Molecular analysis of dimethyl sulphide dehydrogenase from Rhodovulum sulfidophilum: its place in the dimethyl sulphoxide reductase family of microbial molybdopterin-containing enzymes

Dimethyl sulphide dehydrogenase catalyses the oxidation of dimethyl sulphide to dimethyl sulphoxide (DMSO) during photoautotrophic growth of Rhodovulum sulfidophilum . Dimethyl sulphide dehydrogenase was shown to contain bis (molybdopterin guanine dinucleotide)Mo, the form of the pterin molybdenum cofactor unique to enzymes of the DMSO reductase family. Sequence analysis of the ddh gene cluster showed that the ddhA gene encodes a polypeptide with highest sequence similarity to the molybdop-terin-containing subunits of selenate reductase, ethylbenzene dehydrogenase. These polypeptides form a distinct clade within the DMSO reductase family. Further sequence analysis of the ddh gene cluster identified three genes, ddhB , ddhD and ddhC . DdhB showed sequence homology to NarH, suggesting that it contains multiple iron-sulphur clusters. Analysis of the N-terminal signal sequence of DdhA suggests that it is secreted via the Tat secretory system in complex with DdhB, whereas DdhC is probably secreted via a Sec-dependent mechanism. Analysis of a ddhA mutant showed that dimethyl sulphide dehydrogenase was essential for photolithotrophic growth of Rv. sulfidophilum on dimethyl sulphide but not for chemo-trophic growth on the same substrate. Mutational analysis showed that cytochrome c (2) mediated photosynthetic electron transfer from dimethyl sulphide dehydrogenase to the photochemical reaction centre, although this cytochrome was not essential for photoheterotrophic growth of the bacterium.

Exploring privileged structures: the combinatorial synthesis of cyclic peptides

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.

Microampullary organs of a freshwater eel-tailed catfish, Plotosus (tandanus) tandanus

Whole body studies of Plotosus tandanus revealed that ampullary pores occur over the entire body of the fish, but are in higher concentrations in the head region. These pores give rise to a short canal (50-60 mum) produced by columnar epithelial cells bound together by tight junctions and desmosomes. At the junction. of the canal and the ampulla, cuboidal epithelial cells make up the wall. The ampulla consists of layers of collagen fibers that surround flattened epithelial cells in the lateral regions and give rise to supportive cells-that encase a small number of receptor cells (10-15). The ampullary wall comprises several types of cells that are adjoined via tight junctions and desmosomes between cell types. The ovoid receptor cells possess microvilli along the luminar apical area. Beneath this area, the cells are rich in mitochondria and rough endoplasmic reticulum. An unmyelinated neuron adjoins with each receptor cell opposite multiple presynaptic bodies. This form of microampulla has not been previously described within the Family Plotosidae. (C) 2002 Wiley-Liss, Inc.

Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19) using ELISA commercial techniques, and human herpes virus 6 (HHV 6) using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR). RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months), had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17) HPV B19 infection; 76.5% (13 in 17) HHV 6 infection; 5.9% (1 in 17) rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

An outbreak of bat-transmitted human rabies in a village in the Brazilian Amazon

During 45 days without electrical power, 57 individuals (8.7% of the population) from the village of Antônio Dino (municipality of Turiaçu, Northeastern Brazil) were attacked by bats and 16 died from human rabies. The aim of the study was to analyze the factors associated with bat attacks and the development of human rabies. Of the 46 individuals, who suffered bat attacks, 36 (78.3%) were under 17 years of age. The risk factors associated with bat attacks were age under 17 years, having observed bats inside the bedroom and having been without electrical power in the house. Age under 17 years and having been without electrical power in the house were factors associated with human rabies.

The effects of clinical support surfaces on pressure as a risk factor in the development of pressure ulcers, from a radiographical perspective: a narrative literature review

Purpose: Pressure ulcers are a high cost, high volume issue for health and medical care providers, having a detrimental effect on patients and relatives. Pressure ulcer prevention is widely covered in the literature, but little has been published regarding the risk to patients in the radiographical setting. This review of the current literature is to identify findings relevant to radiographical context. Methods: Literature searching was performed using Science Direct and Medline databases. The search was limited to articles published in the last ten years to remain current and excluded studies containing participants less than 17 years of age. In total 14 studies were acquired; three were excluded as they were not relevant. The remaining 11 studies were compared and reviewed. Discussion: Eight of the studies used ‘healthy’ participants and three used symptomatic participants. Nine studies explored interface pressure with a range of pressure mat technologies, two studies measured shear (MRI finite element modelling, and a non-invasive instrument), and one looked at blood flow and haemoglobin oxygenation. A range of surfaces were considered from trauma, nursing and surgical backgrounds for their ability to reduce pressure including standard mattresses, high specification mattresses, rigid and soft layer spine boards, various overlays (gel, air filled, foam). Conclusion: The current literature is not appropriate for the radiographic patient and cannot be extrapolated to a radiologic context. Sufficient evidence is presented in this review to support the need for further work specific to radiography in order to minimise the development of PU in at risk patients.

Severity of malocclusion in adolescents: populational-based study in the north of Minas Gerais, Brazil

ABSTRACT OBJECTIVE To identify the factors associated with severity of malocclusion in a population of adolescents. METHODS In this cross-sectional population-based study, the sample size (n = 761) was calculated considering a prevalence of malocclusion of 50.0%, with a 95% confidence level and a 5.0% precision level. The study adopted correction for the effect of delineation (deff = 2), and a 20.0% increase to offset losses and refusals. Multistage probability cluster sampling was adopted. Trained and calibrated professionals performed the intraoral examinations and interviews in households. The dependent variable (severity of malocclusion) was assessed using the Dental Aesthetic Index (DAI). The independent variables were grouped into five blocks: demographic characteristics, socioeconomic condition, use of dental services, health-related behavior and oral health subjective conditions. The ordinal logistic regression model was used to identify the factors associated with severity of malocclusion. RESULTS We interviewed and examined 736 adolescents (91.5% response rate), 69.9% of whom showed no abnormalities or slight malocclusion. Defined malocclusion was observed in 17.8% of the adolescents, being severe or very severe in 12.6%, with pressing or essential need of orthodontic treatment. The probabilities of greater severity of malocclusion were higher among adolescents who self-reported as black, indigenous, pardo or yellow, with lower per capita income, having harmful oral habits, negative perception of their appearance and perception of social relationship affected by oral health. CONCLUSIONS Severe or very severe malocclusion was more prevalent among socially disadvantaged adolescents, with reported harmful habits and perception of compromised esthetics and social relationships. Given that malocclusion can interfere with the self-esteem of adolescents, it is essential to improve public policy for the inclusion of orthodontic treatment among health care provided to this segment of the population, particularly among those of lower socioeconomic status.

ERICA: prevalence of common mental disorders in Brazilian adolescents

ABSTRACT OBJECTIVE To describe the prevalence of common mental disorders in Brazilian adolescent students, according to geographical macro-regions, school type, sex, and age. METHODS We evaluated 74,589 adolescents who participated in the Cardiovascular Risk Study in Adolescents (ERICA), a cross-sectional, national, school-based study conducted in 2013-2014 in cities with more than 100,000 inhabitants. A self-administered questionnaire and an electronic data collector were employed. The presence of common mental disorders was assessed using the General Health Questionnaire (GHQ-12). We estimated prevalence and 95% confidence intervals of common mental disorders by sex, age, and school type, in Brazil and in the macro-regions, considering the sample design. RESULTS The prevalence of common mental disorders was of 30.0% (95%CI 29.2-30.8), being higher among girls (38.4%; 95%CI 37.1-39.7) when compared to boys (21.6%; 95%CI 20.5-22.8), and among adolescents who were from 15 to 17 years old (33.6%; 95%CI 32.2-35.0) compared to those aged between 12 and 14 years (26.7%; 95%CI 25.8-27.6). The prevalence of common mental disorders increased with age for both sexes, always higher in girls (ranging from 28.1% at 12 years to 44.1% at 17 years) than in boys (ranging from 18.5% at 12 years to 27.7% at 17 years). We did not observe any significant difference by macro-region or school type. Stratified analyses showed higher prevalence of common mental disorders among girls aged from 15 to 17 years of private schools in the North region (53.1; 95%CI 46.8-59.4). CONCLUSIONS The high prevalence of common mental disorders among adolescents and the fact that the symptoms are often vague mean these disorders are not so easily identified by school administrators or even by health services. The results of this study can help the proposition of more specific prevention and control measures, focused on highest risk subgroups.

Schistosoma mansoni: importance of skin and pulmonary phases to concomitant immunity in albino mice

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.

Characterization of the [NiFe] Hydrogenase from the sulfate reducer Desulfovibrio vulgaris Hildenborough

The [NiFe] hydrogenase from Desulfovibrio vulgaris Hildenborough was isolated from the cytoplasmic membranes and characterized by EPR spectroscopy. It has a total molecular mass of 98.7 kDa (subunits of 66.4 and 32.3 kDa), and contains 1 nickel and 12 Fe atoms per heterodimer. The catalytic activities for hydrogen consumption and production were determined to be 174 and 89 umol H2 min-1 mg -1, respectively. As isolated, under aerobic conditions, this hydrogenase exhibits EPR signals characteristic of the nickel centers in [NiFe] hydrogenases (Ni-A signal at gx,y,z=2.32, 2.23 and ~2.0 and Ni-B signal at gx,y,z=2.33, 2.16 and ~2.0) as well as an intense quasi-isotropic signal centered at g=2.02 due to the oxidized [3Fe-4S] center. The redox profile under hydrogen atmosphere is remarkably similar to that of other [NiFe] hydrogenases. The signals observed for the oxidized state disappear, first being substituted by the Ni-C type signal (gx,y,z=2.19, 2.14, ~2.01), which upon long incubation under hydrogen yields the split Ni-C signal due to interaction with the reduced [4Fe-4S] centers.

TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

Nocardial infections: report of 22 cases

Twenty-two cases of nocardial infections were diagnosed in our city between 1977- 1998. All patients whose clinical specimens showed Nocardia spp. at Gram stain, which were further confirmed by culture, were selected to be included in the study. Data from patients who were cured were compared with those from patients who died by statistical tests using EPIINFO version 6.04 software. Six isolates were identified as Nocardia asteroides complex, one as Nocardia asteroides sensu stricto and other as Nocardia brasiliensis. We had 17 cases of lung nocardiosis, being one out of them also a systemic disease. Other four cases of systemic nocardiosis were diagnosed: nocardial brain abscesses (one); nocardiosis of the jejunum (one); multiple cutaneous abscesses (one); and a case of infective nocardial endocarditis of prosthetic aortic valve. One patient had a mycetoma by N. brasiliensis. Fifteen (68.2%) out of 22 patients were immunosuppressed, being most (93.3%) by high-doses corticotherapy. Mortality by nocardial infection was 41%; mortality of systemic nocardiosis was 60%. Nocardiosis has a bad prognosis in immunosuppressed patients and also in non-immunosuppressed patients if the diagnosis is delayed. We propose that the delay in diagnosis should be examined in larger series to document its influence in the prognosis of the disease.

Occurrence of antibodies against Leptospira spp. in horses of the urban area of Londrina, Paraná, Brazil

A total of 320 horses were studied in this paper, both male and female, between two and 17 years of age, which were used for traction of wagons in the urban area of the municipality of Londrina (PR). These animals were kept, after their daily work, in abandoned areas or plots, in the outskirts of the urban area of the city. When these animals were attended by the veterinarians, between 1996 and 2005, none of them presented symptoms suggesting leptospirosis. The most frequent reasons for the visit were loss of weight, unwillingness for work, parasitism, laminess, and wounds. Microscopic Seroagglutination Test (SAM), with 22 Leptospira serovars, was performed in sera sample from all these animals. The aim of this study was to investigate the occurrence of antibodies against Leptospira spp. in horses from the urban area of Londrina (PR). From the samples tested, 214 (66.88%) were considered positive, with titers between 100 and 3200, being that 49 (22.90%) presented antibodies against a single serovar of Leptospira, and 165 (77.10%) samples presented antibodies against two or more serovars simultaneously, where in 88 (53.33%) it was possible to characterize the most likely probable serovar. Antibodies against the serovar Icterohaemorrhagiae were detected in 32 (23.36%) animals.

Low-Spin Heme b3 in the Catalytic Center of Nitric Oxide Reductase from Pseudomonas nautica

Biochemistry, 2011, 50 (20), pp 4251–4262 DOI: 10.1021/bi101605p