bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANKRD49 promotes the metastasis of NCI-H1299 and NCI-H1703 cells via activating JNK-ATF2/c-Jun-MMP-2/9 axis
Authors: Sun Jia , Hu Jin-rui , Liu Chao-feng , Li Yuan , Wang Wei , Fu Rong , Guo Min , Wang Hai-long , Pang Min 
Published: March 2023

AbstractAnkyrin repeat domain 49 (ANKRD49) has been found to highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. We found that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9.In vivoassay showed that ANKRD49 promoted lung metastasis of injected- NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. In conclusion, the present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9.
Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons
Authors: Saito-Diaz Kenyi , Dietrich Paula , Wu Hsueh-Fu , Sun Xin , Jayesh Patel Archie , Gale Wzientek Camryn , Robert Prudden Anthony , Boons Geert-Jan , Chen Shuibing , Studer Lorenz , Xu Bingqian , Dragatsis Ioannis , Zeltner Nadja 
Published: March 2023

AbstractThe peripheral nervous system (PNS) is essential for proper body function. A high percentage of the population suffer nerve degeneration or peripheral damage. For example, over 40% of patients with diabetes or undergoing chemotherapy develop peripheral neuropathies. Despite this, there are major gaps in the knowledge of human PNS development and therefore, there are no available treatments. Familial Dysautonomia (FD) is a devastating disorder that specifically affects the PNS making it an ideal model to study PNS dysfunction. FD is caused by a homozygous point mutation inELP1leading to developmental and degenerative defects in the sensory and autonomic lineages. We previously employed human pluripotent stem cells (hPSCs) to show that peripheral sensory neurons (SNs) are not generated efficiently and degenerate over time in FD. Here, we conducted a chemical screen to identify compounds able to rescue this SN differentiation inefficiency. We identified that genipin, a compound prescribed in Traditional Chinese Medicine for neurodegenerative disorders, restores neural crest and SN development in FD, both in the hPSC model and in a FD mouse model. Additionally, genipin prevented FD neuronal degeneration, suggesting that it could be offered to patients suffering from PNS neurodegenerative disorders. We found that genipin crosslinks the extracellular matrix, increases the stiffness of the ECM, reorganizes the actin cytoskeleton, and promotes transcription of YAP-dependent genes. Finally, we show that genipin enhances axon regeneration in anin vitroaxotomy model in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system, CNS). Our results suggest genipin can be used as a promising drug candidate for treatment of neurodevelopmental and neurodegenerative diseases, and as a enhancer of neuronal regeneration.One sentence summaryGenipin rescues the developmental and degenerative phenotypes of the peripheral neuropathy familial dysautonomia and enhances neuron regeneration after injury.
Expanding Interdisciplinarity: A bibliometric study of medical education using the MEJ-24
Authors: Maggio Lauren A. , Costello Joseph A. , Ninkov Anton B. , Frank Jason R. , Artino Anthony R. 
Published: March 2023

AbstractIntroductionInterdisciplinary research has been deemed to be critical in solving society’s wicked problems, including those relevant to medical education. Medical education research has been assumed to be interdisciplinary. However, researchers have questioned this assumption. The present study, a conceptual replication, provides an analysis using a larger dataset and bibliometric methods to bring more clarity to our understanding on the nature of medical education interdisciplinarity or lack thereof.MethodThe authors retrieved the cited references of all published articles in 24 medical education journals between 2001-2020 from the Web of Science (WoS). We then identified the WoS classifications for the journals of each cited reference.ResultsThe 24 journals published 31,283 articles referencing 723,683 publications. We identified 493,973 (68.3%) of those cited references in 6,618 journals representing 242 categories, which represents 94% of all WoS categories. Close to half of all citations were categorized as “education, scientific disciplines” and “healthcare sciences and services”. Over the two decades studied, we observed consistent growth in the number of references in other categories, such as education, educational research, and nursing. Additionally, the variety of categories represented has also increased from 182 to 233 to include a diversity of topics such as business, management, and linguistics.DiscussionThis study corroborates prior work while also expanding it. Medical education research is built upon a limited range of fields referenced. Yet, the growth in categories over time and the ongoing increased diversity of included categories suggests interdisciplinarity that until now has yet to be recognized and represents a changing story.
Integrating EM and Patch-seq data: Synaptic connectivity and target specificity of predicted Sst transcriptomic types
Authors: Gamlin C.R. , Schneider-Mizell C.M. , Mallory M. , Elabbady L. , Gouwens N. , Williams G. , Mukora A. , Dalley R. , Bodor A. , Brittain D. , Buchanan J. , Bumbarger D. , Kapner D. , Kinn S. , Mahalingam G. , Seshamani S. , Takeno M. , Torres R. , Yin W. , Nicovich P.R. , Bae J.A. , Castro M.A. , Dorkenwald S. , Halageri A. , Jia Z. , Jordan C. , Kemnitz N. , Lee K. , Li K. , Lu R. , Macrina T. , Mitchell E. , Mondal S.S. , Mu S. , Nehoran B. , Popovych S. , Silversmith W. , Turner N.L. , Wong W. , Wu J. , Yu S. , Berg J. , Jarsky T. , Lee B. , Seung H.S. , Zeng H. , Reid R.C. , Collman F. , da Costa N.M. , Sorensen S. A. 
Published: March 2023

AbstractNeural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types1. Neural cell types have previously been defined by morphology2, 3, electrophysiology4, 5, transcriptomic expression6–8, connectivity9–13, or even a combination of such modalities14–16. More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells17–20. Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex21. It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type22, 23known to be Somatostatin positive (Sst+)24, 25, were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.
Knockdown of Atg1 or Atg18 in adult adipocytes impairs lipophagy and reduces lifespan of fruit flies (Drosophila melanogaster)
Authors: Bierlein Mariah , Charles Joseph , Polisuk-Balfour Trevor , Bretscher Heidi , Rice Micaela , Zvonar Jacklyn , Pohl Drake , Winslow Lindsey , Wasie Brennah , Deurloo Sara , Wert Jordan Van , Williams Britney , Ankney Gabrielle , Harmon Zachary , Dann Erica , Azuz Anna , Guzman-Vargas Alex , Kuhns Elizabeth , Neufeld Thomas P. , O’Connor Michael B. , Amissah Felix , Zhu Changqi C. 
Published: March 2023

AbstractAutophagy, a lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes such asAtg1orAtg18in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies, but lifespan reduction phenotype has become apparent whenAtg1RNAi orAtg18RNAi is expressed in a non-tissue-specific manner through aTub-Gal4in adult flies or after lipophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and middle gut stem cells. Over-expression of wildtype Atg1 in adult fly muscle or adipocytes reduces lifespan. High levels of ubiquitinated protein aggregates could be the culprit of the reduced lifespan of Atg1 over-expression flies. Our research data presented here have highlighted the important functions of the key autophagy genes in adult fly adipocytes, enteroblasts, and midgut stem cells for lifespan regulation and their undetermined functions in adult fly muscle and glia.SummaryIn this research, we have demonstrated that the key autophagy genes play important roles in fly lifespan regulation through adult adipose tissues, enteroblasts, and middle gut stem cells.
Mutafy: A webserver to identify high quality mutant protein structures in the Protein Data Bank
Authors: Ness Deborah , Hu Jiajing , Kalia Munishikha , Dobson Richard JB , Al-Chalabi Ammar , Iacoangeli Alfredo 
Published: March 2023

AbstractChanges in the amino acid sequence of proteins resulting from nonsynonymous variants in the genome, can have significant effects on protein folding, stability, dynamics, and function, which may ultimately lead to diseases. The analysis of large sets of disease associated variants is a common approach for the study of pathogenic mechanisms.In-silicomutagenesis experiments based on wildtype structures of target proteins are a common approach to this aim, however these do not account for the effect of variants on folding and might not accurately reflect conformational changes. A growing number of experimentally solved protein structures harbouring disease-associated mutations, including single amino acid variants, are deposited in the worldwide Protein Data Bank (PDB). Nevertheless, identifying high-quality structures for specific missense variants of interest remains challenging due to the growing number of deposited protein structures in the PDB, and the lack of a dedicated interface and annotation system to search and retrieve mutant protein structures. As a result, mutant protein structures in the PDB are a powerful source of information which is largely underused. To address these shortcomings, we have developed Mutafy, a publicly available webserver to identify high quality mutant protein structures. Given input human genes, the webserver finds structures of the corresponding coded wildtype proteins and their available solved mutants, selects high quality structures, annotates them with information from biomedical databases to favour their interpretation and selection, and allows for the interactive exploration of the results and 3D visualisation. Mutafy is publicly available without requiring user registration athttps://mutafy.rosalind.kcl.ac.uk.
Isolation and whole genome characterization of antagonisticPaenibacillus polymyxa188 and its biocontrol potential against several fungi
Authors: Shih Sra-Yh , Chou Ker-Rui , Wu Hung-Yi , Tsai HsinYuan 
Published: March 2023

AbstractDiscovery of new antifungal compounds and biocontrol agents is important due to the emergence of drug-resistant fungi and new fungal pathogens. The aim of this study was to isolate marine bacteria that are able to produce metabolites with antifungal properties. In this study, we isolated aP. polymyxa,named as 188, from a marine sediment sample and evaluated its antifungal ability. The results indicated that the bacterium showed excellent antifungal activity against many pathogenic fungi of plants and humans. The antifungal compounds produced byP. polymyxa188 were extracted and analyzed using MALDI-TOF/MS. The complete genome sequence and biosynthetic gene clusters were characterized, and further to compare the genomes ofP. polymyxa188 with other strains. Various CAZymes were identified inP. polymyxa188. Five antibiotic gene clusters including paenilan, paenibacillin, fusaricidin, polymyxin, and tridecaptin can be found inP. polymyxastrains, but gene clusters of paenilan, paenibacillin, and polymyxin were absent inP. polymyxa188. Our findings provided detail genetic information aboutP. polymyxa188 and suggested thatP. polymyxa188 is the potential agent of biocontrol and disease management.
Serotonergic signaling plays a deeply conserved role in improving oocyte quality
Authors: Aprison Erin Z. , Dzitoyeva Svetlana , Ruvinsky Ilya 
Published: March 2023

AbstractDeclining germline quality is a major cause of reproductive senescence. Potential remedies could be found by studying regulatory pathways that promote germline quality. Several lines of evidence, including aC. elegansmale pheromone ascr#10 that counteracts the effects of germline aging in hermaphrodites, suggest that the nervous system plays an important role in regulating germline quality. Inspired by the fact that serotonin mediates ascr#10 signaling, here we show that serotonin reuptake inhibitors recapitulate the effects of ascr#10 on the germline and promote healthy oocyte aging inC. elegans. Surprisingly, we found that pharmacological increase of serotonin signaling stimulates several developmental processes inD. melanogaster, including improved oocyte quality, although underlying mechanisms appear to be different between worms and flies. Our results reveal a plausibly conserved role for serotonin in maintaining germline quality and identify a class of therapeutic interventions using available compounds that could efficiently forestall reproductive aging.
The importance of identifying red flags in wrist and hand pain: a scoping review protocol
Authors: Rossi Federico , Cordella Marco , Lanfranchi Elena , Marca Roberta La , Mennea Ruggero , Pierazzoli Daniele , Cioeta Matteo , Pellicciari Leonardo 
Published: March 2023

ABSTRACTBackgroundMusculoskeletal pain can be defined as a consequence of a trauma or as a disorder of varying nature, which can be manifested in bones, muscles, tendinous and ligamentous structures, including those of the wrist and hand. However, such pain can mimic pathologies that need further diagnostic investigations; as a consequence, healthcare practitioners have to be able to detect their signs and symptoms, in order to refer the patient to the most appropriate clinician.The current literature lacks of reviews that analyze red flags in the field of wrist and hand pain. The reviewers would like to look for any correlations that could be useful in a correct screening process by clinicians.MethodsThis scoping review will be performed in accordance with the PRISMA extensions for Scoping Reviews (PRISMA-ScR). Studies will be included if they meet the following inclusion criteria: population characterized by wrist and hand pain with or without comorbidities either at the present or in the past. No limits of age, gender and sport activity will be applied. No study design, publication type, and data restrictions will be applied. MEDLINE, Web of Science, Cochrane Library, CINAHL, Embase, PEDro databases will be searched up to February 2023. Two reviewers will independently screen all title, abstracts and full-text studies for inclusion. A data collection form will be developed by the research team to extract the characteristics of the studies included. A tabular and accompanying narrative summary of the information will be provided.ConclusionsThis will be the first scoping review to provide a comprehensive overview of the topic. The results will add meaningful information for future research and clinical practice. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
The relationship between musicianship and pain. Is chronic pain and its management a problem for student musicians only?
Authors: Korte Michaela , Cerci Deniz , Wehry Roman , Timmers Renee , Williamson Victoria J. 
Published: March 2023

AbstractNeuro-biological research into chronic pain has presented reliable evidence of distinct cortical and spinal alterations in chronic pain sufferers compared to healthy individuals. Furthermore, research suggests that musicians are especially vulnerable to frequent and extended pain, supported by recent neurological investigations into musicians’ brain plasticity. However, chronic pain is not simply acute pain plus time, but a separate condition. Little is known about musicians’ emotions and chronic pain-related behaviors. Acquiring such knowledge is a crucial step in understanding how chronic pain is processed by musicians. This study investigated pain catastrophizing as one of the pain-related behaviors and emotions alongside six complementary variables: anxiety, depression, depersonalization, burnout, coping strategies and professional identity. 102 under- and postgraduate students from various higher education institutions participated in an online survey. Students were allocated to three groups according to their main study subject and type of institution: music college musicians, university musicians and university non-musicians. Group testing showed that university non-musicians’ pain catastrophizing was significantly worse compared to music college musicians.Music college musicians and university musicians were less prone to maladaptive pain processes, despite perceiving pain for significantly longer periods of time. This novel finding indicates that chronic pain does not inevitably lead to dysfunctional pain processing for musicians and should be reflected accordingly in order to optimize pain-control. The bio-psycho-socio model of chronic pain provides the most robust framework for future research, with the aim of improving care and wellbeing provision for the management of chronic pain in musicians.
CD32 allows capturing blood cells emergence in slow motion during human embryonic development
Authors: Scarfò Rebecca , Alezz Monah Abou , El Khoury Mahassen , Gersch Amélie , Li Zhong-Yin , Luff Stephanie A. , Valsoni Sara , Cascione Sara , Didelon Emma , Merelli Ivan , Freund Jean-Noël , Sturgeon Christopher M. , Tavian Manuela , Ditadi Andrea 
Published: March 2023

SummaryDuring development, in the embryo proper blood cells emerge from a subset of specialized endothelial cells, named hemogenic endothelial cells (HECs), via a process known as endothelial-to-hematopoietic transition (EHT) driven by time-specific Notch signaling activation1. HECs represent an elusive cell population as they are rare and transient, rapidly generating blood cells, and specific markers are lacking. Therefore, it remains unclear how and when the hematopoietic fate is specified and how blood cell emergence is molecularly regulated. Notably, thorough characterization of this process is essential to guide the generation of therapeutic blood productsin vitrofrom human pluripotent stem cells (hPSCs). To identify specific human HEC markers, we performed transcriptomic analysis of 28-32-day human embryos, a developmental stage characterized by active hematopoiesis. We observed that the expression ofFCGR2B, encoding for the Fc receptor CD32, is highly enriched in the ACE+CD34+endothelial cell population that contains HECs. Functionalex vivoanalyses confirmed that multilineage hematopoietic potential is highly enriched in CD32+endothelial cells isolated from human embryos. In addition, clonal analysis revealed that 90% of CD32+hPSC-derived endothelial cells arebona fideHECs. We leveraged this specificity to study how HECs commit to the blood fate. Remarkably, our analyses indicated that HECs progress through different states culminating with the one identified by CD32 expression. Indeed CD32+HECs no longer require Notch to generate hematopoietic progeny and display full commitment to hematopoiesis even before the expression of hematopoietic markers. These findings provide a precise method for isolating HECs primed to the blood fate from human embryos and hPSC cultures, thus allowing the efficient generation of hematopoietic cellsin vitro.
Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin
Authors: Price Tara R. , Stapleton Donnie S. , Schueler Kathryn L. , Norris Marie K. , Parks Brian W. , Yandell Brian S. , Churchill Gary A. , Holland William L. , Keller Mark P. , Attie Alan D. 
Published: March 2023

AbstractWe and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion ofAbhd2. TheAbhd2KOmice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in maleAbhd2KOmice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.