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Intracellular signaling by mitogen-activated protein (MAP) kinases (MAPK) is involved in many cellular responses and in the regulation of various physiological and pathological conditions. Tight control of the localization and duration of extracellular-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), or p38 MAPK activity is thus a fundamental aspect of cell biology. Several members of the dual-specificity phosphatase (DUSPs) family are able to dephosphorylate MAPK isoforms with different specificity, cellular, and tissue localization. Understanding how these phosphatases are themselves regulated during development or in physiological and pathological conditions is therefore fundamental. Over the years, gene deletion and knockdown studies have completed initial in vitro studies and shed a new light on the global and specific roles of DUSPs in vivo. Whereas DUSP1, DUSP2, and DUSP10 appear as crucial players in the regulation of immune responses, other members of the family, like the ERK-specific DUSP6, were shown to play a major role in development. Recent findings on the involvement of DUSPs in cancer progression and resistance will also be discussed. [ABSTRACT FROM AUTHOR]

Both the human immunodeficiency (HIV) and hepatitis C (HCV) viruses have been associated with insulin resistance (IR). However, our understanding of the prevalence of IR, the underlying mechanisms and predisposing factors is limited, particularly among minority populations. We conducted a study of 333 Hispanic adults including: 76 HIV monoinfected, 62 HCV monoinfected, 97 HIV/HCV co-infected and 98 uninfected controls with a specific focus on HCV infection and liver injury as possible predictors of IR. IR was measured using the Quantitative Insulin Sensitivity Check Index (QUICKI). The majority (55–69%) of participants in all groups had QUICKI values <0.350. Body mass index was associated with IR in all groups. Triglycerides were associated with IR in the uninfected control group only (−1.83, SE = 0.58, P = 0.0022). HCV was associated with IR in participants infected with HIV (−0.012, SE = 0.0046, P = 0.010). Liver injury, as measured by score to assess liver injury (FIB-4) score, was significantly associated with IR independently of HCV infection (−0.0035, SE = 0.0016, P = 0.027). In the HIV/HCV co-infected group, treatment with nucleoside reverse-transcriptase (RT) inhibitors plus non-nucleoside RT inhibitors (−0.021, SE = 0.080, P = 0.048), but not protease inhibitors (−0.000042, SE = 0.0082, P = 0.96) was associated with IR. HCV infection and antiretroviral agents, including nucleoside RT inhibitor plus non-nucleoside RT inhibitor treatment are contributors to IR in HIV infection. Liver injury, as measured by the FIB-4 score, is a predictor of IR independently of HCV infection. [ABSTRACT FROM AUTHOR]

MAP kinases phosphatases (MKPs) belong to the dual-specificity phosphatase family (DUSP) and dephosphorylate phosphothreonine and phosphotyrosine within MAP kinases. We had previously shown that DUSP6/MKP-3 was phosphorylated and degraded upon growth factor stimulation, in a MEK-dependent manner. Here we show that another pathway involved in growth factor signaling, the PI3K/mTOR signaling pathway, accounts for a part of the phosphorylation and degradation of DUSP6 induced by serum growth factors, as evidenced by experiments using pharmacological inhibitors of PI3 kinase and mammalian target of rapamycin (mTOR). Moreover, specific agonists of the mTOR pathway, such as amino acids or insulin/IGF-1, which do not activate extracellular signal regulated kinases (ERKs) in our cellular model, were also able to induce the phosphorylation and degradation of DUSP6. However, a basal activity of MEK was required for the mTOR pathway-mediated phosphorylation to occur. Mutagenesis studies identified serine 159 within DUSP6 as the target of the mTOR pathway. The ERK phosphatase DUSP6 may thus constitute a novel branch-point of the crosstalk between two major signaling pathways induced by growth factors, the MEK/ERK pathway and the PI3K/mTOR pathway.Oncogene (2008) 27, 3685–3691; doi:10.1038/sj.onc.1211040; published online 28 January 2008 [ABSTRACT FROM AUTHOR]

Objectives This study investigated the association of the familial coexistence of child stunting and maternal overweight with indigenous women in Guatemala. Methods We selected 2388 child-mother pairs from the data set of the Living Standards Measurement Study conducted in Guatemala in 2000. This study examined the association between maternal and household characteristics and the nutritional status of children aged 6-60 months and mothers aged 18-49 years by using multivariable logistic regression models. Results Compared with non-indigenous households, a significantly higher percentage of indigenous households exhibited stunted child and overweight mother (SCOM) pairs (15.9 vs. 22.2%). Compared with normal-weight mothers, overweight mothers were less likely to have stunted children [adjusted odds ratio (AOR) 0.66, 95% confidence interval (CI) 0.50-0.88]. However, compared with mothers who were not short and overweight, short and overweight mothers were significantly more likely to have stunted children (AOR 1.80, 95% CI 1.19-2.73) and were more likely to be indigenous women living in urban areas (AOR 3.01, 95% CI 1.19-7.60) or rural areas (AOR 3.02, 95% CI 1.28-7.14). The order of observed prevalence of SCOM pairs in different types of households was as follows: urban indigenous (25.0%), rural indigenous (21.2%), rural non-indigenous (19.8%), and urban non-indigenous households (10.7%). Conclusions for Practice Urban indigenous households were more likely to have SCOM pairs. This study provided useful information for identifying the most vulnerable groups and areas with a high prevalence of the familial coexistence of child stunting and maternal overweight. [ABSTRACT FROM AUTHOR]

Background: Limited data suggest that Puerto Ricans experience greater disability than other ethnic groups, but few studies have examined the factors associated with this apparent difference.Methods: We describe the prevalence of functional limitation and disability in a representative sample of Puerto Rican and Dominican elders in Massachusetts, and in a neighborhood comparison group of non-Hispanic whites (NHWs). We then relate disability scores, based on both prevalence and severity of ADL or IADL limitation, with self-reported history of diagnosed health conditions--adjusting for age, sex, body mass index (BMI; weight kg/height m(2)), income, education, living alone, smoking, and alcohol use.Results: Seventy-five percent of Dominican women and 73% of Puerto Rican women reported difficulty with at least one ADL, compared with 64% of NHW women. Puerto Rican men reported significantly more limitation than did NHW or Dominican men. Conditions significantly associated with at least two disability measures among the NHW included smoking, former heavy alcohol use, arthritis, cataract, respiratory disease, and high BMI, but not stroke, diabetes, history of heart attack, or depression. The patterns for Puerto Ricans differed, with the strongest associations between disability and stroke, arthritis, diabetes, and depression, followed by history of heart attack, high BMI, cataract, poverty status, and respiratory disease. Only arthritis and depression were consistently significantly associated with disability among this smaller sample of Dominican elders.Conclusions: Functional limitation and disability are more prevalent among Puerto Ricans and among Dominican women than among neighborhood NHWs in Massachusetts. Greater disability is associated with the presence of chronic health conditions, which differ by ethnic group. Additional research is needed to further define the social and health factors that contribute to these ethnic differences. [ABSTRACT FROM AUTHOR]