Transcriptional regulation of the sodium-sulfate cotransporter NaSi-1 gene

Inorganic sulfate is one of the most abundant anions in mammalian plasma and is essential for proper cell growth and development, as well as detoxification and activation of many biological compounds. To date, little is understood how physiological levels of sulfate are maintained in the body. Our studies, and of others, have identified the NAS(i)-1 protein to be a functional sulfate transporter in the kidney and intestine, and due to this localization, constitutes a strong candidate gene for maintaining body sulfate homeostasis. Several factors, including hormones and metabolic conditions, have been shown to alter NAS(i)-1 mRNA and protein levels in vivo. In this study, we describe the transcriptional regulation of NaSi-1, with a focus on the mouse NaSi-1 gene (Nas1) that was recently cloned in our laboratory. Vitamin D (1,25-(OH)(2)D-3) and thyroid hormone (T-3) led to an increase in Nas1 promoter activity in OK cells. Mutational analysis of the Nas1 promoter resulted in identification of a direct repeat 6-type vitamin-D-responsive element (DR6 VDRE) at -525 to -508 and an imperfect inverted repeat 0-type T-3 responsive element (IRO T3RE) at -426 to -425 which conferred 1,25-(OH)(2)D-3 and T-3 responsiveness respectively. These findings suggest for vitamin D and thyroid hormone regulation of NaSi-1, may provide important clues to the physiological control of sulfate homeostasis.

Indirect evidence of density-dependent population regulation in Aponomma hydrosauri (Acari : Ixodidae), an ectoparasite of reptiles

The extent to which density-dependent processes regulate natural populations is the subject of an ongoing debate. We contribute evidence to this debate showing that density-dependent processes influence the population dynamics of the ectoparasite Aponomma hydrosauri (Acari: Ixodidae), a tick species that infests reptiles in Australia. The first piece of evidence comes from an unusually long-term dataset on the distribution of ticks among individual hosts. If density-dependent processes are influencing either host mortality or vital rates of the parasite population, and those distributions can be approximated with negative binomial distributions, then general host-parasite models predict that the aggregation coefficient of the parasite distribution will increase with the average intensity of infections. We fit negative binomial distributions to the frequency distributions of ticks on hosts, and find that the estimated aggregation coefficient k increases with increasing average tick density. This pattern indirectly implies that one or more vital rates of the tick population must be changing with increasing tick density, because mortality rates of the tick's main host, the sleepy lizard, Tiliqua rugosa, are unaffected by changes in tick burdens. Our second piece of evidence is a re-analysis of experimental data on the attachment success of individual ticks to lizard hosts using generalized linear modelling. The probability of successful engorgement decreases with increasing numbers of ticks attached to a host. This is direct evidence of a density-dependent process that could lead to an increase in the aggregation coefficient of tick distributions described earlier. The population-scale increase in the aggregation coefficient is indirect evidence of a density-dependent process or processes sufficiently strong to produce a population-wide pattern, and thus also likely to influence population regulation. The direct observation of a density-dependent process is evidence of at least part of the responsible mechanism.

C-terminal sequences in R-Ras are involved in integrin regulation and in plasma membrane microdomain distribution

The small GTPases R-Ras and H-Ras are highly homologous proteins with contrasting biological properties, for example, they differentially modulate integrin affinity: H-Ras suppresses integrin activation in fibroblasts whereas R-Ras can reverse this effect of H-Ras. To gain insight into the sequences directing this divergent phenotype, we investigated a panel of H-Ras/R-Ras chimeras and found that sequences in the R-Ras hypervariable C-terminal region including amino acids 175-203 are required for the R-Ras ability to increase integrin activation in CHO cells; however, the proline-rich site in this region, previously reported to bind the adaptor protein Nck, was not essential for this effect. In addition, we found that the GTPase TC21 behaved similarly to R-Ras. Because the C-termini of Ras proteins can control their subcellular localization, we compared the localization of H-Ras and R-Ras. In contrast to H-Ras, which migrates out of lipid rafts upon activation, we found that activated R-Ras remained localized to lipid rafts. However, functionally distinct H-Ras/R-Ras chimeras containing different C-terminal R-Ras segments localized to lipid rafts irrespective of their integrin phenotype. (C) 2003 Elsevier Inc. All rights reserved.

T cell regulation of the immune response to infection in periodontal diseases

Although T cells have been implicated in the pathogenesis and are considered to be central both in progression and control of the chronic inflammatory periodontal diseases, the precise contribution of T cells to the regulation of tissue destruction has not been fully elucidated. Current dogma suggests that immunity to infection is controlled by distinct T helper 1 (Th1) and T helper 2 (Th2) subsets of T cells classified on the basis of their cytokine profile. Further, a subset of T cells with immunosuppressive function and cytokine profile distinct from Th1 or Th2 has been described and designated as regulatory T cells. Although these regulatory T cells have been considered to maintain self-tolerance resulting in the suppression of auto-immune responses, recent data suggest that these cells may also play a role in preventing infection-induced immunopathology. In this review, the role of functional and regulatory T cells in chronic inflammatory periodontal diseases will be summarized. This should not only provide an insight into the relationship between the immune response to periodontopathic bacteria and disease but should also highlight areas of development for potentially new therapeutic modalities.

Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

Human melanoblasts in culture: Expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3

The BRN2 transcription factor (POU3F2, N-Oct-3) has been implicated in development of the melanocytic lineage and in melanoma. Using a low calcium medium supplemented with stem cell factor, fibroblast growth factor-2, endothelin-3 and cholera toxin, we have established and partially characterised human melanocyte precursor cells, which are unpigmented, contain immature melanosomes and lack L-dihydroxyphenylalanine reactivity. Melanoblast cultures expressed high levels of BRN2 compared to melanocytes, which decreased to a level similar to that of melanocytes when cultured in medium that contained phorbol ester but lacked endothelin-3, stem cell factor and fibroblast growth factor-2. This decrease in BRN2 accompanied a positive L-dihydroxyphenylalanine reaction and induction of melanosome maturation consistent with melanoblast differentiation seen during development. Culture of primary melanocytes in low calcium medium supplemented with stem cell factor, fibroblast growth factor-2 and endothelin-3 caused an increase in BRN2 protein levels with a concomitant change to a melanoblast-like morphology. Synergism between any two of these growth factors was required for BRN2 protein induction, whereas all three factors were required to alter melanocyte morphology and for maximal BRN2 protein expression. These finding implicate BRN2 as an early marker of melanoblasts that may contribute to the hierarchy of melanocytic gene control.

The regulation of complementary health: sacrificing integrity?

In response to the increasing use of complementary and alternative medicine (CAM), governments are exploring ways to ensure patients' safety and respond to complaints. One solution is to establish registration boards and procedures based on the model of existing health practitioner Acts. Registration will require defined minimum standards for competence, which will have to be based on scientific evidence. As scientific evidence accumulates, these modalities are likely to lose their identities as alternative and become assimilated into Western medicine.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

Atividade pioneira na Pol??cia Rodovi??ria Federal e no Brasil: fiscaliza????o de excesso de peso

Anteriormente ?? implementa????o da iniciativa, a situa????o encontrada no trabalho de fiscaliza????o ao excesso de peso nos ve??culos que transitam nas rodovias federais era a de que as multas aplicadas n??o surtiam o efeito de inibir tal pr??tica, uma vez que destinavam-se somente aos propriet??rios dos ve??culos. Atualmente, ap??s a detec????o e autua????o do excesso de peso, confecciona-se um Boletim de Ocorr??ncia Policial que ?? encaminhado ao Minist??rio P??blico Federal, visando ?? responsabiliza????o das empresas que embarcaram as cargas. A partir da??, os envolvidos s??o acionados judicialmente e ?? apresentado o Termo de Ajuste de Conduta. Ap??s o acionamento judicial, as empresas se comprometem a n??o mais transitarem com excesso de peso e assim o fazem. Todo esse servi??o ?? divulgado pela m??dia (emissoras de TV, r??dios e jornais) e por meio da Assessoria de Comunica????o Social do Minist??rio P??blico Federal de Minas Gerais. Sempre acompanhada pelo Poder Judici??rio, essa inova????o j?? ?? vivenciada em algumas cidades e, em outras, est?? em fase de estudos

Processos de qualifica????o do Cadastro ??nico de pol??ticas sociais do Governo Federal

Durante os anos de 2005 e 2006, a Secretaria Nacional de Renda de Cidadania (Senarc/MDS), por interm??dio do Departamento do Cadastro ??nico, conduziu uma s??rie de a????es com o objetivo de aprimorar os procedimentos envolvidos na gest??o do Cadastro ??nico (Cad??nico), contribuindo para a melhoria da fidedignidade e da qualidade dos dados cadastrais e, por conseguinte, dos mecanismos de sele????o e acompanhamento dos programas que utilizam o Cad??nico como base de identifica????o e sele????o de seu p??blico-alvo, em especial, do Programa Bolsa Fam??lia. Este trabalho apresenta as a????es conduzidas para a melhoria e o fortalecimento da gest??o do Cadastro ??nico entre janeiro de 2005 e outubro de 2006, bem como o impacto dessas a????es para a gest??o dos programas usu??rios do Cad??nico. Al??m das a????es diretas relativas ?? gest??o do Cad??nico, s??o tamb??m descritas outras a????es da Senarc que, embora n??o coordenadas pelo Departamento de Cadastro ??nico, influenciaram diretamente as a????es realizadas por esse Departamento

Sistema Nacional de Gest??o de Atividades de Criminal??stica do Departamento de Pol??cia Federal

O Sistema Nacional de Gest??o de Atividades de Criminal??stica foi concebido e desenvolvido com o intuito de racionalizar o acesso ?? informa????o, melhorar o desempenho do trabalho pericial e facilitar a administra????o centralizada da per??cia no Departamento de Pol??cia Federal (DPF). O sistema acompanha o trabalho dos setores de criminal??stica desde a chegada do expediente de servi??o at?? a libera????o do laudo pericial. Nesse trajeto, rastreia documentos, registra resultados intermedi??rios, controla o andamento de filas de trabalho e os volumes de produ????o, pend??ncias e solicita????es. Al??m disso, auxilia a atividade fim na medida em que disponibiliza para consulta todo o acervo digital de documentos e gera conte??do de novos documentos automaticamente a partir de diversos modelos altamente adapt??veis. Finalmente, possui m??dulo de apoio ?? gest??o de recursos humanos integrado ao controle de produ????o. Atualmente, conta com mais de 1.400 usu??rios em todas as 33 unidades da criminal??stica no DPF