Serum and Liver Iron Differently Regulate the Bone Morphogenetic Protein 6 (BMP6)-SMAD Signaling Pathway in Mice

The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is a central regulator of hepcidin expression and systemic iron balance. However, the molecular mechanisms by which iron is sensed to regulate BMP6-SMAD signaling and hepcidin expression are unknown. Here we examined the effects of circulating and tissue iron on Bmp6-Smad pathway activation and hepcidin expression in vivo after acute and chronic enteral iron administration in mice. We demonstrated that both transferrin saturation and liver iron content independently influence hepcidin expression. Although liver iron content is independently positively correlated with hepatic Bmp6 messenger RNA (mRNA) expression and overall activation of the Smad1/5/8 signaling pathway, transferrin saturation activates the downstream Smad1/5/8 signaling cascade, but does not induce Bmp6 mRNA expression in the liver. Hepatic inhibitory Smad7 mRNA expression is increased by both acute and chronic iron administration and mirrors overall activation of the Smad1/5/8 signaling cascade. In contrast to the Smad pathway, the extracellular signal-regulated kinase 1 and 2 (Erk1/2) mitogen-activated protein kinase (Mapk) signaling pathway in the liver is not activated by acute or chronic iron administration in mice. Conclusion: Our data demonstrate that the hepatic Bmp6-Smad signaling pathway is differentially activated by circulating and tissue iron to induce hepcidin expression, whereas the hepatic Erk1/2 signaling pathway is not activated by iron in vivo

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

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The step-by-step approach for farming systems design, in the frame of agroecological transition

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BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice.

BACKGROUND AND AIMS: Abnormal hepcidin regulation is central to the pathogenesis of HFE hemochromatosis. Hepatic bone morphogenetic protein 6 (BMP6)-SMAD signaling is a main regulatory mechanism controlling hepcidin expression, and this pathway was recently demonstrated to be impaired in Hfe knockout (Hfe(-/-)) mice. To more definitively determine whether HFE regulates hepcidin expression through an interaction with the BMP6-SMAD signaling pathway, we investigated whether hepatic Hfe overexpression activates the BMP6-SMAD pathway to induce hepcidin expression. We then investigated whether excess exogenous BMP6 administration overcomes the BMP6-SMAD signaling impairment and ameliorates hemochromatosis in Hfe(-/-) mice.METHODS: The BMP6-SMAD pathway and the effects of neutralizing BMP6 antibody were examined in Hfe transgenic mice (Hfe Tg) compared with wildtype (WT) mice. Hfe(-/-) and WT mice were treated with exogenous BMP6 and analyzed for hepcidin expression and iron parameters.RESULTS: Hfe Tg mice exhibited hepcidin excess and iron deficiency anemia. Hfe Tg mice also exhibited increased hepatic BMP6-SMAD target gene expression compared with WT mice, while anti-BMP6 antibody administration to Hfe Tg mice improved the hepcidin excess and iron deficiency. In Hfe(-/-) mice, supraphysiologic doses of exogenous BMP6 improved hepcidin deficiency, reduced serum iron, and redistributed tissue iron to appropriate storage sites.CONCLUSIONS: HFE interacts with the BMP6-SMAD signaling pathway to regulate hepcidin expression, but HFE is not necessary for hepcidin induction by BMP6. Exogenous BMP6 treatment in mice compensates for the molecular defect underlying Hfe hemochromatosis, and BMP6-like agonists may have a role as an alternative therapeutic strategy for this disease

Social ecological correlates of workplace sedentary behavior

Abstract Background To identify social ecological correlates of objectively measured workplace sedentary behavior. Methods Participants from 24 worksites - across academic, industrial, and government sectors - wore an activPAL-micro accelerometer for 7-days (Jan-Nov 2016). Work time was segmented using daily logs. Sedentary behavior outcomes included time spent sitting, standing, in light intensity physical activity (LPA, stepping cadence 30 min). Outcomes were standardized to an 8 h work day. Two electronic surveys were completed to derive individual (job type and work engagement), cultural (lunch away from the desk, walking at lunch and face-to-face interaction), physical (personal printer and office type) and organizational (sector) factors. Mixed-model analyses with worksite-level clustering were performed to examine multi-level associations. Secondary analyses examined job type and sector as moderators of these associations. All models were adjusted for age, race/ethnicity and gender. Results Participants (N = 478; 72% female; age: 45.0 ± 11.3 years; 77.8% non-Hispanic white) wore the activPAL-micro for 90.2 ± 15.5% of the reported workday. Walking at lunch was positively associated with LPA (5.0 ± 0.5 min/8 h, P < 0.001). Regular face-to-face interaction was negatively associated with prolonged sitting (−11.3 ± 4.8 min/8 h, P < 0.05). Individuals in private offices sat more (20.1 ± 9.1 min/8 h, P < 0.05), stood less (−21.5 ± 8.8 min/8 h, P < 0.05), and engaged in more prolonged sitting (40.9 ± 11.2 min/8 h, P < 0.001) than those in public office space. These associations were further modified by job type and sector. Conclusions Work-specific individual, cultural, physical and organizational factors are associated with workplace sedentary behavior. Associations vary by job type and sector and should be considered in the design of workplace interventions to reduce sedentary behavior. Trial registration Clinical trial No. NCT02566317 ; Registered Sept 22nd 2015

La transformation génétique, un outil pour l'analyse fonctionnelle du génome du riz

Le riz ( Oryza sativa L.) a le double statut de céréale la plus consommée par l'homme et d'espèce modèle pour les monocotylédones. Élucider la fonction des gènes sous-tendant les principaux caractères d'intérêt agronomique chez cette plante contribuerait donc à accélérer non seulement l'amélioration variétale du riz mais aussi celle des autres céréales. La transformation génétique est un outil permettant d'accélérer la découverte de la fonction des gènes et l'innovation variétale. La première plante transgénique de riz a été obtenue dès 1988, et, depuis, les technologies ont régulièrement évolué vers plus d'efficacité et de précision. Nous présentons ici les grandes étapes de l'évolution de ces techniques, ainsi que leurs applications pour l'analyse fonctionnelle des gènes. En particulier, les perspectives ouvertes par de nouveaux sauts technologiques en cours, qui permettent à présent une modification ciblée des génomes sans introduction d'acide désoxyribonucléique (ADN) superflu, seront illustrées et discutées

Desempenho agronômico da cultura do girassol em diferentes condições edafoclimáticas do Sudeste paranaense

O objetivo do presente trabalho foi quantificar as faixas de rendimentos acessíveis em diferentes condições edafoclimáticas do Sudeste paranaense e hierarquizar os fatores relacionados à variabilidade dos rendimentos observados. Foram avaliadas 26 situações culturais em 13 estabelecimentos familiares, em 2007 e 2008. As variáveis de componente do rendimento e estado nutricional da cultura foram determinadas pela coleta de dados em campo, e as variáveis de estado hídrico foram estimadas com o uso de um modelo de simulação do balanço hídrico. Estas foram analisadas pela Análise de Componentes Principais, classificando-se, posteriormente, as observações pela Análise de Agrupamento. Foram utilizadas as cultivares BRS 122, CATISSOL e Helio 250. Foram grupados os valores de rendimento de aquênios em três classes, segundo os seguintes valores médios: rendimentos altos: 1995 kg ha-1; rendimentos médios: 1359 kg ha-1; rendimentos baixos: 961 kg ha-1. Os valores de rendimento de óleo também foram agrupados nas seguintes classes, segundo os seguintes valores médios: rendimentos altos: 927 kg ha-1; rendimentos médios: 543 kg ha-1; rendimentos baixos: 423 kg ha-1. A variabilidade dos rendimentos (aquênios e óleo) foi explicada pela variabilidade no número de aquênios por capítulo. Em 2008, a variabilidade no número de aquênios por capítulo esteve correlacionada à deficiência hídrica em R1-R4 e R4-R6 e aos teores de Ca, B e P no tecido foliar. Ocorreu inibição competitiva entre K e Mg, porém este fenômeno não esteve correlacionado à variabilidade do número de aquênios por capítulo. Ocorreu estresse hídrico durante o enchimento de aquênios, porém este não explicou a variabilidade no rendimento de aquênios e de óleo