Phosphitylation of Primary Carboxamides. Synthesis of Peptide-Oligonucleotide Conjugates with Acylphosphoramidate Linkages

Abstract

N-acylphosphoramidates can be obtained from the reaction of phosphitylated primary carboxamides and an alcohol in the presence of an acid catalyst such as tetrazole and subsequent oxidation. The reaction is useful for the preparation of peptide-oligonucleotide conjugates.     

Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle

Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18–44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at α=0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from 1 to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle.     

Fast energy-aware OLSR routing in VANETs by means of a parallel evolutionary algorithm

This work tackles the problem of reducing the power consumption of the OLSR routing protocol in vehicular networks. Nowadays, energy-aware and green communication protocols are important research topics, specially when deploying wireless mobile networks. This article introduces a fast automatic methodology to search for energy-efficient OLSR configurations by using a parallel evolutionary algorithm. The experimental analysis demonstrates that significant improvements over the standard configuration can be attained in terms of power consumption, with no noteworthy loss in the QoS.     

High prevalence of asthma symptoms in Warao Amerindian children in Venezuela is significantly associated with open-fire cooking: a cross-sectional observational study

Background

The International Study on Asthma and Allergies in Childhood (ISAAC) reported a prevalence of asthma symptoms in 17 centers in nine Latin American countries that was similar to prevalence rates reported in non-tropical countries. It has been proposed that the continuous exposure to infectious diseases in rural populations residing in tropical areas leads to a relatively low prevalence of asthma symptoms. As almost a quarter of Latin American people live in rural tropical areas, the encountered high prevalence of asthma symptoms is remarkable. Wood smoke exposure and environmental tobacco smoke have been identified as possible risk factors for having asthma symptoms.

Methods

We performed a cross-sectional observational study from June 1, 2012 to September 30, 2012 in which we interviewed parents and guardians of Warao Amerindian children from Venezuela. Asthma symptoms were defined according to the ISAAC definition as self-reported wheezing in the last 12 months. The associations between wood smoke exposure and environmental tobacco smoke and the prevalence of asthma symptoms were calculated by means of univariate and multivariable logistic regression analyses.

Results

We included 630 children between two and ten years of age. Asthma symptoms were recorded in 164 of these children (26%). The prevalence of asthma symptoms was associated with the cooking method. Children exposed to the smoke produced by cooking on open wood fires were at higher risk of having asthma symptoms compared to children exposed to cooking with gas (AOR 2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household where more than ten cigarettes were smoked per day and they had a higher risk of having asthma symptoms compared to children who were not exposed to cigarette smoke (AOR 2.69, 95% CI 1.11 - 6.48).

Conclusion

Our findings suggest that children living in rural settings in a household where wood is used for cooking or where more than ten cigarettes are smoked daily have a higher risk of having asthma symptoms.     

A unified framework for diversity gradients: the adaptive trait continuum

Aim Adaptive trait continua are axes of covariation observed in multivariate trait data for a given taxonomic group. These continua quantify and summarize life‐history variation at the inter‐specific level in multi‐specific assemblages. Here we examine whether trait continua can provide a useful framework to link life‐history variation with demographic and evolutionary processes in species richness gradients. Taking an altitudinal species richness gradient for Mediterranean butterflies as a study case, we examined a suite of traits (larval diet breadth, adult phenology, dispersal capacity and wing length) and species‐specific habitat measures (temperature and aridity breadth). We tested whether traits and species‐specific habitat measures tend to co‐vary, whether they are phylogenetically conserved, and whether they are able to explain species distributions and spatial genetic variation in a large number of butterfly assemblages. Location Catalonia, Spain. Methods We formulated predictions associated with species richness gradients and adaptive trait continua. We applied principal components analyses (PCAs), structural equation modelling and phylogenetic generalized least squares models. Results We found that traits and species‐specific habitat measures covaried along a main PCA axis, ranging from multivoltine trophic generalists with high dispersal capacity to univoltine (i.e. one generation per year), trophic specialist species with low dispersal capacity. This trait continuum was closely associated with the observed distributions along the altitudinal gradient and predicted inter‐specific differences in patterns of spatial genetic variability (F_ST and genetic distances), population responses to the impacts of global change and local turnover dynamics. Main conclusions The adaptive trait continuum of Mediterranean butterflies provides an integrative and mechanistic framework to: (1) analyse geographical gradients in species richness, (2) explain inter‐specific differences in population abundances, spatial distributions and demographic trends, (3) explain inter‐specific differences in patterns of genetic variation (F_ST and genetic distances), and (4) study specialist–generalist life‐history transitions frequently involved in butterfly diversification processes.     

Methane-Carbon Flow into the Benthic Food Web at Cold Seeps – A Case Study from the Costa Rica Subduction Zone

Cold seep ecosystems can support enormous biomasses of free-living and symbiotic chemoautotrophic organisms that get their energy from the oxidation of methane or sulfide. Most of this biomass derives from animals that are associated with bacterial symbionts, which are able to metabolize the chemical resources provided by the seeping fluids. Often these systems also harbor dense accumulations of non-symbiotic megafauna, which can be relevant in exporting chemosynthetically fixed carbon from seeps to the surrounding deep sea. Here we investigated the carbon sources of lithodid crabs (Paralomis sp.) feeding on thiotrophic bacterial mats at an active mud volcano at the Costa Rica subduction zone. To evaluate the dietary carbon source of the crabs, we compared the microbial community in stomach contents with surface sediments covered by microbial mats. The stomach content analyses revealed a dominance of epsilonproteobacterial 16S rRNA gene sequences related to the free-living and epibiotic sulfur oxidiser Sulfurovum sp. We also found Sulfurovum sp. as well as members of the genera Arcobacter and Sulfurimonas in mat-covered surface sediments where Epsilonproteobacteria were highly abundant constituting 10% of total cells. Furthermore, we detected substantial amounts of bacterial fatty acids such as i-C15∶0 and C17∶1ω6c with stable carbon isotope compositions as low as −53‰ in the stomach and muscle tissue. These results indicate that the white microbial mats at Mound 12 are comprised of Epsilonproteobacteria and that microbial mat-derived carbon provides an important contribution to the crab''s nutrition. In addition, our lipid analyses also suggest that the crabs feed on other ¹³C-depleted organic matter sources, possibly symbiotic megafauna as well as on photosynthetic carbon sources such as sedimentary detritus.     

A Model of Chronic Nutrient Infusion in the Rat

Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of catheterizing the right jugular vein and left carotid artery under general anesthesia; allowing a 7-day recuperation period; connecting the catheters to the pumps using a swivel and counterweight system that enables the animal to move freely in the cage; and infusing glucose and/or Intralipid (a soybean oil emulsion which generates a mixture of approximately 80% unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This model offers several advantages, including the possibility to finely modulate the target levels of circulating glucose and fatty acids; the option to co-infuse pharmacological compounds; and the relatively short time frame as opposed to dietary models. It can be used to examine the mechanisms of nutrient-induced dysfunction in a variety of organs and to test the effectiveness of drugs in this context.     

Variability within the 10-Year Pollen Rain of a Seasonal Neotropical Forest and Its Implications for Paleoenvironmental and Phenological Research

Tropical paleoecologists use a combination of mud-water interface and modern pollen rain samples (local samples of airborne pollen) to interpret compositional changes within fossil pollen records. Taxonomic similarities between the composition of modern assemblages and fossil samples are the basis of reconstructing paleoclimates and paleoenvironments. Surface sediment samples reflect a time-averaged accumulation of pollen spanning several years or more. Due to experimental constraints, modern pollen rain samples are generally collected over shorter timeframes (1–3 years) and are therefore less likely to capture the full range of natural variability in pollen rain composition and abundance. This potentially biases paleoenvironmental interpretations based on modern pollen rain transfer functions. To determine the degree to which short-term environmental change affects the composition of the aerial pollen flux of Neotropical forests, we sampled ten years of the seasonal pollen rain from Barro Colorado Island, Panama and compared it to climatic and environmental data over the same ten-year span. We establish that the pollen rain effectively captured the strong seasonality and stratification of pollen flow within the forest canopy and that individual taxa had variable sensitivity to seasonal and annual changes in environmental conditions, manifested as changes in pollen productivity. We conclude that modern pollen rain samples capture the reproductive response of moist tropical plants to short-term environmental change, but that consequently, pollen rain-based calibrations need to include longer sampling periods (≥7 years) to reflect the full range of natural variability in the pollen output of a forest and simulate the time-averaging present in sediment samples. Our results also demonstrate that over the long-term, pollen traps placed in the forest understory are representative samples of the pollen output of both canopy and understory vegetation. Aerial pollen traps, therefore, also represent an underutilized means of monitoring the pollen productivity and reproductive behavior of moist tropical forests.     

Tasa estimada de disposición de glucosa en pacientes menores de 18 años con diabetes mellitus tipo 1 y sobrepeso-obesidad

ObjectiveTo assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight.MethodsA total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age.ResultsNo significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3 ± 1.3 vs 10.1 ± 0.8 mg kg^-1min^-1; p < 0.01). Insulin dose was higher in overweight and obese children, especially in IU/m²/day (37.7 vs 36.1 vs 29.4 respectively; p < 0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5 mg/dL respectively; p < 0.01). No correlation was found between waist circumference and the different markers of insulin resistance.ConclusionsValues of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m²/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk.     

Desarrollo global del niño: más allá de la suplementación farmacológica con yodo

Iodine deficiency is a factor that may compromise child development, but is not the only one. Other health determinants, some of them outside the healthcare system, are able to influence development. Fighting iodine deficiency may be a pragmatic and useful strategy if it is found to be not maleficent, beneficial to health, and cost-effective, and does not make us lose the notion that child development goes beyond psychomotor or cognitive performance. This article analyzes such constraints from a critical point of view.