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Multiple comorbidities related to arsenic exposure through drinking water continue to be public problems worldwide, principally in chronically exposed populations, such as those in the Comarca Lagunera (CL), Mexico. In addition, this relationship could be exacerbated by an early life exposure through the placenta and later through breast milk. This study conducted a comparative analysis of arsenic levels in multiple biological samples from pregnant women and their neonates in the CL and the comparison region, Saltillo. Total arsenic levels in placenta, breast milk, blood, and urine were measured in pregnant women and their neonates from rural areas of seven municipalities of the CL using atomic absorption spectrophotometry with hydride generation methodology. The average concentrations of tAs in drinking water were 47.7 µg/L and 0.05 µg/L in the exposed and non-exposed areas, respectively. Mean levels of tAs were 7.80 µg/kg, 77.04 µg/g-Cr, and 4.30 µg/L in placenta, blood, urine, and breast milk, respectively, in mothers, and 107.92 µg/g-Cr in neonates in the exposed group, which were significantly higher than those in the non-exposed area. High levels of urinary arsenic in neonates were maintained 4 days after birth, demonstrating an early arsenic exposure route through the placenta and breast milk. In addition, our study suggested that breastfeeding may reduce arsenic exposure in infants in arsenic-contaminated areas. Further studies are necessary to follow up on comorbidities later in life in neonates and to provide interventions in this region.

Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients. © 2015 by the authors; licensee MDPI, Basel, Switzerland., This work was support in part by Consejería de Salud y Bienestar Social (Junta de Andalucía) Grant (PI05142012), RETICEF (RD06/0013/1014-RD12/0043/0014) and Fondo de Investigación Sanitaria (Instituto Carlos III) Grants (PI12/02141) with co-financing from FEDER (Fondo Europeo de Desarrollo Regional). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.

Aims To analyze the relationship between serum levels of osteocalcin and parameters of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study of 78 patients with T2DM evaluated intima–media thickness, and the prevalence of coronary heart disease, atherosclerotic plaques and aortic calcifications. Serum osteocalcin levels were also determined by radioimmunoassay. Results The patients' mean age was 57.8±6.4 years (duration of diabetes: 13.4 years; mean HbA 1c level: 8.01%), and 37.2% had coronary heart disease, 56% had an abnormal intima–media thickness, 26.9% had carotid plaques and 32.1% had aortic calcifications. Coronary heart disease was associated with higher levels of osteocalcin in male vs female patients (1.95±1.36 vs 0.93±0.86ng/mL, respectively; P =0.006). Also, higher concentrations of osteocalcin were found in female patients with vs without abnormal intima–media thicknesses (2.17±1.84 vs 1.25±0.67ng/mL, respectively; P =0.042), carotid plaques (2.86±2.10 vs 1.43±1.09ng/mL, respectively; P =0.03) and aortic calcifications (2.85±1.97 vs 1.26±0.83ng/mL, respectively; P =0.002). Serum osteocalcin levels were associated with coronary heart disease on multivariate logistic regression (odds ratio: 2.27, 95% confidence interval: 1.21–4.25; P =0.01). Conclusion In T2DM patients, serum osteocalcin levels were associated with parameters of atherosclerosis, suggesting that osteocalcin is involved not only in bone metabolism, but also in atherosclerotic disease.

Vesicle traffic to and from the surface is highly polarized in African trypanosomes. Actin is required for polarized endocytic traffic in bloodstream forms of African trypanosomes but its role in other pathways has remained equivocal. A combination of metabolic pulse chase labelling and surface biotinylation during the chase period along with the use of conditional RNA interference was employed to demonstrate that substantial loss of actin had no effect on the export of newly synthesized proteins to the surface of bloodstream and procyclic forms of Trypanosoma brucei. These results indicated that this trafficking pathway to the surface operates as normal even when actin levels are significantly lower than normal and endocytic activity is abolished. Taken together the data support the view that the secretory and endocytic pathways are not obligatorily coupled.

Summary The structure, genomic organization and transcrlptlon of the gene encoding hlstone H2B In the protozoan parasite Trypansosoma cruzl have been studied. This gene consists of a 746~nucleotide unit, tandemly repeated at least 18 times in each of two clusters. DNA probes corresponding to hlstones H2B and H3 hybridized to different chromosomes revealing that the genes coding for these two hlstones are not physlcally linked in the genome of r. cruzl. The primary transcription product of the H2B gene Is processed by trans-splicing and polyadenylatlon. lnhibltlon of DNA synthesis with aphidicolin resulted in the reductlon of histone H2B mRNA to undetectable levels in about two hours, suggesting that Its abundance is regulated throughout the cell cycle as it occurs in other eukaryotes. in addition, a concomitant inhibition of translation by cyclohexfmide reverted this effect indicating that de novo protein synthesis is required for RNA instability. Hlstone mRNA abundance was dependent on the life-cycle stage of r. cruzl: abundant in amastigotes and epimastlgotes, the dividing forms in the host cell and the Insect vector, respectively, while undetected in trypomastigotes, the parasite’s nondlvidlng life stage.

Proteins from the endocytic pathway in bloodstream forms of Trypanosome brucei are modified by the addition of linear poly-N-acetyllactosamine side chains, which permits their isolation by tomato lectin affinity chromatography. Antibodies against this tomato lectin binding fraction were employed to screen a cDNA expression library from bloodstream forms of T. brucei. Two cDNAs were prominent among those selected. These cDNAs coded for two putative protein disulfide isomerases (PDIs) that respectively contained one and two double-cysteine redox-active sites and corresponded to a single domain PDI and a class 1 PDI. Assays of the purified recombinant proteins demonstrated that both proteins possess isomerase activity, but only the single domain PDI had a reducing activity. These PDIs possess a number of unusual features that distinguish them from previously characterized PDIs. The expression of both is developmentally regulated, they both co-localize with markers of the endocytic pathway, and both are modified by N-glycosylation. The larger PDI possesses N-glycans containing poly-N-acetyllactosamine, a modification that is indicative of processing in the Golgi and suggests the presence of a novel trafficking pathway for PDIs in trypanosomes. Although generally PDIs are considered essential, neither activity appeared to be essential for the growth of trypanosomes, at least in vitro.

SIR2-like proteins have been implicated in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. We report here the molecular and functional characterization of a SIR2-related protein from the protozoan parasite Trypanosoma brucei, which we termed TbSIR2RP1. This protein is a chromosome-associated NAD-dependent enzyme which, in contrast to other known proteins of this family, catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Under- or overexpression of TbSIR2RP1 decreased or increased, respectively, cellular resistance to DNA damage. Treatment of trypanosomal nuclei with a DNA alkylating agent resulted in a significant increase in the level of histone ADP-ribosylation and a concomitant increase in chromatin sensitivity to micrococcal nuclease. Both of these responses correlated with the level of TbSIR2RP1 expression. We propose that histone modification by TbSIR2RP1 is involved in DNA repair.