- Spaceflight effects on biology
- Ion Transport and Channel Regulation
- 3D Printing in Biomedical Research
- Genetics, Aging, and Longevity in Model Organisms
- Ion channel regulation and function
- Cellular transport and secretion
- Space Exploration and Technology
- Renin-Angiotensin System Studies
- Neuroscience and Neuropharmacology Research
- Electrolyte and hormonal disorders
- Hormonal Regulation and Hypertension
- Urinary Bladder and Prostate Research
- Light effects on plants
- Drug Transport and Resistance Mechanisms
- Memory and Neural Mechanisms
- Fungal and yeast genetics research
- Viral Infectious Diseases and Gene Expression in Insects
- Renal and related cancers
- Receptor Mechanisms and Signaling
- Magnetic and Electromagnetic Effects
- Complement system in diseases
- Retinal Development and Disorders
- Space Science and Extraterrestrial Life
- Birth, Development, and Health
- Dialysis and Renal Disease Management
Durham VA Health Care System
2020-2024
Stanford University
2024
Duke University
2008-2021
Tulane University
2001-2021
George Washington University
2015-2021
Durham VA Medical Center
2008-2018
Space Science Institute
2016
Veterans Health Administration
2000-2015
United States Department of Veterans Affairs
1986-2015
VA Office of Research and Development
2013-2015
ObjectiveTo describe the design and ongoing conduct of Million Veteran Program (MVP), as an observational cohort study mega-biobank in Department Veterans Affairs (VA) health care system.Study Design SettingData are being collected from participants using questionnaires, VA electronic record, a blood sample for genomic other testing. Several projects linked to MVP, both peer-reviewed research studies activities help develop infrastructure future, broad-based uses.ResultsFormal planning MVP...
A comprehensive analysis of both the molecular genetic and phenotypic responses any organism to space flight environment has never been accomplished because significant technological logistical hurdles. Moreover, effects on microbial pathogenicity associated infectious disease risks have not studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 compared with identical ground control cultures. Global microarray proteomic analyses revealed that...
Suspension culture remains a popular modality, which manipulates mechanical conditions to maintain the specialized features of cultured cells. The rotating-wall vessel is suspension optimized produce laminar flow and minimize stresses on cell aggregates in culture. This review summarizes engineering principles, allow optimal be established, boundary conditions, limit this process. We suggest that damage optimize differentiation cells, should performed solid-body rotation Couette-flow,...
The present report shows the molecular characterization of rat 460-kDa epithelial glycoprotein that functions as receptor facilitating uptake intrinsic factor-vitamin B<sub>12</sub> complexes in intestine and kidney. same represents also yolk sac target for teratogenic antibodies causing fetal malformations rats. Determination its primary structure by cDNA cloning identified a novel type peripheral membrane characterized cluster eight epidermal growth factor domains followed 27 CUB domains....
Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts toward faster muscle fiber types. To identify changes gene expression that may underlie these adaptations, we used both microarray analysis real-time polymerase chain reaction quantify mRNA levels the gastrocnemius from mice flown on 11-day, 19-h STS-108 shuttle flight normal gravity controls. data also were compared with ground-based unloading model hindlimb suspension, one group pure suspension...
The low-shear environment of optimized rotation suspension culture allows both eukaryotic and prokaryotic cells to assume physiologically relevant phenotypes that have led significant advances in fundamental investigations medical biological importance. This has also been used model microgravity for ground-based studies regarding the impact space flight on physiology. We previously demonstrated modeled (LSMMG) under is a novel environmental signal regulates virulence, stress resistance,...
Hypertension induced by long-term infusion of angiotensin II (Ang II) is associated with augmented intrarenal Ang levels to a greater extent than can be explained on the basis circulating levels. Although part this augmentation due AT 1 receptor–dependent internalization, intracellular compartments involved in accumulation remain unknown. In present study, we sought determine whether trafficking into renal cortical endosomes increased during hypertension, and if so, receptor antagonist,...
Hammond, T. G., E. Benes, K. C. O’Reilly, D. A. Wolf, R. M. Linnehan, J. H. Kaysen, P. L. Allen, and Goodwin. Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle. Physiol Genomics 3: 163–173, 2000.—Three-dimensional suspension is a gravity-limited phenomenon. The balancing forces necessary to keep aggregates in increase directly with aggregate size. This leads self-propagating cycle of cell damage by forces. Cell microgravity avoids this...
Although several heavy metal toxins are delivered to the kidney on carrier protein metallothionein (MT), uncertainty as how MT enters proximal tubular cells limits treatment strategies. Prompted by reports that MT-I interferes with renal uptake of megalin ligand beta(2)-microglobulin in conscious rats, we tested hypothesis binds and mediates its uptake. Three lines evidence suggest binding is critical MT-bound metals. First, megalin, but not cubilin, direct surface plasmon resonance studies....
The transcriptional regulatory protein nuclear factor-kappaB (NF-kappaB) participates in the control of gene expression many modulators inflammatory and immune responses, including adhesion molecules E-selectin intercellular molecule-1 (ICAM-1). NF-kappaB is found cytoplasm complexed with its inhibitory IkappaB. On activation, IkappaB phosphorylated degraded, thereby freeing for translocation to nucleus. We have generated populations endothelial cells expressing wild-type a...
Although myeloma light chains are known to undergo receptor-mediated endocytosis in the kidney, molecular identity of receptor has not been characterized. We examined interaction between cubilin (gp280) and four species isolated from urine patients with multiple myeloma. Four lines evidence identify cubilin, a giant glycoprotein receptor, which is restricted distribution endocytic scavenger pathways potent effects on endosomal trafficking, as potentially physiologically relevant binding site...
The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. nephron sites cellular mechanism accounting for profound increase in Na+ excretion response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters reabsorption of solutes cotransported with proximal tubules rats. Synthetic consisting 26 amino acids, 4 micrograms/kg body...
Abstract BACKGROUND: Chlorantraniliprole is a novel anthranilic diamide insecticide registered for use in vegetables, fruits, grains and turf against variety of insect pests. The objective this article to summarize results acute toxicity testing chlorantraniliprole on seven species parasitic wasps with wide geographic distribution relevance different crops integrated pest management (IPM) programmes. RESULTS: Tier‐1, worst‐case laboratory studies evaluated wasp survival reproduction...
ABSTRACT The lack of readily available experimental systems has limited knowledge pertaining to the development Salmonella -induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at National Aeronautics Space Administration conjunction with cultivation three-dimensional (3-D) aggregates human intestinal tissue study infectivity enterica serovar Typhimurium for epithelium. Immunohistochemical characterization microscopic...
Previous studies in the rat have shown that antibodies to gp280, a protein > 200 kD and closely associated with early endocytic system can induce fetal malformations. Although gp280 is thought act as receptor, its ligand(s) not known. In current study, we report purified from kidney, like intrinsic factor-Cobalamin receptor (IFCR), binds factor-cobalamin (IFCbl) complex an association constant of 0.3 x 10(9) M-1 mediates internalization. Furthermore, raised IFCR inhibited binding...
While Salmonella infects macrophages, this cell population may not be the only one important for disseminating intracellular bacteria from mucosal sites. Dendritic cells (DC) are present in Peyer's patches and mobilized following stimulation. Such characteristics would seem to ideal dissemination of an intracellular, pathogen. However, it has been difficult obtain sufficient numbers DC assess their ability harbor or monitor vivo. In study, problem addressed by expanding vivo using flt3...
In this study, self-organizing map (SOM) gene cluster techniques are applied to the analysis of cDNA microarray expression changes occurring in early stages genitourinary inflammation. We determined time course lipopolysaccharide (LPS)-induced experimental cystitis. Mice were euthanized 0.5, 1, 4, and 24 h after LPS instillation into urinary bladder, was using four replicate Atlas mouse arrays containing 588 known genes at each point. SOM analysis, performed without preconditions, identified...
The luminal surface of mammalian bladder is exposed to urine with a composition widely different from that plasma bathes the basolateral epithelium. Therefore we predict permeability barrier, which likely located in apical membrane (AM), will exhibit low permeabilities water, urea, NH3, H+, and small nonelectrolytes. AM area increases as fills decreases during emptying, process involves cyclical endocytosis reinsertion pool endosomes (AME). Rigid-appearing plaques composed three proteins,...
To evaluate effects of microgravity on virulence, we studied the ability four common clinical pathogens--Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and Candida albicans--to kill wild type Caenorhabditis elegans (C. elegans) nematodes at larval adult stages. Simultaneous studies were performed utilizing spaceflight, clinorotation in a 2-D device, static ground controls. The feeding rate worms for killed E. coli was unaffected by...