NMR Studies of the C-Terminus of alpha4 Reveal Possible Mechanism of Its Interaction with MID1 and Protein Phosphatase 2A

Alpha4 is a regulatory subunit of the protein phosphatase family of enzymes and plays an essential role in regulating the catalytic subunit of PP2A (PP2Ac) within the rapamycin-sensitive signaling pathway. Alpha4 also interacts with MID1, a microtubule-associated ubiquitin E3 ligase that appears to regulate the function of PP2A. The C-terminal region of alpha4 plays a key role in the binding interaction of PP2Ac and MID1. Here we report on the solution structure of a 45-amino acid region derived from the C-terminus of alpha4 (alpha45) that binds tightly to MID1. In aqueous solution, alpha45 has properties of an intrinsically unstructured peptide although chemical shift index and dihedral angle estimation based on chemical shifts of backbone atoms indicate the presence of a transient α-helix. Alpha45 adopts a helix-turn-helix HEAT-like structure in 1% SDS micelles, which may mimic a negatively charged surface for which alpha45 could bind. Alpha45 binds tightly to the Bbox1 domain of MID1 in aqueous solution and adopts a structure consistent with the helix-turn-helix structure observed in 1% SDS. The structure of alpha45 reveals two distinct surfaces, one that can interact with a negatively charged surface, which is present on PP2A, and one that interacts with the Bbox1 domain of MID1

Climate Change, Global Food Security, and the U.S. Food System

This report offers information on climate change as it relates to food security

Concentrações de vitamina A no leite humano e características socioeconômicas e nutricionais maternas: resultados de estudos brasileiros Vitamin A in human milk and socioeconomic and maternal nutritional factors: some results of Brazilian studies

OBJETIVOS: agregar e discutir os resultados de estudos realizados no Brasil que avaliaram a concentração de vitamina A no leite materno. FONTES DOS DADOS: foram pesquisadas as bases LILACS, Banco de Teses da Capes, SciELO (Scientific Electronic Library), e Plataforma Lattes -seção de produção científica. As palavras-chaves utilizadas foram: gestantes, lactante, concentração de vitamina A no leite humano, Brasil. As buscas foram realizadas em 2006 e atualizadas em março de 2008. Foram incluídos todos os estudos localizados. SÍNTESE DOS DADOS: foram localizados 14 estudos, publicados entre 1988 e 2008, heterogêneos quanto ao tamanho da amostra, fase do leite, período do dia da coleta e método de determinação das concentrações de vitamina A. Foram descritas concentrações médias de vitamina A no leite humano entre 0,62 e 4,50 µmol/L. CONCLUSÕES: não houve consenso sobre a relação entre concentração de vitamina A no leite humano e vitamina A dietética, estado nutricional materno, características obstétricas e demográficas e duração da gestação. Sugere-se que estudos futuros utilizem, amostras de leite maduro, coletadas aleatoriamente ao longo dos diferentes períodos do dia, e a utilização do high performance liquid chromatography - HPLC - como método de determinação de vitamina A.<br>OBJECTIVES: to compile the results of Brazilian studies that investigated the vitamin A content of human milk. SOURCES: the searches were performed at LILACS, Banco de Teses da Capes, SciELO (Scientific Electronic Library), and Plataforma Lattes databases. The search strategy was: pregnant, lactating, human milk vitamin A concentration, Brazil. The searches were done in 2006 and updated in March 2008. SUMMARY OF THE FINDINGS: fourteen studies published between 1988 and 2008 were located. These studies were heterogeneous in terms of sample size, milk phase, time of collection and method for determining vitamin A concentrations. The study outcomes described average vitamin A concentrations in human milk ranging from 0.62 to 4.50 µmol/L. CONCLUSIONS: there was no consensus as to the relationship between the vitamin A content of human milk and a diet with a suitable vitamin A content, maternal nutritional status, maternal obstetric and demographical characteristics and duration of pregnancy. The review indicates that future studies should use casual samples of mature milk, and use high performance liquid chromatography - HPLC - as the laboratory technique in order to quantify vitamin A

Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE).

An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2) the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers. The goal of the Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) is to provide guidance for those users represented by the global food and nutrition enterprise. These include researchers (bench and clinical), clinicians providing care/treatment, those developing and evaluating programs/interventions at scale, and those responsible for generating evidence-based policy. The INSPIRE process included convening 5 thematic working groups (WGs) charged with developing summary reports around the following issues: 1) basic overview of the interactions between nutrition, immune function, and the inflammatory response; 2) examination of the evidence regarding the impact of nutrition on immune function and inflammation; 3) evaluation of the impact of inflammation and clinical conditions (acute and chronic) on nutrition; 4) examination of existing and potential new approaches to account for the impact of inflammation on biomarker interpretation and use; and 5) the presentation of new approaches to the study of these relations. Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. This review consists of a summary of the INSPIRE workshop and the WG deliberation

Isolation of human mitotic protein phosphatase complexes:identification of a complex between protein phosphatase 1 and the RNA helicase Ddx21

Metazoan mitosis requires remodelling of sub-cellular structures to ensure proper division of cellular and genetic material. Faults often lead to genomic instability, cell cycle arrests and disease onset. These key structural changes are under tight spatial-temporal and post-translational control, with crucial roles for reversible protein phosphorylation. The phosphoprotein phosphatases PP1 and PP2A are paramount for the timely execution of mitotic entry and exit but their interaction partners and substrates are still largely unresolved. High throughput, mass-spectrometry based studies have limited sensitivity for the detection of low-abundance and transient complexes, a typical feature of many protein phosphatase complexes. Moreover, the limited timeframe during which mitosis takes place reduces the likelihood of identifying mitotic phosphatase complexes in asynchronous cells. Hence, numerous mitotic protein phosphatase complexes still await identification. Here we present a strategy to enrich and identify serine/threonine protein phosphatase complexes at the mitotic spindle. We thus identified a nucleolar RNA helicase, Ddx21/Gu, as a novel, direct PP1 interactor. Furthermore, our results place PP1 within the toposome, a Topoisomerase II alpha (TOPOIIα) containing complex with a key role in mitotic chromatin regulation and cell cycle progression, possibly via regulated protein phosphorylation. This study provides a strategy for the identification of further mitotic PP1 partners and the unravelling of PP1 functions during mitosis