Post-weaning protein malnutrition increases blood pressure and induces endothelial dysfunctions in rats

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10⁻¹⁰–3.10⁻⁴ M) was similar in both groups. Endothelium removal or L-NAME (10⁻⁴ M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10⁻¹⁰–10⁻³ M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model.     

Scaling and adaptations of incisors and cheek teeth in caviomorph rodents (Rodentia,Hystricognathi)

The South American hystricognath rodents are one of the most diverse mammalian clades considering their occupied habitats, locomotor modes and body sizes. This might have been partly evolved by diversification of their masticatory apparatus' structure and its ecological commitment, for example, chisel‐tooth digging. In this phylogeny‐based comparative study, we test the relationship between ecological behavior and mechanical features of their incisors and molariforms. In 33 species of nine families of caviomorph rodents, we analyze incisor attributes related to structural stress resistance and molar features related with grinding capacity, for example, second moment of inertia and enamel index (EI) (enamel band length/occlusal surface area), respectively. Most of these variables scaled isometrically to body mass, with a strong phylogenetic effect. A principal component analysis discrimination on the EI clustered the species according to their geographic distribution. We presume that selective pressures in Andean–Patagonian regions, on particular feeding habits and chisel‐tooth digging behaviors, have modeled the morphological characteristics of the teeth. Subterranean/burrower ctenomyids, coruros, and plains viscachas showed the highest bending/torsion strength and anchorage values for incisors; a simplified enamel pattern in molariforms would be associated with a better grinding of the more abrasive vegetation present in more open and drier biomes. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.     

Distinct Modes of Neuritic Growth in Purkinje Neurons at Different Developmental Stages: Axonal Morphogenesis and Cellular Regulatory Mechanisms

Background

During development, neurons modify their axon growth mode switching from an elongating phase, in which the main axon stem reaches the target territory through growth cone-driven extension, to an arborising phase, when the terminal arbour is formed to establish synaptic connections. To investigate the relative contribution of cell-autonomous factors and environmental signals in the control of these distinct axon growth patterns, we examined the neuritogenesis of Purkinje neurons in cerebellar cultures prepared at elongating (embryonic day 17) or arborising (postnatal day zero) stages of Purkinje axon maturation.

Methodology/Principal Findings

When placed in vitro, Purkinje cells of both ages undergo an initial phase of neurite elongation followed by the development of terminal ramifications. Nevertheless, elongation of the main axon stem prevails in embryonic Purkinje axons, and many of these neurons are totally unable to form terminal branches. On the contrary, all postnatal neurites switch to arbour growth within a few days in culture and spread extensive terminal trees. Regardless of their elongating or arborising pattern, defined growth features (e.g. growth rate and tree extension) of embryonic Purkinje axons remain distinct from those of postnatal neurites. Thus, Purkinje neurons of different ages are endowed with intrinsic stage-specific competence for neuritic growth. Such competence, however, can be modified by environmental cues. Indeed, while exposure to the postnatal environment stimulates the growth of embryonic axons without modifying their phenotype, contact-mediated signals derived from granule cells specifically induce arborising growth and modulate the dynamics of neuritic elongation.

Conclusions/Significance

Cultured Purkinje cells recapitulate an intrinsically coded neuritogenic program, involving initial navigation of the axon towards the target field and subsequent expansion of the terminal arborisation. The execution of this program is regulated by environmental signals that modify the growth competence of Purkinje cells, so to adapt their endogenous properties to the different phases of neuritic morphogenesis.     

An asymmetric approach to preserve common intervals while sorting by reversals

Background  

The reversal distance and optimal sequences of reversals to transform a genome into another are useful tools to analyse evolutionary scenarios. However, the number of sequences is huge and some additional criteria should be used to obtain a more accurate analysis. One strategy is searching for sequences that respect constraints, such as the common intervals (clusters of co-localised genes). Another approach is to explore the whole space of sorting sequences, eventually grouping them into classes of equivalence. Recently both strategies started to be put together, to restrain the space to the sequences that respect constraints. In particular an algorithm has been proposed to list classes whose sorting sequences do not break the common intervals detected between the two inital genomes A and B. This approach may reduce the space of sequences and is symmetric (the result of the analysis sorting A into B can be obtained from the analysis sorting B into A).     

Lymphoid organ alterations enhanced by sub-lethal doses of coronaviruses in experimentally induced Trypanosoma cruzi infection in mice

The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimentally infected with a mildly pathogenic strain of Trypanosoma cruzi was investigated. Mice were inoculated with either T. cruzi, 0.1 median lethal dose (LD50) of coronavirus (mouse hepatitis virus [MHV-3] or virus X), or both pathogens. Levels of parasitemia, mortality, and the extent of pathologic alterations in lymphoid organs were determined. Mice inoculated with T. cruzi had mild alterations in their lymphoid organs and survived infection. In contrast, mice inoculated with both pathogens died, and had significantly higher levels of parasitemia and profound alterations in lymphoid organs. These results indicate that the pathologic profile of T. cruzi infection can be profoundly altered by subclinical infection with coronaviruses.     

No evidence of fetal DNA persistence in maternal plasma after pregnancy

Short- and long-term persistence of fetal DNA in maternal plasma has been investigated. Short-term persistence at very low concentration was detected in 47 out of 105 women within two days after delivery. Twelve out of 13 samples re-tested within three days scored negative. No long-term persistence was detected in 172 women who had previous sons or abortions. Molecular microchimerism due to circulating fetal DNA persisting from previous pregnancies should not hamper non-invasive plasma-based prenatal testing.     

Effects of small concentrations of mercury on the contractile activity of the rat ventricular myocardium

Personal exposure to mercury vapor and the release of mercury from or during removal of amalgam dental fillings increases its blood and plasma concentration. However, it is not known if these very small amounts affect cardiac function. The effects of continuous exposure to 5 and 20 nM of HgCl(2) on the cardiac contractility were investigated in isometric and tetanic contractions of right ventricular strips and in Langendorff perfused rat hearts. The continuous exposure for 2 h produced a small but significant reduction of the isometric twitch force and time to peak tension shortened. Relative post-rest potentiation was not affected by this concentration of HgCl(2) suggesting a lack of action of the metal on the sarcoplasmic reticulum activity. Tetanic tension, in contrast to twitch force, was intensively reduced suggesting an important depressant action on the activity of contractile proteins. In perfused hearts beating spontaneously, isovolumic systolic pressure reduced progressively and the diastolic pressure increased. Although occurring heart rate reduction, it was similar for both controls and mercury treated hearts. Also, time dependent changes in coronary perfusion pressure were similar to controls. Results suggested that cardiac effects may be observed after continuous exposure to very small concentrations of mercury, probably as a result of the cell capacity to concentrate mercury. These results also indicate that continuous professional exposure to mercury followed by its absorption might have toxicological consequences affecting cardiac function, and being considered hazardous.     

Mutant presenilin 1 alters synaptic transmission in cultured hippocampal neurons

Mutations in presenilins are the major cause of familial Alzheimer disease, but the precise pathogenic mechanism by which presenilin (PS) mutations cause synaptic dysfunction leading to memory loss and neurodegeneration remains unclear. Using autaptic hippocampal cultures from transgenic mice expressing human PS1 with the A246E mutation, we demonstrate that mutant PS1 significantly depressed the amplitude of evoked alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptor-mediated synaptic currents. Analysis of the spontaneous miniature synaptic activity revealed a lower frequency of miniature currents but normal miniature amplitude. Both alterations could be rescued by the application of a gamma-secretase blocker. On the other hand, the application of synthetic soluble Abeta42 in wild-type neurons induced the PS1 mutant phenotype on synaptic strength. Together, these findings strongly suggest that the expression of mutant PS1 in cultured neurons depresses synaptic transmission by causing a physical reduction in the number of synapses. This hypothesis is consistent with morphometic and semiquantitative immunohistochemical analysis, revealing a decrease in synaptophysin-positive puncta in PS1 mutant hippocampal neurons.     

Multiplex amplification of large sets of human exons

A new generation of technologies is poised to reduce DNA sequencing costs by several orders of magnitude. But our ability to fully leverage the power of these technologies is crippled by the absence of suitable 'front-end' methods for isolating complex subsets of a mammalian genome at a scale that matches the throughput at which these platforms will routinely operate. We show that targeting oligonucleotides released from programmable microarrays can be used to capture and amplify approximately 10,000 human exons in a single multiplex reaction. Additionally, we show integration of this protocol with ultra-high-throughput sequencing for targeted variation discovery. Although the multiplex capture reaction is highly specific, we found that nonuniform capture is a key issue that will need to be resolved by additional optimization. We anticipate that highly multiplexed methods for targeted amplification will enable the comprehensive resequencing of human exons at a fraction of the cost of whole-genome resequencing.