Engineering modular viral scaffolds for targeted bacterial population editing

Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to precisely manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae. We used this technology to redirect Escherichia coli phage scaffolds to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds to target E. coli by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision this approach accelerating phage biology studies and enabling new technologies for bacterial population editing.

Structure of Anopheles (Diptera: Culicidae) population in areas with different degrees of human settlement: Cantá - Roraima - Brazil

Malaria has still been one of the most important endemic diseases in the Amazonian region. This study presents the impact of human settlements on the structure of Anopheles population. Diversity, abundance, richness and distribution of the genus Anopheles were observed in two areas with different levels of human settlement in the Cantá city, Roraima State, Northern Brazil. The influence of the dry and rainy seasons on mosquito populations was also observed. Mosquito captures were performed between 6:00 and 10:00 pm during the dry (February and November) and rainy (May and August) seasons at four different sites of each area. Among the 11 species of Anopheles identified through the adults' characteristics, An. albitarsis s.l. (45.5%) and An. darlingi (19.2%) were the most abundant in the more intensively anthropized area while An. triannulatus (19.2%) was more common in the less modified area. Other species found were An. nuneztovari (10.9%), An. oswaldoi (2.0%), An. evansae (1.7%), An. brasiliensis (0.6%), An. intermedius (0.3%), An. mediopunctatus (0.5%), An. periassui (0.08%) and An. argyritarsis (0.04%). The highest mosquitoes' population density was observed in May and the lowest one was observed in February and November. These results demonstrate the existence of a high diversity of anophelines in the study areas, showing that anthropic changes in the environment and climate variability affect both the population density and relative abundance of these vectors.

Population Dynamics Modeling of Arapaima gigas

Pirarucu (Arapaima gigas) has been of the most important natural fishing resources of the Amazon region. Due to its economic importance, and the necessity to preserve the species hand, field research concerning the habits and behavior of the pirarucu has been increasing for the last 20 years. The aim of this paper is to present a mathematical model for the pirarucu population dynamics considering the species peculiarities, particularly the male parental care over the offspring. The solution of the dynamical systems indicates three possible equilibrium points for the population. The first corresponds to extinction; the third corresponds to a stable population close to the environmental carrying capacity. The second corresponds to an unstable equilibrium located between extinction and full use of the carrying capacity. It is shown that lack of males’ parental care closes the gap between the point corresponding to the unstable equilibrium and the point of stable non-trivial equilibrium. If guarding failure reaches a critical point the two points coincide and the population tends irreversibly to extinction. If some event tends to destabilize the population equilibrium, as for instance inadequate parental care, the model responds in such a way as to restore the trajectory towards the stable equilibrium point avoiding the route to extinction. The parameters introduced to solve the system of equations are partially derived from limited but reliable field data collected at the Mamirauá Sustainable Development Reserve (MSDR) in the Brazilian Amazonian Region.

Effector memory CD4+ T cells are associated with cognitive performance in a senior population

Objective: Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. Methods: In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Results: Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account. Conclusions: This is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.

Racial inequalities in the socioeconomic, demographic and health conditions of elderly from Maranhão State, Legal Amazon, Brazil: a population-based study

Aging with quality of life does not occur equally among the racial groups of Brazilian elderly, and few studies have analyzed this issue in the states of the Brazilian Legal Amazon. The objective of this study was to investigate racial inequalities in the socioeconomic, demographic and health conditions of elderly residents of Maranhão state, Brazil. The present work is a cross-sectional study of 450 elders aged 60 years or older included in the 2008 National Household Sample Survey. The prevalence of socioeconomic, demographic, health and habit indicators and of risk factors were estimated in white, brown and black racial categories that were self-reported by the survey participants. The chi-square test was used for comparisons (a=5%). The majority of the elderly respondents identified themselves as brown (66.4%) or white (23.3%). There were significant socioeconomic, demographic, habit and lifestyle differences among the racial groups. Most of the black and brown elderly lived alone, reported lower educational levels and were in the lowest quintile for income. These respondents were also highly dependent on the Unified Health System (Sistema Único de Saúde - SUS), exhibited low rates of screening mammograms and lower physical activity levels and had a greater proportion of smokers. However, there was no difference in the prevalence of health indicators or in the proportion of elderly by gender, age, social role in the family or the urban-rural location of the household. These results indicate the presence of racial inequalities in the socioeconomic and demographic status and in the practice of healthy habits and lifestyles among elderly from Maranhão, but suggest equity in health status. The results also suggest the complexity and challenges of interlinking race with socioeconomic aspects, and the findings reinforce the need for the implementation of public policies for these population groups.

Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Património natural e arquitectónico: plano de intervenção na aldeia de Ermelo

Dissertação de mestrado integrado em Arquitectura (área de especialização em Cidade e Território)

Cerebral perfusion and automated individual analysis using SPECT among an obsessive-compulsive population

OBJECTIVE: To make individual assessments using automated quantification methodology in order to screen for perfusion abnormalities in cerebral SPECT examinations among a sample of subjects with OCD. METHODS: Statistical parametric mapping (SPM) was used to compare 26 brain SPECT images from patients with OCD individually with an image bank of 32 normal subjects, using the statistical threshold of p < 0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). The maps were analyzed, and regions presenting voxels that remained above this threshold were sought. RESULTS: Six patients from a sample of 26 OCD images showed abnormalities at cluster or voxel level, considering the criteria described above, which represented 23.07%. However, seven images from the normal group of 32 were also indicated as cases of perfusional abnormality, representing 21.8% of the sample. CONCLUSION: The automated quantification method was not considered to be a useful tool for clinical practice, for analyses complementary to visual inspection.

Avaliação do impacto na saúde da mobilidade no acesso aos Campi Universitários: estudo de caso UMinho

Dissertação de mestrado integrado em Engenharia Civil

Study to determine the cardiovascular risk ofthe population of Guimarães/Vizela, includingthe prevalence of arterial stiffness and early vascular aging syndrome

Tese de Doutoramento em Medicina.

Risk factors for atherosclerosis in an elderly out patient population in the City of São Paulo

OBJECTIVE: To analyze in out clinic elderly patients of both sexes for the prevalence of risk factors for atherosclerosis and study their association with the complications of atherosclerosis. METHODS: Five hundred and sixteen outpatients, 152 men and 364 women, 60 years or older, were studied. The prevalences of hypertension, dyslipidemia, diabetes mellitus, cigarette smoking and obesity were determined in both sexes and compared using the chi-square test. The association between these factors and the presence of atherosclerotic complications was analyzed by logistic regression. RESULTS: The comparative analysis of the factors in both sexes showed that hypertension, total cholesterol > or = 240mg/dL, LDL-cholesterol > or = 160mg/dL, and body mass index >27.5 were more frequent among women, but HDL-cholesterol <35mg/dL and cigarette smoking were more frequent among men, and no difference occurred between sexes in relation to the frequency of triglycerides > or = 250mg/dL and diabetes mellitus. After adjustment of the variables in the regression model, we observed that in the total of elderly patients, risk factors for complications of atherosclerosis were: triglycerides > or = 250mg/dL, hypertension, and male sex. Among men, the risk factors were: LDL-cholesterol > or = 160mg/dL, diabetes mellitus, HDL-cholesterol <35mg/dL and hypertension. Among women, the risk factors were: tryglicerides > or = 250mg/dL and hypertension. CONCLUSION: The results showed that, in the elderly, the risk factors for atherosclerosis persist, but with different behaviors between men and women. The study suggests that the relative importance of the risk factors can change with the aging process.

Trends in mortality due to ischemic heart disease in the municipality of Goiania, Brazil, during the years between 1980 and 1994

OBJECTIVE: To analyze the trends of specific, standardized coefficients of mortality due to ischemic heart disease according to sex and age during the years 1980 and 1994 in the municipality of Goiania, GO, Brazil. METHODS: Data on deaths were retrieved from the Information on Mortality System of the Ministry of Health; population data were obtained from the Foundation of the Brazilian Institute for Geography and Statistics (IBGE). The trends of the specific coefficients were analyzed by triennia of the historical series, including individuals of both sexes from 25 years of age on, partitioned into 6 age groups of ten years intervals. The population data corresponding to the year 1980 were used as the standard for the calculation of each age group coefficient. Analyses were carried out by straight linear regression. RESULTS: Coefficients were greater for males in each triennium of the series and increased with age in both sexes. The study of the trends of the specific age coefficients of both sexes revealed a stable pattern of evolution up to the age of 65-74 years (P>0.05). From 75 years on, a clear-cut decline in mortality due to ischemic heart disease was shown by both sexes. The standardized coefficients also showed a significant decline (p<=0.05). CONCLUSION: The municipality of Goiânia is at present in a stage of epidemiological transition similar to that of developed countries, even though the observed decline is predominantly influenced by the mortality of older individuals (75 years of age or older).

Normal values of echocardiographic measurements. A population-based study

OBJECTIVE: To describe echocardiographic measurements and left ventricular mass in a population sample of healthy adults inhabitants of the urban region of Porto Alegre. METHODS: An analytical, observational, population-based, cross-sectional study was done. Through a multi-stage probability sample, 114 individuals were selected to be submitted to a M-mode and two-dimensional echocardiogram with color Doppler. The analyses were restricted to healthy participants. Echocardiographic measurements were described by mean, standard deviation, 95 percentile and 95% confidence limits. RESULTS: A total of 100 healthy participants, with several characteristics similar to those from the original population, had a complete and reliable echocardiographic examination. The measurements of aorta, left atrium, interventricular septum, left ventricle in systole and diastole, left posterior wall and left ventricular mass, adjusted or not for body surface area or height, were significantly higher in males. The right ventricle size was similar among the genders. Several echocardiographic measurements were within standard normal limits. Interventricular septum, left posterior wall and left ventricular mass, adjusted or not for anthropometric measurements, and aortic dimensions had lower mean and range than the reference limits. CONCLUSION: The means and estimates of distribution for the measurements of interventricular septum, left posterior wall and left ventricular mass found in this survey were lower than those indicated by the international literature and accepted as normal limits.

Trends in death from circulatory diseases in Brazil between 1979 and 1996

OBJECTIVE: To analyze the trends in mortality due to circulatory diseases in men and women aged > or = 30 years in Brazil from 1979 to 1996. METHODS: We analyzed population count data obtained from the IBGE Foundation and mortality data obtained from the System of Information on Mortality of the DATASUS of the Ministry of Health. RESULTS: Circulatory diseases, ischemic heart disease, and cerebrovascular disease were the major causes of death in men and women in Brazil. The standardized age coefficient for circulatory disease in men aged > or = 30 years ranged from 620 to 506 deaths/100,000 inhabitants and in women from 483 to 383 deaths/100,000 inhabitants for the years 1979 and 1996, respectively. In men, the mean coefficient for the period was 586.25 deaths with a significant trend towards a decrease (P<0.001) and a decline of 8.25 deaths/year. In women, the mean coefficient for the period was 439.58 deaths, a significant trend towards a decrease (P<0.001) and a rate of decline of 7.53 deaths/year. The same significant trend towards a decrease in death (P<0.001) was observed for ischemic heart disease and cerebrovascular disease. Risk of death from these causes was always higher for men of any age group (P<0.001). Cerebrovascular disease was the primary cause of death in women. CONCLUSION: Although circulatory diseases have been the major cause of mortality in men and women in the Brazilian population, with a greater participation by cerebrovascular diseases, a trend towards a decrease in the risk of death from these causes is being observed.

Estimation of statistical cure from cancer using population-based data

Dissertação de mestrado em Estatística