genes during bacterial infection of Arabidopsis plants. Examination of humidity’s effect on individual immune pathways showed that the accumulation and signaling of salicylic acid (SA), an essential hormone conferring plant resistance against infectious microbes4,5, are significantly inhibited under high humidity. Surprisingly, NPR1 protein, an SA receptor and central transcriptional co-activator of SA-responsive genes6–9, accumulated to a significantly higher level in the nucleus under high humidity. Further investigation indicated a decreased binding affinity of NPR1 protein to the target gene promoter, suggestive of an “inactive” nature of NPR1, under high humidity and an impaired ubiquitination and degradation of NPR1 protein, likely due to down-regulation of Cullin 3-mediated cellular ubiquitination pathway and 26S proteasome pathway under high humidity. Our study uncovers disruption of NPR1 protein turnover as a major mechanism, by which high humidity dampens plant immune strength against pathogens, and provides new insights into the long-observed air humidity influence on diseases in nature.
Structural and Functional insights into the action mode of a Mitochondrial AAA+ Disaggregase CLPB
Authors: Wu Damu , Liu Yan , Dai Yuhao , Wang Guopeng , Lu Guoliang , Chen Yan , Li Ningning , Lin Jinzhong , Gao Ning 
Published: October 2022

“The authors have withdrawn their manuscript because of duplicate posting. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.The correct preprint can be found athttps://doi.org/10.1101/2022.03.10.483744”
A two-pool mechanism of vesicle release in medial habenula terminals underlies GABABreceptor-mediated potentiation
Authors: Koppensteiner Peter , Bhandari Pradeep , Önal Cihan , Borges-Merjane Carolina , Le Monnier Elodie , Nakamura Yukihiro , Sadakata Tetsushi , Sanbo Makoto , Hirabayashi Masumi , Brose Nils , Jonas Peter , Shigemoto Ryuichi 
Published: October 2022

AbstractGABABreceptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation induces a transition from tonic to phasic release accompanied by a 4-fold increase in readily releasable pool (RRP) size in MHb terminals, mirrored by a similar increase in the docked vesicle number at the presynaptic active zone (AZ). The tonic and phasic release vesicles have distinct coupling distances. We identified two vesicle-associated molecules, synaptoporin and CAPS2, selectively involved in tonic and phasic release, respectively. Synaptoporin mediates augmentation of tonic release and CAPS2 stabilizes readily releasable vesicles during phasic release. A newly developed “Flash and Freeze-fracture” method revealed selective recruitment of CAPS2 to the AZ during phasic release. Thus, we propose a novel two-pool mechanism underlying the GBR-mediated potentiation of release from MHb terminals.
Mice lackingPtprdexhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating
Authors: Ho EV , Welch A , Knowles JA , Dulawa SC 
Published: October 2022

AbstractProtein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linkedPtprdto several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci nearPtprdas genome-wide significant, or strongly suggestive for this trait. We assessedPtprdwild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatiald), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However,PtprdKO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male,PtprdKO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack ofPtprdmay contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.
Palmitoylation regulates neuropilin-2 localization and function in cortical neurons and conveys specificity to semaphorin signaling via palmitoyl acyltransferases
Authors: Koropouli Eleftheria , Wang Qiang , Mejias Rebeca , Hand Randal , Wang Tao , Ginty David D. , Kolodkin Alex L. 
Published: October 2022

ABSTRACTSecreted semaphorin 3F (Sema3F) and semaphorin 3A (Sema3A) exhibit remarkably distinct effects on deep layer excitatory cortical pyramidal neurons; Sema3F mediates dendritic spine pruning, whereas Sema3A promotes the elaboration of basal dendrites. Sema3F and Sema3A signal through distinct holoreceptors that include neuropilin-2 (Nrp-2)/plexinA3 (PlexA3) and neuropilin-1 (Nrp-1)/PlexA4, respectively. We find that Nrp-2 and Nrp-1 are S-palmitoylated in cortical neurons and that palmitoylation of select Nrp-2 cysteines is required for its proper subcellular localization and also for Sema3F/Nrp-2-dependent dendritic spine pruning in cortical neurons, both in vitro and in vivo. Moreover, we show that the palmitoyl acyltransferase DHHC15 is required for Nrp-2 palmitoylation and Sema3F/Nrp-2-dependent dendritic spine pruning, but it is dispensable for Nrp-1 palmitoylation and Sema3A/Nrp-1-dependent basal dendritic elaboration. Therefore, palmitoyl acyltransferase-substrate specificity is essential for establishing compartmentalized neuronal structure and functional responses to extrinsic guidance cues.HIGHLIGHTSNeuropilins (Nrps) are S-palmitoylated in vitro and in vivo in the central nervous systemS-palmitoylation of select Nrp-2 cysteines confers subcellular localization specificity and is required for semaphorin 3F-dependent dendritic spine pruning in cortical neuronsDistinct palmitoyl acyltransferases mediate Nrp-2 and Nrp-1 palmitoylation and function, imparting specificity to semaphorin signaling
Matrix Metalloproteinase Activity During Methamphetamine Cued Relapse
Authors: Lewandowski Stacia I. , Hodebourg Ritchy , Wood Samuel K. , Carter Jordan S. , Nelson Katherine , Kalivas Peter W. , Reichel Carmela M. 
Published: October 2022

AbstractRelapse to drug seeking involves transient synaptic remodeling that occurs in response to drug associated cues. This remodeling includes activation of matrix metalloproteinases (MMPs) to initiate catalytic signaling in the extracellular matrix (ECM) in the nucleus accumbens core (NAcore). We hypothesized that MMP activity would be increased in the NAcore during cue-induced methamphetamine (meth) seeking in a rat model of meth use and relapse. Male and female rats had indwelling jugular catheters and bilateral intracranial cannula targeting the NAcore surgically implanted. Following recovery, rats underwent meth or saline self-administration (6hr/day for 15 days) in which active lever responding was paired with a light+tone stimulus complex, followed by home cage abstinence. Testing occurred after 7 or 30 days of abstinence. On test day, rats were microinjected with a FITC-quenched gelatin substrate that fluoresces following cleavage by MMPs, allowing for the quantification of gelatinase activity by MMP-2 and −9 during cued relapse testing. MMP-2,9 activity was significantly increased in the NAcore by meth cues presentation after 7 and 30 days of abstinence, indicating that remodeling by MMPs occurs during presentation of meth associated cues. Surprisingly, while cue-induced seeking increased between days 7 and 30, suggesting behavioral incubation, MMP-2,9 activity did not increase. These findings indicate that while MMP activation is elicited during meth cue-induced seeking, MMP activation did not parallel the behavioral incubation that occurs during extended drug abstinence.
Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS)
Authors: Ragozzino Forrest J. , Peterson BreeAnne , Karatsoreos Ilia N. , Peters James H. 
Published: October 2022

ABSTRACTCircadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice. We found that spontaneous quantal glutamate release on to NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day / night differences in constitutive postsynaptic action potential firing. In contrast, afferent-evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance; which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre- / postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day.
The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer
Authors: Tabassum Shaheda , Basu Malini , Ghosh Mrinal K 
Published: October 2022

AbstractForkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. p68, an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors. Here, we report a novel mechanism of alliance between p68 and the Wnt/β-catenin pathway in regulating FOXM1 gene expression and driving colon carcinogenesis. Initial bioinformatic analyses highlighted elevated expression levels of FOXM1 and p68 in colorectal cancer datasets. Immunohistochemical assays confirmed that FOXM1 showed a positive correlation with p68 and β-catenin in both normal and colon carcinoma patient samples. Overexpression of p68 and β-catenin increased the protein and mRNA expression profiles of FOXM1, and the converse correlation occurred during downregulation. Mechanistically, overexpression and knockdown of p68 and β-catenin elevated and diminished FOXM1 promoter activity respectively. Additionally, Chromatin immunoprecipitation assay demonstrated the occupancy of p68 and β-catenin at the TCF4/LEF binding element (TBE) sites on the FOXM1 promoter. Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the p68/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by p68 and β-catenin in colorectal cancer.
Effects of supply chain disruptions due to COVID-19 on shareholder value
Authors: Choudhury Nishat Alam , Kim Seongtae , Ramkumar M. 
Published: October 2022

PurposeThe purpose of this research work is to examine the financial effect of supply chain disruptions (SCDs) caused by coronavirus disease 2019 (COVID-19) and how the magnitude of such effects depends on event time and space that may moderate the signaling environment for shareholder behaviors during the pandemic.Design/methodology/approachThis study analyses a sample of 206 SCD events attributed to COVID-19 made by 145 publicly traded firms headquartered in 21 countries for a period between 2020 and 2021. Change in shareholder value is estimated by employing a multi-country event study, followed by estimating the differential effect of SCDs due to the pandemic by event time and space.FindingsOn average, SCDs due to pandemic decrease shareholder value by −2.16%, which is similar to that of pre-pandemic SCDs (88 events for 2018–2019). This negative market reaction remains unchanged regardless of whether stringency measures of the firm's country become more severe. Supply-side disruptions like shutdowns result in a more negative stock market reaction than demand-side disruptions like price hikes. To shareholder value, firm's upstream or downstream position does not matter, but supply chain complexity serves as a positive signal.Originality/valueThis study provides the first empirical evidence on the financial impact of SCDs induced by COVID-19. Combining with signaling theory and event system theory, this study provides a new boundary condition that explains the impact mechanism of SCDs caused by the pandemic.
Organisational capabilities for successful digital transformation: a global analysis of national football associations in the digital age
Authors: Merten Sebastian , Schmidt Sascha L. , Winand Mathieu 
Published: October 2022

PurposeThe aim of this study is to identify organisational capabilities (OC) for a successful digital transformation (DT) and associated structures of internal teams to orchestrate and support DT.Design/methodology/approachAn explorative, qualitative study, comprising semi-structured interviews with 82 executives from 43 diverse National Football Associations (NFA) spread across five continents was conducted.FindingsThe results show that organisational culture, strategic sensitivity, up-to-date ICT-infrastructure, a digitally skilled workforce, leadership support, knowledge management and internal DT-teams are important capabilities to enable successful DT.Research limitations/implicationsDue to the different levels of maturity of digitalisation and the financial constraints, not every NFA intends or is able to assign a full-time staff member exclusively to digital issues. Therefore, the most appropriate person was interviewed in each NFA.Practical implicationsAdapting an organisational culture to the requirements of the digital age is one of the most important steps in implementing DT. It is equally important for the leadership to form the strategic framework and enable the necessary training of employees to improve the results of the digitalisation processes.Originality/valueThis is the first study investigating NFA's DT from a worldwide perspective, identifying the most important factors for successful DT-processes.
Documenting the knowledge of pro-environmental travel behaviour research: a visual analysis using CiteSpace
Authors: Zhang Jiale , Quoquab Farzana 
Published: October 2022

PurposeThe purpose of this study is to present a comprehensive knowledge mapping and an in-depth analysis of pro-environmental travel behaviour research to better understand the global trend in this field that have emerged between 2000 and 2021.Design/methodology/approachIn this study, a visual analysis of 187 scholarly articles between the year 2000 and 2021 related to pro-environmental travel behaviour (PETB) is presented. Using the knowledge mapping based on CiteSpace it presents the current research status, which contains the analysis of collaboration network, co-citation network, and emerging trends.FindingsThe results revealed that the PETB is an emerging topic, which has an increased number of publications in recent years. Though the collaboration network between scholars is dispersed, some countries exert stronger collaboration network. Researchers from England, USA and China have worked more on this topic comparatively. “Pro-environmental norm” is found to be the major concern in regard to PETB, and the theory of planned behaviour (TPB) is the most common theory used by the scholars around the world. Ten articles with the highest citations are found to be the most valuable articles. COVID-19, value orientation, negative spillover, carbon footprints, biospheric and adolescent are some of the latest keywords based on the past two years' literature review, all of which have huge research potential in the future.Originality/valueThis study is among the pioneers to shed some light on the current research progress of PETB by using a bibliometric analysis to provide research directions for scholars. Moreover, this study utilized latest data from 2000 to 2021. The studies which are published before and during the pandemic are also incorporated.
Different facets of bacterial and fungal communities drive soil multifunctionality in grasslands spanning a 3500 km transect
Authors: Ma Linna , Zhang Chaoxue , Xu Xiaofeng , Wang Congwen , Liu Guofang , Liang Cunzhu , Zuo Xiaoan , Wang Chengjie , Lv Yixia , Wang Renzhong 
Published: October 2022

Abstract

Soil microbial communities are essential in regulating ecosystem functions and services. However, the importance of bacterial and fungal communities as predictors of multiple soil functions (i.e. soil multifunctionality) in grassland ecosystems has not been studied systematically.

Here, we measured soil microbial diversity, community composition, biomass and multiple soil functions of 41 sites in five grassland ecosystems spanning a 3500 km northeast–southwest transect. The random forest algorithm was adopted to determine the importance of geographical location, climatic, altitude, edaphic, plant and microbial predictors in driving a proxy of soil multifunctionality (seven soil functions in this study). Moreover, structural equation models were employed to examine the direct and indirect effects of those predictors on soil multifunctionality.

Our results demonstrated that soil multifunctionality was positively driven by soil fungal diversity but not by bacterial diversity. Fungal phylogenetic diversity (presence of different evolutionary lineages) showed stronger positive relationships with soil multifunctionality than taxonomic diversity (richness of species). Dominant bacterial taxa, particularly of phyla Actinobacteria and Proteobacteria, were positively associated with soil multifunctionality, while none of the fungal taxa were found to regulate soil multifunctionality. Furthermore, both fungal and bacterial biomass had significant effects on soil multifunctionality, while the effect of microbial biomass was weaker than that of fungal diversity and bacterial taxa. Importantly, the direct positive effects of soil fungal diversity, dominant bacterial taxa, and fungal and bacterial biomass were maintained after accounting for multiple predictors in grassland ecosystems.

This study provided strong empirical evidence that soil multifunctionality was driven by different facets of the bacterial and fungal communities in the grassland ecosystems. Our results also highlighted that any loss of fungal diversity, dominant bacterial taxa and microbial biomass might reduce soil multifunctionality, exacerbating ecosystem functions and services such as soil fertility, primary production and climate mitigation in grassland ecosystems.

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