Virological study of a dengue type 1 epidemic at Rio de Janeiro

A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46,8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58,2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized.

Reversal of opinion: the implications of the work of Acemoglu and Robinson for marxist thought

This paper describes the implications for Marxist thought of the work of Daron Acemoglu and James Robinson. In the first two periods of this they explained how the rise of democracy brought prosperity to Europe  and why the same process had not worked in Latin America because of the possibility of coups. The implication is that mass poverty can better be alleviated by safeguarding democracy rather than moving to socialism. In the last period A and R have formalized doubts about the efficacy of democracy in this role. The implication here is that Marxists should work to find a system of government that is immune to elite dominance. Hugo Chávez is taken as an example.

NEUROPATHOPHYSIOLOGICAL MECHANISMS IN GLUTARIC ACIDURIA TYPE I: 3-HYDROXYGLUTARIC ACID LEADS TO AMMONIA INCREASE AND NON-APOPTOTIC CELL DEATH

A 3D in vitro model of rat organotypic brain cell cultures in aggregates was used to investigate neurotoxicity mechanisms in glutaric aciduria type I (GA-I). 1 mM glutarate (GA) or 3-hydroxyglutarate (3OHGA) were repeatedly added to the culture media at two different time points. In cultures treated with 3OHGA, we observed an increase in lactate in the medium, pointing to a possible inhibition of Krebs cycle and respiratory chain. We further observed that 3OHGA and to a lesser extend GA induced an increase in ammonia production with concomitant decrease of glutamine concentrations, which may suggest an inhibition of the astrocytic enzyme glutamine synthetase. These previously unreported findings may uncover a pathogenic mechanism in this disease which has deleterious effects on early stages of brain development. By immunohistochemistry we showed that 3OHGA increased non-apoptotic cell death. On the cellular level, 3OHGA and to a lesser extend GA led to cell swelling and loss of astrocytic fibers whereas a loss of oligodendrocytes was only observed for 3OHGA. We conclude that 3OHGAwas the most toxic metabolite in our model for GA-I. 3OHGA induced deleterious effects on glial cells, an increase of ammonia production, and resulted in accentuated cell death of non-apoptotic origin.

T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response.

Activation of dendritic cells (DC) by microbial products via Toll-like receptors (TLR) is instrumental in the induction of immunity. In particular, TLR signaling plays a major role in the instruction of Th1 responses. The development of Th2 responses has been proposed to be independent of the adapter molecule myeloid differentiation factor 88 (MyD88) involved in signal transduction by TLRs. In this study we show that flagellin, the bacterial stimulus for TLR5, drives MyD88-dependent Th2-type immunity in mice. Flagellin promotes the secretion of IL-4 and IL-13 by Ag-specific CD4(+) T cells as well as IgG1 responses. The Th2-biased responses are associated with the maturation of DCs, which are shown to express TLR5. Flagellin-mediated DC activation requires MyD88 and induces NF-kappaB-dependent transcription and the production of low levels of proinflammatory cytokines. In addition, the flagellin-specific response is characterized by the lack of secretion of the Th1-promoting cytokine IL-12 p70. In conclusion, this study suggests that flagellin and, more generally, TLR ligands can control Th2 responses in a MyD88-dependent manner.

Autofluorescence Findings Of A Novel Maculopathy In Patient With Spinocerebellar Ataxia Type 1 And Of A Cone - Rod Type Retinal Dysfunction In Three Generation Family With Spinocerebellar Ataxia Type 7

Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.

Patterns of serologic response to human immunodeficiency virus type 1 (HIV-1) in brazilians with different clinical forms of HIV infection

In order to investigate the IgG HIV-1 antibodies rectivity to structural components of the virus, 85 sera from infected Brazilians, comprising the total spectrum of HIV infection, were analysed by Western blot assay. The sera were confirmed as being positive to HIV with enzyme linked immuno assay (ELISA) and indirect immunofluorescence (IIF). Although the sera from patients reacted less intensively to the gag polypeptide of 55KDa, no distinctive antigen reaction patterns were observed between sera patients with different clinical forms. Because of the higher frequency of reactivity to the gag p24 in AIDS patients, the patterns of anti-HIV IgG responses are similar to those observed in their African counterparts.

Tightening of DNA knots by supercoiling facilitates their unknotting by type II DNA topoisomerases.

Using numerical simulations, we compare properties of knotted DNA molecules that are either torsionally relaxed or supercoiled. We observe that DNA supercoiling tightens knotted portions of DNA molecules and accentuates the difference in curvature between knotted and unknotted regions. The increased curvature of knotted regions is expected to make them preferential substrates of type IIA topoisomerases because various earlier experiments have concluded that type IIA DNA topoisomerases preferentially interact with highly curved DNA regions. The supercoiling-induced tightening of DNA knots observed here shows that torsional tension in DNA may serve to expose DNA knots to the unknotting action of type IIA topoisomerases, and thus explains how these topoisomerases could maintain a low knotting equilibrium in vivo, even for long DNA molecules.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Creation of a carrier-grade telco based on a voice over IP backbone

En aquesta memòria l'autor, fent servir un enfoc modern, redissenya i implementa la plataforma que una empresa de telecomunicacions del segle 21 necessita per poder donar serveis de telefonia i comunicacions als seus usuaris i clients. Al llarg d'aquesta exposició es condueix al lector des d'una fase inicial de disseny fins a la implementació i posada en producció del sistema final desenvolupat, centrant-nos en solucionar les necessitats actuals que això implica. Aquesta memòria cubreix el software, hardware i els processos de negoci associats al repte de fer realitat aquest objectiu, i presenta al lector les múltiples tecnologies emprades per aconseguir-ho, fent emfàsi en la convergència actual de xarxes cap al concepte de xarxes IP i basant-se en aquesta tendència i utilitzant aquesta tecnologia de veu sobre IP per donar forma a la plataforma que finalment, de forma pràctica, es posa en producció.

Metabolic origin of insulin resistance in obesity with and without type 2 (non-insulin-dependent) diabetes mellitus.

A metabolic hypothesis is presented for insulin resistance in obesity, in the presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is based on physiological mechanisms including a series of negative feed-back mechanisms, with the inhibition of the function of the glycogen cycle in skeletal muscle as a consequence of decreased glucose utilization resulting from increased lipid oxidation in the obese. It considers the inhibition of glycogen synthase activity together with inhibition of glucose storage and impaired glucose tolerance. The prolonged duration of increased lipid oxidation, considered as the initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with others based on the inhibition of insulin receptor kinase and of glucose transporter activities.

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.

AIMS/HYPOTHESIS: MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease. METHODS: MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat diet was performed by microarray. The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cells. RESULTS: MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. Functional studies indicate that these expression changes have positive effects on beta cell activities and mass. In contrast, modifications in the levels of miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 primarily occur in diabetic mice and result in increased beta cell apoptosis. These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function, and that additional microRNA deregulation negatively impacting on insulin-secreting cells may cause beta cell demise and diabetes manifestation. CONCLUSIONS/INTERPRETATION: We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs.

A morphological, isoenzymatic and behavioural study of ten populations of Anopheles(Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 (Diptera: culicidae) including from the type-locality - Baradero, Argentina

Anopheles (Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 shows morphological and behavioural variations which results in it being sometimes considered as a major malaria vector and at other times as playing no important role in epidemiology. With the aim of clarifying the taxonomy of the species, comparative morphological and isoenzymatic studies were made in populations from the type-locality, Baradero, Argentina and from 9 different localities inBrazil. Morphological studies consisted of the observation of eggs in scanning electron microscopy, of complete chaetotaxy of larvae and pupae and of the detailed drawing of male and female adults. Only Guajara-Mirim and Rio Branco populations, described previously as Anopheles deaneorum sp.n., showed morphological differences. Isoenzymes were studied using 4th instar larvae homogenate and agarosegel electrophoresis. Eleven enzymatic loci were analyzed. By calculation of Nei's Genetic Distance (D), the populations could be separated into 5 groups: i)Baradero, ii)Marajo, iii)Boa Vista, iv)Angra, Itaguai and Paraipaba and v)Guajara-Mirim and Rio Branco. These groups belong to 2 major clusters called I and II, separated by D = 0.345. In the I cluster are groups i, ii and iii and in II clusteriv and v. In I, D=0.246 separates i and ii from iii, while i is separated by D =0.181 from ii. In II, D = 0.223 between iv and v. Only the population of group vcould be distinguished morphologically from the others, leading to the description of an independent species An. deaneorum.