A5074971628- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Toxin Mechanisms and Immunotoxins
- RNA Research and Splicing
- Artificial Intelligence in Healthcare and Education
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Protein Degradation and Inhibitors
- Advanced Glycation End Products research
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- Topic Modeling
- Clinical Reasoning and Diagnostic Skills
- HIV/AIDS drug development and treatment
- Health and Medical Research Impacts
- Nuclear Structure and Function
- RNA regulation and disease
- Adenosine and Purinergic Signaling
- NF-κB Signaling Pathways
- HIV Research and Treatment
- Tryptophan and brain disorders
Center for Discovery
2020-2025
Hackensack Meridian Health
2024
Seton Hall University
2020
Wayne State University
2007-2017
KU Leuven
1998
University of California, San Diego
1994-1998
Tufts University
1988-1997
Instituto de Biomedicina de Valencia
1994
A 73-kilodalton (kD) intracellular protein was found to bind peptide regions that target proteins for lysosomal degradation in response serum withdrawal. This cross-reacted with a monoclonal antibody raised member of the 70-kD heat shock (hsp70) family, and sequences two internal peptides 73-kD confirm it is this family. In withdrawal, concentration increased severalfold. presence adenosine 5′-triphosphate (ATP) MgCl 2 , enhanced different cell-free assays proteolysis.
AbstractObjective To explore the use of ChatGPT by educators and students in a medical school setting.Method This study used public version launched OpenAI on November 30, 2022 (https://openai.com/blog/chatgpt/). We employed prompts to ask 1) generate content outline for session topics cholesterol, lipoproteins, hyperlipidemia students; 2) produce list learning objectives session; 3) write assessment questions with without clinical vignettes related identified objectives. assessed responses...
Lysosomal uptake and degradation of polypeptides such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribonuclease A (RNase A), RNase S-peptide (residues 1-20 A) are progressively activated in rat liver by starvation before isolation lysosomes. This pathway proteolysis is selective, since it stimulated the heat shock cognate protein 73 kDa (HSC73) ATP-MgCl2, lysosomal could be competed GAPDH but not ovalbumin. portion intracellular HSC73 associated with certain lysosomes, amount...
Previous studies have implicated the heat shock cognate (hsc) protein of 73 kD (hsc73) in stimulating a lysosomal pathway proteolysis that is selective for particular cytosolic proteins. This activated by serum deprivation confluent cultured human fibroblasts. We now show, using indirect immunofluorescence and laser scanning confocal microscopy, (hsp) 70-kD family (hsp70) associated with lysosomes (ly-hsc73). An mAb designated 13D3 specifically recognizes hsc73, this antibody colocalizes an...
Lysosomal degradation of intracellular proteins during serum withdrawal is stimulated by a member the 70-kDa heat shock protein (hsp70) family (Chiang, H.-L., Terlecky, S. R., Plant, C. P., and Dice, J. F. (1989) Science 246, 382-385). This hsp70, isolated affinity chromatography with RNase S-peptide-Sepharose, referred to as 73-kDa peptide recognition (prp73). We now report that prp73 binds several peptides whose degradative rates are increased withdrawal. also pentapeptide, KFERQ, more...
Reactive oxygen species (ROS) are at once unsought by-products of metabolism and critical regulators multiple intracellular signaling cascades. In nonphotosynthetic eukaryotic cells, mitochondria well-investigated major sites ROS generation related signal initiation. Peroxisomes also capable generation, but their contribution to cellular oxidation-reduction (redox) balance events far less well understood. this study, we use a redox-sensitive variant enhanced green fluorescent protein...
Abstract Objective To explore the use of ChatGPT by educators and students in a medical school setting. Method This study used public version launched OpenAI on November 30, 2022 ( https://openai.com/blog/chatgpt/ ). We employed prompts to ask 1) generate content outline for session topics cholesterol, lipoproteins, hyperlipidemia students; 2) produce list learning objectives session; 3) write assessment questions with without clinical vignettes related identified objectives. assessed...
The molecular mechanisms of peroxisome biogenesis have begun to emerge; in contrast, relatively little is known about how the organelle functions as cells age. In this report, we characterize age-related changes peroxisomes human cells. We show that aging compromises peroxisomal targeting signal 1 (PTS1) protein import, affecting particular critical antioxidant enzyme catalase. number and appearance are altered these cells, organelles accumulate PTS1-import receptor, Pex5p, on their...
The discovery of many fatal human disorders resulting from impaired peroxisomal protein import makes the functional characterization peroxins critical. As part our attempt to identify novel genes and gene products involved in proteins, we raised antisera against membrane proteins. One such antiserum inhibited semipermeabilized mammalian cells. This “import inhibiting” antiserum, ab-MF3, specifically recognized a 57-kDa protein. Immunoblot analysis rat liver subcellular fractions demonstrated...
Ribonuclease A (RNase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are selectively taken up degraded by isolated rat liver lysosomes very similar processes. The uptake degradation of both these proteins stimulated the heat shock cognate protein 73 kDa ATP/Mg2+. Both binding RNase GAPDH saturable, requires a protease-sensitive component within lysosomal membrane. competes for vice versa while another protein, ovalbumin, does not compete. S-peptide (amino acids 1-20 also lysosomes,...
Peroxisomes play an important role in human cellular metabolism by housing enzymes involved a number of essential biochemical pathways. Many these are oxidases that transfer hydrogen atoms to molecular oxygen forming peroxide. The organelle also contains catalase, which readily decomposes the peroxide, potentially damaging oxidant. Previous work has demonstrated aging compromises peroxisomal protein import with catalase being particularly affected. resultant imbalance relative ratio was seen...
Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions. Included among these the metabolism hydrogen peroxide other reactive species, molecules whose levels help define oxidative state cells. Loss equilibrium in cells tissues organs potentiates inflammatory responses which can ultimately trigger human disease. The goal this article is to review evidence for connections between peroxisome function, stress, inflammation context health...
We reported previously that lysosomes derived from human diploid fibroblasts import and degrade polypeptides these processes are stimulated by ATP the heat shock cognate protein of 73 kDa (hsc73).We now report several new aspects this in vitro proteolytic pathway.(a) Among four tested, pathway appears to be selective for those containing KFERQ-like peptide motifs.( b ) Substrate proteins specifically bind a protein-containing site on lysosomal membranes.(c) Lysosomes serum-deprived cells...
Purpose.: Preclinical studies have highlighted retinal oxidative stress in the pathogenesis of diabetic retinopathy. We evaluated whether a treatment designed to enhance cellular catalase reduces cells cultured high glucose and mice corrects an imaging biomarker responsive antioxidant therapy (manganese-enhanced magnetic resonance [MEMRI]). Methods.: Human Müller pigment epithelial were chronically exposed normal or levels treated with cell-penetrating derivative peroxisomal enzyme (called...
Abstract Among breast cancer patients, those diagnosed with the triple-negative (TNBC) subtype have worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or HER2 oncogene; therefore, lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against has been put forth based on estimates 30–60% of high levels EGFR. However, results from clinical trials testing inhibitors, alone in...
<sec><title>Objective</title><p>The transition of COVID-19 into the endemic phase in China has posed additional challenges to medical student's well-being, and increased odds mental distress. Although affective temperament traits adult attachment styles accompany crisis-induced stress, whether this applies students yet be determined. The aim present study is test if style can predict stress Chinese...
The growing interest in advanced large language models (LLMs) like ChatGPT has sparked debate about how best to use them various human activities. However, a neglected issue the concerning applications of LLMs is whether they can reason logically and follow rules novel contexts, which are critical for our understanding LLMs. To address this knowledge gap, study investigates five (ChatGPT-4o, Claude, Gemini, Meta AI, Mistral) using word ladder puzzles assess their logical reasoning...
The goal of this study was to use X-ray crystallography investigate the structural basis resistance human immunodeficiency virus type 1 (HIV-1) protease inhibitors. We overexpressed, purified, and crystallized a multidrug-resistant (MDR) HIV-1 enzyme derived from patient failing on several inhibitor-containing regimens. This variant contained codon mutations at positions 10, 36, 46, 54, 63, 71, 82, 84, 90 that confer drug 1.8-angstrom (A) crystal structure MDR isolate reveals an expanded...
<p>There has been growing interest in using large language models (LLMs), especially ChatGPT, medical education because of new possibilities they offer. However, current versions ChatGPT have limitations, including “hallucination” and a propensity to oversimplify complex subjects. Additionally, challenge maximizing ChatGPT’s potential is related users’ “prompt engineering” skill. In this article, we suggest that ChatGPT's limitations are opportunities engage students critical active...