bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Differences in SARS‐Cov‐2 Spike Proteins and their Effects
Authors: Cetin Sena 
Published: May 2022

COVID‐19 is a highly infectious disease that mainly affects the human respiratory system. Coronavirus spike glycoproteins assist in entry and infection of cells by binding to the human ACE2 receptor. Because of this, they are the main target for antibodies and inhibitors (Walls et al., 2020).Some variants of SARS‐CoV‐2 have been classified as Variants of Concern (VOCs). One characteristic of these VOCs is an “increase in transmissibility or detrimental change in COVID‐19 epidemiology” (World Health Organization, 2021) as a result of mutations in the SARS‐CoV‐2 genome. By comparing the structures of the S proteins of SARS‐CoV‐2 (Pango lineage A) and its B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants using PyMOL, we studied the differences in the structure of the receptor binding domain (RBD) of these S proteins, explaining their increased binding affinity to the ACE2 receptor, and their consequent increased transmissibility. The structure of a protein is directly related to its function which is why we think that this investigation is crucial to understanding SARS‐CoV‐2 and its variants. We expect that these regions are important for studying possible impacts on vaccine effectiveness and specific drug targets for SARS‐CoV‐2.
Blockade of Trpm7 in the Carotid Body area attenuated intermittent hypoxia‐induced Hypertension
Authors: Shin Mi Kyung , Kim Lenise J. , Tang Wan‐Yee , Sun Boran , Cui Honggang , Polotsky Vsevolod Y. 
Published: May 2022

RATIONALEObesity leads to high cardiovascular morbidity and mortality via multiple mechanisms including obstructive sleep apnea (OSA) and hypertension. Intermittent hypoxia (IH), a hallmark manifestation of OSA, is an established cause of hypertension. The carotid body (CB) has been implicated in the pathogenesis of hypertension in IH and obesity. We discovered that obesity‐induced hypertension is mediated via the transient receptor potential melastatin 7 (TRPM7) channel in the glomus cells of CB. Here, we investigate the relevance of TRPM7 signaling in CB for the pathogenesis of hypertension by IH. We developed a novel technique allowing continuous sustained release of the TRPM7 inhibitor FTY720 into the CB area using a hydrogel formulation with a single injection abolishing hypertension in obesity for 3 weeks. We hypothesize that IH causes hypertension acting on CB TRPM7.METHODSC57BL/6J male mice (n = 9) were implanted with telemetry in the left femoral artery for continuous blood pressure monitoring and exposed to IH for 5 days. IH was administered by decreasing O2 levels from 21% to 6%, 60 cycles/hr, during the light phase, 9AM ‐9PM. FTY720 hydrogel (n = 5) or control hydrogel (N = 4) were applied locally to the CB region. Blood pressure was recorded at baseline and during IH and the measurement was repeated 2 weeks after hydrogel application.RESULTIH increased mean arterial pressure from 103.8±1.2 mmHg to 114.3±1.4 mmHg on Day 1 of IH and to 113.0±0.6 mmHg on Day 5 of IH respectively. FTY720 hydrogel abolished IH‐induced hypertension by decreasing blood pressure to 106.6±1.6 mmHg (p<0.005) on Day 1 of IH and to 101.5±1.6 mmHg (p<0.001) on Day 5 of IH. In contrast, control hydrogel had no effect on IH‐induced hypertension.CONCLUSIONOur study has shown that inhibition of TRPM7in the carotid bodies abolished IH‐induced hypertension.
Weight Gain, Fibroblast Growth Factor‐23, and Vascular Function in Liver Transplant Recipients
Authors: Martin Linsey F. , Chavez Domenico A. , Bohmke Natalie J. , Miller Austin , Bhati Chandra , Wolver Susan , Siddiqui Mohammad S. , Kirkman Danielle L. 
Published: May 2022

INTRODUCTIONLiver transplant (LT) recipients experience significant weight gain and an increased risk of cardiovascular disease (CVD) after transplant. The pathophysiology of this cardiometabolic burden is not fully understood. In the general population, weight gain and increased adiposity are associated with elevated circulating levels of fibroblast growth factor‐23 (FGF‐23). Increased FGF‐23 has been linked with CVD in other disease populations. This study tested the working hypothesis that weight gain after LT is associated withincreased levels of FGF‐23, that subsequently contribute to vascular dysfunction, an established precursor of CVD.METHODSWe enrolled 21 LT patients (M/F: 9/12; Mean ± SEM, Age: 55 ± 2 yrs) and 8 age matched healthy controls (HC; M/F: 2/6; 47 ± 6 yrs). Vascular endothelial function was assessed with flow‐mediated dilation (FMD) of the brachial artery using duplex ultrasound. Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Serum levels of FGF‐23 were assessed by enzyme linked immunosorbent assay (ELISA).RESULTSHigher body mass index (BMI) values were reported in LT patients (37 ± 1 kg/m2) compared to HC (26 ± 1 kg/m2, p = <0.001). Weight gain (BMI) was positively associated with serum FGF‐23 values (r = 0.5, p = 0.01). Central systolic pressures (125 ± 3 vs. 110 ± 6 mmHg, p = 0.01) and central pulse pressures (51 ± 4 vs. 39 ± 4 mmHg, p = 0.05) were higher in LT patients compared with controls. There was no difference in endothelial function (FMD) in LT patients (4.59 ± 0.55%) compared to their HC counterparts (6.08 ± 0.48%, p = 0.12). FGF‐23 values were not associated with measures of vascular function.CONCLUSIONWeight gain is evident in LT patients and is correlated with higher serum FGF‐23 values. However, our findings do not suggest a relationship between serum levels of FGF‐23 and vascular function in LT recipients.
Specificity of Antibodies for the Identification of Annexin 1 (ANXA1) Protein in Various Types of Cancer
Authors: Olascuaga‐Castillo Karyn , Rubio‐Guevara Susana , Cáceres‐Andonaire Elena , Altamirano‐Sarmiento Dan , Mantilla‐Rodríguez Elena , Hilario‐Vargas Julio , Morgado‐Díaz José , Berezovski Maxim 
Published: May 2022

Annexins are a well‐characterized multigene family of phospholipid‐binding and membrane‐bound proteins that are Ca2+‐regulated. ANXA1 expression is variable in tumor cells, ranging from high levels to none, which is why it is helpful to know the staining potential of various antibodies against the protein. Our research aims to evaluate the specificity of five antibodies used to detect ANXA1 expression in selecting different types of cancer and normal tissue and the differential specificity between the two groups. We examined a data set composed of 2177 samples from The Human Protein Atlas (HPA) as mentioned, cancer patients:1904 samples, and healthy persons: 273 samples. We examined the specificity of five different antibody types of detecting ANXA1 expression (HPA011271, HPA011272, CAB013023, CAB035987, and CAB058693). The specificity of each antibody against ANXA1 protein was evaluated using a staining scale of 0 ‐ 3.00, where 0 indicates no staining, 0.01‐1.0 low staining, 1.01 ‐ 2.0 medium staining, and 2.01 ‐ 3.00 high staining.ResultsCAB013023 had the highest staining values for both cancer and healthy samples; thyroid cancer and endometrial cancer had the highest staining values (2.75 and 2.80, respectively). Breast, head and neck, and bladder normal tissues stained the most intensely in healthy samples (3.00 in all three cases). The antibody's specificity for identifying ANXA1 expression suggests that this may be used as a prognosis and treatment marker in cancer.
Genomic Annotation of Chromosome 3L in Drosophilaananassae
Authors: Cavanaugh Jayda , Merkhofer Evan 
Published: May 2022

The Genomics Education Partnership (GEP) is a nationwide community of more than 100 colleges and universities dedicated to facilitating undergraduate biology education and research. GEP provides training, resources, and mentorship to provide students with experiential learning and research experiences in genomics and bioinformatics. Comparative genomics is important for understanding organismal evolution, adaptation and gene conservation. Comparative genomics also advances the understanding of gene function and homology between species.Drosophila melanogaster is one of the most commonly used model organisms in biomedical science to study fundamental genetics as well as tissue and organ development. The smallest chromosome in Drosophila melanogaster is chromosome 4, also known as the Muller F element, with an estimated size of 5.2 Mb. While the F element has maintained a similar size in many other Drosophila species, it is substantially larger in at least four Drosophila species, one of which is Drosophila ananassae. The D. ananassae Muller F element is more than 18.7 Mb in size. A portion of the D. ananassae genome was annotated for comparison to Drosophila melanogaster. Annotations were completed to generate gene models for genes in Contig 26 of the D. ananassae 3L chromosome (Muller D element) as a comparison to the Muller F element in this species. This was completed using the UCSC Genome Browser, Gene Record Finder, FlyBase, the Basic Local Alignment Search Tool (BLAST) and gene prediction software, such as GENSCAN.Models for four genes were generated from this genomic region: CG8757, Hml, Tsp68C and CG3795. These genes showed a high level of conservation when comparing Drosophila ananassae and Drosophila melanogasterorthologues. The Hml gene codes for hemolectin, which has an orthologue in humans known as the vWB factor. The CG3795 gene has orthologs in multiple species, including Drosophila melanogaster and Drosophila bipectinata, and was recently reported to be involved in proteolysis and serine‐type endopeptidase activity. CG8757, which is predicted to have dehydrogenase activity in D. melanogaster, exhibited synteny with the orthologous gene on the 3L chromosome in Drosophila melanogaster. However, the order of these in D. melanogaster was determined to be different than those annotated in D. ananassae, suggesting a genome rearrangement has occurred in this region. Interestingly, homology with another gene, CG9150, was observed as well. Synteny analysis indicated this gene is located on the X‐chromosome in D. melanogaster, and further analysis suggests a genome rearrangement in this region as well. This annotation has provided some insight to potential genome rearrangements that have occurred in the evolutionary history of these species. Further analysis will provide a greater understanding of how Drosophila genomes have changed over time.
Morphological Description of Olfactory Organ Changes after Acute Nitrite Exposure in Xiphophorus couchianus
Authors: Hughes Hannah , Huertas Mar 
Published: May 2022

This study will explore the effects of acute nitrite exposure in the olfactory organ of Xiphophorus couchianusthrough histological studies. Exposure to aquatic nitrite is known to affect cardiovascular functionality, respiration, and the endocrine and nervous systems in vertebrates. Fish have proven to be beneficial models for studying the effects of aquatic nitrites on vertebrate models. Specifically, the direct interaction of the olfactory system with the aquatic environment offers the opportunity to explore the direct effect of nitrites on the vertebrate nervous system. The olfactory system in fish is incredibly sensitive and allows them the ability to detect odorants across long distances. Thus, the sense of smell in fish is used in a variety of physiological functions (foraging, migration, reproduction, etc.) critical for the survival of the species. For this study, we propose Xiphophorus couchianus as the model species, a live‐bearing fish that uses chemical communication to coordinate reproductive events. We predict that there will be morphological and functional changes in the olfactory tract of X. couchianus due to acute nitrite exposure.To assess the effects of nitrite on olfaction, male X. couchianus were exposed to sublethal levels (0.005 mg/L) of nitrite for forty‐eight hours. The control group consisted of several male X. couchianus that were not previously exposed to nitrite. After forty‐eight hours, their heads were sampled and fixed in bouin. The heads were oriented in paraffin blocks and a microtome was used to cut their noses into 7µm cross sections. The olfactory tract cross sections of the exposed fish were then stained with alcian blue and Gallegos Trichrome staining, and then compared to the olfactory tract of the control group. We found that exposure to nitrite in olfactory tissues changes the morphology of the olfactory organ. More specifically, olfactory epithelium showed signs of inflammation and changes in the morphology of olfactory cells (i.e., hypertrophy and hyperplasia of mucus, several types of receptor cells and lamina propia).To assess the effects of nitrite on olfactory organ function, behavior tests were conducted for both the control and treatment groups. Fish were placed in a two‐choice maze where a food odorant was presented. Fish who were exposed to nitrite showed no preference, whereas the control group clearly preferred the side with the food odorant.Based on the results of this study it can be concluded that nitrite exposure has adverse effects on the morphology of the olfactory tract in X. couchianus and, consequently, hinders typical functioning of relevant olfactory components.
LncRNA Xist Participates in Signaling Pathways Related to Pulmonary Arterial Hypertension and its Comorbidities
Authors: Predescu Dan , Qin Shanshan , Geraci Mark , Mokhlesi Babak , Predescu Sanda 
Published: May 2022

Population‐based studies indicate a female predominance in pulmonary arterial hypertension (PAH) of around 2 – 4 over men for all races/ethnicities and across all ages that have been studied to date. While female gender has long been established as the major clinical risk factor for PAH, other factors such as infections, autoimmune diseases, inflammation, obesity, obstructive sleep apnea and genetic predisposition have also been associated with PAH. Obstructive sleep apnea, a common comorbidity of PAH, leads to intermittent periods of apnea, significant hypoxemia, but importantly, also to hypercapnia both of which, in turn, serve to induce pulmonary arteriolar vasoconstriction and PAH. The mechanistic links between hypoxemia/hypercapnia and vascular remodeling remain unclear. Our studies sought to investigate whether obstructive sleep apnea, contributes to the severity of pulmonary artery endothelial cells (PAECs) PAH phenotype.We recently demonstrated that the increased expression and activity of the long‐noncoding (lnc)RNA‐Xist, essential for X‐chromosome inactivation and dosage compensation of X‐linked genes, drives the imbalance sex/ratio of idiopathic PAH. Using human male and female PAECs of non‐disease controls and PAH patients, in conjunction with molecular cell biology/ biochemistry, and functional approaches, we have found that the PAECs of a female specimen with PAH and obstructive sleep‐apnea displayed the highest increase in Xist expression and proliferation rate. The augmented Xist expression leads to increased expression of the X‐linked gene Elk1, a regulator of cell cycle progression in a tissue‐ and cell‐specific manner, and repression of Klf2, a key transcription factor for endothelial homeostasis and quiescence. These molecular events, more prominent in PAECs of female with PAH and comorbid obstructive sleep apnea, may account for their hyper‐proliferative phenotype. Klf2 also targets several endothelial signature genes that regulate blood pressure, angiogenesis, vascularization etc. Our studies suggest that lncRNA Xist and its signaling network participate in various pathways related to PAH and its comorbidities.
Impact of MeCP2 Overexpression on Myelination Defects Found in Pitt‐Hopkins Syndrome Model Mice
Authors: Freitas Geanne A. , Vermudez Sheryl A. D. , Gogliotti Rocco G. , Niswender Colleen M. 
Published: May 2022

IntroductionStudies examining neurodevelopmental disorders (NDDs) have emphasized a relationship between Pitt Hopkins syndrome (PTHS), which is caused by mutations in the Transcription Factor 4(TCF4) gene, and myelination defects that suggest novel molecular phenotypes in NDDs (Phan et al., 2020). Known phenotypic overlap between PTHS and Rett syndrome (RTT) suggests that there are possible common signaling pathways between the two NDDs. We have found that increasing expression of Methyl‐CpG‐Binding Protein 2 (MeCP2), the causative protein in most cases of RTT, decreases hyperactivity and corrects impairments in learning and memory in a mouse model of PTHS (Tcf4+/‐).AimThe current study sought to understand if the positive effects of MeCP2 overexpression on behavioral phenotypes in the Tcf4+/‐ model were due to a reversal of myelination deficits.Methods/ResultsWe generated four distinct animal genotypes (WT, MECP2Tg1/o, Tcf4+/‐, MECP2Tg1/o; Tcf4+/‐) and performed RNA‐sequencing from the hippocampus and striatum followed by quantitative RT‐PCR, revealing that myelin‐associated genes are differentially expressed in MECP2Tg1/o; Tcf4+/‐ mice in both brain regions. However, Western blotting revealed decreased expression for the myelinating oligodendrocytes (OLs) protein Myelin Oligodendrocyte Glycoprotein (MOG) in mice of both the Tcf4+/‐ and MECP2Tg1/o; Tcf4+/‐ genotypes without changes in the OL precursor cell marker Chondroitin Sulfate Proteoglycan (NG2). We are currently quantifying potential changes in OL morphology and number (mature and immature cells), and myelin synthesis via immunohistochemistry of brain sections.ConclusionsAltogether, our preliminary results indicate that behavioral phenotypic rescue in MECP2Tg1/o; Tcf4+/‐ mice may not result from a correction of myelination deficits characteristic of Tcf4+/‐animals.
Subcellular Protein Expression of Annexin A1 (ANXA1) in Different Types of Cancer
Authors: Olascuaga‐Castillo Karyn , Rubio‐Guevara Susana , Cáceres‐Andonaire Elena , Caballero‐Aquiño Olga , Mantilla‐Rodríguez Elena , Hilario‐Vargas Julio , Morgado‐Díaz José , Berezovski Maxim 
Published: May 2022

Annexin A1 (ANXA1) is a Ca2+‐regulated phospholipid‐binding protein involved in several physiological functions. Further research has shown that this protein might have various roles in cancer development and operate at different levels. This is partially related to the placement of ANXA1 in distinct cellular compartments. ANXA1 is maybe nuclear, cytoplasmic, and membrane‐associated. The goal of this study has been to analyze ANXA1 subcellular localization and expression in different types of cancer.MethodsWe examined 1295 data sets available in The Human Protein Atlas (HPA) (HPA). The research examined the ANXA1 expression in tissue from 1130 cancer and 165 normal samples. A visual categorization method based on staining intensity (I), the proportion of stained cells (F) (F). ANXA1 expression levels as a function of subcellular localization.Q Score (product of E*I) was calculated by the fraction of stained cells (F) and the intensity (I) (I)ResultsIn cancer patients, the predominant subcellular localization was cytoplasmic membranous (53.3 %), whereas, in healthy individuals, the principal was cytoplasmic membranous and nuclear (57.0 %). In terms of staining intensity (Q Score), the highest values were found at the cytoplasmic membranous and nuclear levels (Q Score=5.69). In contrast, the highest Q Score values were found in standard samples at the nuclear level (Q Score=6.0).ConclusionThe subcellular localization of ANXA1 expression may be a helpful diagnostic marker in various cancer types.
Botulinum toxin injection in masseter muscle evokes musculoskeletal impairment of the masticatory system
Authors: BUVINIC SONJA , Blanco Noelia , Vásquez Walter , Quezada Esteban , Eyquem Andrea , Plotkin Lilian , Kupczik Kornelius , Toro‐Ibacache Viviana , Balanta‐Melo Julián 
Published: May 2022

The masticatory system is a finely coordinated machine, where minimal deregulation induces alterations of the whole system. Botulinum toxin type A (BoNTA) injection in masseter muscle is widely used as a clinical/aesthetic procedure. However, the non‐desirable effects of masseter muscle paralysis in neighbor masticatory muscles or mandibular bone are unknown. In the current work, we aimed to evaluate musculoskeletal loss at the masticatory system after BoNTA‐injection in masseter muscle of adult mice.Unilateral paralysis of masseter muscles was induced in male BalbC mice (8 weeks‐old) by single‐injection of BoNTA (0.2U/10 µL) in the right muscle and saline solution in the left muscle. Masticatory muscles (masseter, temporalis, lateral‐ and medial‐pterygoid) and mandibles were dissected after 2‐7‐14d for molecular measurements (qPCR), histology, or morphology (microcomputed tomography). All procedures were approved by the IACUC‐Universidad de Chile (# 20381‐ODO‐UCH). T‐test or Wilcoxon‐test were used for statistical comparisons between BoNTA‐ and Control‐side (n=3‐10, p<0,05).The expression of molecular markers of atrophy (Atrogin1, Murf1) and regeneration (myogenin) significantly increased in the BoNTA‐side, as early as 2‐7d, in the intervened masseter but also in the ipsilateral temporalis and medial pterygoid muscles. There was a time‐dependent reduction in masseter fibers diameter from 2d to 14d. Masseter, temporalis, and medial pterygoid’s volumes significantly reduced in the BoNTA‐injected side at 14d. Interestingly, the volume of lateral pterygoid increased in the BoNTA side, with no change in atrophy/regeneration markers. Microstructural analysis of mandibular condyles demonstrated a progressive bone loss in the BoNTA‐injected side, starting as early as 7d and worsening 14d after the intervention.In conclusion, BoNTA injection in the masseter muscle impairs the whole masticatory system, inducing atrophy of masseter but also the ipsilateral temporalis and medial pterygoid, and even early‐bone loss of the mandibular condyle at the injected side. Then, clinical uses of BoNTA in masticatory muscles should be avoided or carried out under strict morpho‐functional monitoring.
Effects of Antiviral Nucleoside Analogues on the Maintenance of the Mitochondrial Genome
Authors: Bisimwa Hyacintha‐ghislaine M. , Ciesielska Elena J. , Kim Noelle , Oliveira Marcos T. , Ciesielski Grzegorz L. 
Published: May 2022

The outbreak of the COVID‐19 pandemic prompted the search for effective antivirals. Remdesivir (Gilead Sciences) was the first nucleoside analogue approved by the FDA for COVID‐19 treatment, and currently the FDA considers authorization for the use of another analogue, molnupiravir (Merck). Mitochondrial toxicity, resulting from the interference with mitochondrial DNA (mtDNA) replication, is the most common side effect of nucleoside analogues treatment. In addition, defects to the mtDNA synthesis may give rise to heritable mutations, which may be carried undetected for generations before populating mitochondria to the level that onsets a mitochondrial disease. Therefore, nucleoside analogues need to be thoroughly investigated for their impact on the maintenance and integrity of the mitochondrial genome.We recently assessed the effect of remdesivir on the maintenance of the mitochondrial genome. We observed that in in vitro DNA synthesis assays, its triphosphate metabolite may impede the synthetic activity of the mitochondrial replicative polymerase, Pol γ, when in excess over nucleotides. Prompted by this finding, we tested the effect of the nucleoside metabolite of remdesivir on the maintenance and integrity of the mitochondrial genome in proliferating fibroblasts. However, we found no evidence for deleterious effects on the integrity of the mitochondrial genome.We are currently performing an analogical assessment of the effects of molnupiravir on the integrity of the mitochondrial genome. Thus far, we have observed that, unlike remdesivir, molnupiravir is cytotoxic for proliferating fibroblasts and results in a decrease in mtDNA copy number. We are currently testing the impact of molnupiravir on the activity of Pol γ in vitro, and its potential to elicit mutations in the mitochondrial genome in vivo.