bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial fitness influences neuronal excitability of dopaminergic neurons from patients with idiopathic form of Parkinson’s disease
Authors: Chlebanowska Paula , Szlaga Agata , Tejchman-Skrzyszewska Anna , Kot Marta , Konieczny Pawel , Skrzypek Klaudia , Muszynska Agata , Sobocinska Malgorzata , Golebiowska Krystyna , Labaj Pawel , Blasiak Anna , Majka Marcin 
Published: April 2023

AbstractParkinson disease is the second most common neurodegenerative disease defined by presence of Lewy bodies and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). There are three types of PD - familial, early-onset and idiopathic. Idiopathic PD (IPD) accounts for approximately 90% of all PD cases. Mitochondrial dysfunction accompanies the pathogenesis of Parkinson’s disease. Loss of mitochondrial function increases oxidative stress and calcium buffering, which in turn hinders the production of ATP and disrupts the functioning of dopaminergic neurons. The main barrier in PD research was the lack of proper human models to study the mechanisms of PD development and progression. Using induced pluripotent stem (iPS) cells we generated patient-specific dopaminergic neurons.We observed differences in the mitochondria fitness but not differences in mitochondria mass, morphology or membrane potential. Expression of OXPHOS mitochondrial complexes were lower in PD patients in comparison to control group what resulted in changes in mitochondria respiratory status. We observed also lower expression levels of Na+/K+-ATPase subunits and ATP-sensitive K+(K-ATP) channel subunits. The lower oxygen consumption rate and extracellular acidification rate values were observed in dopaminergic progenitors and iPSC from PD patients compared to the control group. Importantly, observed decrease in the availability of ATP and in the energy consumption, as well as changes in acidification, may constitute contributing factors to the observed reduced neuronal excitability of PD patients dopaminergic neurons.
Lightning Pose: improved animal pose estimation via semi-supervised learning, Bayesian ensembling, and cloud-native open-source tools
Authors: Biderman Dan , Whiteway Matthew R , Hurwitz Cole , Greenspan Nicholas , Lee Robert S , Vishnubhotla Ankit , Warren Richard , Pedraja Federico , Noone Dillon , Schartner Michael , Huntenburg Julia M , Khanal Anup , Meijer Guido T , Noel Jean-Paul , Pan-Vazquez Alejandro , Socha Karolina Z , Urai Anne E ,   The International Brain Laboratory, Cunningham John P , Sawtell Nathaniel B , Paninski Liam 
Published: April 2023

AbstractContemporary pose estimation methods enable precise measurements of behavior via supervised deep learning with hand-labeled video frames. Although effective in many cases, the supervised approach requires extensive labeling and often produces outputs that are unreliable for downstream analyses. Here, we introduce “Lightning Pose,” an efficient pose estimation package with three algorithmic contributions. First, in addition to training on a few labeled video frames, we use many unlabeled videos and penalize the network whenever its predictions violate motion continuity, multiple-view geometry, and posture plausibility (semi-supervised learning). Second, we introduce a network architecture that resolves occlusions by predicting pose on any given frame using surrounding unlabeled frames. Third, we refine the pose predictions post-hoc by combining ensembling and Kalman smoothing. Together, these components render pose trajectories more accurate and scientifically usable. We release a cloud application that allows users to label data, train networks, and predict new videos directly from the browser.
A Zika virus protein expression screen inDrosophilato investigate targeted host pathways during development
Authors: Link Nichole , Harnish J Michael , Hull Brooke , Gibson Shelley , Dietze Miranda , Mgbike Uchechukwu E. , Medina-Balcazar Silvia , Shah Priya S. , Yamamoto Shinya 
Published: April 2023

SUMMARYIn the past decade, Zika virus (ZIKV) emerged as a global public health concern. While adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of symptoms caused by this virus including microcephaly. In this study, we generated a toolkit to ectopically express Zika viral proteinsin vivoinDrosophila melanogasterin a tissue-specific manner using the GAL4/UAS system. We use this toolkit to identify phenotypes and host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins cause scorable phenotypes, such as overall lethality, gross morphological defects, reduced brain size, and neuronal function defects. We further use this system to identify strain-dependent phenotypes that may contribute to the increased pathogenesis associated with the more recent outbreak of ZIKV in the Americas. Our work demonstratesDrosophila’suse as an efficientin vivomodel to rapidly decipher how pathogens cause disease and lays the groundwork for further molecular study of ZIKV pathogenesis in flies.
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
Authors: Windham Ian A. , Ragusa Joey V. , Wallace E. Diane , Wagner Colby H. , White Kristen K. , Cohen Sarah 
Published: April 2023

AbstractTheE4variant ofAPOEstrongly predisposes individuals to late-onset Alzheimer’s disease. We demonstrate that in response to neutral lipid synthesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the ER lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts.APOEknockdown promotes fewer, larger LDs containing more unsaturated triglyceride. This LD size distribution phenotype was rescued by chimeric APOE that targets only LDs. APOE4-expressing astrocytes also form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the larger LDs inAPOE4cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition.APOE4is a toxic gain of function variant that causes aberrant LD composition and morphology. We propose thatAPOE4astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation or lipotoxicity, which could contribute to Alzheimer’s disease risk.SummaryWindhamet al. discover that APOE in astrocytes can traffic to lipid droplets (LDs), where it modulates LD composition and size. Astrocytes expressing the Alzheimer’s risk variant APOE4 form large LDs with impaired turnover and increased peroxidation sensitivity.
CaV2.1 α1subunit motifs that control presynaptic CaV2.1 subtype abundance are distinct from CaV2.1 preference
Authors: Li Jianing , Veeraraghavan Priyadharishini , Young Samuel M. 
Published: April 2023

AbstractPresynaptic voltage-gated Ca2+channels (CaV) subtype abundance at mammalian synapses regulates synaptic transmission in health and disease. In the mammalian central nervous system, most presynaptic terminals are CaV2.1 dominant with a developmental reduction in CaV2.2 and CaV2.3 levels, and CaV2 subtype levels are altered in various diseases. However, the molecular mechanisms controlling presynaptic CaV2 subtype levels are largely unsolved. Since the CaV2 α1subunit cytoplasmic regions contain varying levels of sequence conservation, these regions are proposed to control presynaptic CaV2 subtype preference and abundance. To investigate the potential role of these regions, we expressed chimeric CaV2.1 α1subunits containing swapped motifs with the CaV2.2 and CaV2.3 α1subunit on a CaV2.1/CaV2.2 null background at the calyx of Held presynaptic terminal. We found that expression of CaV2.1 α1subunit chimeras containing the CaV2.3 loop II-III region or cytoplasmic C-terminus (CT) resulted in a large reduction of presynaptic Ca2+currents compared to the CaV2.1 α1subunit. However, the Ca2+current sensitivity to the CaV2.1 blocker Agatoxin-IVA, was the same between the chimeras and the CaV2.1 α1subunit. Additionally, we found no reduction in presynaptic Ca2+currents with CaV2.1/2.2 cytoplasmic CT chimeras. We conclude that the motifs in the CaV2.1 loop II-III and CT do not individually regulate CaV2.1 preference, but these motifs control CaV2.1 levels and the CaV2.3 CT contains motifs that negatively regulate presynaptic CaV2.3 levels. We propose that the motifs controlling presynaptic CaV2.1 preference are distinct from those regulating CaV2.1 levels and may act synergistically to impact pathways regulating CaV2.1 preference and abundance.Key points summaryPresynaptic CaV2 subtype abundance regulates neuronal circuit properties, however the mechanisms regulating presynaptic CaV2 subtype abundance and preference remains enigmatic.The CaVα1subunit determines subtype and contains multiple motifs implicated in regulating presynaptic subtype abundance and preference.The CaV2.1 α1subunit domain II-III loop and cytoplasmic C-terminus are positive regulators of presynaptic CaV2.1 abundance but do not regulate preference.The CaV2.3 α1subunit cytoplasmic C-terminus negatively regulates presynaptic CaV2 subtype abundance but not preference while the CaV2.2 α1subunit cytoplasmic C-terminus is not a key regulator of presynaptic CaV2 subtype abundance or preference.The CaV2 α1subunit motifs determining the presynaptic CaV2 preference are distinct from abundance.
Uncovering Co-regulatory Modules and Gene Regulatory Networks in the Heart through Machine Learning-based Analysis of Large-scale Epigenomic Data
Authors: Vahab Naima , Bonu Tarun , Kuhlmann Levin , Ramialison Mirana , Tyagi Sonika 
Published: April 2023

AbstractThe availability of large scale epigenomic data from different cell types and conditions has provided valuable information to evaluate and learn features that predict co-binding of transcription factors (TF). However, previous attempts to develop models for predicting motif cooccurrence were not scalable for global analysis of any combination of motifs or cross-species predictions. Further, mapping co-regulatory modules (CRM) to their gene regulatory networks (GRN) is crucial in understanding the underlying function. Currently, there is no comprehensive pipeline to locate CRM and GRN on a large scale with speed and accuracy. In this study, we analyzed and evaluated different TF binding characteristics that would facilitate co-binding with biological significance to identify all possible clusters of co-binding TFs. We curated the UniBind database, which contains ChIP-Seq data from over 1983 samples and 232 TFs, and implemented two machine learning models to predict CRMs and potential regulatory networks they operate on. We narrowed our focus to study heart related regulatory motifs. Our findings highlight the importance of the NKX family of transcription factors in cardiac development and provide potential targets for further investigation in cardiac disease.
Context-specific and context-invariant computations of interval timing
Authors: Pourmohammadi Ahmad , Sanayei Mehdi 
Published: April 2023

AbstractAn accurate sense of time is crucial in flexible sensorimotor control and other cognitive functions. However, it remains unknown how multiple timing computations in different contexts interact to shape our behavior. We asked humans to perform timing tasks that differed in the sensorimotor domain (sensory timing vs. motor timing) and effector (hand vs. saccadic eye movement). To understand how these different behavioral contexts contribute to timing behavior, we applied a three-stage Bayesian model to behavioral data. We found that these behavioral contexts affect different stages of computations about time. Moreover, our results indicated that the mode of response also affects computations related to measuring and sensing time. These findings suggest that both context-specific and context-invariant computations contribute to shaping our timing behavior.
A multiscale characterization of cortical shape asymmetries in early psychosis
Authors: Chen Yu-Chi , Tiego Jeggan , Segal Ashlea , Chopra Sidhant , Holmes Alexander , Suo Chao , Pang James C. , Fornito Alex , Aquino Kevin M. 
Published: April 2023

ABSTRACTBackgroundPsychosis has often been linked to abnormal cortical asymmetry, but prior results have been inconsistent. Here, we applied a novel spectral shape analysis to characterize cortical shape asymmetries in patients with early psychosis across different spatial scales.MethodsWe used the Human Connectome Project for Early Psychosis dataset (aged 16–35), including 56 healthy controls (male = 37, female = 19) and 112 patients with early psychosis (male = 68, female = 44). We quantified shape variations of each hemisphere over different spatial frequencies and applied a generalized linear model to compare differences between healthy control participants and patients with early psychosis. We further used a canonical correlation analysis (CCA) to examine associations between shape asymmetries and clinical symptoms.ResultsCortical shape asymmetries, spanning wavelengths between about 22 mm and 75 mm, were significantly different between healthy control participants and patients with early psychosis (Cohen’sd= 0.28−0.51), with patients showing greater asymmetry in cortical shape than controls. A single canonical mode linked the asymmetry measures to symptoms (CCAr= 0.45), such that higher cortical asymmetry was correlated with more severe excitement symptoms and less severe emotional distress. In contrast, significant group differences in morphological asymmetries of cortical thickness, surface area, and gyrification at either global or regional levels were not identified.ConclusionsCortical shape asymmetries are more sensitive than other morphological asymmetries in capturing abnormalities in patients with early psychosis. These abnormalities are expressed at coarse spatial scales and are correlated with specific symptom domains.HighlightsCortical shape asymmetries are more sensitive than other cortical asymmetry measures, such as cortical thickness, surface area and gyrification, in capturing abnormalities in patients with early psychosis.The abnormalities in cortical shape asymmetry are expressed at coarse spatial scales and are correlated with excitement and emotional distress symptoms.
Cash conversion cycle and financial performance: evidence from manufacturing firms of Bangladesh
Authors: Karim Rejaul , Mamun Md. Abdullah Al , Kamruzzaman Abu Sadeque Md. 
Published: April 2023

PurposeThe purpose of the present study is to determine how the cash conversion cycle (CCC) affects the financial performance of manufacturing companies in Bangladesh.Design/methodology/approachThe authors have collected data of 61 Dhaka Stock Exchange (DSE)-listed firms from the 10 distinct manufacturing industries of Bangladesh for 18 years, from 2003 to 2020. The data have been analyzed through the two-steps system generalized method of moment (GMM) regression model, using profitability indicators return on asset (ROA) and earnings per share (EPS) as dependent variables, while CCC has been used as the independent variable, whereas asset turnover (ATO) and financial leverage (LEV) were used as control variables to assess the relationship between the CCC and financial performance.FindingsThe findings indicated that CCC has a negative connection with profitability – ROA and EPS, with the connection between CCC and EPS being highly significant. This indicates that reducing the inventory conversion time, reducing the period of receivable collection and making payments to creditors with potential delays might help Bangladeshi manufacturing firms boost their profitability. In addition, the firm-specific characteristics, namely ATO and LEV significantly affect the firm's profitability.Research limitations/implicationsThe research was based only on secondary sources and information was scarce. This research was conducted to determine the impact of the CCC on the corporate profitability of the manufacturing sector solely. There might be many other working capital variables that are still unexplored through this study.Practical implicationsThe current study's findings are consistent with the traditional rule that minimizing the firm's days of the cash cycle may optimize financial performance. The results of this research have added to the existing body of knowledge on the topic of working capital management (WCM). Future research endeavors can be initiated for assessing the impact of the CCC on the firm's profitability in other industrial sectors or to identify other working capital variables that have much impact on corporate profitability.Originality/valueThis study is an original work of the researchers and adds value to the current literature in the domain of WCM and corporate profitability. The present study is the first one that covers firms in all the manufacturing industries in Bangladesh. The corporate managers, creditors, investors and other concerned stakeholders will be benefited from the findings of the present study.
Are gold and cryptocurrency a safe haven for stocks and bonds? Conventional vs Islamic markets during the COVID-19 pandemic
Authors: Widjaja Michaelia , Gaby  , Havidz Shinta Amalina Hazrati 
Published: April 2023

PurposeThis study aims to identify the ability of gold and cryptocurrency (Cryptocurrency Uncertainty Index (UCRY) Price) as safe haven assets (SHA) for stocks and bonds in both conventional (i.e. stock indices and government bonds) and Islamic markets (i.e. Islamic stock indices and Islamic bonds (IB)).Design/methodology/approachThe authors employed the nonadditive panel quantile regression model by Powell (2016). It measured the safe haven characteristics of gold and UCRY Price for stock indices, government bonds, Islamic stocks, and IB under gold circumstances and level of cryptocurrency uncertainty, respectively. The period spanned from 11 March 2020 to 31 December 2021.FindingsThis study discovered three findings, including: (1) gold is a strong safe haven for stocks and bonds in conventional and Islamic markets under bearish conditions; (2) UCRY Price is a strong safe haven for conventional stocks and bonds but only a weak safe haven for Islamic stocks under high crypto uncertainty; and (3) gold offers a safe haven in both emerging and developed countries, while UCRY Price provides a better safe haven in developed than in emerging countries.Practical implicationsGold always wins big for safe haven properties during unstable economy. It can also win over investors who consider shariah compliant products. Therefore, it should be included in an investor's portfolio. Meanwhile, cryptocurrencies are more common for developed countries. Thus, the governments and regulators of emerging countries need to provide more guidance around cryptocurrency so that the societies have better literacy. On top of that, the investors can consider crypto to mitigate risks but with limited safe haven functions.Originality/valueThe originality aspects of this study include: (1) four chosen assets from conventional and Islamic markets altogether (i.e. stock indices, government bonds, Islamic stock indices and IB); (2) indicator countries selected based on the most used and owned cryptocurrencies for the SHA study; and (3) the utilization of UCRY Price as a crypto indicator and a further examination of the SHA study toward four financial assets.
Assessing the significance of retail service quality on shopping frequency: an adaptation of retail service quality (RSQS) model
Authors: Musasa Tinashe , Tlapana Tshepo 
Published: April 2023

PurposeThis study aims to ascertain the significance of retail service quality dimensions on shopping frequency at supermarkets in Durban. This study also adopts the Retail Service Quality Scale (RSQS) to South African supermarket consumers.Design/methodology/approachPrimary data were collected from 399 consumers through mall intercepts using an adapted RSQS. Non-probability convenience sampling was utilised in selecting participants from different malls in Durban. To analyse data the SPSS software was utilised with multiple regression analysis to confirm relationships between variables of the study.FindingsResults indicate a significant linear relationship between retail service quality and shopping frequency. Two of the three dimensions of retail service quality (atmospherics and reliability) have a positive and significant influence on the shopping frequency of consumers whereas one dimension (policy) showed no significant influence on the dependent variable.Research limitations/implicationsFurther studies are recommended in ascertaining the reasons behind an insignificant relationship between policy items of service quality and the shopping frequency of consumers.Practical implicationsThis study highlights the managerial implications of retail service quality on improved shopping frequency of consumers.Originality/valueThis study suggests a lesser emphasis on policy items specifically personal interaction amongst Durban consumers on their shopping frequency. This might be due to cultural differences as well as the importance of self-service and privacy in supermarkets. Furthermore, this study demonstrates the role of context in providing deviations in retail service quality measurement and conceptualisation.
Industry 4.0, circular economy and sustainability in the food industry: a literature review
Authors: Quiroz-Flores Juan Carlos , Aguado-Rodriguez Renato Jose , Zegarra-Aguinaga Edisson Andree , Collao-Diaz Martin Fidel , Flores-Perez Alberto Enrique 
Published: April 2023

PurposeThis paper aims to find the best tools to influence the improvement of sustainability in food supply chains (FSCs) by conducting a systematic review of articles. The reader will learn how the different industry 4.0 tools (I4.0T) benefit the FSC and the limitations of each tool.Design/methodology/approachA review of 436 articles published during the period 2019 to 2022 referenced in the Scopus and Web of Science databases was performed. The review was limited to articles published in English and directly related to Industry 4.0, circular economy and sustainability in the food supply chain.FindingsThe results show different contributions of I4.0, with some being more influential than others in improving sustainability in FSCs; for example, Internet of Things and Blockchain have been shown to contribute more toward transparency, traceability, process optimization and waste reduction.Originality/valueThe paper's contribution consisted of ranking according to their importance and the I4.0T that affect sustainability in FSCs by classifying the aspects of each tool and the sustainability factors through a categorization by the Analysis Hierarchy Process.