A5033383247- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Seismic Waves and Analysis
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Plant Virus Research Studies
- Cytomegalovirus and herpesvirus research
- HIV/AIDS Research and Interventions
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Biochemical and Molecular Research
- Galectins and Cancer Biology
- Cancer Research and Treatments
- Fermentation and Sensory Analysis
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Microbial Metabolic Engineering and Bioproduction
- Caveolin-1 and cellular processes
- RNA Interference and Gene Delivery
- Estrogen and related hormone effects
- Pancreatic function and diabetes
- Neuroendocrine Tumor Research Advances
- Genomics and Phylogenetic Studies
- Microbial metabolism and enzyme function
Saint Louis University
2010-2023
UCLouvain Saint-Louis Brussels
2021
Saint Louis University
2021
Institute of Virology of the Slovak Academy of Sciences
2014
University of Nebraska Medical Center
2003-2006
University of Minnesota, Duluth
2005
Institute of Microbial Technology
2001
APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although prototype for understanding larger mammalian polynucleotide family, no specific chemical inhibitors exist modulate its activity. High-throughput screening identified 34 compounds inhibit catalytic Twenty small molecules contained catechol moieties, which are known be sulfhydryl reactive following oxidation orthoquinone. Located proximal active site, C321...
OBJECTIVE Despite a strong epidemiological association between cigarette smoking and pancreatic diseases, such as cancer chronic pancreatitis, the effects of long-term smoke inhalation on pancreas have not been clearly determined. In present study, we investigated effect pancreas. METHODS Thirty-six female Sprague Dawley rats were exposed to two different doses environmental tobacco averaging 100 mg or 160 mg/m3 total suspended particulate matter (TSP) per m3 for 70 min twice day 12 wk. The...
The taxonomic position of two butane-utilizing bacteria was studied using a polyphasic approach. Biochemical and physiological characteristics indicated these to be members the genus Pseudomonas, showing more similarity Pseudomonas mendocina than any other species. major fatty acids found in strains also pointed their P. mendocina. On hand, DNA-DNA hybridization studies with seven related species belonging gamma-Proteobacteria deltaTm values reassociated molecules clearly showed that do not...
MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon cancer. However, the functions of MUC13 ovarian cancer are unknown. In present study, profile were analyzed to elucidate its potential role diagnosis pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used determine by immunohistochemistry using tissue microarrays 56 additional epithelial (EOC) samples. The...
Abstract Integration of the reverse-transcribed viral DNA into host chromosomes is a critical step in life-cycle retroviruses, including an oncogenic delta(δ)-retrovirus human T-cell leukemia virus type-1 (HTLV-1). Retroviral integrase forms higher order nucleoprotein assembly (intasome) to catalyze integration reaction, which roles factors remain poorly understood. Here, we use cryo-electron microscopy visualize HTLV-1 intasome at 3.7-Å resolution. The structure together with functional...
Human transcriptional coactivator p75/lens epithelium-derived growth factor (LEDGF) binds human immunodeficiency virus type 1 (HIV-1) integrase (IN). We studied the effects of LEDGF on assembly and activity HIV-1 synaptic complexes, which, upon association with a target, mediate concerted integration viral DNA substrates in vitro. found that while augmenting single-ended into target DNA, host was able to either stimulate or abrogate concentration-dependent manner. modestly stimulated (two-...
The assembly mechanism for the human immunodeficiency virus type 1 (HIV) synaptic complex (SC) capable of concerted integration is unknown. Molecular and structural studies have established that HIV SC prototype foamy (PFV) intasome contain a tetramer integrase (IN) catalyzes integration. IN purified in presence mM EDTA 10 MgSO4 was predominately monomer. efficiently promoted micromolar concentrations 3′-OH recessed blunt-ended U5 long terminal repeat (LTR) oligonucleotide (ODN) substrates...
The mouse μ-opioid receptor (MOR) gene has two promoters, referred to as distal and proximal promoter. Previously, our colleagues reported that a 26-base pair (bp) <i>cis</i>-acting element of the MOR activates expression. Here, we report cloning four members poly(C) binding protein (PCBP) family show 26-bp polypyrimidine stretch in promoter interacts with these PCBPs transcription. bind not only single-stranded but also double-stranded DNA. nuclear run-off assay semiquantitative RT-PCR...
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) inserts the viral DNA genome into host chromosomes. Here, by native agarose gel electrophoresis, using recombinant IN with a blunt-ended substrate, we identified synaptic complex (SC), transient early intermediate in integration pathway. The SC consists of two donor ends juxtaposed noncovalently. within were minimally processed (~15%). In time-dependent manner, associated target and progressed to strand transfer (STC), nucleoprotein...
Raltegravir is an FDA approved inhibitor directed against human immunodeficiency virus type 1 (HIV-1) integrase (IN). In this study, we investigated the mechanisms associated with multiple strand transfer inhibitors capable of inhibiting concerted integration by HIV-1 IN. The results show raltegravir, elvitegravir, MK-2048, RDS 1997, and 2197 all appear to encompass a common inhibitory mechanism modifying IN-viral DNA interactions. These structurally different bind inactivate synaptic...
Integration of the retrovirus linear DNA genome into host chromosome is an essential step in viral replication cycle, and catalyzed by integrase (IN). Evidence suggests that IN functions as a dimer cleaves dinucleotide from 3' blunt ends while dimers (tetramer) promotes concerted integration two processed opposite strands target DNA. However, it remains unclear why rather than monomer required for insertion each recessed end. To help address this question, we have analyzed crystal structures...
Abstract Despite conserved catalytic integration mechanisms, retroviral intasomes composed of integrase (IN) and viral DNA possess diverse structures with variable numbers IN subunits. To investigate intasome assembly we employed the Rous sarcoma virus (RSV) dimer that assembles a precursor tetrameric structure in transit to mature octameric intasome. We determined RSV stabilized by HIV-1 strand transfer inhibitor using single particle cryo-electron microscopy. The revealed significant...
Human immunodefi ciency virus type-1 integrase (IN) is a new and novel target for inhibitors.Strand transfer inhibitors effectively prevent concerted integration of viral DNA by IN into the host chromosomes.Raltegravir fi rst approved strand inhibitor treatment HIV-1/ AIDS.We propose mechanistic hypothesis as to "when where" these are active in virus-infected cells.Using native agarose gel electrophoresis, we identified transient synaptic complex (SC) wherein non-covalently juxtaposes two...
The "strand transfer inhibitors" of human immunodeficiency virus type-1 (HIV-1) integrase (IN), so named because their pronounced selectivity for inhibiting strand over 3' OH processing, block replication in vivo and ex prevent concerted integration vitro. We explored the kinetics product formation inhibition within reconstituted synaptic complexes capable integration. Synaptic were formed with viral DNA donors containing either two blunt ends, 3'-OH-processed or one each. determined that...
Twenty-three propane- and butane-utilizing bacteria were isolated from soil samples collected oilfields. Three of them have been identified as Rhodococcus sp. IMT35, Pseudomonas IMT37 MT40. SDS-PAGE analysis the membrane IMT35 revealed presence at least four polypeptides induced by propane. Polyclonal antibody raised against a 58 kDa polypeptide specifically detected which actively utilizing propane or butane. Immunoscreening genomic library in λgt11 with this resulted isolation clone...
The disappointing current therapeutic approaches for pancreatic cancer (PC) represent an urgent need the development of novel methods to control disease. Based on a recent report effectiveness enzyme therapy, we examined effect porcine extracts (PPE) human PC xenografts in nude mice.The malignant cell line AsPC1 was transplanted into pancreas male beige XID mice that were treated or not with PPE drinking water. survival, size, and volume tumors, plasma levels, fecal fat, urine as expression...
The hunt for a compound which inhibits the HIV-1 integrase had been painstakingly difficult. Integrase is essential viral replication as it mediates integration of DNA genome into host resulting in establishment permanent provirus. Persistent efforts have resulted discovery Raltegravir (Isentress, MK-0518), first inhibitor approved by US Food and Drug Administration treatment infected patients. Numerous clinical studies with raltegravir found to be safe effective naïve well experienced...
We determined conditions to produce milligram quantities of the soluble Rous sarcoma virus (RSV) synaptic complex that is kinetically trapped by HIV strand transfer inhibitors (STIs). Concerted integration catalyzed RSV integrase (IN) effectively inhibited STIs. Optimized assembly required IN, a gain-of-function 3'-OH-recessed U3 oligonucleotide, and an STI under specific maintain solubility at 4 °C. A C-terminal truncated IN (1-269 residues) produced homogeneous population eluted ∼ 151,000...