A5005308920- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Glycosylation and Glycoproteins Research
- Yersinia bacterium, plague, ectoparasites research
- Vector-borne infectious diseases
- Gastrointestinal motility and disorders
- Gastroesophageal reflux and treatments
- Anesthesia and Pain Management
- Fusion materials and technologies
- Pancreatic and Hepatic Oncology Research
- Neuropeptides and Animal Physiology
- Nuclear Materials and Properties
- Microbial Natural Products and Biosynthesis
- Asymmetric Synthesis and Catalysis
- Bacillus and Francisella bacterial research
- X-ray Diffraction in Crystallography
- Click Chemistry and Applications
- Biochemical Analysis and Sensing Techniques
- Crystallization and Solubility Studies
- Synthesis and Catalytic Reactions
- Plant-based Medicinal Research
- Synthesis of Organic Compounds
- Organic and Inorganic Chemical Reactions
- Pain Management and Opioid Use
National Institute of Allergy and Infectious Diseases
1994-2024
National Institutes of Health
1994-2024
Imperial College London
2005-2024
Henry Ford Health System
2023
University of Michigan
2019-2021
Michigan Center for Translational Pathology
2020
Theravance Biopharma (United States)
2008-2019
University of Veterinary Medicine
2007
University of Oxford
1998-2005
University of Cambridge
2005
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the molecules that contribute to pathogenesis CA-MRSA is incomplete. We tested hypothesis alpha-hemolysin (Hla) contributes severity USA300 in mice determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Deltahla) strains caused lesions a mouse infection model were...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few effective therapeutic options. PDAC characterized by an extensive fibroinflammatory stroma that includes abundant infiltrating immune cells. Tumor-associated macrophages (TAM) are prevalent within the and key drivers of immunosuppression. TAMs in human murine elevated expression apolipoprotein E (ApoE), mediates cholesterol metabolism has known roles cardiovascular Alzheimer's disease but no role PDAC. We report here...
Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized severe local lymphadenitis that progresses rapidly to systemic infection life-threatening septicemia. Here, we show although flea-borne transmission usually leads plague in mice, it can also lead primary septicemic plague. However, intradermal injection of Y. pestis, commonly used mimic fleabite, only A strain lacking the plasmid-encoded cell-surface plasminogen activator, which avirulent or s.c. injection, was...
A majority of monoclonal antibodies (mAbs) raised against soluble oligomeric human immunodeficiency virus type 1 isolate IIIB (HIV-1IIIB) envelope (env) glycoprotein reacted with conformational epitopes within the gp120 or gp41 subunits. Of 35 mAbs directed gp41, 21 preferentially env. subset these only env oligomers (oligomer-specific mAbs). In contrast, 27 subunit more strongly than monomers, and none were oligomer-specific. However, 50% anti-gp120 recognized monomeric env, suggesting that...
Plague is a zoonosis transmitted by fleas and caused the gram-negative bacterium Yersinia pestis. During infection, plasmidic caf1M1A1 operon that encodes Y. pestis F1 protein capsule highly expressed, anti-F1 antibodies are protective. Surprisingly, not required for virulence after injection of cultured bacteria, even though it an antiphagocytic factor capsule-deficient strains rarely isolated. We found caf-negative mutant was impaired in either flea colonization or mice intradermal...
The interaction of Zircaloy fuel cladding components with coolant water in a nuclear reactor leads to embrittlement and potentially delayed hydride cracking (DHC). We explore rate controlling mechanisms for the detrimental DHC process via Discrete Dislocation Plasticity (DDP) modelling an intragranular -hydride, informed by Crystal Finite Element (CPFE) analysis notched Zircaloy-4 (Zr-4) polycrystal. It is believed that nano-hydride plasticity occurs under background (polycrystalline) stress...
We introduce a general protocol for obtaining the charge basis density matrix of superconducting quantum circuit. Inspired by cavity state tomography, our combines Josephson-energy pulse sequences and projective charge-basis readout to access off-diagonal elements matrix, scheme we thus dub tomography. simulate reconstruction ground target transmon using Aharonov-Casher effect in probe qubit realise show Hilbert-Schmidt distance can detect deviations from correct model Hamiltonian. Unlocking...
ABSTRACT The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system that transfers six Yop effector proteins into host cells. One these proteins, YopJ, has been shown to disrupt cell signaling pathways involved in proinflammatory cytokine production and induce macrophage apoptosis vitro. YopJ-dependent mesenteric lymph nodes also demonstrated mouse model pseudotuberculosis infection. These results suggest YopJ attenuates innate adaptive immune...
Yersinia pestis diverged from pseudotuberculosis</= 20 000 years ago, during which time it evolved to be transmitted by fleas. In comparing the ability of these closely related species infect rat flea Xenopsylla cheopis, we found that Y. pseudotuberculosis, unlike pestis, is orally toxic Fleas showed signs acute toxicity, including diarrhoea, immediately after feeding on blood containing pseudotuberculosis in response protein toxin(s) produced bacteria. Adherence midgut and large...
Pancreatic ductal adenocarcinoma (PDA) initiation and progression are accompanied by an immunosuppressive inflammatory response. Here, we evaluated the immunomodulatory role of chemosensory signaling in metaplastic tuft cells (MTCs) analyzing GNAT3, a gustatory pathway G-protein expressed MTCs, during PDA progression.
The solution-phase conformational properties of tetrameric and octameric chains C-glycosyl α-d-lyxofuranose configured tetrahydrofuran amino acids (where the C-2 C-5 substituents on ring are trans to each other) were examined using NMR IR CD in organic solvents. Studies by demonstrated that chloroform solution, tetramer 7 does not adopt a hydrogen-bonded conformation whereas octamer 10 populates well-defined helical secondary structure stabilized 16-membered (i, i − 3) interresidue hydrogen...
Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent intravenously in mice. Presumably, Ybt required to provide sufficient at peripheral injection site, suggesting that would be an essential virulence factor for plague. Here, using flea-to-mouse transmission model, we show strain causes fatal plague low incidence transmitted...
An acid catalysed ring rearrangement of a triflate derivative D-mannono-?-lactone 6 is the key step in synthesis C-glycosyl sugar amino derivatives 3 and 4, examples carbohydrate building blocks with specific conformational preferences suitable for incorporation into combinatorial amide libraries; homo-oligomerisation via solution phase coupling procedures affords furanose carbopeptoids 1 which adopt novel state secondary structures.
The multi-gram syntheses of two epimeric six-carbon tetrahydrofurancarboxylates based upon a D-arabinofuranose template are described. An approach to 3-O-benzyl protected derivatives is also detailed. Introduction nitrogen at C-6 these scaffolds leads the generation building blocks suitable for oligomers which possess well defined secondary structures. Radical bromination facilitates introduction C-2, afford anomeric α-amino acid elaborated unnatural diastereomers potent herbicidal natural...