University of Texas Health Science Center at Houston

About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.

Endocarditis and biofilm-associated pili of Enterococcus faecalis

Abstract: Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production of E. faecalis strain OG1RF. In addition, immunogold electron microscopy using antisera against EbpA-EbpC proteins as well as patient serum demonstrated that E. faecalis produces pleomorphic surface pili. Assembly of pili and their cell wall attachment appeared to occur via a mechanism of cross-linking of the Ebp proteins by the designated SrtC. Importantly, a nonpiliated, allelic replacement mutant was significantly attenuated in an endocarditis model. These biologically important surface pili, which are antigenic in humans during endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful immunotarget for studies aimed at prevention and/or treatment of this pathogen.

A Nonhyperthermophilic Common Ancestor to Extant Life Forms

Abstract: The G+C nucleotide content of ribosomal RNA (rRNA) sequences is strongly correlated with the optimal growth temperature of prokaryotes. This property allows inference of the environmental temperature of the common ancestor to all life forms from knowledge of the G+C content of its rRNA sequences. A model of sequence evolution, assuming varying G+C content among lineages and unequal substitution rates among sites, was devised to estimate ancestral base compositions. This method was applied to rRNA sequences of various species representing the major lineages of life. The inferred G+C content of the common ancestor to extant life forms appears incompatible with survival at high temperature. This finding challenges a widely accepted hypothesis about the origin of life.

LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker

Abstract: There is a pressing need to identify prognostic markers of metastatic disease and targets for treatment. Combining highthroughput RNA sequencing, functional characterization, mechanistic studies and clinical validation, we identify leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis suppressor downstream of the microRNA miR-9 and upstream of Hippo signaling. Restoring LIFR expression in highly malignant tumor cells suppresses metastasis by triggering a Hippo kinase cascade that leads to phosphorylation, cytoplasmic retention and functional inactivation of the transcriptional coactivator YES-associated protein (YAP). Conversely, loss of LIFR in nonmetastatic breast cancer cells induces migration, invasion and metastatic colonization through activation of YAP. LIFR is downregulated in human breast carcinomas and inversely correlates with metastasis. Notably, in approximately 1,000 nonmetastatic breast tumors, LIFR expression status correlated with metastasis-free, recurrence-free and overall survival outcomes in the patients. These findings identify LIFR as a metastasis suppressor that functions through the Hippo-YAP pathway and has significant prognostic power.

Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease.

Abstract: Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear.Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment.Methods: A detailed analysis of data obtained over the two years of the study was performed.Measurements and Main Results: Using a longitudinal joint model, we analyzed FVC, total lung capacity, transitional dyspnea index, Rodnan skin scores, and the Health Assessment Questionnaire–Disability Index during the second year, after adjusting for baseline values, baseline fibrosis score, and nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months ...