Infant mortality in Brazil, 1980-2000: A spatial panel data analysis

Background: Infant mortality is an important measure of human development, related to the level of welfare of a society. In order to inform public policy, various studies have tried to identify the factors that influence, at an aggregated level, infant mortality. The objective of this paper is to analyze the regional pattern of infant mortality in Brazil, evaluating the effect of infrastructure, socio-economic, and demographic variables to understand its distribution across the country. Methods: Regressions including socio-economic and living conditions variables are conducted in a structure of panel data. More specifically, a spatial panel data model with fixed effects and a spatial error autocorrelation structure is used to help to solve spatial dependence problems. The use of a spatial modeling approach takes into account the potential presence of spillovers between neighboring spatial units. The spatial units considered are Minimum Comparable Areas, defined to provide a consistent definition across Census years. Data are drawn from the 1980, 1991 and 2000 Census of Brazil, and from data collected by the Ministry of Health (DATASUS). In order to identify the influence of health care infrastructure, variables related to the number of public and private hospitals are included. Results: The results indicate that the panel model with spatial effects provides the best fit to the data. The analysis confirms that the provision of health care infrastructure and social policy measures (e. g. improving education attainment) are linked to reduced rates of infant mortality. An original finding concerns the role of spatial effects in the analysis of IMR. Spillover effects associated with health infrastructure and water and sanitation facilities imply that there are regional benefits beyond the unit of analysis. Conclusions: A spatial modeling approach is important to produce reliable estimates in the analysis of panel IMR data. Substantively, this paper contributes to our understanding of the physical and social factors that influence IMR in the case of a developing country.

A Simple Artificial Life Model Explains Irrational Behavior in Human Decision-Making

Although praised for their rationality, humans often make poor decisions, even in simple situations. In the repeated binary choice experiment, an individual has to choose repeatedly between the same two alternatives, where a reward is assigned to one of them with fixed probability. The optimal strategy is to perseverate with choosing the alternative with the best expected return. Whereas many species perseverate, humans tend to match the frequencies of their choices to the frequencies of the alternatives, a sub-optimal strategy known as probability matching. Our goal was to find the primary cognitive constraints under which a set of simple evolutionary rules can lead to such contrasting behaviors. We simulated the evolution of artificial populations, wherein the fitness of each animat (artificial animal) depended on its ability to predict the next element of a sequence made up of a repeating binary string of varying size. When the string was short relative to the animats' neural capacity, they could learn it and correctly predict the next element of the sequence. When it was long, they could not learn it, turning to the next best option: to perseverate. Animats from the last generation then performed the task of predicting the next element of a non-periodical binary sequence. We found that, whereas animats with smaller neural capacity kept perseverating with the best alternative as before, animats with larger neural capacity, which had previously been able to learn the pattern of repeating strings, adopted probability matching, being outperformed by the perseverating animats. Our results demonstrate how the ability to make predictions in an environment endowed with regular patterns may lead to probability matching under less structured conditions. They point to probability matching as a likely by-product of adaptive cognitive strategies that were crucial in human evolution, but may lead to sub-optimal performances in other environments.

The Microbiome of Brazilian Mangrove Sediments as Revealed by Metagenomics

Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04) in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments.

Cyanobacterial diversity in the phyllosphere of a mangrove forest

The cyanobacterial community colonizing phyllosphere in a well-preserved Brazilian mangrove ecosystem was assessed using cultivation-independent molecular approaches. Leaves of trees that occupy this environment (Rhizophora mangle, Avicennia schaueriana and Laguncularia racemosa) were collected along a transect beginning at the margin of the bay and extending upland. The results demonstrated that the phyllosphere of R.similar to mangle and L.similar to racemosa harbor similar assemblages of cyanobacteria at each point along the transect. A.similar to schaueriana, found only in the coastal portions of the transect, was colonized by assemblages with lower richness than the other trees. However, the results indicated that spatial location was a stronger driver of cyanobacterial community composition than plant species. Distinct cyanobacterial communities were observed at each location along the coast-to-upland transect. Clone library analysis allowed identification of 19 genera of cyanobacteria and demonstrated the presence of several uncultivated taxa. A predominance of sequences affiliated with the orders Nostocales and Oscillatoriales was observed, with a remarkable number of sequences similar to genera Symphyonemopsis/Brasilonema (order Nostocales). The results demonstrated that phyllosphere cyanobacteria in this mangrove forest ecosystem are influenced by environmental conditions as the primary driver at the ecosystem scale, with tree species exerting some effect on community structure at the local scale.

Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma

Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell's energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GR alpha and ER beta in lung tissue. Allergic airway inflammation caused reduction in mtGR alpha, mtER beta, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GR alpha and ER beta in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease.

Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.

High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease

Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

Leishmania Promastigotes Lack Phosphatidylserine but Bind Annexin V upon Permeabilization or Miltefosine Treatment

The protozoan parasite Leishmania is an intracellular pathogen infecting and replicating inside vertebrate host macrophages. A recent model suggests that promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells by exposing phosphatidylserine (PS) at the cell surface to trigger their phagocytic uptake into host macrophages. PS presentation at the cell surface is typically analyzed using fluorescence-labeled annexin V. Here we show that Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon permeabilization or miltefosine treatment. However, combined lipid analysis by thin-layer chromatography, mass spectrometry and 31 P nuclear magnetic resonance (NMR) spectroscopy revealed that Leishmania promastigotes lack any detectable amount of PS. Instead, we identified several other phospholipid classes such phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and phosphatidylinositol as candidate lipids enabling annexin V staining.

Platelet-rich plasma stimulates cytokine expression and alkaline phosphatase activity in osteoblast-derived osteosarcoma cells

Objective: The aim of this study was to investigate the effects of PRP on SAOS-2 cells in terms of cytokine expression, cell activity and oxidative stress. Design: Cell line SAOS-2 (1 x 10(5) cells/mL) were grown in culture medium alpha-MEM with 10% FBS for 24 h and stimulated (or not) with PRP at concentrations of 3, 10 and 20%, LPS (E. coli, 10 g/mL) and IL-1 beta (1 mg/mL) for 24 h. The supernatant was collected and analyzed for the expression of cytokines in a panel array, ALP using a commercial kit and NO2- with Griess reaction method. Also, the cells were analyzed using Western blot for RANKL and slot blotting for nitrotyrosine expression. Result: There were no significant differences amongst the groups in terms of NO2-, protein nitrotyrosine content and RANKL expression. However, all stimuli increased ALP activity and in case of PRP, it was in a dose-dependent manner (p < 0.001). Also, all stimuli induced an increase in cytokines and chemokines expression, but only PRP promoted an increase of component C5, sICAM-1 and RANTES expression. Whilst IL-1 receptor antagonist (IL-1ra) expression was down-regulated by PRP, both LPS and IL-1 beta caused up-regulation of this cytokine. Conclusions: PRP can stimulate osteoblast activity and cytokine/chemokine release, as well as indicate some of the mediators that can (and cannot) be involved in this activation. (C) 2012 Elsevier Ltd. All rights reserved.

Nine New Species of Bugula Oken (Bryozoa: Cheilostomata) in Brazilian Shallow Waters

Background: Bugula is a speciose genus of marine bryozoans, represented by both endemic and cosmopolitan species distributed in tropical and temperate waters and important to marine biologists because of the occurrence of many species in harbor and fouling communities, therefore as potential invaders. The southeastern Brazilian coast in the southern Atlantic hosts the highest known diversity of the genus, a status intimately associated with the intensity of collecting efforts. Methodology: Morphological data based on the examination of living specimens, scanning electron and light microscopic images, and morphometric analyses were used to assess the diversity of Bugula along the coastal areas of southern, northeastern, and southeastern Brazil. In this study, morphological species boundaries were based mainly on avicularian characters. For two morphologically very similar species, boundaries are partially supported by 16 S rDNA molecular data. Results: Nine species are newly described from Brazil, as follows: Bugula bowiei n. sp. (= Bugula turrita sensu Marcus, 1937) from the southern, northeastern, and southeastern coasts; Bugula foliolata n. sp. (= Bugula flabellata sensu Marcus, 1938), Bugula guara n. sp., Bugula biota n. sp. and Bugula ingens n. sp from the southeastern coast; Bugula gnoma n. sp. and Bugula alba n. sp. from the northeastern coast; Bugula rochae n. sp. (= Bugula uniserialis sensu Marcus, 1937) from the southern coast; and Bugula migottoi n. sp., from the southeastern and southern coasts. Conclusion: The results contribute to the morphological characterization and the knowledge of the species richness of the genus in the southwestern Atlantic (i.e., Brazil), through the description of new species in poorly sampled areas and also on the southeastern coast of that country. Additionally, the taxonomic status of the Brazilian specimens attributed to B. flabellata, B. turrita and B. uniserialis are clarified by detailed studies on zooidal and avicularia morphology.

Brazilian research on extremophiles in the context of astrobiology

Extremophiles are organisms adapted to grow at extreme ranges of environmental variables, such as high or low temperatures, acid or alkaline medium, high salt concentration, high pressures and so forth. Most extremophiles are micro-organisms that belong to the Archaea and Bacteria domains, and are widely spread across the world, which include the polar regions, volcanoes, deserts, deep oceanic sediments, hydrothermal vents, hypersaline lakes, acid and alkaline water bodies, and other extreme environments considered hostile to human life. Despite the tropical climate, Brazil has a wide range of ecosystems which include some permanent or seasonally extreme environments. For example, the Cerrado is a biome with very low soil pH with high Al+3 concentration, the mangroves in the Brazilian coast are anaerobic and saline, Pantanal has thousands of alkaline-saline lakes, the Caatinga arid and hot soils and the deep sea sediments in the Brazilian ocean shelf. These environments harbour extremophilic organisms that, coupled with the high natural biodiversity in Brazil, could be explored for different purposes. However, only a few projects in Brazil intended to study the extremophiles. In the frame of astrobiology, for example, these organisms could provide important models for defining the limits of life and hypothesize about life outside Earth. Brazilian microbiologists have, however, studied the extremophilic micro-organisms inhabiting non-Brazilian environments, such as the Antarctic continent. The experience and previous results obtained from the Brazilian Antarctic Program (PROANTAR) provide important results that are directly related to astrobiology. This article is a brief synopsis of the Brazilian experience in researching extremophiles, indicating the most important results related to astrobiology and some future perspectives in this area. Received 29 February 2012, accepted 25 May 2012, first published online 11 July 2012

Effects of type I collagen coating on titanium osseointegration: histomorphometric, cellular and molecular analyses

The investigation of titanium (Ti) surface modifications aiming to increase implant osseointegration is one of the most active research areas in dental implantology. This study was carried out to evaluate the benefits of coating Ti with type I collagen on the osseointegration of dental implants. Acid etched Ti implants (AETi), either untreated or coated with type I collagen (ColTi), were placed in dog mandibles for three and eight weeks for histomorphometric, cellular and molecular evaluations of bone tissue response. While the histological aspects were essentially the same with both implants being surrounded by lamellar bone trabeculae, histomorphometric analysis showed more abundant bone formation in ColTi, mainly at three weeks. Cellular evaluation showed that cells harvested from bone fragments in close contact with ColTi display lower proliferative capacity and higher alkaline phosphatase activity, phenotypic features associated with more differentiated osteoblasts. Confirming these findings, molecular analyses showed that ColTi implants up-regulates the expression of a panel of genes well known as osteoblast markers. Our results present a set of evidences that coating AETi with collagen fastens the osseointegration by stimulating bone formation at the cellular and molecular levels, making this combination of morphological and biochemical modification a promising approach to treat Ti surfaces.

Epicoccum nigrum P16, a Sugarcane Endophyte, Produces Antifungal Compounds and Induces Root Growth

Background: Sugarcane is one of the most important crops in Brazil, mainly because of its use in biofuel production. Recent studies have sought to determine the role of sugarcane endophytic microbial diversity in microorganism-plant interactions, and their biotechnological potential. Epicoccum nigrum is an important sugarcane endophytic fungus that has been associated with the biological control of phytopathogens, and the production of secondary metabolites. In spite of several studies carried out to define the better conditions to use E. nigrum in different crops, little is known about the establishment of an endophytic interaction, and its potential effects on plant physiology. Methodology/Principal Findings: We report an approach based on inoculation followed by re-isolation, molecular monitoring, microscopic analysis, plant growth responses to fungal colonization, and antimicrobial activity tests to study the basic aspects of the E. nigrum endophytic interaction with sugarcane, and the effects of colonization on plant physiology. The results indicate that E. nigrum was capable of increasing the root system biomass and producing compounds that inhibit the in vitro growth of sugarcane pathogens Fusarium verticillioides, Colletotrichum falcatum, Ceratocystis paradoxa, and Xanthomomas albilineans. In addition, E. nigrum preferentially colonizes the sugarcane surface and, occasionally, the endophytic environment. Conclusions/Significance: Our work demonstrates that E. nigrum has great potential for sugarcane crop application because it is capable of increasing the root system biomass and controlling pathogens. The study of the basic aspects of the interaction of E. nigrum with sugarcane demonstrated the facultative endophytism of E. nigrum and its preference for the phylloplane environment, which should be considered in future studies of biocontrol using this species. In addition, this work contributes to the knowledge of the interaction of this ubiquitous endophyte with the host plant, and also to a better use of microbial endophytes in agriculture.

HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/ RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.

Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) gamma Activators and Pan-PPAR Partial Agonists

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) gamma to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPAR gamma ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPAR gamma LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPAR gamma LBD, stronger partial agonists with full length PPAR gamma and exhibit full blockade of PPAR gamma phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPAR gamma also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/beta-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPAR gamma modulators with useful clinical profiles among natural products.