Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Preference and consumption of a taste enhanced meat meal by older hospital patients: a pilot study

BACKGROUND: Older hospital patients are considered to be at risk of malnutrition due to insufficient dietary intake. OBJECTIVE: To determine whether taste enhancement, using ingredients naturally high in umami compounds, increases preference and consumption of a meal by older hospital patients. METHODS: 31 patients (65–92 years) on elderly carewards in aUKNHS Trust hospital took part in a single-blinded preference and consumption study. They tasted two meats (control and enhanced, presented in balanced order) and stated their preference. At lunch, control and enhanced cottage pie and gravy were served concurrently; patients were asked to consume ad libitum and intake was measured. RESULTS: Taste enhanced meat was significantly preferred (P = 0.001). Although mean consumption was higher for the enhanced compared to control meal (137 g versus 119 g), with higher levels of energy (103 kcal versus 82 kcal) and protein (4.6 g versus 3.4 g) consumed; differences were not significant. CONCLUSIONS: Natural ingredients rich in umami taste compounds can successfully be used to increase preference of meat based meals by older hospital patients. Larger trials are needed to determine whether such increases in preference can significantly increase consumption.

Genetic, structural, and molecular insights into the function of ras of complex proteins domains

Ras of complex proteins (ROC) domains were identified in 2003 as GTP binding modules in large multidomain proteins from Dictyostelium discoideum. Research into the function of these domains exploded with their identification in a number of proteins linked to human disease, including leucine-rich repeat kinase 2 (LRRK2) and death-associated protein kinase 1 (DAPK1) in Parkinson’s disease and cancer, respectively. This surge in research has resulted in a growing body of data revealing the role that ROC domains play in regulating protein function and signaling pathways. In this review, recent advances in the structural informa- tion available for proteins containing ROC domains, along with insights into enzymatic function and the integration of ROC domains as molecular switches in a cellular and organismal context, are explored.

Regulation of actin assembly by SCAR/WAVE proteins.

Actin reorganization is a tightly regulated process that co-ordinates complex cellular events, such as cell migration, chemotaxis, phagocytosis and adhesion, but the molecular mechanisms that underlie these processes are not well understood. SCAR (suppressor of cAMP receptor)/WAVE [WASP (Wiskott-Aldrich syndrome protein)-family verprolin homology protein] proteins are members of the conserved WASP family of cytoskeletal regulators, which play a critical role in actin dynamics by triggering Arp2/3 (actin-related protein 2/3)-dependent actin nucleation. SCAR/WAVEs are thought to be regulated by a pentameric complex which also contains Abi (Abl-interactor), Nap (Nck-associated protein), PIR121 (p53-inducible mRNA 121) and HSPC300 (haematopoietic stem progenitor cell 300), but the structural organization of the complex and the contribution of its individual components to the regulation of SCAR/WAVE function remain unclear. Additional features of SCAR/WAVE regulation are highlighted by the discovery of other interactors and distinct complexes. It is likely that the combinatorial assembly of different components of SCAR/WAVE complexes will prove to be vital for their roles at the centre of dynamic actin reorganization.

Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients

Amyotrophic lateral sclerosis (ALS) is an incurable neuromuscular disease that leads to a profound loss of life quality and premature death. Around 10% of the cases are inherited and ALS8 is an autosomal dominant form of familial ALS caused by mutations in the vamp-associated protein B/C (VAPB) gene. The VAPB protein is involved in many cellular processes and it likely contributes to the pathogenesis of other forms of ALS besides ALS8. A number of successful drug tests in ALS animal models could not be translated to humans underscoring the need for novel approaches. The induced pluripotent stem cells (iPSC) technology brings new hope, since it can be used to model and investigate diseases in vitro. Here we present an additional tool to study ALS based on ALS8-iPSC. Fibroblasts from ALS8 patients and their non-carrier siblings were successfully reprogrammed to a pluripotent state and differentiated into motor neurons. We show for the first time that VAPB protein levels are reduced in ALS8-derived motor neurons but, in contrast to over-expression systems, cytoplasmic aggregates could not be identified. Our results suggest that optimal levels of VAPB may play a central role in the pathogenesis of ALS8, in agreement with the observed reduction of VAPB in sporadic ALS.

Gene Expression Profiling of Cultured Cells From Brainstem of Newborn Spontaneously Hypertensive and Wistar Kyoto Rats

The spontaneously hypertensive rat (SHR) is a good model to study several diseases such as the attention-deficit hyperactivity disorder, cardiopulmonary impairment, nephropathy, as well as hypertension, which is a multifactor disease that possibly involves alterations in gene expression in hypertensive relative to normotensive subjects. In this study, we used high-density oligoarrays to compare gene expression profiles in cultured neurons and glia from brainstem of newborn normotensive Wistar Kyoto (WKY) and SHR rats. We found 376 genes differentially expressed between SHR and WKY brainstem cells that preferentially map to 17 metabolic/signaling pathways. Some of the pathways and regulated genes identified herein are obviously related to cardiovascular regulation; in addition there are several genes differentially expressed in SHR not yet associated to hypertension, which may be attributed to other differences between SHR and WKY strains. This constitute a rich resource for the identification and characterization of novel genes associated to phenotypic differences observed in SHR relative to WKY, including hypertension. In conclusion, this study describes for the first time the gene profiling pattern of brainstem cells from SHR and WKY rats, which opens up new possibilities and strategies of investigation and possible therapeutics to hypertension, as well as for the understanding of the brain contribution to phenotypic differences between SHR and WKY rats.

Differences and similarities of postprandial lipemia in rodents and humans

Background: The rat has been a mainstay of physiological and metabolic research, and more recently mice. This study aimed at characterizing the postprandial triglyceride profile of two members of the Muridae family: the Wistar rats (Rattus norvegicus albinus) and C57BL/6 mice (Mus musculus) plus comparing them to the profile obtained in humans. Methods: Thirty-one male and twelve female Wistar rats, ten C57BL/6 male and nine female mice received a liquid meal containing fat (17%), protein (4%) and carbohydrates (4%), providing 2 g fat/Kg. Thirty-one men and twenty-nine women received a standardized liquid meal containing fat (25%), dextromaltose (55%), protein (14%), and vitamins and minerals (6%), and providing 40 g of fat per square meter of body surface. Serial blood samples were collected at 2, 4, 6, 8 and 10 h after the ingestion in rats, at 1, 2, 3, 4, 5 and 6 h in mice and in humans at 2, 4, 6 and 8 h. Wilcoxon and Mann-Whitney tests were used. Results/Discussion: The triglyceride responses were evaluated after the oral fat loads. Fasting and postprandial triglyceridemia were determined sequentially in blood sample. AUC, AUIC, AR, RR and late peaks were determined. Conclusions: Rats are prone to respond in a pro-atherogenic manner. The responses in mice were closer to the ones in healthy men. This study presents striking differences in postprandial triglycerides patterns between rats and mice not correlated to baseline triglycerides, the animal baseline body weight or fat load in all animal groups.

Estudo eritroleucométrico e proteinograma sérico do sangue do cordão umbilical e jugular de eqüinos ao nascimento e de suas respectivas mães

Colheram-se amostras de sangue do cordão umbilical (SCU) e do sangue circulante de cinco eqüinos neonatos, imediatamente após o nascimento, e o sangue da própria mãe, utilizando-se um sistema a vácuo. O material foi submetido à contagem global de hemácias e leucócitos e à determinação do volume globular e da concentração de hemoglobina; à contagem diferencial de leucócitos em esfregaços sangüíneos; e ao cálculo dos índices eritrocitométricos. Foram realizadas a dosagem de proteínas séricas totais e a eletroforese das proteínas séricas em gel de agarose. Não houve diferenças significativas entre os parâmetros do SCU e do sangue da jugular dos potros. No SCU dos potros observaram-se valores mais elevados para contagem global de hemácias (9,75x10(6)/µl), dosagem de hemoglobina (14,65g/dl) e concentração de hemoglobina corpuscular média (37,23g/dl); e valores menores para volume corpuscular médio (40,50fl), proteína total (4,37g/dl), alfa-globulinas (0,65g/dl), beta-globulinas (1,10g/dl), gama-globulinas (0g/dl) e contagens global (5,40 x 10³/µl) e diferencial de leucócitos, exceto contagem de neutrófilos bastonetes e monócitos, quando comparados com os valores obtidos no sangue de suas mães.

Associations between LEP, DGAT1 and FABP4 gene polymorphisms and carcass and meat traits in Nelore and crossbred beef cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genome-Wide Analysis of Differentially Expressed Genes During the Early Stages of Tomato Infection by a Potyvirus

Plant responses against pathogens cause up-and downward shifts in gene expression. To identify differentially expressed genes in a plant-virus interaction, susceptible tomato plants were inoculated with the potyvirus Pepper yellow mosaic virus (PepYMV) and a subtractive library was constructed from inoculated leaves at 72 h after inoculation. Several genes were identified as upregulated, including genes involved in plant defense responses (e. g., pathogenesis-related protein 5), regulation of the cell cycle (e. g., cytokinin-repressed proteins), signal transduction (e. g., CAX-interacting protein 4, SNF1 kinase), transcriptional regulators (e. g., WRKY and SCARECROW transcription factors), stress response proteins (e. g., Hsp90, DNA-J, 20S proteasome alpha subunit B, translationally controlled tumor protein), ubiquitins (e. g., polyubiquitin, ubiquitin activating enzyme 2), among others. Downregulated genes were also identified, which likewise display identity with genes involved in several metabolic pathways. Differential expression of selected genes was validated by macroarray analysis and quantitative real-time polymerase chain reaction. The possible roles played by some of these genes in the viral infection cycle are discussed.

Proteomic profiling of the molecular targets of interactions of the mastoparan peptide Protopolybia MP-III at the level of endosomal membranes from rat mast cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of ammoniation and moisture-content on the quality of signal grass (Brachiaria-decumbens stapf) hay

The experiment was carried out to evaluate the effects of two moisture levels (18-20% and 13-15%) and three anhydrous ammonia levels (0.0; 1.5; 3.0% of NH3) on the quality of Brachiaria decumbens Stapf hay. The hay was bailed in April and weighed and treated under plastic cover during 30 days. The hay presented a similar chemical composition when bailed with high or low moisture. The percentages of NDF (80.59; 77.61; 76.10%); hemicellulose (32.56; 29.48; 28.76%) and lignin (9.53; 8.21; 7.54% decreased and the percentages of crude protein (4.04; 11.35; 13.22%) and IVDMD (36.78; 49.72; 54.33%) increased as the NH3 level increased. The fractions ADF, cellulose, and ADIN did not change due to the ammoniation. The incidence of fungi decreased with application of NH3 being the better results obtained with the 1.5% treatments.

Indução da expressão da Glicerol-3-Fosfato desidrogenase em levedura

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Extrato de levedura (Saccharomyces cerevisiae) e prebiótico na dieta pré-inicial para frangos de corte criados em diferentes temperaturas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)