A5091364493- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Escherichia coli research studies
- RNA and protein synthesis mechanisms
- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Bacterial biofilms and quorum sensing
- Antibiotic Resistance in Bacteria
- Neurological disorders and treatments
- RNA modifications and cancer
- Parkinson's Disease Mechanisms and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Metal-Organic Frameworks: Synthesis and Applications
- Cellular Mechanics and Interactions
- Salmonella and Campylobacter epidemiology
- Blood properties and coagulation
- Genetics and Neurodevelopmental Disorders
- Cell Adhesion Molecules Research
- Yersinia bacterium, plague, ectoparasites research
- Molecular Biology Techniques and Applications
- Advanced Glycation End Products research
- Multiple Myeloma Research and Treatments
- Pharmacological Effects of Natural Compounds
- Mitochondrial Function and Pathology
- Power Line Communications and Noise
Eisai (United States)
2024
University of Calgary
2018-2021
University of Toronto
2011-2021
Ecology and Ecosystem Health
2018
Massachusetts General Hospital
2002-2017
Harvard University
2015-2017
University College London
2017
CHDI Foundation
2015-2017
University of British Columbia
2017
University of Iowa
2017
Parkinson's disease (PD) is most commonly a sporadic illness, and characterized by degeneration of substantia nigra dopamine (DA) neurons abnormal cytoplasmic aggregates α-synuclein. Rarely, PD may be caused missense mutations in MPTP, neurotoxin that inhibits mitochondrial complex I, prototype for an environmental cause because it produces pattern DA neurodegeneration closely resembles the neuropathology PD. Here we show α-synuclein null mice display striking resistance to MPTP-induced...
ABSTRACT Elongation factor P (EF-P) is a universally conserved bacterial translation homologous to eukaryotic/archaeal initiation 5A. In Salmonella , deletion of the efp gene results in pleiotropic phenotypes, including increased susceptibility numerous cellular stressors. Only limited number proteins are affected by loss EF-P, and it has recently been determined that EF-P plays critical role rescuing ribosomes stalled at PPP PPG peptide sequences. Here we present an unbiased vivo...
Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD).A total 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. primary end point outcome at 12 months Total Motor Score 4 subscale (TMS-4). Analysis covariance (ANCOVA) and chi2 test response, defined as...
Elongation factor P (EF-P) is required for the efficient synthesis of proteins with stretches consecutive prolines and other motifs that would otherwise lead to ribosome pausing. However, previous reports also demonstrated levels most diprolyl-containing are not altered by deletion efp. To define particular sequences trigger stalling at diprolyl (PPX) motifs, we used profiling monitor global occupancy in Escherichia coli strains lacking EF-P. Only 2.8% PPX caused significant ribosomal...
The type VI secretion system (T6SS) is a lethal microbial weapon that injects large needle-like structure carrying toxic effectors into recipient cells through physical penetration. How recipients respond to force and remains elusive. Here, we use series of effector mutants Vibrio cholerae determine how T6SS elicits response in Pseudomonas aeruginosa Escherichia coli. We show TseL, but no other or puncture, triggers the tit-for-tat P. H1-T6SS. Although E. coli sensitive all periplasmically...
ABSTRACT Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established importance this modification in Salmonella stress resistance. Here we report that, like poxA yjeK mutants, strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, detergents enhanced resistance compound S -nitrosoglutathione. The phenotypes are largely explained membrane...
Ribosome stalling during translation can be caused by a number of characterized mechanisms. However, the impact elongation stalls on protein levels is variable, and reasons for this are often unclear. To investigate relationship, we examined bacterial factor P (EF-P), which plays critical role in rescuing ribosomes stalled at specific amino acid sequences including polyproline motifs. In previous proteomic analyses both Salmonella Escherichia coli efp mutants, it was evident that not all...
Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity ribosome vitro. The additional hydroxylation EF-P same by YfcM has also recently been described. roles modified unmodified during different steps translation, how this correlates to its physiological role cell, have linked synthesis polyproline stretches proteins. Polysome analysis indicated that functions...
Significance Assembly, firing, and recycling of the type 6 secretion system (T6SS) organelle is a costly process as each event ejects hundreds inner-tube Hcp molecules. In comparison to bacteria whose T6SSs are tightly regulated, bacterial strains that constitutively display T6SS activity would seem inefficient in their deployment T6SS, especially if interrupted by environmental conditions reduce available cellular energy. Here we have discovered quantity-sensing feedback control avoids...
Genetic editing has revolutionized biotechnology, but delivery of endonuclease genes as DNA can lead to aberrant integration or overexpression, leading off-target effects. Here, we develop a mechanism deliver Cre recombinase protein by engineering the bacterial type six secretion system (T6SS). Using multiple T6SS fusion proteins, Aeromonas dhakensis attenuated Vibrio cholerae donor strains, and gain-of-function cassette for detecting recombination, demonstrate successful active directly...
Itaconate is a dicarboxylic acid that inhibits the isocitrate lyase enzyme of bacterial glyoxylate shunt. Activated macrophages have been shown to produce itaconate, suggesting these immune cells may employ this metabolite as weapon against invading bacteria. Here, we demonstrate in vitro, itaconate can exhibit bactericidal effects under acidic conditions similar pH macrophage phagosome. In parallel, successful pathogens, including Salmonella, acquired genetic operon encoding degradation...
The cell wall is a physical scaffold that all transenvelope complexes have to cross for assembly. However, the wall-deficient state has been described as common condition found in both Gram-negative and Gram-positive pathogens during persistent infections. Loss of known pleiotropic physiological effects, but how membrane-anchored large cellular organelles adapt this unique less completely understood. Our study examined assembly T6SS spheroplast cells. We report elastic nature contractile...
OBJECTIVE: We assessed electrocardiograms (ECG) from a large cohort of patients with early Huntington's disease (HD), to determine the prevalence ECG abnormalities in HD population BACKGROUND: is an autosomal dominant progressive neurodegenerative disorder due CAG triplet repeat expansion Huntington gene on chromosome 4q. There increasing evidence that, addition central nervous system pathology, peripheral organs and tissues may also be affected. Significant cardiac dysregulation has been...
Bacteria have evolved to sense and respond their environment by altering gene expression metabolism promote growth survival. In this work we demonstrate that Salmonella displays an extensive (>30 hour) lag in when subcultured into media where dicarboxylates such as succinate are the sole carbon source. This is regulated part RpoS, RssB anti-adaptor IraP, translation elongation factor P, a lesser degree stringent response. We also show small amounts of proline or citrate can trigger early...
Abstract The type six secretion system (T6SS) is a prevalent bacterial weapon delivering toxic effector proteins into nearby competitors. In addition to immunity genes that protect against particular effector, alternate yet crucial nonspecific defences have also recently been identified. To systematically identify influencing T6SS susceptibility in numerous species, we designed Tn-Seq-based competition assay. Combined with follow-up analyses using E. coli and V. cholerae gene knockout...
Biotechnologies such as gene therapy have brought DNA vectors to the forefront of pharmaceuticals. The quality starting material plays a pivotal role in determining final product quality. Here, we examined fidelity replication using enzymatic methods (
Abstract Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid‐beta (Aβ) protofibrils, was formally evaluated as treatment for early Alzheimer’s disease in phase 2 study (Study 201) and the 3 Clarity AD study. These trials both included an 18‐month, randomized (core) open‐label extension (OLE) where eligible participants received lecanemab up 30 months date. Clinical (CDR‐SB, ADAS‐Cog14, ADCS‐MCI‐ADL), biomarker (PET, Aβ42/40 ratio, ptau181) safety outcomes...