Human microbiota in health and disease

Each human body plays host to a microbial population which is both numerically vast (at around 1014 microbial cells) and phenomenally diverse (over 1,000 species). The majority of the microbial species in the gut have not been cultured but the application of culture-independent approaches for high throughput diversity and functionality analysis has allowed characterisation of the diverse microbial phylotypes present in health and disease. Studies in monozygotic twins, showing that these retain highly similar microbiota decades after birth and initial colonisation, are strongly indicative that diversity of the microbiome is host-specific and affected by the genotype. Microbial diversity in the human body is reflected in both richness and evenness. Diversity increases steeply from birth reaching its highest point in early adulthood, before declining in older age. However, in healthy subjects there appears to be a core of microbial phylotypes which remains relatively stable over time. Studies of individuals from diverse geopraphies suggest that clusters of intestinal bacterial groups tend to occur together, constituting ‘enterotypes’. So variation in intestinal microbiota is stratified rather than continuous and there may be a limited number of host/microbial states which respond differently to environmental influences. Exploration of enterotypes and functional groups may provide biomarkers for disease and insights into the potential for new treatments based on manipulation of the microbiome. In health, the microbiota interact with host defences and exist in harmonious homeostasis which can then be disturbed by invading organisms or when ‘carpet bombing’ by antibiotics occurs. In a portion of individuals with infections, the disease will resolve itself without the need for antibiotics and microbial homeostasis with the host’s defences is restored. The administration of probiotics (live microorganisms which when administered in adequate amounts confer a health benefit on the host) represents an artificial way to enhance or stimulate these natural processes. The study of innate mechanisms of antimicrobial defence on the skin, including the production of numerous antimicrobial peptides (AMPs), has shown an important role for skin commensal organisms. These organisms may produce AMPs, and also amplify the innate immune responses to pathogens by activating signalling pathways and processing host produced AMPs. Research continues into how to enhance and manipulate the role of commensal organisms on the skin. The challenges of skin infection (including diseases caused by multiply resistant organisms) and infestations remain considerable. The potential to re-colonise the skin to replace or reduce pathogens, and exploring the relationship between microbiota elsewhere and skin diseases are among a growing list of research targets. Lactobacillus species are among the best known ‘beneficial’ bacterial members of the human microbiota. Of the approximately 120 species known, about 15 are known to occur in the human vagina. These organisms have multiple properties, including the production of lactic acid, hydrogen peroxide and bacteriocins, which render the vagina inhospitable to potential pathogens. Depletion of the of the normal Lactobacillus population and overgrowth of vaginal anaerobes, accompanied by the loss of normal vaginal acidity can lead to bacterial vaginosis – the commonest cause of abnormal vaginal discharge in women. Some vaginal anaerobes are associated with the formation of vaginal biofilms which serve to act as a reservoir of organisms which persists after standard antibiotic therapy of bacterial vaginosis and may help to account for the characteristically high relapse rate in the condition. Administration of Lactobacillus species both vaginally and orally have shown beneficial effects in the treatment of bacterial vaginosis and such treatments have an excellent overall safety record. Candida albicans is a frequent coloniser of human skin and mucosal membranes, and is a normal part of the microbiota in the mouth, gut and vagina. Nevertheless Candida albicans is the most common fungal pathogen worldwide and is a leading cause of serious and often fatal nosocomial infections. What turns this organism from a commensal to a pathogen is a combination of increasing virulence in the organism and predisposing host factors that compromise immunity. There has been considerable research into the use of probiotic Lactobacillus spp. in vaginal candidiasis. Studies in reconstituted human epithelium and monolayer cell cultures have shown that L. rhamnosus GG can protect mucosa from damage caused by Candida albicans, and enhance the immune responses of mucosal surfaces. Such findings offer the promise that the use of such probiotic bacteria could provide new options for antifungal therapy. Studies of changes of the human intestinal microbiota in health and disease are complicated by its size and diversity. The Alimentary Pharmabiotic Centre in Cork (Republic of Ireland) has the mission to ‘mine microbes for mankind’ and its work illustrates the potential benefits of understanding the gut microbiota. Work undertaken at the centre includes: mapping changes in the microbiota with age; studies of the interaction between the microbiota and the gut; potential interactions between the gut microbiota and the central nervous system; the potential for probiotics to act as anti-infectives including through the production of bacteriocins; and the characterisation of interactions between gut microbiota and bile acids which have important roles as signalling molecules and in immunity. The important disease entity where the role of the gut microbiota appears to be central is the Irritable Bowel Syndrome (IBS). IBS patients show evidence of immune activation, impaired gut barrier function and abnormal gut microbiota. Studies with probiotics have shown that these organisms can exert anti-inflammatory effects in inflammatory bowel disease and may strengthen the gut barrier in IBS of the diarrhoea-predominant type. Formal randomised trials of probiotics in IBS show mixed results with limited benefit for some but not all. Studies confirm that administered probiotics can survive and temporarily colonise the gut. They can also stimulate the numbers of other lactic acid bacilli in the gut, and reduce the numbers of pathogens. However consuming live organisms is not the only way to influence gut microbiota. Dietary prebiotics are selectively fermented ingredients that can change the composition and/or activity of the gastrointestinal microbiota in beneficial ways. Dietary components that reach the colon, and are available to influence the microbiota include poorly digestible carbohydrates, such as non-starch polysaccharides, resistant starch, non-digestible oligosaccharides (NDOs) and polyphenols. Mixtures of probiotic and prebiotic ingredients that can selectively stimulate growth or activity of health promoting bacteria have been termed ‘synbiotics’. All of these approaches can influence gut microbial ecology, mainly to increase bifidobacteria and lactobacilli, but metagenomic approaches may reveal wider effects. Characterising how these changes produce physiological benefits may enable broader use of these tactics in health and disease in the future. The current status of probiotic products commercially available worldwide is less than ideal. Prevalent problems include misidentification of ingredient organisms and poor viability of probiotic microorganisms leading to inadequate shelf life. On occasions these problems mean that some commercially available products cannot be considered to meet the definition of a probiotic product. Given the potential benefits of manipulating the human microbiota for beneficial effects, there is a clear need for improved regulation of probiotics. The potential importance of the human microbiota cannot be overstated. ‘We feed our microbes, they talk to us and we benefit. We just have to understand and then exploit this.’ (Willem de Vos).

Simulated last glacial maximum D14Catm and the deep glacial ocean carbon reservoir

∆14Catm has been estimated as 420 ± 80‰ (IntCal09) during the Last Glacial Maximum (LGM) compared to preindustrial times (0‰), but mechanisms explaining this difference are not yet resolved. ∆14Catm is a function of both cosmogenic production in the high atmosphere and of carbon cycling and partitioning in the Earth system. 10Be-based reconstructions show a contribution of the cosmogenic production term of only 200 ± 200‰ in the LGM. The remaining 220‰ have thus to be explained by changes in the carbon cycle. Recently, Bouttes et al. (2010, 2011) proposed to explain most of the difference in pCO2atm and δ13C between glacial and interglacial times as a result of brine-induced ocean stratification in the Southern Ocean. This mechanism involves the formation of very saline water masses that contribute to high carbon storage in the deep ocean. During glacial times, the sinking of brines is enhanced and more carbon is stored in the deep ocean, lowering pCO2atm. Moreover, the sinking of brines induces increased stratification in the Southern Ocean, which keeps the deep ocean well isolated from the surface. Such an isolated ocean reservoir would be characterized by a low ∆14C signature. Evidence of such 14C-depleted deep waters during the LGM has recently been found in the Southern Ocean (Skinner et al. 2010). The degassing of this carbon with low ∆14C would then reduce ∆14Catm throughout the deglaciation. We have further developed the CLIMBER-2 model to include a cosmogenic production of 14C as well as an interactive atmospheric 14C reservoir. We investigate the role of both the sinking of brine and cosmogenic production, alongside iron fertilization mechanisms, to explain changes in ∆14Catm during the last deglaciation. In our simulations, not only is the sinking of brine mechanism consistent with past ∆14C data, but it also explains most of the differences in pCO2atm and ∆14Catm between the LGM and preindustrial times. Finally, this study represents the first time to our knowledge that a model experiment explains glacial-interglacial differences in pCO2atm, δ13C, and ∆14C together with a coherent LGM climate.

Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota

BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients. METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker β7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with β7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFβ production by T cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.

The double Caldeira-Leggett model: Derivation and solutions of the master equations, reservoir-induced interactions and decoherence

In this paper we analyze the double Caldeira-Leggett model: the path integral approach to two interacting dissipative harmonic oscillators. Assuming a general form of the interaction between the oscillators, we consider two different situations: (i) when each oscillator is coupled to its own reservoir, and (ii) when both oscillators are coupled to a common reservoir. After deriving and solving the master equation for each case, we analyze the decoherence process of particular entanglements in the positional space of both oscillators. To analyze the decoherence mechanism we have derived a general decay function, for the off-diagonal peaks of the density matrix, which applies both to common and separate reservoirs. We have also identified the expected interaction between the two dissipative oscillators induced by their common reservoir. Such a reservoir-induced interaction, which gives rise to interesting collective damping effects, such as the emergence of relaxation- and decoherence-free subspaces, is shown to be blurred by the high-temperature regime considered in this study. However, we find that different interactions between the dissipative oscillators, described by rotating or counter-rotating terms, result in different decay rates for the interference terms of the density matrix. (C) 2010 Elsevier B.V. All rights reserved.

Expression of differential genes involved in the maintenance of water balance in human skin by Piptadenia colubrina extract

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Changes in abiotic characteristics of water in the Paranapanema River and three lateral lagoons at mouth zone of the Jurumirim Reservoir during the flood period, São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spatial and temporal distribution of the zoobenthos community during the filling up period of Porto Primavera Reservoir (Paraná River, Brazil)

Este estudo é parte do monitoramento limnológico empreendido pela Companhia Energética do Estado de São Paulo (CESP) durante o processo de enchimento do reservatório de Porto Primavera (Usina Hidrelétrica Engenheiro Sérgio Motta). Este reservatório, localizado no alto rio Paraná, entre os Estados de São Paulo e Mato Grosso, é o quarto maior do país. A primeira etapa de enchimento do lago começou em dezembro de 1998 e a segunda em março de 2001. Amostras para a análise da comunidade bentônica e das características sedimentológicas foram coletadas trimestralmente entre agosto de 1999 e novembro de 2001 e também em agosto de 2002 (11 campanhas). As coletas foram feitas em 13 estações de amostragem distribuídas no reservatório e em uma localizada a jusante da barragem. 128 táxons de invertebrados foram encontrados, sendo Mollusca, Annelida, Insecta e Nematoda os grupos dominantes durante praticamente todos os meses analisados. A classe Insecta foi a melhor representada, com 9 diferentes ordens, dentro das quais os Diptera contribuíram com a ocorrência de 63 táxons. A espécie exótica de bivalve Corbicula fluminea foi registrada em todas as estações de amostragem mostrando sua grande capacidade para colonizar novos habitats em regiões neotropicais. Variações consideráveis na densidade da fauna foram observadas para os diferentes períodos e locais analisados. A densidade máxima (média de 7812 ind.m-2) foi registrada no centro do reservatório enquanto que as densidades mínimas foram registradas na zona lacustre próxima à barragem (média de 9 ind.m-2). A maior riqueza de espécies por local/período (24 táxons) foi encontrada no trecho superior do reservatório (trecho fluvial). A diversidade máxima foi observada nas zonas superior e central do reservatório, com valores de 3.82 e 3.86 (bits.ind-1) no início (agosto/1999) e final (agosto/2002) do processo de enchimento, respectivamente. Não foi encontrado um padrão de distribuição dos grupos faunísticos que pudesse estar associado com a textura granulométrica dos diferentes locais amostrados. Por outro lado, constatou-se a diminuição, ou mesmo a não ocorrência de organismos, nas estações com elevada concentração de matéria orgânica (>40%) em baixo estado de degradação (grandes detritos vegetais). Tal fato pode estar relacionado com a falta de depósitos de sedimentos, dificultando a fixação de organismos da fauna bentônica, bem como com condições químicas mais redutoras em função da intensidade dos processos de decomposição da fitomassa inundada.

Immunologic aspects of West syndrome and evidence of plasma inhibitory effects on T cell function

OBJETIVO: O objetivo deste estudo foi determinar o perfil da deficiência imune em um grupo bem definido de epilepsia: crianças com síndrome de West (SW) e seus padrões EEG de evolução, idade-dependentes, como os complexos onda-aguda- onda lenta generalizadas da síndrome de Lenox-Gastaut (SLG) e as pontas multifocais independentes (PMI). MÉTODO: Um grupo de 50 crianças, 33 com SW, 10 com SLG, 7 com PMI e 20 crianças sadias (controle) foram avaliadas em relação aos seguintes parâmetros:determinação de subpopulações de linfócitos T (CD1, CD3, CD4 e CD8), relação CD4/CD8 e resposta proliferativa de linfócitos frente a fitohemaglutinina (PHA), na presença de plasma autólogo ou de plasma AB (homólogo). A prova cutânea de sensibilização ao Dinitroclorobenzeno (DNCB) foi realizada apenas nos pacientes. Os níveis séricos de IgG, IgA e IgM foram comparados aos valores normais em crianças Brasileiras, em diferentes faixas etárias. RESULTADOS: A resposta ao DNCB foi ausente ou fracamente reativa em 76% dos pacientes. Níveis séricos elevados de IgG (45,7%) e de IgM (61,4%) e baixos de IgA (23,9%) foram detectados nos pacientes. A determinação das subpopulações de linfócitos T em sangue periférico mostrou: deficiência nas proporções de células CD3+ (p<0,05) e de CD4+ (p<0,05), aumento de CD8+ (p<0,01) e diminuição da relação CD4 / CD8 (p<0,001). A proporção de células CD1+ no grupo controle manteve-se menor que 3%, enquanto que em 18% dos pacientes esses níveis variaram entre 3 e 11%. A resposta proliferativa de linfócitos frente a PHA revelou índices blastogênicos significativamente mais baixos apenas quando células dos pacientes foram cultivadas na presença do próprio plasma (plasma autólogo). Quando estas células foram cultivadas na presença de plasma AB, não se evidenciou diferença significativa em relação ao grupo controle. CONCLUSÃO: A imunodeficiência na SW caracterizou-se por: anergia, alteração de imunidade mediada por células e dos níveis de imunoglobulinas, presença de timócitos imaturos na circulação periférica e deficiência funcional de linfócitos T induzida por fatores plasmáticos inibidores. Discutem-se as principais evidências de disfunção imune como imunodeficiência e autoimunidade.

Diversity of fish species in the River Paranapanema Jurumirim Reservoir transition region (São Paulo, Brazil)

The diversity of fish species in an transition zone between the River Paranapanema and the head mouth of the Jurumirim Reservoir was evaluated. Fish samples were collected from October 1995 to September 1996, by experimental fishing (gill-nets and sieve), in three marginal shallow lagoons and two channel river zones, Gill-net collections resulted in 21 taxons of native fishes. Detritivorous Characiformes such as Steindachnerina insculpta were predominant Sieve collections resulted in 31 taxa and the Tetragonopterinae subfamily was the most representative group, which included small species as Cheirodon stenodon. The equitability index characterized the high heterogeneity of fish numeric abundance, reflecting the dominance of a few groups. A significant relationship between biotic and abiotic variables was indicated by the first canonical function. In comparison with other regions of the drainage basin, the ecotone zone studied indicated a higher species richness and, in the case of some species, fishes in all stages of development. This study demonstrated the necessity to preserve the ecological zone for the fishing and fishery management in the reservoir.

Testicular biopsy with Tru-Cut needle in conjunction with fibrin adhesive or nylon suture: assessment of post-biopsy testicular function in rams

Testicular biopsy has been a complementary technique for clinical and research purposes to evaluate reproductive function in males. However, hemorrhage, inflammation, degeneration, and adhesion are factors that might limit the use of this procedure. In order to minimize these potential problems, fibrin glue derived from snake venom, a tissue adhesive with sealing, hemostatic, and healing properties, was used in conjunction with bilateral testicular biopsy with the Tru-Cut needle and was compared with a more conventional technique that uses nylon suture. Thirty mature rams were randomly assigned to three groups of 10 animals each, as follows: nonsurgical control group (no scrotal surgery, or biopsy); biopsy + glue group (fibrin glue on puncture sites and skin incisions) and biopsy + suture group (compression with swab on puncture sites and suturing of skin incision). The surgeries of the rams in the biopsy groups were performed on the same day, which was designated Day 0 for all three groups. Data of scrotal circumference, number of spermatozoa per ejaculum, percentage of morphologically abnormal spermatozoa, spermatozoa motility, and serum testosterone concentrations from Days -7, 20, 40, 60, 80 and 100 were evaluated. There were no significant differences between groups within days for any of the parameters evaluated. In conclusion, the testicular biopsy procedure using the Tru-Cut needle in conjunction with conventional nylon suture or the more novel fibrin glue in rams did not affect any of the parameters of testicular function evaluated in this study and was shown to be relatively simple, safe and efficient. (C) 2002 Published by Elsevier B.V. B.V.

Artificial reefs and their effects on fish assemblages in a Brazilian reservoir and Tailrace

In this paper, we evaluate the effects of artificial reefs on fish assemblages in a hypereutrophic reservoir and in the lotic zone immediately below dam. Fish diversity was highest in the lotic zone relative to the reservoir. We also found an inverse relationship between diversity and distance from the river margin. Catches near the artificial reefs were more diverse than in control areas. A seasonal effect, possibly caused by variation in temperature, was significant in all comparisons. We argue that, in a scale of local effects, the ecological function of these structures would be similar to refuges.

Software for calculation of reservoir active capacity with the sequent-peak algorithm

It is presented a software developed with Delphi programming language to compute the reservoir's annual regulated active storage, based on the sequent-peak algorithm. Mathematical models used for that purpose generally require extended hydrological series. Usually, the analysis of those series is performed with spreadsheets or graphical representations. Based on that, it was developed a software for calculation of reservoir active capacity. An example calculation is shown by 30-years (from 1977 to 2009) monthly mean flow historical data, from Corrente River, located at São Francisco River Basin, Brazil. As an additional tool, an interface was developed to manage water resources, helping to manipulate data and to point out information that it would be of interest to the user. Moreover, with that interface irrigation districts where water consumption is higher can be analyzed as a function of specific seasonal water demands situations. From a practical application, it is possible to conclude that the program provides the calculation originally proposed. It was designed to keep information organized and retrievable at any time, and to show simulation on seasonal water demands throughout the year, contributing with the elements of study concerning reservoir projects. This program, with its functionality, is an important tool for decision making in the water resources management.

Does spinal block through tattooed skin cause histological changes in nervous tissue and meninges?: an experimental model in rabbits

Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles. Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 μL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain. None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Tissue coring containing ink pigments was noted in all GI smears from the spinal needles used to puncture the tattooed skin. On the basis of the present results, intrathecal injection of saline through a needle inserted through tattooed skin is capable of producing histological changes over the meninges of rabbits. Ink fragments were entrapped inside the spinal needles, despite the presence of a stylet.

Soybean yield in relation to distance from the Itaipu reservoir

Crops close to small water bodies may exhibit changes in yield if the water mass causes significant changes in the microclimate of areas near the reservoir shoreline. The scientific literature describes this effect as occurring gradually, with higher intensity in the sites near the shoreline and decreasing intensity with distance from the reservoir. Experiments with two soybean cultivars were conducted during four crop seasons to evaluate soybean yield in relation to distance from the Itaipu reservoir and determine the effect of air temperature and water availability on soybean crop yield. Fifteen experimental sites were distributed in three transects perpendicular to the Itaipu reservoir, covering an area at approximately 10 km from the shoreline. The yield gradient between the site closest to the reservoir and the sites farther away in each transect did not show a consistent trend, but varied as a function of distance, crop season, and cultivar. This finding indicates that the Itaipu reservoir does not affect the yield of soybean plants grown within approximately 10 km from the shoreline. In addition, the variation in yield among the experimental sites was not attributed to thermal conditions because the temperature was similar within transects. However, the crop water availability was responsible for higher differences in yield among the neighboring experimental sites related to water stress caused by spatial variability in rainfall, especially during the soybean reproductive period in January and February.

Net power optimization of an irreversible Otto cycle using ECOP and ecological function

This paper presents an analysis of an irreversible Otto cycle aiming to optimize the net power through ECOP and ecological function. The studied cycle operates between two thermal reservoirs of infinite thermal capacity, with internal irreversibilities derived from non-isentropic behavior of compression and expansion processes, irreversibilities from thermal resistance in heat exchangers and heat leakage from the high temperature reservoir to the low temperature reservoir. Analytical expressions are applied for the power outputs optimized by the ECOP, by the ecological function and by the maximum power criteria, in conjunction with a graphic analysis, in which some cycle operation parameters are analyzed for an increased comprehension of the effects of the irreversibilities in the optimized power.