Studies on male genitalia of sarcophagidae (Diptera) based on scanning electron microscope observations

Male genitalia of Oxyvinia exicisa (Lopes), Oxysarcodexia thomax (Walker), O. fluminensis Lopes, Sarcodexia lambens (Wiedemann), Peckia chrysostoma (Wiedemann) and Liopygia ruficornis (Fabricius) were studied based on scanning electron microscope photography. Some important details were evidentiated with this method.

Kangaroo mother care diminishes pain from heel lance in very preterm neonates: a crossover trial.

BACKGROUND: Skin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates. METHODS: Preterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU's in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results. RESULTS: PIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852-9.889) versus 10.677 (95%CI 9.563-11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103-142) versus 193 seconds (95%CI 158-227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition. CONCLUSION: Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis. TRIAL REGISTRATION: (Current Controlled Trials) ISRCTN63551708.

Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

On the morphology of Laevapex vazi n. sp. from Brazil (Mollusca: Pulmonata: Basommatophora: Ancylidae)

A description of Laevapex vazi n. sp. based on 8 specimens collectec in Ourinhos, state of São Paulo, is presented. Shell thin, diaphanous, with a light brown periostracum and moderately elliptical opening. Apex not pointed, smooth, situated on the right posterior region of the shell, inclined to the right often reaching the edge of the shell or extending beyond it. Concentric lines clearly visible; radial striation not visible or when perceptible very thin, here and there. Ratios: shell width/shell lenght = 0,60 - 0,67 (mean = 0,63); shell height/shell length = 0,50 - 0,61 (mean = 0,55); shell height/shell width = 0,33 - 0,40 (mean = 0,35). Body of normal ancylid type; mantle pigmentation concentrated on the left side; three muscles are seen: a round posterior one on the left side, an elliptical muscle on the right anterior side and an almost almond-shaped one on the left anterior side. Tentacles with a medium core of black pigment. Pseudobranch two-lobed and folded, the dorsal lobe smaller than the vetral one. Ovotestis with 20 unbranched diverticula, around a short collecting canal. Ovispermiduct with an enlargement with several round outpocketings constituting the seminal vesicle. Carrefour as a round sac. Albumen gland almost cylindrical with several acinous diverticula. Elongated nidamental gland continous with the galndular wall of the uterus; uterus flattened and thin-walled. Spermathecal body almost rounded. Pear-shaped prostate without diverticula. Penial complex without flagellum but with well-developed ultra-penis and penis. Jaw horseshoe shaped. Radular forma 20.1.20; raquidian tooth quadricuspid, asymmetrical. The genus Laevapex Walker, 1903 is recorded for the first time in Brazil. It is easily distinguished from South American Gundlachia Pfeiffer, 1849 by its penial complex. Laevapex vazi is dedicated to Dr. Jorge Faria Vaz, from SUCEN-SP, who have been sent to me the specimens.

Scanning electron microscopy of the male genitalia of Sarcophagidae (Diptera)

The male genitalia of nine species of Sarcophagidae (Diptera) - Goniophyto honsuensis Rohdendorf, 1962, Tricharaea brevicornis (Wiedemann, 1830), Chaetoravinia derelicta (Walker, 1852), Austrohartigia spinigena (Rondani, 1864), Chrysagria duodecimpunctata Townsend, 1935, Boettcheria bisetosa Parker, 1914, Lipoptilocnema lanei Townsend, 1934, L. crispina (Lopes, 1938) and Euboettcheria alvarengai Lopes & Tibana, 1982 - were examined by scanning electron microscope (SEM) and the main morphological features are descirbed.

HCF-1 is cleaved in the active site of O-GlcNAc transferase.

Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.

Evaluation of the purified fraction of Wilbrandia (c. f. ) verticillata for antitumour activity

Cucurbatacins are known to produce cytotoxic and anticancer activities. Two novel norcucurbitacin glucosides (Wvl and Wv2) have recently been isolated from a purified fraction obtained from the rhizome of Wilbrandia verticillata. The present study evaluates the cytotoxic and anti-tumour activities of the norcucurbitacins. We have found a regular cytotoxicity in KB cells (Cy50 = 12µg/ml) as well as a significant inhibition in the Walker 256 carcinosarcoma growth (approximately 75%).

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Interespecific competition between Peckia chrysostoma and Adiscochaeta ingens (Diptera: Sarcophagidae) larvae reared in laboratory

Groups of 10 and 20 first instar larvae of Peckia chrysostoma (Wiedemann, 1830) were combined in a proteic source media with groups of the same number of first instar larvae of Adiscochaeta ingens (Walker, 1849) under the environmental conditions of Rio de Janeiro, RJ, Brasil. P. chrysostoma and A. ingens obtained average competitive potentials of 94.0 ± 2.0% and 31.0 ± 5.0% respectively. In the second experiment, larvae of P. chrysostoma were introduced approximately 15 hr after the introduction of A. ingens larvae (whose majority had already passed to the second instar) in the media. The corresponding average competitive potential of P. chrysostoma (82.0 ± 2.0%) was decreased when compared to the first experiment, but still greater than that of A. ingens (64.5 ± 9.5%). The competitive potential of A. ingens, however, increased significatively, demonstrating the influence of its previous colonization in the media for achieving a higher viability. In both experiments the competitive potential of P. chrysostoma was greater and similar to observations cited in the literature. Control-groups of each species were observed, individually, for the comparison. The mean value obtained for P. chrysostoma was 94.0 ± 3.7% (0.0% [experiment 1] and only 12.8% [experiment 2] greater than the average competitive factor). For A. ingens the average was 86.0 ± 7.3% (64.0% [experiment 1] and 25.0% [experiment 2] greater than average competitive factor).

Resistance to oxidative stress is associated with metastasis in mucocutaneous leishmaniasis.

Mucocutaneous leishmaniasis (MCL) in South and Central America is characterized by the dissemination (metastasis) of Leishmania Viannia subgenus parasites from a cutaneous lesion to nasopharyngeal tissues. Little is known about the pathogenesis of MCL, especially with regard to the virulence of the parasites and the process of metastatic dissemination. We previously examined the functional relationship between cytoplasmic peroxiredoxin and metastatic phenotype using highly, infrequently, and nonmetastatic clones isolated from an L. (V.) guyanensis strain previously shown to be highly metastatic in golden hamsters. Distinct forms of cytoplasmic peroxiredoxin were identified and found to be associated with the metastatic phenotype. We report here that peroxidase activity in the presence of hydrogen peroxide and infectivity differs between metastatic and nonmetastatic L. (V.) guyanensis clones. After hydrogen peroxide treatment or heat shock, peroxiredoxin was detected preferentially as dimers in metastatic L. (V.) guyanensis clones and in L. (V.) panamensis strains from patients with MCL, compared with nonmetastatic parasites. These data provide evidence that resistance to the first microbicidal response of the host cell by Leishmania promastigotes is linked to peroxiredoxin conformation and may be relevant to intracellular survival and persistence, which are prerequisites for the development of metastatic disease.

Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide.

Patients with stage I-III melanoma were vaccinated with the modified HLA-A2-binding gp100(209-2M)-peptide after complete surgical resection of their primary lesion and sentinel node biopsy. Cytoplasmic interferon-gamma production by freshly thawed peripheral blood mononuclear cells (direct ex vivo analysis) or by peripheral blood mononuclear cells subjected to 1 cycle of in vitro sensitization with peptide, interleukin-2, and interleukin-15 was measured following restimulation with the modified and native gp100 peptides, and also A2gp100 melanoma cell lines. Peptide-reactive and tumor-reactive T cells were detected in 79% and 66% of selected patients, respectively. Patients could be classified into 3 groups according to their vaccine-elicited T-cell responses. One group of patients responded only to the modified peptide used for immunization, whereas another group of patients reacted to both the modified and native gp100 peptides, but not to naturally processed gp100 antigen on melanoma cells. In the third group of patients, circulating CD8 T cells recognized A2gp100 melanoma cell lines and also both the modified and native peptides. T cells with a low functional avidity, which were capable of lysing tumor cells only if tumor cells were first pulsed by the exogenous administration of native gp100(209-217) peptide were identified in most patients. These results indicate that vaccination with a modified gp100 peptide induced a heterogeneous group of gp100-specific T cells with a spectrum of functional avidities; however, high avidity, tumor-reactive T cells were detected in the majority of patients.

Cooperative expression of junctional adhesion molecule-C and -B supports growth and invasion of glioma.

Brain invasion is a biological hallmark of glioma that contributes to its aggressiveness and limits the potential of surgery and irradiation. Deregulated expression of adhesion molecules on glioma cells is thought to contribute to this process. Junctional adhesion molecules (JAMs) include several IgSF members involved in leukocyte trafficking, angiogenesis, and cell polarity. They are expressed mainly by endothelial cells, white blood cells, and platelets. Here, we report JAM-C expression by human gliomas, but not by their normal cellular counterpart. This expression correlates with the expression of genes involved in cytoskeleton remodeling and cell migration. These genes, identified by a transcriptomic approach, include poliovirus receptor and cystein-rich 61, both known to promote glioma invasion, as well as actin filament associated protein, a c-Src binding partner. Gliomas also aberrantly express JAM-B, a high affinity JAM-C ligand. Their interaction activates the c-Src proto-oncogene, a central upstream molecule in the pathways regulating cell migration and invasion. In the tumor microenvironment, this co-expression may thus promote glioma invasion through paracrine stimuli from both tumor cells and endothelial cells. Accordingly, JAM-C/B blocking antibodies impair in vivo glioma growth and invasion, highlighting the potential of JAM-C and JAM-B as new targets for the treatment of human gliomas.

The separate and combined effects of MHC genotype, parasite clone, and host gender on the course of malaria in mice.

BACKGROUND: The link between host MHC (major histocompatibility complex) genotype and malaria is largely based on correlative data with little or no experimental control of potential confounding factors. We used an experimental mouse model to test for main effects of MHC-haplotypes, MHC heterozygosity, and MHC x parasite clone interactions. We experimentally infected MHC-congenic mice (F2 segregants, homo- and heterozygotes, males and females) with one of two clones of Plasmodium chabaudi and recorded disease progression. RESULTS: We found that MHC haplotype and parasite clone each have a significant influence on the course of the disease, but there was no significant host genotype by parasite genotype interaction. We found no evidence for overdominance nor any other sort of heterozygote advantage or disadvantage. CONCLUSION: When tested under experimental conditions, variation in the MHC can significantly influence the course of malaria. However, MHC heterozygote advantage through overdominance or dominance of resistance cannot be assumed in the case of single-strain infections. Future studies might focus on the interaction between MHC heterozygosity and multiple-clone infections.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Rates and determinants of virologic and immunological response to HAART resumption after treatment interruption in HIV-1 clinical practice.

OBJECTIVE: To describe CD4 and HIV RNA changes during treatment resumption (TR) after treatment interruption (TI) compared with response to first highly active antiretroviral therapy (HAART) and to investigate predictors. METHODS: Using Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) data, we identified subjects who interrupted first HAART, not initiated during primary infection. We estimated rate of CD4 change during TR and time from TR to HIV RNA<500 copies per milliliter and subsequent rebound and factors associated with these outcomes. RESULTS: Of 281 persons treated for median 18.4 months before interrupting, 259 resumed HAART. CD4 increases in the first 3 months on HAART were similar pre-TI and post-TI but after 3 months were significantly higher during pre-TI HAART, with median +106 and +172 cells per microliter at 3 and 18 months, respectively, during initial HAART compared with +99 and +142 cells per microliter during post-TI HAART, respectively. Subjects with lower CD4 counts at TI, aged older than 40 years, and those resuming the same HAART as their pre-TI regimen had lower CD4 increases during the first 3 months of TR. The majority (86%) of individuals reinitiating therapy achieved HIV RNA<500 copies per milliliter. CONCLUSIONS: Immune reconstitution after TI is generally poorer than after first HAART, particularly for patients aged older than 40 years at TI and those with poorer immunological responses to pre-TI HAART. Reinitiation of the same HAART regimen as pre-TI also seems to have unfavorable outcomes.