University of Texas Medical Branch

About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.

Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA.

Abstract: 8-oxoguanine (8-oxoG), ring-opened purines (formamidopyrimidines or Fapys), and other oxidized DNA base lesions generated by reactive oxygen species are often mutagenic and toxic, and have been implicated in the etiology of many diseases, including cancer, and in aging. Repair of these lesions in all organisms occurs primarily via the DNA base excision repair pathway, initiated with their excision by DNA glycosylase/AP lyases, which are of two classes. One class utilizes an internal Lys residue as the active site nucleophile, and includes Escherichia coli Nth and both known mammalian DNA glycosylase/AP lyases, namely, OGG1 and NTH1. E. coli MutM and its paralog Nei, which comprise the second class, use N-terminal Pro as the active site. Here, we report the presence of two human orthologs of E. coli mutM nei genes in the human genome database, and characterize one of their products. Based on the substrate preference, we have named it NEH1 (Nei homolog). The 44-kDa, wild-type recombinant NEH1, purified to homogeneity from E. coli, excises Fapys from damaged DNA, and oxidized pyrimidines and 8-oxoG from oligodeoxynucleotides. Inactivation of the enzyme because of either deletion of N-terminal Pro or Histag fusion at the N terminus supports the role of N-terminal Pro as its active site. The tissue-specific levels of NEH1 and OGG1 mRNAs are distinct, and S phase-specific increase in NEH1 at both RNA and protein levels suggests that NEH1 is involved in replication-associated repair of oxidized bases.

Emotional well-being predicts subsequent functional independence and survival.

Abstract: OBJECTIVE: To determine whether positive affect has an independent effect on functional status, mobility, and survival in an older Mexican American sample DESIGN: A 2-year prospective cohort study SETTING: Five Southwestern states: Texas, California, Arizona, New Mexico, and Colorado PARTICPANTS: A population-based sample of 2282 Mexican Americans aged 65 to 99 who reported no functional limitations at baseline interview MEASUREMENTS: In-home interviews in 1993–1994 and again in 1995–1996 assessed demographic variables, health conditions, activities of daily living, performance-based mobility, survival, and a rating of positive and negative affect RESULTS: In multivariate analyses, there was a direct relationship between positive affect scores at baseline and mobility, functional status, and survival 2 years later, controlling for functional status, sociodemographic variables, major chronic conditions, body mass index (BMI), smoking status, drinking status, and negative affect at baseline Subjects with high positive affect were half as likely (odds ratio (OR) = 048; 95% confidence interval (CI) 029, 093) to become disabled in activities of daily living (ADLs), two-thirds as likely (OR = 064; 95% CI 051, 079) to have a slow walking speed, and half as likely (OR 053; 95% CI 030, 093) to have died during the 2-year follow-up compared to those with lower positive affect scores CONCLUSIONS: Our results support the concept that positive affect, or emotional well-being, is different from the absence of depression or negative affect Positive affect seems to protect individuals against physical declines in old age J Am Geriatr Soc 48: 473–478, 2000

Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism.

Abstract: Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.

Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments.

Abstract: Second messenger cAMP regulates many cellular functions through its effectors, such as cAMP-dependent protein kinase (PKA) and Epac (exchange proteins directly activated by cAMP). Spatial and temporal control of cAMP signaling is crucial to differential regulation of cellular targets involved in various signaling cascades. To investigate the compartmentalized cAMP signaling, we constructed fluorescent indicators that report intracellular cAMP dynamics and Epac activation by sandwiching the full-length Epac1 between cyan and yellow mutants of GFP. Elevations of cAMP decreased FRET and increased the ratio of cyan-to-yellow emissions by 10–30% in living mammalian cells. This response can be reversed by removing cAMP-elevating agents and abolished by mutating the critical residue responsible for cAMP binding. Targeting of the reporter to the plasma membrane, where cAMP is produced in response to the activation of β-adrenergic receptor, revealed a faster cAMP response at the membrane than in the cytoplasm and mitochondria. Simultaneous imaging with targeted cAMP indicator and PKA activity reporter allowed the detection of a much delayed PKA response in the nucleus after the rapid accumulation of cAMP at the plasma membrane of the same cell, despite the immediate presence of a pool of cAMP in the nucleus. Thus, cAMP dynamics and the activation of its effectors are precisely controlled spatiotemporally in vivo.