bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Attenuating Effects of 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) on the Expression of Proteins Involved in Alzheimer's Disease in LPS/IFNγ Activated BV‐2 Microglial Cells.
Authors: Mendonca Patricia , Taka Equar , Soliman Karam F. 
Published: June 2021

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder associated with memory and cognition impairment. The main pathological hallmarks are abnormal intraneuronal cytoskeletal changes, known as neurofibrillary tangles, and the extracellular protein deposits of amyloid beta plaques (Aβ). Although the currently available drugs for AD do not prevent or reverse the formation of Aβ deposits, medicinal plants have been reported for possible anti‐AD activity and are promising therapeutic agents for neurodegenerative disorders. 1,2,3,4,6‐Penta‐O‐galloyl‐β‐D‐glucose (PGG), which is a naturally occurring polyphenolic compound, has shown to exhibit anti‐aggregation activity on Alzheimer's Aβ proteins. Its oral intake reduced Aβ plaque burden and Aβ peptide content in brain tissue of transgenic mice. In this study, we investigated the effect of PGG on the expression of proteins involved in neurodegenerative diseases in LPS/IFNγ activated BV‐2 microglial cells. Proteomic results identified 17 proteins whose expression level was significantly downregulated by PGG, including septin‐7, ataxin‐2, and adenylosuccinate synthetase isozyme 2 (ADSS). These proteins were previously described as being expressed in neurodegenerative diseases and/or involved in the Wnt signaling pathway, which is associated with the development of neuronal circuits and control of AD pathogenesis. PGG inhibitory effect on ataxin‐2, septin‐7, and ADSS was confirmed at the protein and transcription level, and the proteins were classified according to biological processes and molecular functions using NCBI and PANTHER databases. Since these selected proteins are involved in synapse impairment induced by Aβ protein, they are interesting candidates for possible involvement in the underlying mechanisms of synaptic dysfunction in neurodegenerative diseases. Therefore, these results suggest that PGG may have a role in halting neuropathologic effects of AD by targeting ataxin‐2, septin‐7, and ADSS.Support or Funding InformationSupported by NIH Grants G12 MD007582 and P20 MD 006738This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elp1‐dependent Shp1 Phosphatase Regulation and its Essential Role in Familial Dysautonomia Pathogenesis
Authors: Tourtellotte Warren G. 
Published: June 2021

Familial Dysautonomia (FD; Riley‐Day Syndrome; HSAN3) is a rare heritable disease characterized by debilitating sensory and sympathetic neuropathy. It is caused by a germline mutation of the Elp1 gene that leads to exon mis‐splicing, nonsense‐mediated truncation of the Elp1 protein and loss of Elp1 protein primarily in sympathetic and nociceptive sensory neurons. How Elp1 functions in FD disease‐vulnerable neurons is very poorly understood.Using Elp1 conditional knockout mice that we generated to recapitulate the molecular and physiologic phenotypes associated with human FD, we identified abnormalities in sympathetic neurons that explain the pathophysiologic basis for disease. Sympathetic neurons isolated from Elp1 conditional knockout mice have abnormalities in nerve growth factor signaling which is essential for their survival. NGF is normally acquired from peripheral tissues by innervating axons and NGF retrograde signal transduction to the neuron cell body is essential for their normal survival and differentiation. We found that sympathetic neurons lacking Elp1 have abnormalities in retrograde NGF signaling and as a consequence they have impaired survival and differentiation in response to NGF. After binding to NGF, the terminal axon TrkA (NTRK1) receptors are internalized and phosphorylated to activate downstream signaling pathways essential for sympathetic neuron survival and differentiation. We found that Elp1‐ deficient neurons normally bind NGF and they normally internalize and activate (phosphorylate) TrkA receptors in response to NGF. However in the absence of Elp1, TrkA receptor phosphorylation, which is essential for activation and downstream signaling, was markedly diminished. Shp1 phosphatase, which normally binds to TrkA receptors and terminates signaling by dephosphorylation, was found to be hyperactivated in the absence of Elp1. Shp1 hyperactivation results in precocious TrkA receptor dephosphorylation and attenuation of retrograde signaling. Pharmacological treatment with either Shp1 phosphatase inhibitors or molecular inhibition of Shp1 phosphatase activity resulted in complete rescue of TrkA dephosphorylation and restoration of normal NGF‐dependent retrograde neuron survival.These results demonstrate that sympathetic neuron death in patients with FD is due to loss for normal retrograde NGF signaling mediated by Shp1 phosphatase hyperactivity and precocious attenuation of TrkA signaling. Inhibition of Shp1 phosphatase activity may provide a novel therapy for sympathetic neuron loss in FD. Future studies are focused on understanding how Elp1 regulates Shp1 phosphatase activity and whether it may regulate Shp1 phosphatase activity in other signal transduction pathways involved in immune function and oncogenesis.Support or Funding InformationSupport: NIH: NICHD, NINDS and NOD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Search for Hidden Germline Mutations in Bilateral Retinoblastoma
Authors: Okonkwo Oluchukwu 
Published: June 2021

Retinoblastoma (RB) is a cancer in the retina that develops in children usually under the age of five and can cause blindness, loss of the affected eye, or death by metastasis, if not diagnosed and treated early. It arises as a result of bi‐allelic inactivation of the RB1 gene in a retinal cell that prevents the production of the pRB protein, causing uncontrollable cell proliferation in the retina. The Genetic Diagnostic Laboratory in the Perelman School of Medicine at the University of Pennsylvania has used Sanger sequencing to identify disease‐causing mutations in the RB1 gene in thousands of individuals diagnosed with bilateral retinoblastoma. Current testing focuses on coding regions and splice site consensus sequences, and various mutations have been found in 97% of individuals tested. This study aimed to identify pathogenic exonic or deep intronic mutations in the germline of six individuals which belong to the 3% of mutation‐negative cases. For three of these individuals, RNA isolated from the lymphocytes of the whole blood was converted into cDNA, RB1 transcript amplified with gene specific primers and sequenced by Sanger sequencing. The cDNA of RB1 had indicated one sample had a heterozygous deletion of exon 10, but the cause of the exonic deletion was unknown. To investigate this, several primer pairs were designed to amplify and sequence regions flanking the deleted region in the genomic DNA, and an inversion between exons 10 and 11 was suspected. For the other two patients, who are sisters, an exonic deletion of exon 2 was found but proven to be benign. For the other three individuals, previous Sanger sequencing of exons had not indicated the presence of any pathogenic mutations. An AmpliSeq panel of three hundred and four primer pairs was designed to amplify and sequence both coding and non‐coding regions spanning the RB1 gene. Amplicons were prepared using genomic DNA isolated from these three individuals and next generation sequencing on the Ion Torrent PGM platform was performed. Upon analysis, three pathogenic mutations present at low allele frequencies were identified in each individual. These were low frequency mosaic mutations that may not be detected through Sanger sequencing. Therefore, the AmpliSeq design panel can provide information about intronic mutations and low frequency mosaic mutations, and it can serve as an assay complimentary to Sanger sequencing when investigating missing mutations in RB1 gene.Support or Funding InformationJennifer Richards‐Yutz, Tappan Ganguly, Eric Toorens, Jennifer Rosado, Richard Grant, Kimberly Moran, Arupa Ganguly. Genetic Diagnostic Laboratory at the University of Pennsylvania, Philadelphia, PAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of High‐fidelity Patient Simulation Training on Medical Student Self‐efficacy and Competence
Authors: Klein Barbie 
Published: June 2021

High‐fidelity patient simulation (HFPS) is an instructional adjunct that incorporates realistic physical environments with interactive computerized patient manikins for training and assessment. This research compared the self‐efficacy ratings and competence, as measured by Objective Structured Clinical Examination (OSCE) scores, between medical students exposed to HFPS (intervention) and medical students with little to no exposure with this pedagogy (control). The groups that were examined included: first‐year (MS1), second‐year (MS2), and third‐year (MS3) medical students. A questionnaire was developed and validated to assess clinical self‐efficacy of patient care. Compared to the control groups, average OSCE composite scores were higher for the MS1 (93.49, SD = 4.24) and MS3 intervention groups (75.27, SD = 5.39), but differences were not significant (MS1: t(27) = 1.090, p = .285; MS3: t(7) = 2.263, p = .058). Pearson's correlations between average self‐efficacy ratings and OSCE scores exhibited negative correlations for all control groups, ranging from weak to strong. Weak to moderate positive correlations were observed for the MS1 and MS3 intervention groups. Both MS2 intervention and control groups had moderate negative correlations, suggesting the MS2 intervention group and all control groups inaccurately assessed their actual ability to successfully provide patient care. Although statistical significance was not achieved, the general trends observed are consistent with the literature and warrant further investigation into the dynamic interactions of HFPS exposure on medical student self‐efficacy and external measures of competence.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of a novel anatomy education tool for teaching dermatomes, cutaneous nerve maps and surface anatomy concepts: The Dry‐Erase Anatomy Mannequin (DrEAM)
Authors: Maini Arjun K. O. , Farias Anna 
Published: June 2021

Dermatomes are areas of skin whose sensory innervation can be traced back to a single spinal nerve. Knowledge of dermatome patterns is fundamental to the study of human surface anatomy and is diagnostically useful for a range of neurologic pathologies and injuries. Dermatomes and other surface anatomy concepts are often visually depicted in lectures and textbooks through illustrations. Such visual depictions are two‐dimensional and typically only show the anterior and posterior surface maps of the body side‐by‐side. However, dermatomes and other surface projections, such as cutaneous nerve maps, are 3D shapes that often pass continuously from anterior to posterior. Thus, learning these concepts from such limited visual depictions can provide perceptual challenges to anatomy students who must eventually apply 2D mental schema onto their 3D patients. Additionally, there is a relative lack of emphasis placed on teaching surface anatomy, both within textbooks and as part of formal anatomy curricula. Various instructional methods and low‐fidelity models have been developed by others attempting to convey surface anatomy concepts including body painting exercises and drawing on cloth‐covered anatomy models, to name a few.Here, we report the development of a new educational tool: The Dry‐Erase Anatomy Mannequin (DrEAM). Our novel low‐fidelity learning tool consists of common retail clothing mannequins coated in a commercially available dry‐erase finish and allows students to mark, erase and remark 3D surface anatomy shapes and contours, such as dermatomes, using dry‐erase markers. We also document our recent deployment of the tool as part of our “Dermatome Day” ‐ an informal, interactive extracurricular anatomy teaching session for undergraduate medical students. Other potential use‐cases for the DrEAM in teaching surface anatomy concepts within a range of health professions curricula are further proposed. Lastly, we discuss the formal evaluation of the DrEAM to determine its efficacy in improving student learning outcomes related to surface anatomy concepts as compared to other traditionally used methods. We hypothesize that its use will promote increased understanding of surface anatomy concepts amongst medical students and lead to their improved performance on related test questions when compared to more traditional teaching methods.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Strategies and Approaches to Improve the Efficacy of Targeted Therapy in Gastric Cancer
Authors: Kitahara Shuji , Duda Dan , Matsui Aya , Shigeta Kohei , Aoki Shuichi , Ezaki Taichi 
Published: June 2021

Gastric cancer (GC) is the third most common cancer and the second most deadly cancer worldwide. The vast majority of GCs are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification. In all subtypes, a tumor microenvironment (TME) characterized by active angiogenesis, fibrosis and inflammation is critical in the local and metastatic progression of these tumors. This is in part due to increased hypoxia and suppression of the immune system's ability to fight the cancer. VEGF is a key factor for this abnormal structure and function of the TME of GC. Using surgical samples, we found that tumor angiogenesis is increased with clinical stage progression. In addition, we found that a substantial fraction of GC cells expressed receptor (VEGFR)‐2. Blocking VEGFR2 pathway is a standard of care in GC. However, clinical responses are transient and the survival benefits are limited in GC patients. One of the cues to drive evasive resistance is hypoxia, which can be further increased after treatment with potent anti‐VEGF drugs. Interestingly, using low does anti‐VEGFR‐2 antibodies could transiently normalize tumor vasculature and convert the immunosuppressive TME into an immunostimulatory one. This effect could improve the outcome of various immunotherapies by increasing flow and oxygenation in other cancers. To examine the role of VEGFR‐2 in GC, we blocked VEGFR‐2 in tumor cells versus endothelial cells using species specific monoclonal antibodies and orthotopic models of human GC xenografts in immunodeficient mice. In these experiments, blocking VEGFR2 in endothelial cells normalized tumor blood vessels and reduced hypoxia and fibrosis, which was not seen when blocking VEGFR2 in GC cell. Moreover, a growth delay was seen only when blocking VEGFR2 in endothelial cells. These data are important because anti‐angiogenic therapy might potentially shift the TME towards promotion of anti‐tumor response to other therapies. These studies might lead to rapid implementation of the new combination therapy with anti angiogenic agent into clinical trials through our collaborations.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Catalase and glutathione reductase co‐localize with insulin in pancreatic beta cells of normal and diabetic rats
Authors: Adeghate Ernest , Al Darmaki Reem , Baniyas May , D'Souza Crystal , Lotfy Mohamed , Tariq Saeed 
Published: June 2021

BackgroundLong‐term diabetes mellitus (DM) is associated with hyperglycemia. Hyperglycemia causes oxidative stress which may subsequently reduce the level of endogenous antioxidants. Hyperglycemia‐induced tissue stress has been implicated in the formation of advanced glycated end products and other factors responsible for the development of short and long‐term complications of DM.AimsOur study aims to determine whether catalase (CAT)‐ and glutathione reductase (GR) are present in pancreatic islet cells and if yes, which of the islet cells contain CAT and or GR?MethodsDM was induced in adult male Wistar rats with streptozotocin (60 mg/kg body wt., intraperitoneal). Four weeks after the induction of DM, the rats were anesthetized and part of the pancreas was removed, incubated overnight in Zamboni's fixative and processed for double‐labelled immunofluorescence using antibodies against insulin, glucagon, somatostatin, pancreatic polypeptide, CAT and GR. A portion of the fresh pancreatic was also processed for immunoelectron microscopy using different gold particle sizes as probes for either pancreatic hormone or antioxidant.ResultsThe number of insulin‐, CAT‐ and GR‐immunoreactive cells was significantly (p < 0.05) reduced after the onset of DM. In contrast, the percentage distribution of glucagon‐, somatostatin‐, and pancreatic polypeptide‐positive cells increased in pancreatic islets of diabetic rats, when compared to non‐diabetic controls. CAT and GR were observed in insulin‐containing pancreatic beta cells. A decrease in the number of insulin‐secreting cells was associated with a concomitant reduction in either CAT or GR. Immunoelectron microscopy showed that CAT‐ and GR‐labelled immunogold particles are present in association with insulin in secretory granules of pancreatic beta cell. The number of insulin‐, CAT‐ and GR‐coated gold particles was markedly (p < 0.05) reduced in pancreatic beta cells of diabetic rats.ConclusionCo‐localization of CAT and GR with insulin suggests that these antioxidants may play role in the maintenance of pancreatic beta cell structure and function.Support or Funding InformationSupported by research grants from the CMHS (Grant # NP‐14‐32) NP and UAEU (Grant # ZCHS‐7‐2014)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemically Altered Epigenetic Landscape: Transcriptional Reprogramming at Precise Space and Time
Authors: islam kabirul 
Published: June 2021

Epigenetics is a set of DNA sequence‐independent biochemical processes which dictate the transcriptional potential of a gene and are essential to the phenotypic diversity of multicellular organisms. Cells employ a range of epigenetic mechanisms, most prominent being covalent chemical modifications, such as DNA and histone methylation. A wide range of proteins partakes in establishing (writers), recognizing (readers) and removing (erasers) these chemical entities in the chromatin for gene regulation to occur. We have engineered the protein‐ligand and protein‐protein interfaces of these biochemical pairs by employing the bump‐hole approach to develop orthogonal epigenetic regulators. These engineered epigenetic machines are employed to construct a non‐native chromatin landscape suitable for reprogramming gene expression with high temporal control in response to the cues administered by the ‘bumped’ ligands and inhibitors.Support or Funding InformationUniversity of Pittsburgh and the National Institute of HealthThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Rift Valley Fever Virus Nucleocapsid Protein Binds to C/D Box Motifs of snoRNA
Authors: Hayashi Miyuki , Hornak Katherine E. , Lachy Jean‐Marc , Lodmell J. Stephen 
Published: June 2021

Rift Valley fever virus (RVFV) is a mosquito‐borne RNA virus that infects livestock and humans. RVFV is widespread in Africa and the Arabian Peninsula, however, no approved vaccines or treatments are available. Nucleocapsid (N) protein in RVFV is RNA binding protein and recognizes its binding target possibly by interacting with a secondary structure or specific sequence of RNA. N protein encapsidates viral RNA in virions to protect its genome. Early in the infection cycle N protein expression is very high, and is more abundant than would be required to interact only with viral RNA. Therefore, it is possible that N protein not only encapsidates its genome but has other functions during infection. In fact we showed, using systematic evolution of ligands by exponential enrichment (SELEX) and cross‐linking, immunoprecipitation and deep sequencing (CLIP‐seq) that N protein is able to bind host RNAs as well as RVFV genomic RNAs. In this study, we investigated characteristics of N protein binding partners. Our data show that N protein preferentially binds to RNAs that contain CUGA/UGA motifs. These motifs are also highly represented in the C and D boxes in small nucleolar RNAs (snoRNAs), whose usual function is to direct 2′‐O‐methylation of specific nucleotides in rRNA. In addition, our CLIP‐seq data, showed that N protein prefers binding to box C/D class snoRNAs over other classes of stable RNAs. Together, these data strongly suggest a non‐canonical function for N protein during RVFV infection that involves binding of small nucleolar RNAs, although the downstream effect of this binding interaction is still incompletely understood and is under investigation.Support or Funding InformationThis project was supported by NIH grants R15AI105737 to JSL and NIGMS P20GM103546 (S. Sprang, PI)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.