Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands

BACKGROUND: The exclusion of individuals with elevated acute phase proteins has been advocated in order to improve prevalence estimates of vitamin A deficiency in surveys, but it is unclear whether this will lead to sampling bias. The purpose of the study was to determine whether the exclusion of individuals with elevated acute phase proteins is associated with sampling bias and to characterize inflammation in children with night blindness. METHODS: In a survey in the Republic of the Marshall Islands involving 281 children, aged 1–5 years, serum retinol, C-reactive protein (CRP), and α(1)-acid glycoprotein (AGP) were measured. RESULTS: Of 281 children, 24 (8.5%) had night blindness and 165 (58.7%) had serum retinol <0.70 μmol/L. Of 248 children with AGP and CRP measurements, 123 (49.6%) had elevated acute phase proteins (CRP >5 mg/L and/or AGP >1000 mg/L). Among children with and without night blindness, the proportion with serum retinol <0.70 μmol/L was 79.2% and 56.8% (P = 0.03) and with anemia was 58.3% and 35.7% (P = 0.029), respectively. The proportion of children with serum retinol <0.70 μmol/L was 52.0% after excluding children with elevated acute phase proteins. Among children with and without elevated acute phase proteins, mean age was 2.8 vs 3.2 years (P = 0.016), the proportion of boys was 43.1% vs. 54.3% (P = 0.075), with no hospitalizations in the last year was 11.0% vs 23.6% (P = 0.024), and with anemia was 43.8% vs 31.7% (P = 0.05), respectively. CONCLUSIONS: Exclusion of children with inflammation in this survey of vitamin A deficiency does not improve prevalence estimates for vitamin A deficiency and instead leads to sampling bias for variables such as age, gender, anemia, and hospitalization history

Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs)

Intrinsically disordered proteins (IDPs) are proteins that usually do not adopt well-defined native structures when isolated in solution under physiological conditions. Numerous IDPs have close relationships with human diseases such as tumor, Parkinson disease, Alzheimer disease, diabetes, and so on. These disease-associated IDPs commonly play principal roles in the disease-associated protein-protein interaction networks. Most of them in the disease datasets have more interactants and hence the size of the disease-associated IDPs interaction network is simultaneously increased. For example, the tumor suppressor protein p53 is an intrinsically disordered protein and also a hub protein in the p53 interaction network; α-synuclein, an intrinsically disordered protein involved in Parkinson diseases, is also a hub of the protein network. The disease-associated IDPs may provide potential targets for drugs modulating protein-protein interaction networks. Therefore, novel strategies for drug discovery based on IDPs are in the ascendant. It is dependent on the features of IDPs to develop the novel strategies. It is found out that IDPs have unique structural features such as high flexibility and random coil-like conformations which enable them to participate in both the “one to many” and “many to one” interaction. Accordingly, in order to promote novel strategies for drug discovery, it is essential that more and more features of IDPs are revealed by experimental and computing methods

Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators

Complete folding is not a prerequisite for protein function, as disordered and partially folded states of proteins frequently perform essential biological functions. In order to understand their functions at the molecular level, we utilized diverse experimental measurements to calculate ensemble models of three non-homologous, intrinsically disordered proteins: I-2, spinophilin and DARPP-32, which bind to and regulate protein phosphatase 1 (PP1). The models demonstrate that these proteins have dissimilar propensities for secondary and tertiary structure in their unbound forms. Direct comparison of these ensemble models with recently determined PP1 complex structures suggests a significant role for transient, pre-formed structure in the interactions of these proteins with PP1. Finally, we generated an ensemble model of partially disordered I-2 bound to PP1 that provides insight into the relationship between flexibility and biological function in this dynamic complex

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

Food security—the ability to obtain and use sufficient amounts of safe and nutritious food—is a fundamental human need. Climate change is very likely to affect global, regional, and local food security by disrupting food availability, decreasing access to food, and making food utilization more difficult. Food security exists “when all people at all times have physical, social, and economic access to sufficient, safe, and nutritious food to meet their dietary needs and food preferences for an active and healthy life” and affects people through both under- and overconsumption. Food security requires that food be simultaneously (1) available—that it exist in a particular place at a particular time, (2) that people can access that food through economic or other means, (3) that people can utilize the food that is available and accessible to them, and (4) that each of these components be stable over time. Constrictions within any of these components can result in food insecurity. Food is provisioned through a food system that manifests in diverse ways across the globe. The food system includes all activities related to producing, transporting, trading, storing, processing, packaging, wholesaling, retailing, consuming, and disposing of food. Whether an individual food system includes few, many, or all of these elements, each is susceptible to risks from a changing climate. Human activities, such as burning fossil fuels and deforestation, have increased global greenhouse gas concentrations; atmospheric carbon dioxide levels have risen from 280 parts per million (ppm) in the late 1700s to today’s level of about 400 ppm. Concentrations continue to rise, though future levels depend on choices and development pathways yet to be determined. Additionally, the future condition of the food system depends upon socioeconomic trajectories that are external to the food system itself. For these reasons, a range of possible emissions futures and socioeconomic pathways have been considered by this assessment. The Climate Change, Global Food Security, and U.S. Food System assessment represents a consensus of authors and includes contributors from 19 Federal, academic, nongovernmental, and intergovernmental organizations in four countries, identifying climate-change effects on global food security through 2100, and analyzing the United States’ likely connections with that world. The assessment finds that climate change is likely to diminish continued progress on global food security through production disruptions leading to local availability limitations and price increases, interrupted transport conduits, and diminished food safety, among other causes. The risks are greatest for the global poor and in tropical regions. In the near term, some high-latitude production export regions may benefit from changes in climate. As part of a highly integrated global food system, consumers and producers in the United States are likely to be affected by these changes. The type and price of food imports from other regions are likely to change, as are export demands placed upon U.S. producers and the transportation, processing, and storage systems that enable global trade. Demand for food and other types of assistance may increase, as may demand for advanced technologies to manage changing conditions. Adaptation across the food system has great potential to manage climate-change effects on food security, and the complexity of the food system offers multiple potential points of intervention for decision makers at every level, from households to nations and international governance structures. However, effective adaptation is subject to highly localized conditions and socioeconomic factors, and the technical feasibility of an adaptive intervention is not necessarily a guarantee of its application if it is unaffordable or does not provide benefits within a relatively short time frame, particularly for smaller operations around the world with limited capacity for long-term investments. The accurate identification of needs and vulnerabilities, and the effective targeting of adaptive practices and technologies across the full scope of the food system, are central to improving global food security in a changing climate