Red blood cells derived from peripheral blood and bone marrow CD34+ human haematopoietic stem cells are permissive to Plasmodium parasites infection

The production of fully functional human red cells in vitro from haematopoietic stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs from cord blood represented a major improvement to develop the continuous culture system for Plasmodium vivax. Here, we demonstrated that CD34+hHSCs from peripheral blood and bone marrow can be expanded and differentiated to reticulocytes using a novel stromal cell. Moreover, these reticulocytes and mature red blood cells express surface markers for entrance of malaria parasites contain adult haemoglobin and are also permissive to invasion by P. vivax and Plasmodium falciparum parasites.     

Body Size and Morph as Drivers of Copulation Duration in a Male Dimorphic Damselfly

Copulation duration is often highly variable within and among species. Here, we explore the roles of body size, male morph, morph frequency, and alternative reproductive tactics to explain copulation duration in the damselfly Paraphlebia zoe. P. zoe has two male morphs (pigmented or hyaline wings) which differ in reproductive tactics (territorial or non‐territorial behaviors). We also analyze the effects of season as the frequencies of both morphs tend to vary along the reproductive season. In the first non‐experimental year, we found that the relationship between body size and copulation duration depended on the time of year. Early in the season, body size positively correlated with copulation duration, while late in the year, body size negatively correlated with copulation duration. In the second experimental year (when we reversed the frequency of male morphs in the middle of the season: making pigmented males less frequent than hyaline males), size influenced copulation duration as well as morph – body size positively correlated with copulation duration, and hyaline males mated for longer than pigmented males. Contrary to our prediction, changes to the relative abundances of morphs did not influence copulation duration. Hyaline males may be under selection for longer copulation durations to compensate for their reduced access to females, as long copulations potentially lead to more rival sperm to be removed from the female sperm storage organs and/or increased mate guarding. We do not discard, however, other explanations that drive variation in copulation duration such as cryptic female choice and/or predation.     

Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry

Background

Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry.

Materials and Methods

23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression.

Results

Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12–1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70–0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps.

Conclusions

SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.     

Type 2 Diabetes Elicits Lower Nitric Oxide,Bradykinin Concentration and Kallikrein Activity Together with Higher DesArg9-BK and Reduced Post-Exercise Hypotension Compared to Non-Diabetic Condition

This study compared the plasma kallikrein activity (PKA), bradykinin concentration (BK), DesArg⁹-BK production, nitric oxide release (NO) and blood pressure (BP) response after moderate-intensity aerobic exercise performed by individuals with and without type 2 diabetes. Ten subjects with type 2 diabetes (T2D) and 10 without type 2 diabetes (ND) underwent three sessions: 1) maximal incremental test on cycle ergometer to determine lactate threshold (LT); 2) 20-min of constant-load exercise on cycle ergometer, at 90% LT and; 3) control session. BP and oxygen uptake were measured at rest and at 15, 30 and 45 min post-exercise. Venous blood samples were collected at 15 and 45 minutes of the recovery period for further analysis of PKA, BK and DesArg⁹-BK. Nitrite plus nitrate (NOx) was analyzed at 15 minutes post exercise. The ND group presented post-exercise hypotension (PEH) of systolic blood pressure and mean arterial pressure on the 90% LT session but T2D group did not. Plasma NOx increased ~24.4% for ND and ~13.8% for T2D group 15min after the exercise session. Additionally, only ND individuals showed increases in PKA and BK in response to exercise and only T2D group showed increased DesArg⁹-BK production. It was concluded that T2D individuals presented lower PKA, BK and NOx release as well as higher DesArg⁹-BK production and reduced PEH in relation to ND participants after a single exercise session.     

Cellular Growth and Mitochondrial Ultrastructure of Leishmania (Viannia) braziliensis Promastigotes Are Affected by the Iron Chelator 2,2-Dipyridyl

Background

Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V.) braziliensis.

Methodology/Principal Findings

In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V.) braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites'' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.

Conclusions

Iron chelation leads to a multifactorial response that results in cellular collapse, starting with the interruption of cell proliferation and culminating in marked mitochondrial impairment in some parasites and their subsequent cell death, whereas others may survive and resume proliferating.     

Pathway Evidence of How Musical Perception Predicts Word-Level Reading Ability in Children with Reading Difficulties

Objective

To investigate whether specific domains of musical perception (temporal and melodic domains) predict the word-level reading skills of eight- to ten-year-old children (n = 235) with reading difficulties, normal quotient of intelligence, and no previous exposure to music education classes.

Method

A general-specific solution of the Montreal Battery of Evaluation of Amusia (MBEA), which underlies a musical perception construct and is constituted by three latent factors (the general, temporal, and the melodic domain), was regressed on word-level reading skills (rate of correct isolated words/non-words read per minute).

Results

General and melodic latent domains predicted word-level reading skills.     

Proliferation of Purple Sulphur Bacteria at the Sediment Surface Affects Intertidal Mat Diversity and Functionality

There is a relative absence of studies dealing with mats of purple sulphur bacteria in the intertidal zone. These bacteria display an array of metabolic pathways that allow them to disperse and develop under a wide variety of conditions, making these mats important in terms of ecosystem processes and functions. Mass blooms of purple sulphur bacteria develop during summer on sediments in the intertidal zone especially on macroalgal deposits. The microbial composition of different types of mats differentially affected by the development of purple sulphur bacteria was examined, at low tide, using a set of biochemical markers (fatty acids, pigments) and composition was assessed against their influence on ecosystem functions (sediment cohesiveness, CO₂ fixation). We demonstrated that proliferation of purple sulphur bacteria has a major impact on intertidal mats diversity and functions. Indeed, assemblages dominated by purple sulphur bacteria (Chromatiaceae) were efficient exopolymer producers and their biostabilisation potential was significant. In addition, the massive growth of purple sulphur bacteria resulted in a net CO₂ degassing whereas diatom dominated biofilms represented a net CO₂ sink.     

Discovery of a novel sub-class of ROMK channel inhibitors typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one

A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents.     

Acute Right Coronary artery Occlusion During Cooled-Tip Radiofrequency Ablation of the Cavotricuspid Isthmus

Cooled-tip radiofrequencycatheter ablation of the cavotricuspid isthmus, performed after pulmonary vein isolation, resulted in acute occlusion of the posterolateral branch of the right coronary artery in a 49-year-old male with previously known right coronary artery disease. The occlusion was successfully stented. It is conceivable that previously diseased coronary arteries are more prone to be damaged during ablation.