bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Assessment of Hassall's Corpuscles in Human Foetal Thymuses
Authors: Sahni Suhalika S , Gupta Richa , Gupta Tulika , Aggarwal Anjali 
Published: November 2023

ObjectiveHassall's corpuscles are unique component of the thymic medulla, which participate in the physiological activities of the thymus. Although, they have role in maturation and differentiation of thymocytes, their function still remains an enigma. Present study proposes immunohistochemical criteria for assessing structural and functional characteristics of Hassall's corpuscles using antibodies against cytokeratin markers in human fetuses.MethodsHassall's corpuscles of 30 aborted human fetuses of various gestational ages (12 to 31 weeks) were studied by using CK5, CK8 and CK14 antibodies.ResultsHassall's corpuscles exhibited positivity for CK5, CK8 from 13 weeks onwards, while CK14 positivity was seen after 16 weeks. CK8 and CK14 positivity was seen around the periphery, while CK5 positivity was observed both at peripheral and central part of Hassall's corpuscles. Two major growth spurts were observed after 16 and 22 weeks of gestation.ConclusionsDemonstration of CK5, CK8 and CK14 (markers for simple and stratified epithelium) in Hassall's corpuscles from thymic medulla of human fetuses support the hypothesis that thymus undergoes sequential stages of differentiation similar to the epidermal tissue. This study enriches the information about structural and functional aspects of Hassall's bodies. This knowledge is crucial and can be used to treat various immunodeficiency diseases of skin and thymic tissue by acquiring progenitor stem cells from fetal thymic tissue.Support or Funding InformationDirector PGIMER, Chandigarh
Looking beyond phalangeal length and curvature: Functional correlation between manual phalangeal articular and collateral ligamentous morpohology and anthropoid locomotor adaptations
Authors: Deane Andrew S. , Tocheri Matthew , Wiles Kathleen 
Published: November 2023

Primates exhibit more diversity in locomotor behavior than any other mammalian order. Discrete locomotor adaptations are characterized by distinct patterns of phalangeal orientation with dissimilar patterns of mechanical loading. Phalangeal shaft length and curvature are frequently used to infer locomotion in fossil anthropoids given the direct and repetitive contact between the hand and substrate; however, most fossil anthropoid phalanges are fragmentary or incomplete. Given that articular epiphyses and associated collateral ligaments are subject to the same locomotor behaviour‐specific mechanical loading that influences longitudinal shaft curvature and length, it is reasonable to predict that the proximal and distal articular surface morphology and collateral ligament fossae (CLF) are also influenced, at least in part, by locomotion.We test the hypothesis that anthropoid phalangeal articular and collateral ligament fossae (CLF) morphology (i.e. contour curvature, size) varies with respect to locomotion and that more terrestrial primates experiencing higher compressive loads will have larger CLF's and increased mediolateral articular contour curvatures to resist mediolateral joint displacement. Segmented 3D models of proximal and distal articular surfaces and CLF's were obtained for the proximal phalanges (digits 2–5) of 16 locomotor diverse anthropoid genera (n=234 individuals). Direct comparisons among individual taxa and locomotor groupings reveal that articular and CLF morphology is a composite function of size, phylogeny, and locomotion but that more terrestrial primates have greater mediolateral articular contour curvatures and larger, deeper CLF's relative to more arboreal primates who have less mediolaterally restrictive joints with increased dorsoventral curvatures and smaller CLF's.
Epstein‐Barr Viral microRNAs Coordinately Repress Human Transcripts in Inflammatory and Apoptotic Pathways
Authors: Kolakada Divya , Katrak Callahan , Riley Kasandra 
Published: November 2023

Epstein–Barr virus (EBV) infects 95% of the world population and is involved in the pathogenesis of Burkitt's (B cell) lymphoma, nasopharyngeal carcinoma, and other cancers in humans. In various states of latent infection and disease, EBV differentially expresses at least 49 mature microRNAs (miRNAs) from two major genomic clusters.To identify potential miRNA‐mRNA pairs, we previously employed the high‐throughput sequencing and crosslinking immunoprecipitation (HITS‐CLIP) method to globally identify mRNA targets of both host and viral miRNAs expressed in unperturbed, EBV‐transformed B cells. Among the human transcripts regulated by EBV miRNAs (n = 1664), the most significantly enriched were involved in the regulation of transcription (n = 328) and apoptosis (n = 132). Detailed bioinformatic exploration of these transcripts predicted that the expression of ten or more key inflammatory/apoptosis proteins may be regulated by one or more EBV miRNAs.In the present study, we combined HITS‐CLIP and bioinformatic predictions with luciferase reporter assays and Western blot analyses to identify and experimentally validate at single‐nucleotide resolution the 3′‐untranslated regions of select apoptotic and inflammatory transcripts bound by EBV miRNAs. Our findings suggest that certain EBV miRNAs co‐target specific transcripts to deregulate the host signaling machinery in a very complex manner during latent infection.Support or Funding InformationK.R. is supported by Critchfield Research Grants, the Rollins Student‐Faculty Collaborative Scholarship Program, the Edward W. and Stella C. Van Houten Memorial Fund, and the Herbert E. Hellewege Research Fund.
Identification and characterization of population heterogeneity of Vibrio cholerae in vivo
Authors: Nguyen Y Nhu , Shull Lauren Marie , Camilli Andrew 
Published: November 2023

Vibrio cholerae is a facultative pathogen that is found naturally in aquatic environments around the world. Upon ingestion of contaminated water or food, V. cholerae can colonize the human small intestine and induce profuse secretory diarrhea known as rice water stool (RWS). During the course of the infection V. cholerae undergoes through various transcriptional changes to adapt to the shifting environment. In the early stage of infection, bacteria rapidly replicate and increase expression of key virulence factors. The middle stage of infection is characterized by upregulation of the chemotaxis and flagellar genes. This allows V. cholerae to exit the luminal fluid of the small intestine. Finally in the late stage of infection, chemotaxis becomes repressed as V. cholerae is shed in the RWS. Studies have shown that V. cholerae exiting the mammalian host can enter into a hyperinfectious state. These hyperinfectious bacteria have been implicated to be major contributors in household transmission of the disease. Factors that promote hyperinfectivity are still largely unknown.Other studies have demonstrated that host‐passed bacteria upregulate important late genes that prepare V. cholerae transition into the aquatic environment. For example, several of these late genes are involved in metabolism and are shown to be important for V. cholerae survival in pond water. One such gene is glpK, which encodes for a glycerol kinase and plays an important role in glycerol metabolism. By quantitative real time PCR, previous work has shown that mice‐passaged V. cholerae had an increased expression of glpK by 10‐ to 14‐fold. However, using recombination‐based in vivo expression technology (RIVET), our lab demonstrated that only 27% of the bacterial population exiting the host induces glpk expression. This suggests that glpK is highly expressed during the late stage of infection but only in a quarter of the population. These results led to the idea that the population of V. cholerae leaving the host may be heterogeneous, in which one subset of the population undergoes preparation for survival in the aquatic environment while the other remains hyperinfectious and therefore, can be more fit for rapid transmission to the next host. To examine this heterogeneous population in vivo, we generated a chromosomal GFP‐transcriptional fusion to glpK in the wave three Haiti V. cholerae strain. Using this strain we infected infant rabbits, which serve as an animal model for cholera in humans, and showed that only a subset of the host‐passed vibrios express GFP or glpK. This is consistent with previous RIVET studies. We will use fluorescence‐activated cell sorting (FACS) to separate the two populations and perform RNA‐seq to study their transcriptomes. Analysis of the subpopulation will provide further understanding of the mechanism of transmission and dissemination of V. cholerae.
Characterizing the mechanism of trogocytosis in Entamoeba histolytica
Authors: Feeney Shea E. , Ralston Katherine S. 
Published: November 2023

E. histolytica (histo‐: tissue; lytic‐: dissolving) is a eukaryotic pathogen that can invade and destroy intestinal tissue. Tissue damage is likely to result from direct, contact‐dependent killing of human cells by amoebae. An improved understanding of this process would allow us to define the mechanism of pathogenesis. Our lab discovered that amoebae kill human cells by ingesting “bites,” an unusual strategy for cell warfare termed trogocytosis (trogo‐: nibble). The mechanism underlying trogocytosis, i.e. how an amoeba extracts bites from a living human cell, is unknown. Interestingly, amoebae ingest dead human cells whole via phagocytosis (phago‐: devour). While some aspects are shared with phagocytosis, nibbling is different from eating entire cells. Therefore, I hypothesize that, while some aspects are likely shared with phagocytosis, amoebic trogocytosis also requires signaling machinery distinct from phagocytosis. I aim to identify and characterize genes required for E. histolytica trogocytosis by using two complementary approaches: transcriptomics analysis and forward genetics. There is evidence that both phagocytosis and trogocytosis are transcriptionally regulated in E. histolytica, thus I am using RNA‐seq analysis to examine differential gene expression in amoebae undergoing trogocytosis versus phagocytosis. My preliminary results with imaging flow cytometry have established a method to quantify and optimize the number of amoebae performing either trogocytosis or phagocytosis respectively, setting the stage for RNA‐seq analysis. Preliminary studies for the forward genetics selection approach provide proof of principle that ingestion mutants can be isolated by selection. Results from these approaches will help to define the mechanism for trogocytosis. Since trogocytosis appears to be a fundamental form of eukaryotic cell‐cell interaction that is exaggerated and exploited for cell killing by microbes, a deeper understanding of the mechanism will have broad impact.Support or Funding InformationNIH MCB T32 GM007377; NIH NIAID K22 Career Transition Award Al108814
Comparison of postprandial hypoglycemic effect of Ecklonia cava extract in healthy subjects using three different challenge models
Authors: Kim Yunsoo , Lee Hyo Jin , Ahn Young sook , Kwon Oran 
Published: November 2023

Repetitive postprandial fluctuation in glucose concentration evokes significant increases in risks of cardiovascular disease, visceral adiposity, and insulin resistance. Ecklonia cava (seapolynol) is a brown alga that is abundant in Jeju Island, Korea. It contains a variety of phloroglucinol‐based polyphenols, as phlorotannins that have inhibitory activities against α—amylase and α‐glucosidase in vitro. According to a recent publication, Ecklonia cava extract (EC) exhibited a peak plasma concentration of bioactive compounds and their metabolites more than 2 hours after oral ingestion. Based on this background information, we intended to compare the postprandial hypoglycemic effects of EC in healthy subjects by performing three independent randomized controlled crossover trials. The first study was performed in a high‐carbohydrate meal challenge (four slices of white bread with strawberry jam). Blood responses were determined at 0, 15, 30, 60, 120 and 180 min. The second study was performed using a high fat and carbohydrate formula (60g fat and 75g maltose). The blood samples were obtained at the same time intervals with the first study. The last study was conducted by providing two consecutive maltose loadings (75 g for each) with a 2‐hour interval. Blood samples were obtained at 0, 15, 30, 60, 120, 135, 150, 180 and 240 min for determination of glucose and insulin levels. The EC administration showed a significant reduction in postprandial glucose and insulin levels during the first 30 min when compared with the placebo group; and in postprandial triglyceride level at 180 min. The most effective dose was determined at 360 mg. The high‐fat and carbohydrate formula showed a less sensitive phenotype compared with either a high‐carbohydrate meal challenge or a maltose loading.Support or Funding InformationThis work was supported by the Bio‐Synergy Research Project (NRF‐2012M3A9C4048761) from the Ministry of Science, ICT, and Future Planning, and the BK21PLUS (Brain Korea 21 plus) program (22a20130012143) from the Ministry of Education, Republic of Korea
Melatonin improves insulin resistance and hepatic steatosis through attenuation of ER stress
Authors: Heo Jeein 
Published: November 2023

Non‐alcoholic fatty liver disease (NAFLD) is increasingly recognized as one of the most common liver diseases. However, there is no specific way to treat or prevent it. Melatonin is a key molecule to regulate body rhythms. It also acts as a potent anti‐oxidant, and the melatonin deficiency is associated with various diseases, including diabetes and obesity; however, the action mechanism is not well known. In addition, fetuin‐A is one of the hepatokines and is known to be associated with insulin resistance and type 2 diabetes. However, it is not known whether melatonin can improve hepatic insulin resistance by down‐regulation of fetuin‐A expression.We used HepG2 cells as a model to study whether melatonin can reduce palmitic acid‐induced insulin resistance. In HepG2 cells treated with (300 uM) of palmitic acid, phosphorylated AKT expression was decreased and fetuin‐A expression was increased, but this effect was inhibited by the treatment of 10 uM of melatonin. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, IRE‐1, and PERK. In addition, thapsigargin, an ER stress activator, increased the expression of fetuin‐A, and ER stress markers, and it was inhibited by melatonin treatment.In addition, in the high fat diet (HFD) mice, oral treatment of 100 mg/kg/day melatonin for 10 weeks decreased body weight, epididymal fat mass, and hepatic steatosis. Insulin sensitivity and glucose tolerance was improved and plasma insulin was decreased by melatonin in HFD mice. Fetuin‐A expression in liver and serum of HFD mice was decreased by melatonin treatment. ER stress markers in liver of HFD mice was decreased by melatonin.Therefore, we suggest that melatonin can improve hepatic insulin resistance and hepatic steatosis, and this may be due to the reduction of ER stress and resultant fetuin‐A expression.Support or Funding InformationThis work was supported by Research Grant (2015R1C1A2A010520) of National Research Foundation of Korea.
The role of the subunits of the Conserved Oligomeric Golgi Complex in filamentous growth of the fungus Aspergillus nidulans
Authors: Gremillion Sara 
Published: November 2023

Filamentous fungi grow as thin, highly‐branched cells with new, polarized growth occurring at the tips. Growth is maintained by the continuous export of plasma membrane and cell wall materials via vesicles from the Golgi apparatus. In order to maintain proper Golgi function, this organelle must continually recycle membrane components and enzymes lost by departing vesicles. The Conserved Oligomeric Golgi (COG) complex is a tethering complex involved in the docking of retrograde vesicles within the Golgi. Using the filamentous fungus Aspergillus nidulans, we are studying the eight subunits of the COG complex, COG1–8. Through a promoter replacement strategy, we have created new strains of A. nidulans that express COG proteins at lower‐than‐normal levels in order to determine which subunits are important for the function of this complex, and therefore, important for growth. When expression of the subunits COG1–4 is reduced, fungal cells are unable to maintain polarized growth. Alternatively, under‐expression of subunits COG5–8 does not appear to have a negative effect on filamentous growth.Support or Funding InformationThis research is supported by internal grants provided by Armstrong State University.
Cellular Proteases Prime Extracellular Vesicles for Intercellular Communication
Authors: Qing Enya , Hantak Michael , Gallagher Tom 
Published: November 2023

Extracellular vesicles (EVs) can mediate intercellular communication by encasing cytoplasmic cargo and transferring this luminal material into nearby cells. This EV‐mediated transfer process is important for maintaining metazoan homeostasis (a positive effect) and is also implicated in metastatic tumor progression (a negative effect). To transfer cytoplasmic cargo, an EV must fuse its membrane with the plasma or endosomal cell membrane on a target cell. A poor understanding of this fusion process has hindered EV biology.We and others are impressed by the similarities between EVs and enveloped viruses. During enveloped virus infection, luminal cargos are transferred through an analogous fusion process. Activating viral membrane fusion frequently requires host proteases. Therefore, we hypothesized that cellular proteases prime EV‐mediated cargo transfers. We quantified EV cargo transfers with a membrane fusion‐dependent reporter complementation assay, where signals are generated only after EV‐mediated delivery of reporter (luciferase) proteins. We found that transmembrane protease serine 2 (TMPRSS2), a protease known to activate several viral fusion‐catalyzing enyzmes, profoundly increased EV‐mediated cargo transfers. TMPRSS2 mediated its effects within the cells producing EVs, suggesting the existence of a protease‐primed, virus‐like fusogen that traffics on EVs to prompt EV‐target cell coalescence and cargo delivery. Our findings may offer increased understanding of EVs and their roles in regulating crucial biological processes, and may provide tools to manipulate EVs for therapeutic purposes.
MELAS and POLG exhibit high rates of hypertension with differential resistance to anti‐hypertensive drugs suggesting divergent pathogenic mechanisms
Authors: Pauls Andrew David , Nevay Dayna‐Lynn , Young Dana , Sandhu Vikrant , Yeung Darwin F , Tsang Michael MY , Tsang Teresa SM , Mattman Andre , Mezei Michelle M , Poburko Damon 
Published: November 2023

BackgroundWe previously reported elevated hypertension (HT) rates in adults with the m.3243A>G mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) mutation. The cause of HT in MELAS is not known but could be linked to dysautonomia and endothelial dysfunction. Hypertension is also reported in transgenic mice that have an error‐prone gamma DNA polymerase (POLG) that increases mtDNA mutation rate. In contrast to MELAS, HT in POLG−/− mice appears to be due to hypertrophy of the tunica media. It is not known if humans with pathogenic POLG mutations similarly exhibit HT, and whether the hemodynamic basis of HT in MELAS and POLG are consistent with common or distinct pathogenic mechanisms.PurposeWe aimed to examine whether POLG patients have an increased risk of HT, and whether the hemodynamics and therapeutic sensitivity of such HT resembles that of HT in MELAS patients. Specifically, we hypothesized that POLG patients would be prone to isolated systolic HT, while MELAS patients should exhibit remodeling of resistance vessels.MethodsWe conducted a chart review at the Adult Metabolic Disease Clinic, Vancouver General Hospital of 35 MELAS and 26 POLG patients in accordance with institutional human research ethics guidelines. Demographic factors, including age, weight, BMI, sex, smoking status and diabetes status were collected. Patients were scored as hypertensive if they were on anti‐hypertensive drugs or had consistently elevated blood pressure measurements in accordance with the Canadian Hypertension Education Program Guidelines.ResultsMELAS and POLG patients showed increased prevalence of HT (20–39 yr age group: 30% MELAS, 14% POLG; 40–59 yr: 71%, 57%; 60–79 yr: 83%, 81%) compared to the Canadian population. Hypertension was not associated with sex, smoking or BMI, and exceeded expected levels given 50% of MELAS patients were diabetic. In the 40–59 and 60–79 yr age groups, antihypertensive drugs controlled systolic blood pressure in MELAS but not in POLG patients (40–59 yr: POLG 145 ± 21 mmHg n = 8 vs MELAS 122 ± 23 n = 12; 60–79 yr: POLG 157 ± 6 n=4 vs MELAS 134 ± 21 n=5), while diastolic blood pressure did not differ between MELAS and POLG. Preliminary analyses suggest that MELAS, but not POLG, patients exhibit elevated peripheral resistance despite therapeutic correction of blood pressure.ConclusionsMELAS and POLG increase the risk of HT, which can increase the propensity for cardiac hypertrophy and cerebrovascular problems. Signs of vascular remodeling as a contributor to HT suggest that early therapeutic treatment at the onset of pre‐hypertension may be warranted to prevent and control HT in these diseases, especially POLG. These findings warrant detailed hemodynamic assessments in larger populations.
Improving the Recruitment, Retention, and Success of Students in STEM Disciplines
Authors: Baker Dianne M , Slunt Kelli M 
Published: November 2023

The University of Mary Washington, a public and primarily undergraduate liberal arts institution, is completing a five‐year STEM Talent Expansion through Research, Engagement, Preparation, and Scholarships (STEREPS) project. This NSF‐DUE funded project was designed to test and assess ways to enhance interest in STEM careers and student performance STEM education, with a focus on underrepresented student populations. To increase student interest in STEM, and to recruit underrepresented students to major in STEM fields at UMW, we implemented a summer STEM research mentoring program for rising high school seniors, and offered small scholarships to entering and continuing STEM majors. To improve student success in STEM courses, we implemented an enhanced summer bridge program, including a new interdisciplinary course (IDIS 101) aimed to develop skills necessary for STEM courses, and a peer‐assisted student study (PASS) program during the academic year to increase success in traditionally challenging gateway courses. Analysis to date indicates that the summer research program was effective in recruiting students to study STEM fields at UMW, and that PASS participation was associated with higher grades in the introductory chemistry courses. The assessment of the efficacy of the summer bridge program is underway. Our lessons and conclusions about best practices will be discussed.Support or Funding InformationSupport for this work was provided by the National Science Foundation's Science, Technology, Engineering, and Mathematics Talent Expansion Program (STEP) under Award No. 1068150.