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 & Poison control. 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.

DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1.

Abstract: Activation of the ataxia telangiectasia mutated (ATM) kinase triggers diverse cellular responses to ionizing radiation (IR), including the initiation of cell cycle checkpoints. Histone H2AX, p53 binding-protein 1 (53BP1) and Chk2 are targets of ATM-mediated phosphorylation, but little is known about their roles in signalling the presence of DNA damage. Here, we show that mice lacking either H2AX or 53BP1, but not Chk2, manifest a G2-M checkpoint defect close to that observed in ATM(-/-) cells after exposure to low, but not high, doses of IR. Moreover, H2AX regulates the ability of 53BP1 to efficiently accumulate into IR-induced foci. We propose that at threshold levels of DNA damage, H2AX-mediated concentration of 53BP1 at double-strand breaks is essential for the amplification of signals that might otherwise be insufficient to prevent entry of damaged cells into mitosis.

The versatile bacterial type iv secretion systems

Abstract: Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis — genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.

A taxonomy of behaviour change methods: an Intervention Mapping approach.

Abstract: In this paper, we introduce the Intervention Mapping (IM) taxonomy of behaviour change methods and its potential to be developed into a coding taxonomy. That is, although IM and its taxonomy of behaviour change methods are not in fact new, because IM was originally developed as a tool for intervention development, this potential was not immediately apparent. Second, in explaining the IM taxonomy and defining the relevant constructs, we call attention to the existence of parameters for effectiveness of methods, and explicate the related distinction between theory-based methods and practical applications and the probability that poor translation of methods may lead to erroneous conclusions as to method-effectiveness. Third, we recommend a minimal set of intervention characteristics that may be reported when intervention descriptions and evaluations are published. Specifying these characteristics can greatly enhance the quality of our meta-analyses and other literature syntheses. In conclusion, the dynamics of behaviour change are such that any taxonomy of methods of behaviour change needs to acknowledge the importance of, and provide instruments for dealing with, three conditions for effectiveness for behaviour change methods. For a behaviour change method to be effective: (1) it must target a determinant that predicts behaviour; (2) it must be able to change that determinant; (3) it must be translated into a practical application in a way that preserves the parameters for effectiveness and fits with the target population, culture, and context. Thus, taxonomies of methods of behaviour change must distinguish the specific determinants that are targeted, practical, specific applications, and the theory-based methods they embody. In addition, taxonomies should acknowledge that the lists of behaviour change methods will be used by, and should be used by, intervention developers. Ideally, the taxonomy should be readily usable for this goal; but alternatively, it should be clear how the information in the taxonomy can be used in practice. The IM taxonomy satisfies these requirements, and it would be beneficial if other taxonomies would be extended to also meet these needs.

Identification of IL-17-producing FOXP3⁺ regulatory T cells in humans

Abstract: IL-17–producing CD4 + T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-β, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORγt. The maintenance, expansion, and further differentiation of the committed Th17 cells depend on IL-1β and IL-23. IL-17 was originally found produced by circulating human CD45RO + memory T cells. A recent study found that human Th17 memory cells selectively express high levels of CCR6. In this study, we report that human peripheral blood and lymphoid tissue contain a significant number of CD4 + FOXP3 + T cells that express CCR6 and have the capacity to produce IL-17 upon activation. These cells coexpress FOXP3 and RORγt transcription factors. The CD4 + FOXP3 + CCR6 + IL-17–producing cells strongly inhibit the proliferation of CD4 + responder T cells. CD4 + CD25 high -derived T-cell clones express FOXP3, RORγt, and IL-17 and maintain their suppressive function via a cell-cell contact mechanism. We further show that human CD4 + FOXP3 + CCR6 − regulatory T (Treg) cells differentiate into IL-17 producer cells upon T-cell receptor stimulation in the presence of IL-1β, IL-2, IL-21, IL-23, and human serum. This, together with the finding that human thymus does not contain IL-17–producing Treg cells, suggests that the IL-17 + FOXP3 + Treg cells are generated in the periphery. IL-17–producing Treg cells may play critical roles in antimicrobial defense, while controlling autoimmunity and inflammation.

Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci.

Abstract: To explain the long-term persistence of polymorphic alleles (trans-specific polymorphism) at the major histocompatibility complex (MHC) loci in rodents and primates, a computer simulation study was conducted about the coalescence time of different alleles sampled under various forms of selection. At the same time, average heterozygosity, the number of alleles in a sample, and the rate of codon substitution were examined to explain the mechanism of maintenance of polymorphism at the MHC loci. The results obtained are as follows. (1) The coalescence time for neutral alleles is too short to explain the trans-specific polymorphism at the MHC loci. (2) Under overdominant selection, the coalescence time can be tens of millions of years, depending on the parameter values used. The average heterozygosity and the number of alleles observed are also high enough to explain MHC polymorphism. (3) The pathogen adaptation model proposed by Snell is incapable of explaining MHC polymorphism, since the coalescence time for this model is too short and the expected heterozygosity and the expected number of alleles are too small. (4) From the mathematical point of view, the minority advantage model of frequency-dependent selection is capable of explaining a high degree of polymorphism and trans-specific polymorphism. (5) The molecular mimicry hypothesis also gives a sufficiently long coalescence time when the mutation rate is low in the host but very high in the parasite. However, the expected heterozygosity and the expected number of alleles tend to be too small. (6) Consideration of the molecular mechanism of the function of MHC molecules and other biological observations suggest that the most important factor for the maintenance of MHC polymorphism is overdominant selection. However, some experiments are necessary to distinguish between the overdominance and frequency-dependent selection hypotheses.