Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.ConclusionsThis population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia

Exploring the effects of demonstration and enactment in facilitating recall of instructions in working memory

Across the lifespan the ability to follow instructions is essential for the successful completion of a multitude of daily activities. This ability will often rely on the storage and processing of information in working memory, and previous research in this domain has found that self-enactment at encoding or observing other-enactment at encoding (demonstration) improves performance at recall. However, no working memory research has directly compared these manipulations. Experiment 1 explored the effects of both self-enactment and demonstration on young adults’ (N=48) recall of action-object instruction sequences (e.g. ‘spin the circle, tap the square’). Both manipulations improved recall, with demonstration providing relatively larger boosts to performance across conditions. More detailed analyses suggested that this improvement was driven by improving the representations of actions, rather than objects, in these action-object sequences. Experiment 2 (N=24) explored this further, removing the objects from the physical environment and comparing partial demonstration (i.e. action-only or object-only) with no or full demonstration. The results showed that partial demonstration only benefitted features that were demonstrated, while full demonstration improved memory for actions, objects and their pairings. Overall these experiments indicate how self-enactment, and particularly demonstration, can benefit verbal recall of instruction sequences through the engagement of visuo-motor processes that provide additional forms of coding to support working memory performance

Vitamins and Perinatal Outcomes Among HIV-Negative Women in Tanzania.

Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes. In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death. The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001). Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].)

Panarchy use in environmental science for risk and resilience planning

Environmental sciences have an important role in informing sustainable management of built environments by providing insights about the drivers and potentially negative impacts of global environmental change. Here, we discuss panarchy theory, a multi-scale hierarchical concept that accounts for the dynamism of complex socio-ecological systems, especially for those systems with strong cross-scale feedbacks. The idea of panarchy underlies much of system resilience, focusing on how systems respond to known and unknown threats. Panarchy theory can provide a framework for qualitative and quantitative research and application in the environmental sciences, which can in turn inform the ongoing efforts in sociotechnical resilience thinking and adaptive and transformative approaches to managemen

Are published standards for haematological indices in pregnancy applicable across populations: an evaluation in healthy pregnant Jamaican women

<p>Abstract</p> <p>Background</p> <p>The haematological profile of the pregnant woman has an impact on the outcome of the pregnancy. Published guidelines indicate acceptable levels for haematological indices in pregnancy but they are population specific. Indicators of haemoglobin concentration are the most commonly utilized of the indices. These published international norms are used across populations, however, there is no evidence confirming their applicability to a population such as the Jamaican pregnant woman. This study was therefore undertaken with the intent of documenting the haematological profile of pregnant primigravid Jamaican women and comparing these to the established norms to determine whether the norms apply or whether there was a need to establish local norms.</p> <p>Methods</p> <p>This was a longitudinal study done on a cohort of 157 healthy primigravid women ages 15 to 25 and without anaemia, and who were recruited from the antenatal clinic of the University Hospital of the West Indies, Kingston, Jamaica. The haemoglobin concentration, packed cell volume, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, white blood cell count, red blood cell count and platelet count were measured on samples of blood obtained from each consenting participant during each of the three trimesters. The results were analysed using SPSS for windows (Version 11) and the data expressed as means ± S.D. Means were compared using the student's paired <it>t-test</it>. Comparison was then made with the international norms as recommended by the United States Center for Disease Control (1989). Ethical approval for this study was obtained from the University Hospital of the West Indies/University of the West Indies Ethics Committee.</p> <p>Results</p> <p>The results showed changes by trimester in all measured variables. For most of the indices the changes achieved levels of significance across trimesters. These changes were however in keeping with the expected physiological response in pregnancy and the values were similar to the published international norms.</p> <p>Conclusion</p> <p>The findings suggest that the international norms for haematological indices in pregnancy are applicable across populations and to the pregnant Jamaican primigravid woman. This finding may be reassuring to others with a similar population and stage of development as Jamaica.</p

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents