Structural and functional papez circuit integrity in amyotrophic lateral sclerosis

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit—a circuit known to participate in memory processes—is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established

Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice

Differential Patterns of Synaptotagmin7 mRNA Expression in Rats with Kainate- and Pilocarpine-Induced Seizures

Previous studies in rat models of neurodegenerative disorders have shown disregulation of striatal synaptotagmin7 mRNA. Here we explored the expression of synaptotagmin7 mRNA in the brains of rats with seizures triggered by the glutamatergic agonist kainate (10 mg/kg) or by the muscarinic agonist pilocarpine (30 mg/kg) in LiCl (3 mEq/kg) pre-treated (24 h) rats, in a time-course experiment (30 min - 1 day). After kainate-induced seizures, synaptotagmin7 mRNA levels were transiently and uniformly increased throughout the dorsal and ventral striatum (accumbens) at 8 and 12 h, but not at 24 h, followed at 24 h by somewhat variable upregulation within different parts of the cerebral cortex, amigdala and thalamic nuclei, the hippocampus and the lateral septum. By contrast, after LiCl/pilocarpine-induced seizures, there was a more prolonged increase of striatal Synaptotagmin7 mRNA levels (at 8, 12 and 24 h), but only in the ventromedial striatum, while in some other of the aforementioned brain regions there was a decline to below the basal levels. After systemic post-treatment with muscarinic antagonist scopolamine in a dose of 2 mg/kg the seizures were either extinguished or attenuated. In scopolamine post-treated animals with extinguished seizures the striatal synaptotagmin7 mRNA levels (at 12 h after the onset of seizures) were not different from the levels in control animals without seizures, while in rats with attenuated seizures, the upregulation closely resembled kainate seizures-like pattern of striatal upregulation. In the dose of 1 mg/kg, scopolamine did not significantly affect the progression of pilocarpine-induced seizures or pilocarpine seizures-like pattern of striatal upregulation of synaptotagmin7 mRNA. In control experiments, equivalent doses of scopolamine per se did not affect the expression of synaptotagmin7 mRNA. We conclude that here described differential time course and pattern of synaptotagmin7 mRNA expression imply regional differences of pathophysiological brain activation and plasticity in these two models of seizures

Genetic variability in five populations of Partamona helleri (Hymenoptera, Apidae) from Minas Gerais State, Brazil

Partamona is a Neotropical genus of stingless bees that comprises 33 species distributed from Mexico to southern Brazil. These bees are well-adapted to anthropic environments and build their nests in several substrates. In this study, 66 colonies of Partamona helleri from five localities in the Brazilian state of Minas Gerais (São Miguel do Anta, Teixeiras, Porto Firme, Viçosa and Rio Vermelho) were analyzed using nine microsatellite loci in order to assess their genetic variability. Low levels of observed (Ho = 0.099-0.137) and expected (H e = 0.128-0.145) heterozygosity were encountered and revealed discrete genetic differentiation among the populations (F ST = 0.025). AMOVA further showed that most of the total genetic variation (94.24%) in P. helleri was explained by the variability within local populations

Association between physical activity in daily life and pulmonary function in adult smokers

Objective: To determine whether the level of physical activity in daily life (PADL) is associated with pulmonary function in adult smokers. Methods: We selected 62 adult smokers from among the participants of an epidemiological study conducted in the city of Santos, Brazil. The subjects underwent forced spirometry for pulmonary function assessment. The level of PADL was assessed by the International Physical Activity Questionnaire and triaxial accelerometry, the device being used for seven days. The minimum level of PADL, in terms of quantity and intensity, was defined as 150 min/week of moderate to vigorous physical activity. Correlations between the studied variables were tested with Pearson's or Spearman's correlation coefficient, depending on the distribution of the variables. We used linear multiple regression in order to analyze the influence of PADL on the spirometric variables. The level of significance was set at 5%. Results: Evaluating all predictors, corrected for confounding factors, and using pulmonary function data as outcome variables, we found no significant associations between physical inactivity, as determined by accelerometry, and spirometric indices. The values for FVC were lower among the participants with arterial hypertension, and FEV1/FVC ratios were lower among those with diabetes mellitus. Obese participants and those with dyslipidemia presented with lower values for FVC and FEV1. Conclusions: Our results suggest that there is no consistent association between physical inactivity and pulmonary function in adult smokers. Smoking history should be given special attention in COPD prevention strategies, as should cardiovascular and metabolic comorbidities

Alcohol consumption and risky sexual practices: the pattern of nursing students from the Spanish University

OBJECTIVE: to determine the prevalence of substance abuse and unsafe sexual practices and to analyze the relationship between them, in nursing students at the University of Seville. METHOD: quantitative methodological approach with a descriptive cross-sectional design. The population was composed of first year nursing students in the University of Seville, during the academic year 2010-2011 (N=510), with consecutive opportunistic sampling composed of students who attended class on the scheduled day (n=291). RESULTS: a high prevalence of alcohol consumption, and increased likelihood of not using protective measures during sexual practices when alcohol had been consumed, was present. CONCLUSION: these findings are consistent with those obtained in the same population in Brazil, and highlight the need to strengthen in the nursing curriculum, the transverse axis related to the prevention of substance abuse, especially alcohol

An Engineering Approach to Extending Lifespan in C. elegans

We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome

IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts