Season of birth as a risk factor for multiple sclerosis in Brazil

Risk factors for development of multiple sclerosis (MS) are still a matter of debate. Latitude gradient, vitamin D deficiency and season of birth are among the most investigated environmental factors associated with the disease. Several international studies suggest that birth in spring is a substantial risk factor for MS. We investigated the season of birth as a potential risk for MS in different geographical regions of Brazil. We conducted a cross-sectional retrospective study with 2257 clinically definite MS patients enrolled in 13 Brazilian MS clinics in the south, southeast, and northeast regions of Brazil. Demographic and clinical data relating to date of birth and clinical features of the disease were collected and analysed, and subsequently compared with birth date among the general Brazilian population. The distribution of date of birth of MS patients showed an increase in spring and a decrease in autumn, with no difference being observed in the other seasons. In conclusion, season of birth is a probable risk factor for MS in most parts of Brazil. These findings may be related to the role that vitamin D plays in MS pathogenesis. © 2013 Elsevier B.V. All rights reserved.

The role of obesity as a modifying factor in patients undergoing non-surgical periodontal therapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein

The human ZC3H14 gene encodes an evolutionarily conserved Cys(3)His zinc finger protein that binds specifically to polyadenosine RNA and is thus postulated to modulate post-transcriptional gene expression. Expressed sequence tag (EST) data predicts multiple splice variants of both human and mouse ZC3H14. Analysis of ZC3H14 expression in both human cell lines and mouse tissues confirms the presence of multiple alternatively spliced transcripts. Although all of these transcripts encode protein isoforms that contain the conserved C-terminal zinc finger domain, suggesting that they could all bind to polyadenosine RNA, they differ in other functionally important domains. Most of the alternative transcripts encode closely related proteins (termed isoforms 1, 2. 3, and 3short) that differ primarily in the inclusion of three small exons, 9, 10, and 11, resulting in predicted protein isoforms ranging from 82 to 64 kDa. Each of these closely related isoforms contains predicted classical nuclear localization signals (cNLS) within exons 7 and 11. Consistent with the presence of these putative nuclear targeting signals, these ZC3H14 isoforms are all localized to the nucleus. In contrast, an additional transcript encodes a smaller protein (34 kDa) with an alternative first exon (isoform, 4). Consistent with the absence of the predicted cNLS motifs located in exons 7 and 11, ZC3H14 isoform 4 is localized to the cytoplasm. Both EST data and experimental data suggest that this variant is enriched in testes and brain. Using an antibody that detects endogenous ZC3H14 isoforms 1-3 reveals localization of these isoforms to nuclear speckles. These speckles co-localize with the splicing factor, SC35, suggesting a role for nuclear ZC3H14 in mRNA processing. Taken together, these results demonstrate that multiple transcripts encoding several ZC3H14 isoforms exist in vivo. Both nuclear and cytoplasmic ZC3H14 isoforms could have distinct effects on gene expression mediated by the common Cys(3)His zinc finger polyadenosine RNA binding domain. (C) 2009 Elsevier B.V. All rights reserved.

High power factor dimmable electronic ballast for multiple tubular fluorescent lamps

This paper presents a dimmable electronic ballast designed for multiple fluorescent lamps applications. A ZCS-PWM Boost rectifier and a classical resonant Full-Bridge inverter compose this new electronic ballast, providing conditions for the obtaining of high input power-factor, and soft-switching processes for all semiconductor devices employed in the structure. The instantaneous average input current control technique is employed in the Boost rectifier. Concerning the Full-Bridge inverter, it is controlled by the imposition of phase-shift in the current processed through the sets of resonant filters + lamps, according to an adaptation in a specially designed control IC, called IR2159. Experimental results are presented in order to validate the analyses developed in this paper.

Role of Peritubular Capillaries and Vascular Endothelial Growth Factor in Chronic Allograft Nephropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin-6 expression through multiple mitogen-activated protein kinase pathways in periodontal ligament fibroblasts

Actinobacillus actinomycetemcomitans plays a major role in the pathogenesis of aggressive periodontitis. Lipopolysaccharide (LPS) derived from A. actinomycetemcomitans is a key factor in inflammatory cytokine generation within periodontal tissues. In this study, we identify major mitogen-activated protein kinase (MAPK) signaling pathways induced by A. actinomycetemcomitans LPS, Escherichia coli LPS and interleukin-1 beta (IL-1 beta) in a murine periodontal ligament (mPDL) fibroblast cell line. Immunoblot analysis was used to assess the phosphorylated forms of p38, extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) MAPK following stimulation with A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta. IL-6 mRNA induction was detected via reverse transcription-polymerase chain reaction, while protein levels were quantified via enzyme-linked immunosorbent assays (ELISA). We utilized biochemical inhibitors of p38, ERK and JNK MAPK to identify the MAPK signaling pathways needed for IL-6 expression. Additional use of stable mPDL cell lines containing dominant negative mutant constructs of MAPK kinase-3 and -6 (MKK-3/6) and p38 null mutant mouse embryonic fibroblast (MEF) cells were used to substantiate the biochemical inhibitor data. Blocking p38 MAPK with SB203580 reduced the induction of IL-6 mRNA by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by > 70%, > 95% and similar to 60%, respectively. IL-6 ELISA indicated that blocking p38 MAPK reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by similar to 60%, similar to 50% and similar to 70%, respectively. All MAPK inhibitors significantly reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta whereas only p38 inhibitors consistently reduced the A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta induction of IL-6 mRNA steady-state levels. The contribution of p38 MAPK LPS-induced IL-6 expression was confirmed using MKK-3/6 dominant negative stable mPDL cell lines. Wild-type and p38 alpha(-/-) MEF cells provided additional evidence to support the role of p38 alpha MAPK in A. actinomycetemcomitans LPS-stimulated IL-6. Our results indicate that induction of IL-6 by E. coli LPS, IL-1 beta and A. actinomycetemcomitans LPS requires signaling through MKK-3-p38 alpha ERK, JNK and p38 MAPK in mPDL cells.

Macrophage Migration Inhibitory Factor in the Paraventricular Nucleus Plays a Major Role in the Sympathoexcitatory Response to Salt

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 mug ml(-1)) or F1 (100 and 200 mug ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. on the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.

Thermistor behaviour and electric conduction analysis of Ni-doped niobate ferroelectric: the role of multiple beta parameters

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

ADJUSTED F FACTOR FOR MULTIPLE-OUTLET PIPES.

An adjusted F factor to compute pressure head loss in pipes having multiple, equally spaced outlets is derived for any given distance from the first outlet to the beginning of the pipe. The proposed factor is dependent on the number of outlets and is expressed as a function of the J. E. Christiansen's F factor. It may be useful to irrigation engineers to estimate friction in sprinkle and trickle irrigation laterals and manifolds, as well as gated pipes.

A unity power factor multiple isolated outputs switching mode power supply using a single switch

The authors present an offline switching power supply with multiple isolated outputs and unity power factor with the use of only one power processing stage, based on the DC-DC SEPIC (single ended primary inductance converter) modulated by variable hysteresis current control. The principle of operation, the theoretical analysis, the design procedure, an example, and simulation results are presented. A laboratory prototype, rated at 160 W, operating at a maximum switching frequency of 100 kHz, with isolated outputs rated at +5 V/15 A -5 V/1 A, +12 V/6 A and -12 V/1 A, has been built given an input power factor near unity.