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.

Protein misfolding and neurodegeneration.

Abstract: A key molecular pathway implicated in diverse neurodegenerative diseases is the misfolding, aggregation, and accumulation of proteins in the brain. Compelling evidence strongly supports the hypothesis that accumulation of misfolded proteins leads to synaptic dysfunction, neuronal apoptosis, brain damage, and disease. However, the mechanism by which protein misfolding and aggregation trigger neurodegeneration and the identity of the neurotoxic structure is still unclear. The aim of this article is to review the literature around the molecular mechanism and role of misfolded protein aggregates in neurodegeneration and the potential for the misfolding process to lead to a transmissible form of disease by a prion-based model of propagation.

Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation.

Abstract: The question of how genetic material controls phenotypic expression was posed 60 years ago by Hermann Muller (1922), but the ability to answer the question awaited the development of biochemical techniques capable of dissecting and comparing purified proteins (Moore et al., 1958; Edman and Sjoquist, 1956; Ingram, 1957). Human haptoglobin has served as an unexpected source of information relating the mechanisms involved in genetic rearrangements to the linear sequence of amino acids within a protein. After developing a potent technique, starch gel electrophoresis, which proved capable of resolving and identifying previously unknown inherited variations in many human plasma proteins, Oliver Smithies and co-workers (Smithies, 1959; Smithies et al., 1962a, 1962b) demonstrated that serum haptoglobin molecules from different individuals varied one from another in a heritable way. Haptoglobin has served as an impressive paradigm of how genetic rearrangements can construct a polymorphic system and how, in the evolutionary process, old proteins can obtain new functions by utilizing amino acid sequences which have been ever so slightly altered. Excellent reviews have been written about haptoglobin, which can be consulted for further detail (Javid, 1978; Putnam, 1975; Pintera, 1971; Sutton, 1970; Giblett, 1969; Kirk, 1968; Schultze and Heremans, 1966). This review will emphasize recent developments in analyzing the composition of the haptoglobin molecules and the evolutionary implications of these findings.

Tripartite Structure of Positive and Negative Affect, Depression, and Anxiety in Child and Adolescent Psychiatric Inpatients

Abstract: The tripartite model of depression and anxiety suggests that depression and anxiety have shared (generalized negative affect) and specific (anhedonia and physiological hyperarousal) components. In one of the 1st studies to examine the structure of mood-related symptoms in youngsters, this model was tested among 116 child and adolescent psychiatric inpatients, ages 8-16 (M = 12.46; SD = 2.33). Consistent with the tripartite model, a 3-factor (Depression, Anxiety, and Negative Affect) model represented the observed data well. Follow-up analyses suggested that a nonhierarchical arrangement of the 3 factors may be preferable to a hierarchical one.

Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase (CBS) and cystathionine γ lyase (CSE)

Abstract: Background and Purpose Hydrogen sulfide (H2S) is a signalling molecule that belongs to the gasotransmitter family. Two major sources for endogenous enzymatic production of H2S are cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). In the present study, we examined the selectivity of commonly used pharmacological inhibitors of H2S biosynthesis towards CSE and CBS. Experimental Approach To address this question, human CSE or CBS enzymes were expressed and purified from Escherichia coli as fusion proteins with GSH-S-transferase. After purification, the activity of the recombinant enzymes was tested using the methylene blue method. Key Results β-cyanoalanine (BCA) was more potent in inhibiting CSE than propargylglycine (PAG) (IC50 14 ± 0.2 μM vs. 40 ± 8 μM respectively). Similar to PAG, L-aminoethoxyvinylglycine (AVG) only inhibited CSE, but did so at much lower concentrations. On the other hand, aminooxyacetic acid (AOAA), a frequently used CBS inhibitor, was more potent in inhibiting CSE compared with BCA and PAG (IC50 1.1 ± 0.1 μM); the IC50 for AOAA for inhibiting CBS was 8.5 ± 0.7 μM. In line with our biochemical observations, relaxation to L-cysteine was blocked by AOAA in aortic rings that lacked CBS expression. Trifluoroalanine and hydroxylamine, two compounds that have also been used to block H2S biosynthesis, blocked the activity of CBS and CSE. Trifluoroalanine had a fourfold lower IC50 for CBS versus CSE, while hydroxylamine was 60-fold more selective against CSE. Conclusions and Implications In conclusion, although PAG, AVG and BCA exhibit selectivity in inhibiting CSE versus CBS, no selective pharmacological CBS inhibitor is currently available.