bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct cellular expression and subcellular localization of Kv2 voltage-gated K+channel subtypes in dorsal root ganglion neurons conserved between mice and humans
Authors: Stewart Robert G. , Camacena Miriam , Copits Bryan A. , Sack Jon T. 
Published: March 2023

ABSTRACTThe distinct organization of Kv2 voltage-gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1, and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co-express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization is similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1, in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.Significance statementThe subcellular distribution of Kv2 voltage-gated potassium channels enable compartment-specific modulation of membrane excitability and organization of membrane contact sites. Here we identify subcellular distributions of the Kv2 paralogs, Kv2.1 and Kv2.2, in somatosensory neurons that bear similarities to and distinctions from central neurons. The distribution of Kv2 channels is similar in mouse and human somatosensory neurons. These results identify unique locations of Kv2 channels in somatosensory neurons that could enable roles in sensory information processing.
Detection of SARS-CoV-2 in Schools Using Built Environment Testing in Ottawa, Canada: A Multi-Facility Prospective Surveillance Study
Authors: Thampi Nisha , Burhunduli Tasha , Strain Jamie , Raudanskis Ashley , Moggridge Jason A. , Hinz Aaron , Doukhanine Evgueni , Castellani  , Fralick  , Kassen Rees , McCready Janine , Nott Caroline , Wong  , MacFadden Derek R. 
Published: March 2023

AbstractClassroom and staffroom floor swabs across six elementary schools in Ottawa, Canada were tested for SARS-CoV-2. Schools in neighbourhoods with historically elevated COVID-19 burden had lower environmental swab positivity. Environmental test positivity did not correlate with student grade groups, school-level absenteeism, pediatric COVID-19-related hospitalizations, or community SARS-CoV-2 wastewater levels.SummaryEnvironmental SARS-CoV-2 sampling was performed in six schools in Ottawa, Canada. The percentage of floor swabs detecting SARS-CoV2 was not correlated with absenteeism, pediatric hospitalizations, or wastewater data. Schools in neighbourhoods with previously elevated COVID-19 rates had lower test positivity.
Molnupiravir’s real-world effectiveness in COVID-19 non-hospitalized patients at high risk of severe disease: a single-center study
Authors: Gmizic I , Todorovic N , Sabanovic M , Kekic N , Boskovic N , Milosevic I , Stevanovic G 
Published: March 2023

ABSTRACTObjectiveTo assess the real-world effectiveness of molnupiravir (MOL) in reducing the need for hospitalization in at-risk, non-hospitalized patients with confirmed COVID-19.MethodsA single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19 treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia.ResultsBetween December 15th, 2021, and February 15th, 2022, 320 patients were eligible for inclusion in the study. Of these, 165 received treatment with molnupiravir (51.6%), while both groups were similar in gender and age distribution. The treatment group had a higher proportion of vaccination (75.2% vs. 51%, p<0.001) but was similar to the control group in terms of multiple comorbidity predomination (65.5% vs. 65.2%, p 0.956). The majority of patients who received MOL didn’t require hospitalization (92.7 vs. 24.5%, p<0.001) and needed oxygen supplementation less frequently than those in the control group (0.6% vs. 31%, p<0.001). During the follow-up period of 12.12±3.5 days, none of the patients on MOL were admitted to the Intensive Care Unit (vs. 10.3%, p<0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021, p<0.001).ConclussionOur study has proven the effectiveness of molnupiravir in preventing hospitalization in a population at risk for developing severe forms of COVID-19.
Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3
Authors: Kobori Chie , Takagi Ryo , Yokomizo Ryo , Yoshihara Sakie , Mori Mai , Takahashi Hiroto , Javaregowda Palaksha Kanive , Akiyama Tomohiko , Ko Minoru S.H. , Kishi Kazuo , Umezawa Akihiro 
Published: March 2023

AbstractBackgroundMelanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytesin vitrois too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps.MethodWe differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use.ResultWe successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice.ConclusionThe robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.
Extracellular vesicles of Euryarchaeida: precursor to eukaryotic membrane trafficking
Authors: Mills Joshua , Gebhard L. Johanna , Schubotz Florence , Shevchenko Anna , Speth Daan R. , Liao Yan , Duggin Iain G. , Marchfelder Anita , Erdmann Susanne 
Published: March 2023

SUMMARYSince their discovery, extracellular vesicles (EVs) have changed our view on how organisms interact with their extracellular world. EVs are able to traffic a diverse array of molecules across different species and even domains, facilitating numerous functions. In this study, we investigate EV production inHaloferax volcanii, as representative for Euryarchaeida. We uncover that EVs enclose RNA, with specific transcripts preferentially enriched, including those with regulatory potential, and conclude that EVs can act as an RNA communication system between haloarchaea. We demonstrate the key role of an EV-associated Ras superfamily GTPase for EV formation inH. volcaniithat is also present across other diverse evolutionary branches of Archaea. Ras superfamily GTPases are key players in eukaryotic intracellular vesicle formation and trafficking mechanisms that have been crucial for the emergence of Eukaryotes. Therefore, we propose that archaeal EV formation could reveal insights into the origin of the compartmentalized eukaryotic cell.
FMRP regulates tangential neuronal migration via MAP1B
Authors: Messaoudi Salima , Allam Ada , Stoufflet Julie , Paillard Théo , Fouquet Coralie , Doulazmi Mohamed , Le Ven Anaïs , Trembleau Alain , Caillé Isabelle 
Published: March 2023

ABSTRACTThe Fragile X Syndrome (FXS) represents the most prevalent form of inherited intellectual disability and is the first monogenic cause of Autism Spectrum Disorder. FXS results from the absence of the RNA-binding protein FMRP (Fragile X Messenger Ribonucleoprotein).Neuronal migration is an essential step of brain development allowing displacement of neurons from their germinal niches to their final integration site. The precise role of FMRP in neuronal migration remains largely unexplored.Using live imaging of postnatal Rostral Migratory Stream (RMS) neurons in Fmr1-null mice, we observed that the absence of FMRP leads to delayed neuronal migration and altered trajectory, associated with defects of centrosomal movement. RNA-interference-induced knockdown ofFmr1shows that these migratory defects are cell-autonomous. Notably, the primary FMRP mRNA target implicated in these migratory defects is MAP1B (Microtubule-Associated Protein 1B). Knocking-down MAP1B expression effectively rescued most of the observed migratory defects. Finally, we elucidate the molecular mechanisms at play by demonstrating that the absence of FMRP induces defects in the cage of microtubules surrounding the nucleus of migrating neurons, which is rescued by MAP1B knockdown.Our findings reveal a novel neurodevelopmental role for FMRP in collaboration with MAP1B, jointly orchestrating neuronal migration by influencing the microtubular cytoskeleton.
Transcriptional adaptation of drug-tolerantMycobacterium tuberculosisin mice
Authors: Wynn Elizabeth A , Dide-Agossou Christian , Reichlen Matthew , Rossmassler Karen , Al Mubarak Reem , Reid Justin J , Tabor Samuel T , Born Sarah E M , Ransom Monica R , Davidson Rebecca M , Walton Kendra N , Benoit Jeanne B , Hoppers Amanda , Bauman Allison A , Massoudi Lisa M , Dolganov Gregory , Nahid Payam , Voskuil Martin I , Robertson Gregory T , Moore Camille M , Walter Nicholas D 
Published: March 2023

ABSTRACTTranscriptome evaluation ofMycobacterium tuberculosisin the lungs of laboratory animals during long-term treatment has been limited by extremely low abundance of bacterial mRNA relative to eukaryotic RNA. Here we report a targeted amplification RNA sequencing method called SEARCH-TB. After confirming that SEARCH-TB recapitulates conventional RNA-seqin vitro, we applied SEARCH-TB toMycobacterium tuberculosis-infected BALB/c mice treated for up to 28 days with the global standard isoniazid, rifampin, pyrazinamide, and ethambutol regimen. We compared results in mice with 8-day exposure to the same regimenin vitro. After treatment of mice for 28 days, SEARCH-TB suggested broad suppression of genes associated with bacterial growth, transcription, translation, synthesis of rRNA proteins and immunogenic secretory peptides. Adaptation of drug-stressedMycobacterium tuberculosisappeared to include a metabolic transition from ATP-maximizing respiration towards lower-efficiency pathways, modification and recycling of cell wall components, large-scale regulatory reprogramming, and reconfiguration of efflux pumps expression. Despite markedly different expression at pre-treatment baseline, murine andin vitrosamples had broadly similar transcriptional change during treatment. The differences observed likely indicate the importance of immunity and pharmacokinetics in the mouse. By elucidating the long-term effect of tuberculosis treatment on bacterial cellular processesin vivo, SEARCH-TB represents a highly granular pharmacodynamic monitoring tool with potential to enhance evaluation of new regimens and thereby accelerate progress towards a new generation of more effective tuberculosis treatment.
Cell-type-specific efferocytosis determines functional plasticity of alveolar macrophages
Authors: Better Julian , Wetstein Michael , Estiri Mohammad , Malainou Christina , Ferrero Maximiliano Ruben , Langelage Martin , Kuznetsova Irina , Vazquez-Armendariz Ivonne , Kimmig Lucas , Mansouri Siavash , Savai Rajkumar , Wilhelm Jochen , Alexopoulos Ioannis , Sommer Natascha , Herold Susanne , Matt Ulrich 
Published: March 2023

AbstractResolution of lung injuries is vital to maintain gas exchange. Concurrently, there is an increased risk of secondary bacterial infections. Alveolar macrophages (AMs) are crucial to clear bacteria and control initiation and resolution of inflammation, but environmental cues that switch functional phenotypes of AMs remain elusive. Here, we discovered an incapacity of AMs to mount an effective immune response to bacteria during resolution of inflammation. AM efferocytosis of neutrophils (PMNs), a hallmark of resolution of inflammation, switched mitochondrial metabolism to shift AM functions. Mechanistically, PMN-derived myeloperoxidase (MPO) fueled canonical glutaminolysis via uncoupling protein 2 (UCP2) resulting in decreased mtROS-dependent killing of bacteria and secretion of pro-inflammatory cytokines. Instead, MPO-enhanced UCP2 expression inhibited mitochondrial hyperpolarization and boosted efferocytosis irrespective of the presence of bacterial pathogens. In contrast, efferocytosis of epithelial cells resulted in a distinct anti-inflammatory phenotype of AMs maintaining phenotypic plasticity towards bacteria. Overall, uptake of apoptotic PMNs switches AMs to prioritize resolution of inflammation over antibacterial responses and similarly affects murine macrophages at extra-pulmonary sites, and human AMs.One sentence summaryNeutrophil efferocytosis reprograms mitochondrial metabolism to switch alveolar macrophages to a pro-resolution phenotype at the cost of bacterial control.
Does macroeconomic stability promote economic growth? Some econometric evidence from SAARC countries
Authors: Siddik Md. Nur Alam 
Published: March 2023

PurposeThe main purpose of this research is to examine the influence of macroeconomic stability on economic growth of SAARC (South Asian Association for Regional Cooperation) countries.Design/methodology/approachUsing panel data of 1991–2020, fixed effect regression analysis, pooled ordinary least squares and generalized method of moments techniques have been conducted to demonstrate whether macroeconomic stability contributes to economic growth. Moreover, cross-sectional dependency test, unit root test, correlation analysis and granger causality tests have been run.FindingsRobust findings indicate that inflation has negative impacts on economic growth which indicates that lower level of macroeconomic instability promotes countries’ economic growth. This study also observed that foreign direct investment, domestic credit delivered to private sector, currency exchange and institutional difference across countries are affirmatively connected while labor force is negatively associated with economic growth.Originality/valueEmpirical findings of this study signify that macroeconomic stability have significant effects on economic growth. Findings of this study have superior contributions for the policy makers to achieve sustainable economic growth.
Scaling organizational agility: key insights from an incumbent firm's agile transformation
Authors: Hutter Katja , Brendgens Ferry-Michael , Gauster Sebastian Peter , Matzler Kurt 
Published: March 2023

PurposeThis paper aims to examine the key challenges experienced and lessons learned when organizations undergo large-scale agile transformations and seeks to answer the question of how incumbent firms achieve agility at scale.Design/methodology/approachBuilding on a case study of a multinational corporation seeking to scale up agility, the authors combined 36 semistructured interviews with secondary data from the organization to analyze its transformation since the early planning period.FindingsThe results show how incumbent firms develop and successfully integrate agility-enhancing capabilities to sense, seize and transform in times of digital transformation and rapid change. The findings highlight how agility can be established initially at the divisional level, namely with a key accelerator in the form of a center of competence, and later prepared to be scaled up across the organization. Moreover, the authors abstract and organize the findings according to the dynamic capabilities framework and offer propositions of how companies can achieve organizational agility by scaling up agility from a divisional to an organizational level.Practical implicationsAlong with in-depth insights into agile transformations, this article provides practitioners with guidance for developing agility-enhancing capabilities within incumbent organizations and creating, scaling and managing agility across them.Originality/valueExamining the case of a multinational corporation's exceptional, pioneering effort to scale agility, this article addresses the strategic importance of agility and explains how organizational agility can serve incumbent firms in industries characterized by uncertainty and intense competition.
Formal salesforce controls and service-sales ambidexterity: the moderating role of salespeople's grit
Authors: Amenuvor Fortune Edem , Mensah Kobby , Nkukpornu Atsu , Boateng Henry , Akasreku Frank , Owusu-Antwi Kwasi 
Published: March 2023

PurposeThe study examines the effects of behavior-based and outcome-based control systems on service-sales ambidexterity, role conflict, emotional exhaustion and job performance in salespeople.Design/methodology/approachData are collected from 704 salespeople in Ghana. The proposed hypotheses are tested through the structural equations modeling technique.FindingsThe study finds that both behavior-based and outcome-based controls have positive and significant effects on service-sales ambidexterity in salespeople. Similarly, the study discovers that service-sales ambidexterity has a positive and significant impact on both role conflict and emotional exhaustion in salespeople. The study also finds that role conflict and emotional exhaustion both have a negative impact on job performance. Finally, the study finds that salespeople's grit moderates the negative relationship between emotional exhaustion and job performance.Practical implicationsThe results imply that while salespeople's service-sales ambidexterity may be beneficial to their individual and firm performance, it may also lead to role conflict and emotional exhaustion.Originality/valueThe current study demonstrates how control mechanisms can lead to service-sales ambidexterity in salespeople and how this can lead to role conflict and emotional exhaustion.
Explaining resilience model of historical bazaars using artificial neural network
Authors: Heydari Torkamani Mina , Shahbazi Yaser , Belali Oskoyi Azita 
Published: March 2023

PurposeHistorical bazaars, a huge treasure of Iranian culture, art and economy, are places for social capital development. Un-supervised management in past decades has led to the demolition and change of historical bazaars and negligence of its different aspects. The present research aims to investigate the resilience of historical bazaars preserving their identity and different developments.Design/methodology/approachThe artificial neural network (ANN) has been applied to investigate the resilience of historical bazaars. This model consists of three main networks for evaluating the resilience of historical networks in terms of adaptability, variability and reactivity.FindingsThe ANN proposed to evaluate the resilience of historic bazaars based on the mentioned factors is efficient. By calculating mean squared error (MSE), the model accuracy for evaluating adaptability, variability and reactivity were obtained at 7.62e-25, 2.91e-24 and 1.51e-24. The correlation coefficient was obtained at a significance level of 99%. This indicates the considerable effectiveness of the artificial intelligence model in modeling and predicting the qualitative properties of historical bazaars resilience.Originality/valueThis paper clarifies indexes and components of resilience in terms of adaptability, variability and reactivity. Then, the ANN model is obtained with the least error and very high accuracy that predict the resilience of historical bazaars.
Dialog chatbot as an interactive online tool in enhancing ESP vocabulary learning
Authors: Qasem Fawaz , Ghaleb Mukhtar , Mahdi Hassan Saleh , Al Khateeb Ahmed , Al Fadda Hind 
Published: March 2023

PurposeBased on an experimental study on English for Specific Purposes (ESP) students, at the Business Department at the University of Bisha, the purpose of the study is to examine the effect of chatbot use on learning ESP in online classrooms during COVID-19 and find out how Dialogflow chabot can be a useful and interactive online platform to help ESP learners in learning vocabulary well.Design/methodology/approachThe research paper is based on an experimental study of two groups, an experiential group and a controlled group. Two tests were carried out. Pre-tests and post-test of vocabulary knowledge were conducted for both groups to explore the usefulness of using the Dialogflow chatbot in learning ESP vocabulary. A designed chatbot content was prepared and included all the vocabulary details related to words' synonyms and a brief explanation of words’ meanings. An informal interview is another tool used in the study. The purpose of using the interview with the participants was to elicit more data from the participants about using the chatbot and about how and in what aspects chatbot using the conversational program was useful and productive.FindingsThe findings of the study explored that the use of chatbots plays a major role in enhancing and learning ESP vocabulary. That was clear as the results showed that the students who used the chatbot Dialogflow in the experimental group outperformed their counterparts in the control group.Research limitations/implicationsThe study displays an important pedagogical implication as the use of chatbots could be applied in several settings to improve language learning in general or learning ESP courses in particular. Chatbot creates an interesting environment to foster build good interactions where negotiation of meaning takes place clearly seems to be of great benefit to help learners advance in their L2 lexical development.Originality/valueExamining and exploring whether the use of chatbots plays a major role in enhancing and learning ESP vocabulary in English as Foreign Language setting.