Genetic Control of Mosquitoes: population suppression strategies

Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

Lethal effects of abamectin on the aquatic organisms Daphnia similis, Chironomus xanthus and Danio rerio

Abamectin is used as an acaricide and insecticide for fruits, vegetables and ornamental plants, as well as a parasiticide for animals. One of the major problems of applying pesticides to crops is the likelihood of contaminating aquatic ecosystems by drift or runoff. Therefore, toxicity tests in the laboratory are important tools to predict the effects of chemical substances in aquatic ecosystems. The aim of this study was to assess the potential hazards of abamectin to the freshwater biota and consequently the possible losses of ecological services in contaminated water bodies. For this purpose, we identified the toxicity of abamectin on daphnids, insects and fish. Abamectin was highly toxic, with an EC50 48 h for Daphnia similis of 5.1 ng L-1, LC50 96 h for Chironomus xanthus of 2.67 mu g L-1 and LC50 48 h for Danio rerio of 33 mu g L-1. (C) 2011 Elsevier Ltd. All rights reserved.

Synthesis and Photodynamic Effect of New Highly Photostable Decacationically Armed [60]- and [70]Fullerene Decaiodide Monoadducts To Target Pathogenic Bacteria and Cancer Cells

Novel water-soluble decacationically armed C-60 and C-70 decaiodide monoadducts, C-60- and C-70[>M(C3N6+C3)(2)], were synthesized, characterized, and applied as photosensitizers and potential nano-PDT agents against pathogenic bacteria and cancer cells. A high number of cationic charges per fullerene cage and H-bonding moieties were designed for rapid binding to the anionic residues displayed on the outer parts of bacterial cell walls. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C-70[>M(C3N6+C3)(2)] produced more HO center dot than C-60[>M(C3N6+C3)(2)], in addition to O-1(2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C-60[>M(C3N6+C3)(2)] and C-70[>M(C3N6+C3)(2)], respectively. The hypothesis is that O-1(2) can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO center dot to cause real damage.

Evaluation of the Sensitivity of Freshwater Organisms Used in Toxicity Tests of Wastewater from Explosives Company

Explosives industries are a source of toxic discharge. The aim of this study was to compare organisms sensitivity (Daphnia similis, Danio rerio, Escherichia coli and Pseudomonas putida) in detecting acute toxicity in wastewater from two explosives, 2,4,6-TNT (TNT) and nitrocellulose. The samples were collected from an explosives company in the Paraiba Valley, So Paulo, Brazil. The effluents from TNT and nitrocellulose production were very toxic for tested organisms. Statistical tests indicated that D. similis and D. rerio were the most sensitive organisms for toxicity detection in effluents from 2,4,6-TNT and nitrocellulose production. The P. putida bacteria was the organism considered the least sensitive in indicating toxicity in effluents from nitrocellulose.

Genome Sequence of Exiguobacterium antarcticum B7, Isolated from a Biofilm in Ginger Lake, King George Island, Antarctica

Exiguobacterium antarcticum is a psychotropic bacterium isolated for the first time from microbial mats of Lake Fryxell in Antarctica. Many organisms of the genus Exiguobacterium are extremophiles and have properties of biotechnological interest, e. g., the capacity to adapt to cold, which make this genus a target for discovering new enzymes, such as lipases and proteases, in addition to improving our understanding of the mechanisms of adaptation and survival at low temperatures. This study presents the genome of E. antarcticum B7, isolated from a biofilm sample of Ginger Lake on King George Island, Antarctic peninsula.

The remarkable solar twin HIP 56948: a prime target in the quest for other Earths

Context. The Sun shows abundance anomalies relative to most solar twins. If the abundance peculiarities are due to the formation of inner rocky planets, that would mean that only a small fraction of solar type stars may host terrestrial planets. Aims. In this work we study HIP 56948, the best solar twin known to date, to determine with an unparalleled precision how similar it is to the Sun in its physical properties, chemical composition and planet architecture. We explore whether the abundances anomalies may be due to pollution from stellar ejecta or to terrestrial planet formation. Methods. We perform a differential abundance analysis (both in LTE and NLTE) using high resolution (R similar to 100 000) high S/N (600-650) Keck HIRES spectra of the Sun (as reflected from the asteroid Ceres) and HIP 56948. We use precise radial velocity data from the McDonald and Keck observatories to search for planets around this star. Results. We achieve a precision of sigma less than or similar to 0.003 dex for several elements. Including errors in stellar parameters the total uncertainty is as low as sigma similar or equal to 0.005 dex (1%), which is unprecedented in elemental abundance studies. The similarities between HIP 56948 and the Sun are astonishing. HIP 56948 is only 17 +/- 7 K hotter than the Sun, and log g, [Fe/H] and microturbulence velocity are only +0.02 +/- 0.02 dex, +0.02 +/- 0.01 dex and +0.01 +/- 0.01 km s(-1) higher than solar, respectively. Our precise stellar parameters and a differential isochrone analysis shows that HIP 56948 has a mass of 1.02 +/- 0.02 M-circle dot and that it is similar to 1 Gyr younger than the Sun, as constrained by isochrones, chromospheric activity, Li and rotation. Both stars show a chemical abundance pattern that differs from most solar twins, but the refractory elements (those with condensation temperature T-cond greater than or similar to 1000 K) are slightly (similar to 0.01 dex) more depleted in the Sun than in HIP 56948. The trend with T-cond in differential abundances (twins -HIP 56948) can be reproduced very well by adding similar to 3 M-circle plus of a mix of Earth and meteoritic material, to the convection zone of HIP 56948. The element-to-element scatter of the Earth/meteoritic mix for the case of hypothetical rocky planets around HIP 56948 is only 0.0047 dex. From our radial velocity monitoring we find no indications of giant planets interior to or within the habitable zone of HIP 56948. Conclusions. We conclude that HIP 56948 is an excellent candidate to host a planetary system like our own, including the possible presence of inner terrestrial planets. Its striking similarity to the Sun and its mature age makes HIP 56948 a prime target in the quest for other Earths and SETI endeavors.

The Role of Target Therapies in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Background: Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) may be one of the most prevalent forms of pulmonary arterial hypertension (PAH) worldwide. However, the clinical and hemodynamical response to specific PAH therapy in Sch-PAH is not known. Methods: We retrospectively analyzed the charts of all patients with Sch-PAH who initiated specific PAH treatment between June 2003 and June 2010 in a single PAH reference center in Sao Paulo, Brazil. Clinical and hemodynamical data were retrospectively collected and evaluated in two periods: baseline and posttreatment. Results: The study population consisted of 12 patients with Sch-PAH. They were treated with phosphodiseterase-5 inhibitors (seven patients), endothelin receptor antagonists (four patients), or combination therapy (one patient). Mean treatment period was 34.9 +/- 15.5 months. Patients with Sch-PAH presented significant improvements in terms of functional class, 6-min walk test distance (439 +/- 85 to 492 +/- 79 m, P = .032), cardiac index (2.66 +/- 0.59 to 3.08 +/- 0.68 L/min/m(2), P = .028), and indexed pulmonary vascular resistance (20.7 +/- 11.6 to 15.9 +/- 9 W/m(2), P = .038) with the introduction of specific PAH treatment. Conclusions: We conclude that specific PAH therapy may be of benefit to patients with Sch-PAH, considering clinical, functional, and hemodynamic parameters. CHEST 2012; 141(4):923-928

Evolution of time-control mechanisms in subterranean organisms: cave fishes under light-dark cycles (Teleostei: Siluriformes, Characiformes)

Subterranean organisms are excellent models for chronobiological studies, yet relatively few taxa have been investigated with this focus. Former results were interpreted as a pattern of regression of circadian locomotor activity rhythms in troglobitic (exclusively subterranean) species. In this paper we report results of experiments with cave fishes showing variable degrees of troglomorphism (reduction of eyes, melanic pigmentation and other specializations related to the hypogean life) submitted to light-dark cycles, preceded and followed by several days in constant darkness. Samples from seven species have been monitored in our laboratory for the detection of significant circadian rhythms in locomotor activity: S. typhlops, an extremely troglomophic species, presented the lowest number of significant components in the circadian range (only one individual out of eight in DD1 and three other fish in LD), all weak (low values of spectral power). Higher incidence of circadian components was observed for P. kronei - only one among six studied catfish without significant circadian rhythms under DD1 and DD2; spectral powers were generally high. Intermediate situations were observed for the remaining species, however all of them presented relatively strong significant rhythms under LD. Residual oscillations (circadian rhythms in DD2) were detected in at least part of the studied individuals of all species but S. typhlops, without a correlation with spectral powers of LD rhythms, i.e., individuals exhibiting residual oscillations were not necessarily those with the strongest LD rhythms. In conclusion, the accumulated evidence for troglobitic fishes strongly supports the hypothesis of external, environmental selection for circadian locomotor rhythms.

Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.

Evaluation of different selective media for enumeration of probiotic micro-organisms in combination with yogurt starter cultures in fermented milk

The aim of this study was to assess selective plating methodologies for the enumeration and identification of Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium animalis ssp. lactis in fermented milks. Seven agar media (MRS with added sorbitol, clindamycin or vancomycin, acidified MRS, RCA with added aniline blue and dicloxacilin, M17 and ST) were evaluated. The results showed that RCA dicloxacilin agar was suitable for the selective enumeration of B. animalis ssp. lactis in fermented milk. Either MRS (acidified) or M17 agar could be used for enumeration of L. delbrueckii ssp. bulgaricus and S. thermophilus, respectively. MRS media containing antibiotics were effective for the enumeration of the probiotic organisms (L. rhamnosus and L. acidophilus) inoculated in fermented milks.

The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase

Polyamine biosynthesis enzymes are promising drug targets for the treatment of leishmaniasis, Chagas' disease and African sleeping sickness. Arginase, which is a metallohydrolase, is the first enzyme involved in polyamine biosynthesis and converts arginine into ornithine and urea. Ornithine is used in the polyamine pathway that is essential for cell proliferation and ROS detoxification by trypanothione. The flavonols quercetin and quercitrin have been described as antitrypanosomal and antileishmanial compounds, and their ability to inhibit arginase was tested in this work. We characterized the inhibition of recombinant arginase from Leishmania (Leishmania) amazonensis by quercetin, quercitrin and isoquercitrin. The IC50 values for quercetin, quercitrin and isoquercitrin were estimated to be 3.8, 10 and 4.3 mu M, respectively. Quercetin is a mixed inhibitor, whereas quercitrin and isoquercitrin are uncompetitive inhibitors of L. (L.) amazonensis arginase. Quercetin interacts with the substrate L-arginine and the cofactor Mn2+ at pH 9.6, whereas quercitrin and isoquercitrin do not interact with the enzyme's cofactor or substrate. Docking analysis of these flavonols suggests that the cathecol group of the three compounds interact with Asp129, which is involved in metal bridge formation for the cofactors Mn-A(2+) and Mn-B(2+) in the active site of arginase. These results help to elucidate the mechanism of action of leishmanicidal flavonols and offer new perspectives for drug design against Leishmania infection based on interactions between arginase and flavones. (C) 2012 Elsevier Inc. All rights reserved.

Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases

Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies; that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of Sao Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

Gases and volatile compounds associated with micro-organisms in blown pack spoilage of Brazilian vacuum-packed beef

This study correlated the composition of the spoilage bacterial flora with the main gaseous and volatile organic compounds (VOCs) found in the package headspace of spoiled, chilled, vacuum-packed meat. Fifteen chilled, vacuum-packed beef samples, suffering from blown pack spoilage, were studied using 16S rRNA clone sequencing. More than 50% of the bacteria were identified as lactic acid bacteria (LAB), followed by clostridia and enterobacteria. Fifty-one volatile compounds were detected in the spoiled samples. Although the major spoilage compounds were identified as alcohols and aldehydes, CO2 was identified as the major gas in the spoiled samples by headspace technique. Different species of bacteria contribute to different volatile compounds during meat spoilage. LAB played an important role in blown pack deterioration of the Brazilian beef studied.

Identification and expression analysis of microRNAs and targets in the biofuel crop sugarcane

Abstract Background MicroRNAs (miRNAs) are small regulatory RNAs, some of which are conserved in diverse plant genomes. Therefore, computational identification and further experimental validation of miRNAs from non-model organisms is both feasible and instrumental for addressing miRNA-based gene regulation and evolution. Sugarcane (Saccharum spp.) is an important biofuel crop with publicly available expressed sequence tag and genomic survey sequence databases, but little is known about miRNAs and their targets in this highly polyploid species. Results In this study, we have computationally identified 19 distinct sugarcane miRNA precursors, of which several are highly similar with their sorghum homologs at both nucleotide and secondary structure levels. The accumulation pattern of mature miRNAs varies in organs/tissues from the commercial sugarcane hybrid as well as in its corresponding founder species S. officinarum and S. spontaneum. Using sugarcane MIR827 as a query, we found a novel MIR827 precursor in the sorghum genome. Based on our computational tool, a total of 46 potential targets were identified for the 19 sugarcane miRNAs. Several targets for highly conserved miRNAs are transcription factors that play important roles in plant development. Conversely, target genes of lineage-specific miRNAs seem to play roles in diverse physiological processes, such as SsCBP1. SsCBP1 was experimentally confirmed to be a target for the monocot-specific miR528. Our findings support the notion that the regulation of SsCBP1 by miR528 is shared at least within graminaceous monocots, and this miRNA-based post-transcriptional regulation evolved exclusively within the monocots lineage after the divergence from eudicots. Conclusions Using publicly available nucleotide databases, 19 sugarcane miRNA precursors and one new sorghum miRNA precursor were identified and classified into 14 families. Comparative analyses between sugarcane and sorghum suggest that these two species retain homologous miRNAs and targets in their genomes. Such conservation may help to clarify specific aspects of miRNA regulation and evolution in the polyploid sugarcane. Finally, our dataset provides a framework for future studies on sugarcane RNAi-dependent regulatory mechanisms.

Mönckeberg's sclerosis – is the artery the only target of calcification?

Abstract Background Since its first description, Mönckeberg's sclerosis has only been related to arterial media calcification, being listed among the primary diseases of the vessels. Case presentation We report here a clinically and histologically confirmed case of Mönckeberg's sclerosis in which the patient presented with massive areas of soft tissue calcifications in the pharynx and larynx. Polysomnographic parameters showed severe obstructive apnea refractory to nasal continuous positive airway pressure. Clinical and laboratory findings excluded concomitant endocrine or rheumatological diseases. Conclusion Our data provide a new insight about Mönckeberg's sclerosis, i.e., the fact that the etiopathogenic process involved in the phenomenon of calcification may not be restricted only to the arteries, but may occur in the entire organism. Further studies of the etiopathogenesis of this disease are needed.