Vertebral osteomyelitis is characterised by increased RANK/OPG and RANKL/OPG expression ratios in vertebral bodies and intervertebral discs.

Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients. 14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism. Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs. In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO.

[Antibiotic stewardship (ABS)-strategies for urologists in private practice and hospitals]. / "Antibiotic-stewardship"(ABS)-Strategien in der urologischen Praxis und Klinik.

Antibiotics are effective and safe drugs which have saved millions of lives since their inception. The World Health organization (WHO) has identified increasing antibiotic resistance worldwide as one of the greatest health problems of our time. The most common indications for antibiotic therapy include urinary tract infections, but according to current data, a very high percentage of these are not treated in accordance with guidelines. To prevent the continuous selection of resistant bacteria, and undesirable or even dangerous side effects such as by avoiding damage to the patient's microbiome, strategies through antibiotic stewardship (ABS) are urgently needed. Especially for urologists in outpatient care, this requires new, innovative and sustainable training concepts that keep knowledge continuously up-to-date and support appropriate antibiotic prescriptions.

Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO).

Trimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO uptake into renal proximal tubular cells. Here we investigated the potential role of multidrug and toxin extrusion protein 1 (MATE1) for translocation of TMAO across the luminal membrane of proximal tubular cells. HEK293 cells stably expressing OCT2 (HEK-OCT2) or MATE1 (HEK-MATE1) were used for uptake studies. Transcellular transport of TMAO was investigated using monolayers of MDCK control cells (MDCK-Co) as well as single- (MDCK-OCT2, MDCK-MATE1) and double-transfected cells (MDCK-OCT2-MATE1). In line with previous studies, HEK-OCT2 cells revealed a 2.4-fold uptake of TMAO compared to control cells (p < 0.001), whereas no significant uptake was observed in HEK-MATE1. In monolayers of MDCK cells, polarised TMAO transcellular transport was not significantly different between MDCK-Co and MDCK-OCT2 cells, but significantly increased in MDCK-MATE1 (p < 0.05) and MDCK-OCT2-MATE1 cells (p < 0.001). The OCT/MATE inhibitor trimethoprim abolished TMAO translocation in MDCK-OCT2-MATE1 cells (p < 0.05). The present data suggest that MATE1 contributes to renal elimination of TMAO. For selected MATE substrates, such as TMAO, uptake studies using non-polarised MATE-expressing cells can reveal false negative results compared to studies using polarised monolayers.

Reference point insensitive molecular data analysis.

MOTIVATION: In biomedicine, every molecular measurement is relative to a reference point, like a fixed aliquot of RNA extracted from a tissue, a defined number of blood cells, or a defined volume of biofluid. Reference points are often chosen for practical reasons. For example, we might want to assess the metabolome of a diseased organ but can only measure metabolites in blood or urine. In this case, the observable data only indirectly reflects the disease state. The statistical implications of these discrepancies in reference points have not yet been discussed. RESULTS: Here, we show that reference point discrepancies compromise the performance of regression models like the LASSO. As an alternative, we suggest zero-sum regression for a reference point insensitive analysis. We show that zero-sum regression is superior to the LASSO in case of a poor choice of reference point both in simulations and in an application that integrates intestinal microbiome analysis with metabolomics. Moreover, we describe a novel coordinate descent based algorithm to fit zero-sum elastic nets. AVAILABILITY AND IMPLEMENTATION: The R-package "zeroSum" can be downloaded at https://github.com/rehbergT/zeroSum Moreover, we provide all R-scripts and data used to produce the results of this manuscript as Supplementary Material CONTACT: Michael.Altenbuchinger@ukr.de, Thorsten.Rehberg@ukr.de and Rainer.Spang@ukr.deSupplementary information: Supplementary material is available at Bioinformatics online.

Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation.

Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 µmoL/mmoL crea, P<0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome.

Coleoptera associated with macrophytes of the genus Salvinia in four oxbow lakes in two river basins in southeast Brazil.

Macrophytes in oxbow lakes represent an important substrate for the Coleoptera. Two oxbow lakes the Rio Paranapanema were studied and the other two Rio Mogi-Guaçu, in the State de São Paulo, Brasil. In this study, there is greater similarity between the communities of Coleoptera of lakes greater connectivity with the main river channel or the difference in the species of Salvinia collected in the lakes studied interferes Coleoptera fauna that uses as substrate. A total of 9,222 specimens of Coleoptera were collected and identified in 10 families and 40 genera. The analysis MDS for abundance of Coleoptera showed the grouping of the oxbow lakes the Paranapanema River and a distancing the oxbow lakes the Mogi-Guaçu. The PERMANOVA test did not reveal any difference in the fauna between the wet and dry periods. It was concluded that the connectivity between river and lake is not decisive for the richness and abundance of aquatic fauna of Coleoptera. Therefore, the richness and abundance of aquatic Coleoptera associated vary with the species of Salvinia used as substrate.

Coleoptera associated with macrophytes of the genus Salvinia in four oxbow lakes in two river basins in southeast Brazil

Abstract Macrophytes in oxbow lakes represent an important substrate for the Coleoptera. Two oxbow lakes the Rio Paranapanema were studied and the other two Rio Mogi-Guaçu, in the State de São Paulo, Brasil. In this study, there is greater similarity between the communities of Coleoptera of lakes greater connectivity with the main river channel or the difference in the species of Salvinia collected in the lakes studied interferes Coleoptera fauna that uses as substrate. A total of 9,222 specimens of Coleoptera were collected and identified in 10 families and 40 genera. The analysis MDS for abundance of Coleoptera showed the grouping of the oxbow lakes the Paranapanema River and a distancing the oxbow lakes the Mogi-Guaçu. The PERMANOVA test did not reveal any difference in the fauna between the wet and dry periods. It was concluded that the connectivity between river and lake is not decisive for the richness and abundance of aquatic fauna of Coleoptera. Therefore, the richness and abundance of aquatic Coleoptera associated vary with the species of Salvinia used as substrate.

Resumo As macrófitas em lagoas marginais constituem um importante substrato para os Coleoptera. Foram estudadas duas lagoas marginais ao Rio Paranapanema e outras duas ao Rio Mogi-Guaçu, no estado de São Paulo, Brasil. Neste estudo, haverá maior similaridade entre as comunidades de Coleoptera das lagoas de maior conectividade com o canal princial do rio ou a diferença na espécie de Salvinia coletada nas lagoas estudadas interfere na fauna de Coleoptera que a utiliza como substrato. Foram coligidos 9.222 espécimes de Coleoptera sendo identificadas 10 famílias e 40 gêneros. A análise MDS para abundância de Coleoptera mostrou o agrupamento das lagoas marginais ao Rio Paranapanema e um distanciamento das lagoas marginais ao Rio Mogi-Guaçu. Os resultados da análise PERMANOVA não mostraram diferença na composição faunística entre os períodos de chuva e seca. Concluiu-se que a conectividade entre rio e lagoa não é determinante para a riqueza e abundância da fauna de Coleoptera aquáticos. Portanto, a riqueza e a abundância de Coleoptera aquáticos associados variam com as espécies de Salvinia utilizadas como substrato.

Coleoptera associated with macrophytes of the genus Salvinia in four oxbow lakes in two river basins in southeast Brazil / Coleoptera associados à Salvinia em quatro lagoas marginais pertencentes a duas bacias hidrográficas no estado de São Paulo, Brasil

Abstract Macrophytes in oxbow lakes represent an important substrate for the Coleoptera. Two oxbow lakes the Rio Paranapanema were studied and the other two Rio Mogi-Guaçu, in the State de São Paulo, Brasil. In this study, there is greater similarity between the communities of Coleoptera of lakes greater connectivity with the main river channel or the difference in the species of Salvinia collected in the lakes studied interferes Coleoptera fauna that uses as substrate. A total of 9,222 specimens of Coleoptera were collected and identified in 10 families and 40 genera. The analysis MDS for abundance of Coleoptera showed the grouping of the oxbow lakes the Paranapanema River and a distancing the oxbow lakes the Mogi-Guaçu. The PERMANOVA test did not reveal any difference in the fauna between the wet and dry periods. It was concluded that the connectivity between river and lake is not decisive for the richness and abundance of aquatic fauna of Coleoptera. Therefore, the richness and abundance of aquatic Coleoptera associated vary with the species of Salvinia used as substrate.

Resumo As macrófitas em lagoas marginais constituem um importante substrato para os Coleoptera. Foram estudadas duas lagoas marginais ao Rio Paranapanema e outras duas ao Rio Mogi-Guaçu, no estado de São Paulo, Brasil. Neste estudo, haverá maior similaridade entre as comunidades de Coleoptera das lagoas de maior conectividade com o canal princial do rio ou a diferença na espécie de Salvinia coletada nas lagoas estudadas interfere na fauna de Coleoptera que a utiliza como substrato. Foram coligidos 9.222 espécimes de Coleoptera sendo identificadas 10 famílias e 40 gêneros. A análise MDS para abundância de Coleoptera mostrou o agrupamento das lagoas marginais ao Rio Paranapanema e um distanciamento das lagoas marginais ao Rio Mogi-Guaçu. Os resultados da análise PERMANOVA não mostraram diferença na composição faunística entre os períodos de chuva e seca. Concluiu-se que a conectividade entre rio e lagoa não é determinante para a riqueza e abundância da fauna de Coleoptera aquáticos. Portanto, a riqueza e a abundância de Coleoptera aquáticos associados variam com as espécies de Salvinia utilizadas como substrato.

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis.

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia.

Variation in body size of Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) in Atlantic Rainforest streams in response to hydraulic disturbance / Variação no tamanho corpóreo de Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) em córregos da Mata Atlântica sob perturbação hidráulica

In this study, patterns of body size of Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) were investigated along a gradient of change in speed of flow conditions in streams of low order in the Atlantic Rainforest in southeastern Brazil. Specifically, the hypothesis that the distribution of P. clavicornis larvae vary in size in response to variations in the speed of flow in streams was tested. A Surber sampler was used to collect larvae from the streambed during two sampling periods, defined by the rain regime: August in the dry season and February in the rainy season. Possible differences in mean measured body size were tested by analysis of variance (ANOVA). The ANOVA result indicated for all measurements on the larvae collected in first-order streams (head width, prothoracic width and total body length), there were significant differences indicating a morphometric variation due to changing hydraulic conditions, the smallest larvae being associated with the period of greater rainfall. However, the larger streams (3rd order), where the rain events had less impact on the larval size, varied widely. The results of this study suggest that the interstitial space is important for the protection of the larvae from water flow, and that populations of P. clavicornis have high plasticity, a key feature for the occupation of unstable environments for this species. These results are important for an understanding of the life history and behavioural characteristics of the species, which allow them to persist in streams along a gradient of flow disturbance.

Neste estudo, padrões de tamanho do corpo de Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) foram investigados ao longo de um gradiente de variação de velocidade da corrente em córregos de baixa ordem da Mata Atlântica. Especificamente, buscou-se testar a hipótese de que a distribuição de larvas de P. clavicornis com diferentes tamanhos corpóreos respondem às variações na velocidade da corrente em córregos. As coletas das larvas foram realizadas com um amostrador de Surber durante dois períodos amostrais, definidos pelo regime de chuvas: agosto - estação seca e fevereiro - estação chuvosa. Possíveis diferenças nas medidas de tamanho do corpo foram testadas através de uma análise de variância (ANOVA). Os resultados da ANOVA indicaram para todas as medidas das larvas coletadas nos córregos de primeira ordem (largura da cabeça, largura do protórax e comprimento total do corpo) encontramos diferenças significativas, indicando uma variação morfométrica com as mudanças das condições hidráulicas, onde as larvas menores foram associadas aos períodos de maior precipitação. No entanto, em córregos maiores (3a ordem), os eventos de chuva tiveram menor impacto no tamanho dos indivíduos, com a ocorrência de larvas com diferentes tamanhos. Os resultados deste estudo sugerem que os espaços intersticiais são importantes para a proteção das larvas contra a velocidade da corrente e que as populações de P. clavicornis possuem alta plasticidade, sendo uma característica fundamental para a ocupação desta espécie em ambientes instáveis. Esses resultados são importantes para a compreensão da história de vida e características comportamentais da espécie, que permitem persistir em córregos ao longo de gradiente de perturbação do fluxo.

Lignocellulolytic enzymes and bacteria associated with the digestive tracts of Stenochironomus (Diptera: Chironomidae) larvae.

We analyzed the digestive activity of the enzymes that digest cellulose and hemicellulose and the bacterial community that is capable of hydrolyzing wood compounds in the digestive tracts of Stenochironomus (Diptera: Chironomidae) larvae, which are miners of decomposing submerged tree and bush branches. Based on quantification of reducing sugars, these larvae have a limited capacity for cellulose degradation but a good capacity for xylan hydrolysis. We isolated 31 types of colonies from two larval morphotypes, of which 19 tested positive for the capacity to hydrolyze at least one of the four substrates that were used as the main carbon source in the culture media. Their woody compound degradation capacity was assessed using colorimetric tests. The bacteria were identified by the analysis of the 16S rRNA gene. None of the bacteria were capable of degrading lignin. The genus Pseudomonas had the greatest species richness; Bacillus spp exhibited the greatest capacity for degrading the different substrates, and Sphingobium was found in both morphotypes. Microorganisms participate in the degradation of wood consumed by Stenochironomus larvae. This is the first report of lignocellulolytic bacteria and enzymes in the digestive tracts of mining chironomids.

Variation in body size of Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) in Atlantic Rainforest streams in response to hydraulic disturbance.

In this study, patterns of body size of Phanocerus clavicornis Sharp, 1882 (Coleoptera: Elmidae: Larainae) were investigated along a gradient of change in speed of flow conditions in streams of low order in the Atlantic Rainforest in southeastern Brazil. Specifically, the hypothesis that the distribution of P. clavicornis larvae vary in size in response to variations in the speed of flow in streams was tested. A Surber sampler was used to collect larvae from the streambed during two sampling periods, defined by the rain regime: August in the dry season and February in the rainy season. Possible differences in mean measured body size were tested by analysis of variance (ANOVA). The ANOVA result indicated for all measurements on the larvae collected in first-order streams (head width, prothoracic width and total body length), there were significant differences indicating a morphometric variation due to changing hydraulic conditions, the smallest larvae being associated with the period of greater rainfall. However, the larger streams (3rd order), where the rain events had less impact on the larval size, varied widely. The results of this study suggest that the interstitial space is important for the protection of the larvae from water flow, and that populations of P. clavicornis have high plasticity, a key feature for the occupation of unstable environments for this species. These results are important for an understanding of the life history and behavioural characteristics of the species, which allow them to persist in streams along a gradient of flow disturbance.

Fatal anthrax infection in a heroin user from southern Germany, June 2012.

Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of Bacillus anthracis. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.

Water beetles in mountainous regions in southeastern Brazil.

Inventories provide information on the state of biodiversity at a site or for a geographic region. Species inventories are the basis for systematic study and critical to ecology, biogeography and identification of biological indicators and key species. They also provide key information for assessments of environmental change, for natural resource conservation or recovery of degraded ecosystems. Thus, inventories play a key role in planning strategies for conservation and sustainable use. This study aimed to inventory the fauna of water beetles, larvae and adults, in two mountainous regions in the state of São Paulo, in Serra da Mantiqueira (Parque Estadual de Campos do Jordão and Pindamonhangaba region) and in Serra do Mar (Santa Virgínia and Picinguaba Divisions) as well as to generate information about the habitats used by the different genera recorded. Specimens were collected in lotic and lentic systems, between the years 2005 to 2010. In total 14,492 specimens were collected and 16 families and 50 genera of Coleoptera were identified. This study in mountainous regions showed a significant portion of the faunal composition of South America and the state of São Paulo. The composition of the fauna, in terms of richness and abundance by family, indicated the predominance of Elmidae, followed by Hydrophilidae and Dytiscidae. Despite the diversity found, the results of estimated richness indicated the need for additional sampling effort for both regions, since the curves of estimated richness did not reach an asymptote, suggesting that new species can be found in future surveys.

Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs).

The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human ß-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin.

Macroinvertebrates in low-order streams in two fragments of Atlantic Forest in different states of conservation, in the State of São Paulo (Brazil).

The presence of a riparian forest is one of the main factors that act directly on the ecology of a fluvial system, and the relation of the forest and the lotic environments might have an important influence on the distribution of the macroinvertebrates. In this context, the benthic macroinvertebrate communities in four low-order streams in São Paulo (Brazil) were analysed, with the aim of assessing the state of recovery of the surrounding forest fragments. The benthic organisms were sampled in the winter, a period of low rainfall. Of the 6,331 specimens of macroinvertebrates collected, 124 taxa belonging to 48 families were identified. The results showed greater diversity in the Canchim Farm streams and greater abundance in the Lake Park streams. Cluster analysis showed that the stream Canchim distanced itself from the others, being considered reference.

Benthic macroinvertebrates of a tropical lake: Lake Caçó, MA, Brazil.

Benthic communities are highly relevant in the study of aquatic ecosystems, both for their role in the functioning of the ecosystem and also as markers or indicators of paleo-conditions. Their distribution, as in other communities, is conditioned by abiotic and biotic factors and to their interactions, which determine the structure of the community that is established. The aim of this study was to determine the taxonomic composition, abundance and spatial distribution of the benthic community, by collecting at 20 sampling sites in Caçó Lake (State of Maranhão, Brazil). Seasonal variation in these community parameters was analysed and related to the seasonal displacement of the Intertropical Convergence Zone. The results indicated that changes occur in the taxa richness, diversity and density of the benthic species of this lake that are mainly related to seasonality. All those parameters were higher in the dry than in the rainy period. The family Chironomidae (Diptera, Insecta) was the most important component of the community, representing approximately 50% of the total benthic fauna of the lake. The identification of the Chironomidae currently occurring in Lake Caçó is relevant, even at the genus level, considering the fact that this group produces fossilizing remains and could perhaps be good paleolimnological and paleoclimatic tracers that could be used to make inferences on past lake and climate conditions.

Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT.

MLL/AF4 and AML/MTG8 represent two leukemic fusion genes, which are most frequently found in infant acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), respectively. We examined the influence of MLL/AF4 and AML1/MTG8 fusion genes on the expression of TERT coding for the telomerase protein subunit, and subsequently telomerase activity in t(4;11)-positive ALL and t(8;21)-positive cell lines, respectively. MLL/AF4 suppression diminished telomerase activity and expression of TERT. Blocking pro-apoptotic caspase activation in conjunction with MLL/AF4 knockdown enhanced the inhibition of TERT gene expression, which suggests that MLL/AF4 depletion does not reduce TERT expression levels by inducing apoptosis. Knockdown of HOXA7, a direct transcriptional target of MLL/AF4 fusion gene, caused a reduction of telomerase and TERT to an extent similar to that observed with MLL/AF4 suppression. Chromatin immunoprecipitation of SEM cells, using ectopically expressed FLAG-tagged Hoxa7, indicates HOXA7 binding site in the TERT promoter region. Furthermore, suppression of the AML1/MTG8 fusion gene was associated with severely reduced clonogenicity, induction of replicative senescence, impaired TERT expression and accelerated telomere shortening. We thus present findings that show a mechanistic link between leukemic fusion proteins, essential for development and maintenance of leukemia, and telomerase, a key element of both normal and malignant self-renewal.

Benthic macroinvertebrates of a tropical lake: lake Caçó, MA, Brazil / Macroinvertebrados bentônicos de um lago tropical: lago Caço, MA, Brasil

Benthic communities are highly relevant in the study of aquatic ecosystems, both for their role in the functioning of the ecosystem and also as markers or indicators of paleo-conditions. Their distribution, as in other communities, is conditioned by abiotic and biotic factors and to their interactions, which determine the structure of the community that is established. The aim of this study was to determine the taxonomic composition, abundance and spatial distribution of the benthic community, by collecting at 20 sampling sites in Caçó Lake (State of Maranhão, Brazil). Seasonal variation in these community parameters was analysed and related to the seasonal displacement of the Intertropical Convergence Zone. The results indicated that changes occur in the taxa richness, diversity and density of the benthic species of this lake that are mainly related to seasonality. All those parameters were higher in the dry than in the rainy period. The family Chironomidae (Diptera, Insecta) was the most important component of the community, representing approximately 50 percent of the total benthic fauna of the lake. The identification of the Chironomidae currently occurring in Lake Caçó is relevant, even at the genus level, considering the fact that this group produces fossilizing remains and could perhaps be good paleolimnological and paleoclimatic tracers that could be used to make inferences on past lake and climate conditions.

As comunidades bentônicas são relevantes nos ecossistemas aquáticos devido ao seu papel no seu funcionamento e também como marcadores ou indicadores de paleocondições. Sua distribuição, similarmente à de outras comunidades, é condicionada por fatores abióticos e bióticos e pela interação entre eles, determinando a estrutura da comunidade que se estabelecerá. O objetivo do presente trabalho foi determinar a composição taxonômica, a abundância e a distribuição espacial da comunidade bentônica, amostrando-se em 20 pontos na lagoa do Caçó (Estado do Maranhão, Brasil). As variações sazonais nas características desta comunidade foram analisadas e relacionadas ao deslocamento sazonal da Zona de Convergência Intertropical. Os resultados indicaram que ocorrem mudanças na riqueza de taxons, diversidade e densidade da comunidade bentônica deste lago que são principalmente relacionadas à sazonalidade. Todas as variáveis analisadas foram maiores no período seco do que no chuvoso. Os organismos pertencentes à família Chironomidae (Diptera, Insecta) foram os mais importantes componentes da comunidade, representando aproximadamente 50 por cento do total da fauna. A identificação dos Chironomidae atualmente presentes no Lago Caçó, mesmo em nível de gênero, é relevante, considerando-se o fato de que as larvas deste grupo produzem remanescentes fósseis que podem ser bons traçadores paleolimnológicos e paleoclimáticos, podendo ser utilizados para fazer inferências sobre as condições passadas neste lago e no clima regional.