The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Rest and Dobutamine stress echocardiography in the evaluation of mid-term results of mitral valve repair in Barlow's disease

BACKGROUND: Surgical "anatomical" repair is the most frequent technique used to correct mitral regurgitation due to severe myxomatous valve disease. Debate, however, persists on the efficacy of this technique, as well as on the durability of the repaired valve, and on its functioning and hemodynamics under stress conditions. Thus, a basal and Dobutamine echocardiographic (DSE) study was carried out to evaluate these parameters at mid-term follow-up. METHODS AND RESULTS: Twenty patients selected for the study (12 men and 8 women, mean age 60 ± 9 years) underwent pre- and post-operative transthoracic echocardiography (TTE) and intra-operative transesophageal echocardiography (TEE). At mid-term follow-up (20 ± 5 months) all patients underwent rest TTE and DSE (3 min. dose increments up to 40 microg/Kg/min protocol). Pre-discharge and one-month TTE showed absence of MR in 11 pts., trivial or mild MR in 9 pts. and normal mitral valve area and gradients. Mid-term TTE showed decrease in left atrial and ventricular dimension, in pulmonary artery pressure (sPAP) and grade of MR. During DSE a significant increase in mitral valve area, maximum and mean gradients, sPAP, heart rate and cardiac output and a decrease in systolic annular diameter and left ventricular volume were found; in 6 pts. a transient left ventricular outflow tract obstruction was observed. CONCLUSION: Basal and Dobutamine stress echocardiography proved to be valuable tools for evaluation of mid-term results of mitral valve repair. In our study population, the surgical technique employed had a favourable impact on several cardiac parameters, evaluated by these methods

Associative Vocabulary Learning: Development and Testing of Two Paradigms for the (Re-) Acquisition of Action- and Object-Related Words

Despite a growing number of studies, the neurophysiology of adult vocabulary acquisition is still poorly understood. One reason is that paradigms that can easily be combined with neuroscientfic methods are rare. Here, we tested the efficiency of two paradigms for vocabulary (re-) acquisition, and compared the learning of novel words for actions and objects. Cortical networks involved in adult native-language word processing are widespread, with differences postulated between words for objects and actions. Words and what they stand for are supposed to be grounded in perceptual and sensorimotor brain circuits depending on their meaning. If there are specific brain representations for different word categories, we hypothesized behavioural differences in the learning of action-related and object-related words. Paradigm A, with the learning of novel words for body-related actions spread out over a number of days, revealed fast learning of these new action words, and stable retention up to 4 weeks after training. The single-session Paradigm B employed objects and actions. Performance during acquisition did not differ between action-related and object-related words (time*word category: p = 0.01), but the translation rate was clearly better for object-related (79%) than for action-related words (53%, p = 0.002). Both paradigms yielded robust associative learning of novel action-related words, as previously demonstrated for object-related words. Translation success differed for action- and object-related words, which may indicate different neural mechanisms. The paradigms tested here are well suited to investigate such differences with neuroscientific means. Given the stable retention and minimal requirements for conscious effort, these learning paradigms are promising for vocabulary re-learning in brain-lesioned people. In combination with neuroimaging, neuro-stimulation or pharmacological intervention, they may well advance the understanding of language learning to optimize therapeutic strategies

Analysis of Dehydration and Strength in Elite Badminton Players

Background: The negative effects of dehydration on aerobic activities are well established. However, it is unknown how dehydration affects intermittent sports performance. The purpose of this study was to identify the level of dehydration in elite badminton players and its relation to muscle strength and power production. Methodology: Seventy matches from the National Spanish badminton championship were analyzed (46 men?s singles and 24 women?s singles). Before and after each match, jump height and power production were determined during a countermovement jump on a force platform. Participants? body weight and a urine sample were also obtained before and after each match. The amount of liquid that the players drank during the match was also calculated by weighing their individual drinking bottles. Results and Discussion: Sweat rate during the game was 1.1460.46 l/h in men and 1.0260.64 l/h in women. The players rehydrated at a rate of 1.1060.55 l/h and 1.0160.44 l/h in the male and female groups respectively. Thus, the dehydration attained during the game was only 0.3760.50% in men and 0.3260.83% in women. No differences were found in any of the parameters analyzed during the vertical jump (men: from 31.8265.29 to 32.9064.49 W/kg; p.0.05, women: from 26.3664.73 to 27.2564.44 W/kg; p.0.05). Post-exercise urine samples revealed proteinuria (60.9% of cases in men and 66.7% in women), leukocyturia (men = 43.5% and women = 50.0%) and erythrocyturia (men = 50.0% and women = 21.7%). Conclusions: Despite a moderate sweat rate, badminton players adequately hydrated during a game and thus the dehydration attained was low. The badminton match did not cause muscle fatigue but it significantly increased the prevalence of proteinuria, leukocyturia and erythrocyturia

Genomic rearrangements in BRCA1 and BRCA2: A literature review

Women with mutations in the breast cancer genes BRCA1 or BRCA2 have an increased lifetime risk of developing breast, ovarian and other BRCA-associated cancers. However, the number of detected germline mutations in families with hereditary breast and ovarian cancer (HBOC) syndrome is lower than expected based upon genetic linkage data. Undetected deleterious mutations in the BRCA genes in some high-risk families are due to the presence of intragenic rearrangements such as deletions, duplications or insertions that span whole exons. This article reviews the molecular aspects of BRCA1 and BRCA2 rearrangements and their frequency among different populations. An overview of the techniques used to screen for large rearrangements in BRCA1 and BRCA2 is also presented. The detection of rearrangements in BRCA genes, especially BRCA1, offers a promising outlook for mutation screening in clinical practice, particularly in HBOC families that test negative for a germline mutation assessed by traditional methods

NPY Neuron-Specific Y2 Receptors Regulate Adipose Tissue and Trabecular Bone but Not Cortical Bone Homeostasis in Mice

BACKGROUND: Y2 receptor signalling is known to be important in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone physiology. Y2 receptors are located post-synaptically as well as acting as auto receptors on NPY-expressing neurons, and the different roles of these two populations of Y2 receptors in the regulation of energy homeostasis and body composition are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We thus generated two conditional knockout mouse models, Y2(lox/lox) and NPYCre/+;Y2(lox/lox), in which Y2 receptors can be selectively ablated either in the hypothalamus or specifically in hypothalamic NPY-producing neurons of adult mice. Specific deletion of hypothalamic Y2 receptors increases food intake and body weight compared to controls. Importantly, specific ablation of hypothalamic Y2 receptors on NPY-containing neurons results in a significantly greater adiposity in female but not male mice, accompanied by increased hepatic triglyceride levels, decreased expression of liver carnitine palmitoyltransferase (CPT1) and increased expression of muscle phosphorylated acetyl-CoA carboxylase (ACC). While food intake, body weight, femur length, bone mineral content, density and cortical bone volume and thickness are not significantly altered, trabecular bone volume and number were significantly increased by hypothalamic Y2 deletion on NPY-expressing neurons. Interestingly, in situ hybridisation reveals increased NPY and decreased proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of mice with hypothalamus-specific deletion of Y2 receptors in NPY neurons, consistent with a negative feedback mechanism between NPY expression and Y2 receptors on NPY-ergic neurons. CONCLUSIONS/SIGNIFICANCE: Taken together these data demonstrate the anti-obesogenic role of Y2 receptors in the brain, notably on NPY-ergic neurons, possibly via inhibition of NPY neurons and concomitant stimulation of POMC-expressing neurons in the arcuate nucleus of the hypothalamus, reducing lipogenic pathways in liver and/or skeletal muscle in females. These data also reveal as an anti-osteogenic effect of Y2 receptors on hypothalamic NPY-expressing neurons on trabecular but not on cortical bone

The Biology and Economics of Coral Growth

To protect natural coral reefs, it is of utmost importance to understand how the growth of the main reef-building organisms—the zooxanthellate scleractinian corals—is controlled. Understanding coral growth is also relevant for coral aquaculture, which is a rapidly developing business. This review paper provides a comprehensive overview of factors that can influence the growth of zooxanthellate scleractinian corals, with particular emphasis on interactions between these factors. Furthermore, the kinetic principles underlying coral growth are discussed. The reviewed information is put into an economic perspective by making an estimation of the costs of coral aquaculture

Sugarcane (Saccharum X officinarum): A Reference Study for the Regulation of Genetically Modified Cultivars in Brazil

Global interest in sugarcane has increased significantly in recent years due to its economic impact on sustainable energy production. Sugarcane breeding and better agronomic practices have contributed to a huge increase in sugarcane yield in the last 30 years. Additional increases in sugarcane yield are expected to result from the use of biotechnology tools in the near future. Genetically modified (GM) sugarcane that incorporates genes to increase resistance to biotic and abiotic stresses could play a major role in achieving this goal. However, to bring GM sugarcane to the market, it is necessary to follow a regulatory process that will evaluate the environmental and health impacts of this crop. The regulatory review process is usually accomplished through a comparison of the biology and composition of the GM cultivar and a non-GM counterpart. This review intends to provide information on non-GM sugarcane biology, genetics, breeding, agronomic management, processing, products and byproducts, as well as the current technologies used to develop GM sugarcane, with the aim of assisting regulators in the decision-making process regarding the commercial release of GM sugarcane cultivars