bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial transcriptomics reveals molecular dysfunction associated with Lewy pathology
Authors: Goralski Thomas , Meyerdirk Lindsay , Breton Libby , Brasseur Laura , Kurgat Kevin , DeWeerd Daniella , Turner Lisa , Becker Katelyn , Adams Marie , Newhouse Daniel , Henderson Michael X. 
Published: May 2023

AbstractLewy pathology composed of α-synuclein is the key pathological hallmark of Parkinson’s disease (PD), found both in dopaminergic neurons that control motor function, and throughout cortical regions that control cognitive function. Recent work has investigated which dopaminergic neurons are most susceptible to death, but little is known about which neurons are vulnerable to developing Lewy pathology and what molecular changes an aggregate induces. In the current study, we use spatial transcriptomics to selectively capture whole transcriptome signatures from cortical neurons with Lewy pathology compared to those without pathology in the same brains. We find, both in PD and in a mouse model of PD, that there are specific classes of excitatory neurons that are vulnerable to developing Lewy pathology in the cortex. Further, we identify conserved gene expression changes in aggregate-bearing neurons that we designate the Lewy-associated molecular dysfunction from aggregates (LAMDA) signature. This gene signature indicates that neurons with aggregates downregulate synaptic, mitochondrial, ubiquitin-proteasome, endo-lysosomal, and cytoskeletal genes and upregulate DNA repair and complement/cytokine genes. However, beyond DNA repair gene upregulation, we find that neurons also activate apoptotic pathways, suggesting that if DNA repair fails, neurons undergo programmed cell death. Our results identify neurons vulnerable to Lewy pathology in the PD cortex and identify a conserved signature of molecular dysfunction in both mice and humans.
Endocytic down-regulation of the striatal dopamine transporter by amphetamine in sensitized mice in sex-dependent manner
Authors: Bagalkot Tarique , Sorkin Alexander 
Published: May 2023

ABSTRACTDopamine transporter (DAT) controls dopamine signaling in the brain through the reuptake of synaptically released dopamine. DAT is a target of abused psychostimulants such as amphetamine (Amph). Acute Amph is proposed to cause transient DAT endocytosis which among other Amph effects on dopaminergic neurons elevates extracellular dopamine. However, the effects of repeated Amph abuse, leading to behavioral sensitization and drug addiction, on DAT traffic are unknown. Hence, we developed a 14-day Amph-sensitization protocol in knock-in mice expressing HA-epitope tagged DAT (HA-DAT) and investigated effects of Amph challenge on HA-DAT in sensitized animals. Amph challenge resulted in the highest locomotor activity on day 14 in both sexes, which was however sustained for 1 hour in male but not female mice. Strikingly, significant (by 30-60%) reduction in the amount of the HA-DAT protein in striatum was observed in response to Amph challenge of sensitized males but not females. Amph reduced Vmax of dopamine transport in striatal synaptosomes of males without changing Km values. Consistently, immunofluorescence microscopy revealed a significant increase of HA-DAT co-localization with the endosomal protein VPS35 only in males. Amph-induced HA-DAT down-regulation in the striatum of sensitized mice was blocked by chloroquine, vacuolin-1 (inhibitor of PIKfive kinase), and inhibitor of Rho-associated kinases (ROCK1/2), indicative of the involvement of endocytic trafficking in DAT down-regulation. Interestingly, HA-DAT protein down-regulation was observed in nucleus accumbens and not in dorsal striatum. We propose that Amph challenge in sensitized mice leads to ROCK-dependent endocytosis and post-endocytic traffic of DAT in a brain-region-specific and sex-dependent manner.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation
Authors: Isbister James B. , Ecker András , Pokorny Christoph , Bolaños-Puchet Sirio , Egas Santander Daniela , Arnaudon Alexis , Awile Omar , Barros-Zulaica Natali , Blanco Alonso Jorge , Boci Elvis , Chindemi Giuseppe , Courcol Jean-Denis , Damart Tanguy , Delemontex Thomas , Dietz Alexander , Ficarelli Gianluca , Gevaert Mike , Herttuainen Joni , Ivaska Genrich , Ji Weina , Keller Daniel , King James , Kumbhar Pramod , Lapere Samuel , Litvak Polina , Mandge Darshan , Muller Eilif B. , Pereira Fernando , Planas Judit , Ranjan Rajnish , Reva Maria , Romani Armando , Rössert Christian , Schürmann Felix , Sood Vishal , Teska Aleksandra , Tuncel Anil , Van Geit Werner , Wolf Matthias , Markram Henry , Ramaswamy Srikanth , Reimann Michael W. 
Published: May 2023

SummaryCortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to studyin vivo. Large-scale, biophysically detailed models offer a tool which can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically-detailed neurons, and 13.2 billion local and mid-range synapses.In silicotools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome which included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation and investigation.
The phototrophic bacteriaRhodomicrobiumspp. are novel chassis for bioplastic production
Authors: Conners Eric M. , Rengasamy Karthikeyan , Bose Arpita 
Published: May 2023

SummaryPolyhydroxybutyrate (PHB) is a bio-based, biodegradable alternative to petroleum-based plastics. PHB production at industrial scales remains infeasible, in part due to insufficient yields and high costs. Addressing these challenges requires identifying novel biological chassis for PHB production and modifying known biological chassis to enhance production using sustainable, renewable inputs. Here, we take the former approach and present the first description of PHB production by two prosthecate photosynthetic purple non-sulfur bacteria (PNSB),Rhodomicrobium vannieliiandRhodomicrobium udaipurense.We show that both species produce PHB across photoheterotrophic, photoautotrophic, photoferrotrophic, and photoelectrotrophic growth conditions. Both species show the greatest PHB titers during photoheterotrophic growth on butyrate with dinitrogen gas as a nitrogen source (up to 44.08 mg/L), while photoelectrotrophic growth demonstrated the lowest titers (up to 0.13 mg/L). These titers are both greater (photoheterotrophy) and less (photoelectrotrophy) than those observed previously in a related PNSB,Rhodopseudomonas palustrisTIE-1. On the other hand, we observe the highest electron yields during photoautotrophic growth with hydrogen gas or ferrous iron electron donors, and these electron yields were generally greater than those observed previously in TIE-1. These data suggest that non model organisms likeRhodomicrobiumshould be explored for sustainable PHB production and highlights utility in exploring novel biological chassis.
Metabolic FRET sensors in intact organs: Applying spectral unmixing to acquire reliable signals
Authors: Gándara Lautaro , Durrieu Lucía , Wappner Pablo 
Published: May 2023

ABSTRACTIn multicellular organisms, metabolic coordination across multiple tissues and cell types is essential to satisfy regionalized energetic requirements and respond coherently to changing environmental conditions. However, most metabolic assays require the destruction of the biological sample, with a concomitant loss of spatial information. Fluorescent metabolic sensors and probes are among the most user-friendly techniques for collecting metabolic information with spatial resolution. In a previous work, we have adapted to an animal system,Drosophila melanogaster, genetically encoded metabolic FRET-based sensors that had been previously developed in single-cell systems. These sensors provide semi-quantitative data on the stationary concentrations of key metabolites of the bioenergetic metabolism: lactate, pyruvate, and 2-oxoglutarate. The use of these sensors in intact organs required the development of an image processing method that minimizes the contribution of spatially complex autofluorescence patterns, that would obscure the FRET signals. In this article, we describe the fundamentals of intramolecular hetero-FRET, the technology on which these sensors are based. Finally, using data from the lactate sensor expressed in the larval brain as a case study, we show step by step how to process the fluorescence signal to obtain reliable FRET values.
PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate
Authors: Chessa Tamara , Jung Piotr , Suire Sabine , Anwar Arqum , Anderson Karen E. , Barneda David , Kielkowska Anna , Sadiq Barzan A. , Felisbino Sergio , Oxley David , Spensberger Dominik , Segonds-Pichon Anne , Wilson Michael , Walker Simon , Okkenhaug Hanneke , Cosulich Sabina , Hawkins Phillip T. , Stephens Len R. 
Published: May 2023

SummaryThe PIP3/PI3K network is a central regulator of metabolism and is frequently activated in cancer, commonly by loss of the PIP3/PI(3,4)P2-phosphatase, PTEN. Despite huge investment, the drivers of the PI3K network in normal tissues and how they adapt to overactivation are unclear.We find that in healthy mouse prostate PI3K activity is driven by RTK/IRS signalling and constrained by pathway-feedback. In the absence of PTEN, the network is dramatically remodelled. A poorly understood, YXXM and PIP3/PI(3,4)P2-binding PH domain-containing, adaptor, PLEKHS1, became the dominant activator and was required to sustain PIP3, AKT-phosphorylation and growth in PTEN-null prostate. This was because PLEKHS1 evaded pathway-feedback and experienced enhanced PI3K and SRC-family kinase-dependent phosphorylation of Y258XXM, eliciting PI3K activation.hPLEKHS1-mRNA and activating-Y419-phosphorylation of hSRC correlated with PI3K-pathway activity in human prostate cancers. We propose that in PTEN-null cells, receptor-independent, SRC-dependent tyrosine-phosphorylation of PLEKHS1 creates positive-feedback that escapes homeostasis, drives PIP3- signalling and supports tumour progression.
Songbird mesostriatal dopamine pathways are spatially segregated before the onset of vocal learning
Authors: Ramarao Malavika , Roeser Andrea , Jones Caleb , Goldberg Jesse H. 
Published: May 2023

AbstractDiverse dopamine (DA) pathways send distinct reinforcement signals to different striatal regions. In adult songbirds, a DA pathway from the ventral tegmental area (VTA) to Area X, the striatal nucleus of the song system, carries singing-related performance error signals important for learning. Meanwhile, a parallel DA pathway to a medial striatal area (MST) arises from a distinct group of neighboring DA neurons that lack connectivity to song circuits and do not encode song error. To test if the structural and functional segregation of these two pathways depends on singing experience, we carried out anatomical studies early in development before the onset of song learning. We find that distinct VTA neurons project to either Area X or MST in juvenile birds before the onset of substantial vocal practice. Quantitative comparisons of early juveniles (30-35 dph), late juveniles (60-65 dph), and adult (>90 dph) brains revealed an outsized expansion in the number of Area X-projecting and MST-projecting VTA neurons over development. These results show that a mesostriatal DA system dedicated to social communication can exist and be spatially segregated before the onset of vocal practice and associated sensorimotor experience.
Effects of anthropomorphized virus warnings and perceived cuteness on compliance intention
Authors: Xiang Liang , Park Hyun Jung 
Published: May 2023

PurposeThis study investigated the anthropomorphism of the pandemic virus and its downstream effects by examining how warnings trigger viewers' risk perceptions and motivate them to pursue protection.Design/methodology/approachThree experiments were conducted. The first was a two-part (virus: anthropomorphic vs non-anthropomorphic) between-subject design that measured the participants' risk perception and compliance intention. The second experiment used a three-part (cuteness: cute vs non-cute vs control) between-subjects design. The third experiment used a three-part (cuteness: cute vs non-cute vs control) by two-part (aggressive guidance: present vs absent) between-subject design.FindingsAnthropomorphism of the virus increased risk perception, thus influencing protective behavior and the effectiveness of warning signs, but only when the message was not perceived as cute. Aggressive messages and cute images of baby schemata enhanced compliance intention to warning guidelines.Practical implicationsThe results provide a theoretical basis for studying the effectiveness of anthropomorphized warning signs and suggest implications for the impact of anthropomorphism on risk communication and compliance.Originality/valueThis study highlights that cuteness, often accompanied by anthropomorphism, may evoke inferences that reduce the effect of risk communication to induce compliance intention. Furthermore, the authors discovered that a more persuasive message appeals to mitigate the maladaptive responses to cute warnings.
Political connections, board ethnicity and value relevance in Mauritius
Authors: Mustun Tasneem , Abdul Wahab Effiezal Aswadi 
Published: May 2023

PurposeThe paper aims to investigate the impact of political connections and board ethnicity on the value relevance of earnings and book value in Mauritius.Design/methodology/approachThis study is based on a sample of 541 Mauritian-listed firm-year observations for 2001–2016. Financial and board diversity data have been collected using the listed firms’ annual reports and from reports published by the Stock Exchange of Mauritius. Political connection data was derived from the directory of Chief of State and Cabinet members. The research hypotheses were empirically tested using a modified Ohlson (1995) price model.FindingsThis study shows that political connections negatively impact the value relevance of earnings and book value. The authors find that firms with Franco-Mauritian directors will constrain political connections’ negative impact. The authors find contrasting results for Indo-Mauritian directors since they form an integral part of the government in Mauritius.Originality/valueThis study contributes to the scarce accounting literature in Mauritius. Firstly, no study has investigated the relationship between the value relevance of accounting information and political connections in Mauritius. Secondly, Mauritius’s capital market is dominated by a non-indigenous ethnic group, Franco-Mauritians, who remain the economic elite. Hence, Mauritius presents an opportunity to bring forth another important aspect in the capital market and corporate governance; diversity on the board of directors. Therefore, the study extends to the political connections and board diversity literature.
The influence of digital competence of academicians on students’ engagement at university level: moderating effect of the pandemic outbreak
Authors: Aldhaen Esra 
Published: May 2023

Purpose
The purpose of this study is to investigate how the digital competence of academicians influences students’ engagement in learning activities in the face of the pandemic outbreak. In addition to this, the paper investigates how digital competence influences each dimension of student engagement (cognitive, affective and behavioural).

Design/methodology/approach
A cross-sectional, quantitative and explanatory research design was used to conduct the study. Data were gathered with an adopted questionnaire administered to a randomly selected sample of 500 university faculty members who were not digitally literate prior to the outbreak of the pandemic. Apart from the goodness of data tests, inferential statistics were applied to test hypotheses.

Findings
Results indicate a significant influence of teachers’ digital competence on student engagement and the pandemic outbreak positively moderates the relationship. Digital competence equally influences all three dimensions of student engagement.

Practical implications
The outbreak of COVID-19 made the adoption of digital life more compulsive and the nations with already available digital infrastructure and digital competence effectively minimized the adverse effect of social distancing as a result of the pandemic outbreak. Findings emphasize practitioners to focus on the digital capacity building of academicians and the provision of digital infrastructure to facilitate student engagement.

Social implications
Society is transforming into a hi-tech lifestyle and technological advancement is penetrating almost every sphere of life at an unprecedented pace. From the digitalization of day-to-day affairs to e-governance, the adoption of technology is becoming a new normal. The outbreak of the pandemic overtook academic institutions equally. So, the social distancing compelled academicians and other stakeholders of universities to switchover from in-campus classes to online classes. The findings enrich the existing body of literature by explaining how digital competence has a determining role in ensuring student engagement amid the COVID-19 outbreak.

Originality/value
This research is a seminal work, as it tests the influence of digital competence on student engagement with the moderating role of the pandemic outbreak. To the best of the author’s knowledge, existing literature does not present this kind of research.
Multi-frequency information transmission among constituents and global equity returns: a sustainable and conventional way of investing
Authors: Asafo-Adjei Emmanuel , Adam Anokye M. , Owusu Junior Peterson , Arthur Clement Lamboi , Seidu Baba Adibura 
Published: May 2023

PurposeThis study investigates information flow of market constituents and global indices at multi-frequencies.Design/methodology/approachThe study’s findings were obtained using the Improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (I-CEEMDAN)-based cluster analysis executed for Rényi effective transfer entropy (RETE).FindingsThe authors find that significant negative information flows among sustainability equities (SEs) and conventional equities (CEs) at most multi-frequencies, which exacerbates diversification benefits. The information flows are mostly bi-directional, highlighting the importance of stock markets' constituents and their global indices in portfolio construction.Research limitations/implicationsThe authors advocate that both SE and CE markets are mostly heterogeneous, revealing some levels of markets inefficiencies.Originality/valueThe empirical literature on CEs is replete with several dynamics, revealing their returns behaviour for diversification purposes, leaving very little to know about the returns behaviour of SE. Wherein, an avalanche of several initiatives on Corporate Social Responsibility (CSR) enjoin firms to operate socially responsible, but investors need to have a clear reason to remain sustainable into the foreseeable future period. Accordingly, the humble desire of investors is the formation of a well-diversified portfolio and would highly demand stocks to the extent that they form a reliable portfolio, especially, amid SEs and/or CEs.
Analyzing blockchain-based supply chain resilience strategies: resource-based perspective
Authors: Nagariya Ramji , Mukherjee Subhodeep , Baral Manish Mohan , Chittipaka Venkataiah 
Published: May 2023

PurposeThis research tries to find the blockchain-based resilience strategies that can help the supply chains of micro, small, and medium-sized enterprises (MSMEs) to recover from the disruptions and work effectively in a resource-based view perspective.Design/methodology/approachEight broad strategies and 32 sub-strategies are identified from the literature review. Delphi study was carried out, and detailed discussion with 16 experts helped in finalizing these strategies. Further, the best-worst method (BWM) prioritized these strategies.FindingsThe findings suggests that “building social capital,” improving “coordination capabilities,” “sensitivity towards market,” “flexibility in process and production,” “reduction in process and lead time,”and “having a resource efficiency and redundancy” are the top strategies on which the top management should focus to overcome the situations of disruptions and enhance performance of MSMEs.Practical implicationsThe blockchain-based strategies will enable the companies in tracing the products from the company to customers. Further, the customers will be able to identify their manufacturers, the raw materials used in manufacturing, and the life and quality of raw used materials. Altogether the textile industry will become more sensitive toward environmental practices.Originality/valueThe previous research has not identified and evaluated the blockchain-based resilience strategies, and therefore this study tries to fill this gap. This study used a smaller sample from the experts, so the results may vary if the larger data set is used and hypothesis testing can be done.
How do we elicit more user feedback in the social Q&A community? A consideration of the expertise-required question
Authors: Zhou Mi , Meng Bo , Fan Weiguo 
Published: May 2023

PurposeThe current study aims to investigate the factors that impact the feedback received on answers to questions in social Q&A communities and whether the expertise-required question influences the role of these factors on the feedback.Design/methodology/approachTo understand the antecedents and consequences that influence the feedback received on answers to online community questions, the elaboration likelihood model (ELM) is applied in this study. The authors use web data crawling methods and a combination of quantitative analyses. The data for this study came from Zhihu; in total, 353,775 responses were obtained to 1,531 questions, ranging from 49 to 23,681 responses per question. Each answer received 0 to 113,892 likes and 0 to 6,250 comments.FindingsThe answers' cognitive and emotional components and the answerer's influence positively affect user feedback behavior. In addition, the expertise-required question moderates the effects of the answer's cognitive component and emotional component on the user feedback, moderating the effects of the answerer's influence on the user approval feedback.Originality/valueThis study builds upon a limited yet growing body of literature on a theme of great relevance to scholars, practitioners and social media users concerning the effects of the connotation of answers (i.e. their cognitive and emotional components) and the answerer's influence on user feedback (i.e. approval and collaborative feedback) in social Q&A communities. The authors further consider the moderating role of the domain expertise required by the question (expertise-required question). The ELM model is applied to explore the relationships between questions, answers and feedback. The findings of this study add a new perspective to the research on user feedback and have implications for the management of social Q&A communities.