Sand fly fauna (Diptera: Psychodidae) from the Goytacazes National Forest and surrounding areas of southeastern Brazil

Most studies of the sand fly fauna in southeastern Brazil are conducted in the peridomiciliary environment of leishmaniasis endemic regions. Therefore, to increase the knowledge about diversity and richness of sand fly conservation areas, we describe here the sand fly fauna from the National Forest of Goytacazes (NFG), state of Espírito Santo, Brazil, and its surroundings areas. We also used sand fly fauna records from eight conservations units within the state of Espírito Santo to understand the similarity and relationships among them. The sand flies were simultaneously collected from June, 2008 to May, 2009 in two different environments: a preserved environment represented by the NFG and a modified environment represented by a peridomicile. To establish the similarity among the conservation units, we used a method very similar to parsimony analysis of endemism. We collected 2,466 sand fly specimens belonging to 13 species. Pressatia choti and Nyssomyia intermedia were the most abundant sand fly species. Ny. intermedia is a known vector of Leishmania braziliensis and epidemiological surveillance must be conducted in the area. We discuss aspects regarding the diversity of sand flies as well as the risk of transmission of Leishmania parasites in the area. We also provide for the first time a hypothesis of similarity relationships among conservation units within the state of Espírito Santo.     

Pre-clinical and clinical significance of heparanase in Ewing's sarcoma

Heparanase is an endoglycosidase that specifically cleaves heparan sulphate side chains of heparan sulphate proteoglycans, activity that is strongly implicated in cell migration and invasion associated with tumour metastasis, angiogenesis and inflammation. Heparanase up-regulation was documented in an increasing number of human carcinomas, correlating with reduced post-operative survival rate and enhanced tumour angiogenesis. Expression and significance of heparanase in human sarcomas has not been so far reported. Here, we applied the Ewing's sarcoma cell line TC71 and demonstrated a potent inhibition of cell invasion in vitro and tumour xenograft growth in vivo upon treatment with a specific inhibitor of heparanase enzymatic activity (compound SST0001, non-anticoagulant N-acetylated, glycol split heparin). Next, we examined heparanase expression and cellular localization by immunostaining of a cohort of 69 patients diagnosed with Ewing's sarcoma. Heparanase staining was noted in all patients. Notably, heparanase staining intensity correlated with increased tumour size (P = 0.04) and with patients' age (P = 0.03), two prognostic factors associated with a worse outcome. Our study indicates that heparanase expression is induced in Ewing's sarcoma and associates with poor prognosis. Moreover, it encourages the inclusion of heparanase inhibitors (i.e. SST0001) in newly developed therapeutic modalities directed against Ewing's sarcoma and likely other malignancies.     

Uric acid deposits and estivation in the invasive apple-snail, Pomacea canaliculata

The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45 days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20 min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.     

Detrimental effects of environmental tobacco smoke in relation to asthma severity

Background

Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown.

Methods

In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity.

Findings

From 2002–2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage.

Interpretation

ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.     

miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors

Introduction

Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information.

Methods

We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods.

Results

We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process.

Conclusion

This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.     

Differential expression of insect and plant specific adhesin genes, Mad1 and Mad2, in Metarhizium robertsii

Metarhizium robertsii is an entomopathogenic fungus that is also plant rhizosphere competent. Two adhesin-encoding genes, Metarhizium adhesin-like protein 1 (Mad1) and Mad2, are involved in insect pathogenesis or plant root colonization, respectively. Here we examined the differential expression of the Mad genes when grown on a variety of soluble (carbohydrates and plant root exudate) and insoluble substrates (locust, tobacco hornworm, and cockroach cuticle, chitin, tomato stems, cellulose, and starch) and during insect, Plutella xylostella, infection. On insect cuticles Mad1 was up regulated, whereas bean root exudate and tomato stems resulted in the up regulation of Mad2. During the early stages of insect infection Mad1 was expressed while Mad2 was not expressed until fungal hyphae emerged and conidiated on the insect cadaver. The regulation of Mad2 was compared to that of other stress-related genes (heat shock protein (Hsp)30, Hsp70, and starvation stress gene A (ssgA)). Mad2 was generally up regulated by nutrient starvation (similar to ssgA) but not by pH, temperature, oxidative or osmotic stresses. Whereas Hsp30 and Hsp70 were generally up regulated at 37 °C or by oxidative stress even under nutrient enriched conditions. We fused the promoter of the Mad2 gene to a marker gene (green fluorescent protein (GFP)) and confirmed that Mad2 was up regulated when M. robertsii was grown in the presence of nutrient starvation. Examination of the promoter region of Mad2 revealed that it possessed two copies of a stress-response element (STRE) known to be regulated under the general stress-response pathway.