A5066722125- Cancer-related Molecular Pathways
- Enzyme Structure and Function
- Microtubule and mitosis dynamics
- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- Advanced NMR Techniques and Applications
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Advanced Breast Cancer Therapies
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- DNA Repair Mechanisms
- Peripheral Nerve Disorders
- Chronic Lymphocytic Leukemia Research
- Memory and Neural Mechanisms
- Virology and Viral Diseases
- Orthopedic Surgery and Rehabilitation
- Pneumonia and Respiratory Infections
- Multiple Myeloma Research and Treatments
- Neuroendocrine Tumor Research Advances
- Tendon Structure and Treatment
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Protein Degradation and Inhibitors
- Bacterial Infections and Vaccines
National Student Clearinghouse Research Center
2025
Medical University of South Carolina
2022-2024
Newcastle University
2017-2022
Creighton University
2022
Google (United States)
2018
Manchester Royal Infirmary
2015
Public Health England
2015
Washington University in St. Louis
2012
University of Arizona
2006
West Virginia University
1993-2002
Identifying ligand binding sites on proteins is a critical step in target-based drug discovery. Current approaches to this require resource-intensive screening of large libraries lead-like or fragment molecules. Here, we describe an efficient and effective experimental approach mapping interaction using set halogenated compounds expressing paired hydrogen-bonding motifs, termed FragLites. The FragLites identify productive drug-like interactions, which are identified sensitively unambiguously...
There are conflicting data on whether age reduces the response of skeleton to mechanical stimuli. We examined this question in female BALB/c mice different ages, ranging from young middle-aged (2, 4, 7, 12 months). first assessed markers bone turnover control (non-loaded) mice. Serum osteocalcin and CTX declined significantly 2 4 months (p<0.001). were similar age-related declines tibial mRNA expression osteoblast- osteoclast-related genes, most notably late osteoblast/matrix genes. For...
Abstract Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and activate ensembles nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) typically promote, D2-class MSNs oppose, drug seeking. We found mice, cocaine conditioning upregulated transiently activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), a small subset NAc neurons. The...
Repeated use of illicit drugs produces long-lasting and prepotent drug-cue associations that increase vulnerability for relapse in individuals with a substance disorder. Epigenetic factors, like histone deacetylase 5 (HDAC5), play key role regulating the formation associations, but underlying mechanisms remain unclear. We used combination molecular biology, cultured cells, tandem mass spectrometry, activity measurements, co-immunoprecipitation, dynamics simulations to assess HDAC5...
Agents that can modulate colonic environment and control dysregulated signaling are being evaluated for their chemopreventive potential in colon cancer. Ursodeoxycholate (UDCA) has shown preclinical animal models of cancer, but the mechanism behind it remains unknown. Here biological effects UDCA were examined to understand its chemoprevention Our data suggests suppress growth a wide variety cancer cell lines induce low level apoptosis cells. We also found treatment induces alteration...
The SCFSKP2 ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution stable containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated the CDK regulatory subunit CKS1. further show that a direct interaction between SKP2 N-terminal motif cyclin A can stabilize SKP1-SKP2-CDK2-cyclin in absence identify binding site on demonstrate is not present E. This distinct from but overlapping with features mediate other...
Opioid use produces enduring associations between drug reinforcement/euphoria and discreet or diffuse cues in the drug-taking environment. These powerful can trigger relapse individuals recovering from opioid disorder (OUD). Here, we sought to determine whether epigenetic enzyme, histone deacetylase 5 (HDAC5), regulates relapse-associated behavior an animal model of OUD. We examined effects nucleus accumbens (NAc) HDAC5 on both heroin- sucrose-seeking behaviors using operant...
A new surgical technique with a set of instruments has been developed for the release carpal tunnel. The allows division transverse ligament through short skin incision (1.5 to 2 cm) wrist flexion crease under direct visualization. used on 237 patients 275 cases tunnel (38 bilateral). Following release, median time activities daily living was 7 days 60 compensation and 6 193 noncompensation (22 provided no information living). return work 49 51 workers 20 64 workers. overall relief rate...
The development of ligands for biological targets is critically dependent on the identification sites proteins that bind molecules with high affinity. A set compounds, called FragLites, can identify such sites, along interactions required to gain affinity, by X-ray crystallography. We demonstrate utility FragLites in mapping binding bromodomain BRD4 and ATAD2 FragLite comparable a full fragment screen identifying ligand key interactions. extend analogous compounds derived from amino acids...
Background. In 2010, mass vaccination with a then-new meningococcal A polysaccharide–tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds Bamako, Mali. Whether PsA-TT effectively boosts tetanus immunity population heterogeneous baseline is not known. We assessed the impact of on (TT) by quantifying age- and sex-specific prior 2 years after introduction.
The mitotic checkpoint complex (MCC) is formed from two sub-complexes of CDC20-MAD2 and BUBR1-BUB3, current models suggest that it generated exclusively by the kinetochores after nuclear envelope breakdown (NEBD). However, neither sub-complex has been visualised in vivo, when where they are during cell cycle their response to different SAC conditions remains elusive. Using single analysis HeLa cells, we show regulated with a "Bell" shaped profile peaks at prometaphase. Its formation begins...
Abstract Use of addictive substances creates powerful drug-cue associations that often trigger relapse. Drug seeking is gated in the nucleus accumbens (NAc) by competing activation D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs) promote, and D2 (D2-MSNs) oppose, drug seeking. We show here ensemble NAc induce neuronal activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), required for cocaine-context associations. In addition, NPAS4 functions within...