The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

UNLABELLED: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116.

The High Prevalence and Diversity of Chlamydiales DNA within Ixodes ricinus Ticks Suggest a Role for Ticks as Reservoirs and Vectors of Chlamydia-Related Bacteria.

The Chlamydiales order is composed of nine families of strictly intracellular bacteria. Among them, Chlamydia trachomatis, C. pneumoniae, and C. psittaci are established human pathogens, whereas Waddlia chondrophila and Parachlamydia acanthamoebae have emerged as new pathogens in humans. However, despite their medical importance, their biodiversity and ecology remain to be studied. Even if arthropods and, particularly, ticks are well known to be vectors of numerous infectious agents such as viruses and bacteria, virtually nothing is known about ticks and chlamydia. This study investigated the prevalence of Chlamydiae in ticks. Specifically, 62,889 Ixodes ricinus ticks, consolidated into 8,534 pools, were sampled in 172 collection sites throughout Switzerland and were investigated using pan-Chlamydiales quantitative PCR (qPCR) for the presence of Chlamydiales DNA. Among the pools, 543 (6.4%) gave positive results and the estimated prevalence in individual ticks was 0.89%. Among those pools with positive results, we obtained 16S rRNA sequences for 359 samples, allowing classification of Chlamydiales DNA at the family level. A high level of biodiversity was observed, since six of the nine families belonging to the Chlamydiales order were detected. Those most common were Parachlamydiaceae (33.1%) and Rhabdochlamydiaceae (29.2%). "Unclassified Chlamydiales" (31.8%) were also often detected. Thanks to the huge amount of Chlamydiales DNA recovered from ticks, this report opens up new perspectives on further work focusing on whole-genome sequencing to increase our knowledge about Chlamydiales biodiversity. This report of an epidemiological study also demonstrates the presence of Chlamydia-related bacteria within Ixodes ricinus ticks and suggests a role for ticks in the transmission of and as a reservoir for these emerging pathogenic Chlamydia-related bacteria.

From Regional Landslide Detection to Site-Specific Slope Deformation Monitoring and Modelling Based on Active Remote Sensors

Landslide processes can have direct and indirect consequences affecting human lives and activities. In order to improve landslide risk management procedures, this PhD thesis aims to investigate capabilities of active LiDAR and RaDAR sensors for landslides detection and characterization at regional scales, spatial risk assessment over large areas and slope instabilities monitoring and modelling at site-specific scales. At regional scales, we first demonstrated recent boat-based mobile LiDAR capabilities to model topography of the Normand coastal cliffs. By comparing annual acquisitions, we validated as well our approach to detect surface changes and thus map rock collapses, landslides and toe erosions affecting the shoreline at a county scale. Then, we applied a spaceborne InSAR approach to detect large slope instabilities in Argentina. Based on both phase and amplitude RaDAR signals, we extracted decisive information to detect, characterize and monitor two unknown extremely slow landslides, and to quantify water level variations of an involved close dam reservoir. Finally, advanced investigations on fragmental rockfall risk assessment were conducted along roads of the Val de Bagnes, by improving approaches of the Slope Angle Distribution and the FlowR software. Therefore, both rock-mass-failure susceptibilities and relative frequencies of block propagations were assessed and rockfall hazard and risk maps could be established at the valley scale. At slope-specific scales, in the Swiss Alps, we first integrated ground-based InSAR and terrestrial LiDAR acquisitions to map, monitor and model the Perraire rock slope deformation. By interpreting both methods individually and originally integrated as well, we therefore delimited the rockslide borders, computed volumes and highlighted non-uniform translational displacements along a wedge failure surface. Finally, we studied specific requirements and practical issues experimented on early warning systems of some of the most studied landslides worldwide. As a result, we highlighted valuable key recommendations to design new reliable systems; in addition, we also underlined conceptual issues that must be solved to improve current procedures. To sum up, the diversity of experimented situations brought an extensive experience that revealed the potential and limitations of both methods and highlighted as well the necessity of their complementary and integrated uses.

Efeito do campo magnético na precipitação de parafinas

In the oil industry, the paraffination phenomenon is a major problem during oil production, displacement and treatment. Paraffin deposition in subsea flowlines, surface equipment, production string or even in the reservoir, can cause significant and increasing oil losses. To minimize paraffin precipitation, the application of magnetic field in the petroleum path has been suggested based on empiric studies. In this study, we assembled a labscale magnetic conditioner to determine the influence of magnetic field on the physical-chemical properties of two fluids : oil and a paraffin mixture. We observed that magnetic field reduce sample aparent viscosity due to crystal morphology alteration.

Automatização de um destilador d'água

A simple and inexpensive device to automate a water distilling apparatus is shown. It is composed by a magnetic floater placed in the water reservoir and a level control unit, which acts over the heating element circuit. In order to provide water saving, an electromagnetic valve is inserted in the water supply inlet. Some suggestions for the adaptation to other types of equipment are also offered.

Bordetella pertussis - Vaccination and Strain Variation

Pertussis or whooping cough is a highly contagious vaccine-preventable disease of the human respiratory tract caused by the Bordetella pertussis bacteria. In Finland, pertussis vaccinations were started in 1952 leading to a dramatic decrease in the morbidity and mortality. In the late 1990s, the incidence of pertussis increased despite the high vaccination coverage. Strain variation has been connected to the re-emergence of pertussis in countries with long history of pertussis vaccination. In 2005, the pertussis vaccine and the vaccination schedule were changed in Finland. The molecular epidemiology and the strain variation of the B. pertussis isolates were examined in Finland and in countries with similar (France) and different (Sweden) vaccination history. Continuous evolution of the B. pertussis population in Finland was observed since the 1950s, and the recently circulating isolates were antigenically different from the vaccine strains. Comparison of the circulating isolates from Finland, France and Sweden did not refer to significant differences. Certain type of strains noticed in France already in 1994 mainly caused the recent epidemics in Sweden (1999) and in Finland (2003-4). On several occasions, a new type of strains first appeared in Sweden and some years later in Finland. The B. pertussis isolates from the infants were shown to be similar to those from the other age groups. It is suggested that the strains originate from the same reservoir among adolescents and adults. The strain variation does not seem to have a major effect on the morbidity among recently vaccinated individuals, but it might play a role among those who are in the waning phase of immunity. The incidence of pertussis in Finland has remained low since the change of the vaccination programme. This might be related to the epidemic nature of pertussis and the near future will show the real effectiveness of the new vaccination programme. At present, many infants are infected because they are too young to be immunised with the current schedule. New strategies or vaccines are needed to protect those who are the most vulnerable.

Relações da atividade agropecuária com parâmetros físicos químicos da água

Water Quality Index (WQI) was used during summer and winter of 1994 and 1995 in the final section of Onça and Feijão streams, downstream Broa Reservoir (São Carlos/SP) to evaluate agricultural and catlleman effects. In Onça stream water quality was "acceptable" in winter and "inappropriate to conventional treatment" in the summer. In Feijão stream the water had an "excellent" quality in winter and "good" in the summer. A MANOVA (Multivariate Analysis of Variance) has used to discriminate seasons and streams. Correlation (p<0,05) among the variables was tested. Water temperature, turbidity, pH and fecal bacteria are highly correlated and can be one of the factors that cause WQI change by seasons.

Propulsor pneumático versátil e isento de pulsação para sistemas de análise em fluxo

Aquarium air pumps are proposed and evaluated as pneumatic liquid propulsion devices for flow injection and continuos flow analysis (FIA and CFA) systems. This kind of pump is widely available at a very low cost and it can sustain a pressure around of 4 psi (0.28 bar) indefinitely. By applying this air pressure onto a solution contained in a reservoir flask, it is possible to reach flow rates of up to 12.5 mL min-1 for circuits comprising reactors, made from 0.8 i.d. tubing with a length of 100 cm. The precise adjustment of flow rate below the maximum one can be made with a simplified needle valve or inserting in series a short length of capillary tube. The absence of flow pulsation is a definite advantage in comparison with peristaltic pumps, especially when amperometric detection is elected, as confirmed experimentally in FIA and CF applications.

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP

Confecção de um perfurador de lamínulas de vidro por corrosão ácida

A simple device for glass plate drilling, which is an important step in microfabrication procedures, is described. A reservoir of concentrated hydrofluoric acid with a hole in its bottom is affixed against the glass plate. Leakage is prevented by using a neoprene O-ring. A plastic pipet tip inserted in the reservoir, close to the corrosion region, provides forced convection by pressure variations inside it. A device to make 5 simultaneous holes in a plate is also presented. For a 140 µm thickness alkaline glass lamina and 1/8" O-ring, 5 holes are drilled in 20 min.

Carbono do solo e a mitigação da mudança climática global

The soils of the world contain more carbon than the combined total amounts occurring in vegetation and the atmosphere. Hence soils are a major reservoir of carbon in terrestrial ecosystems and an important sink. Recently, emphasis has been placed on the need to sequester carbon from atmospheric carbon dioxide into soil organic matter because of international concerns about greenhouse gas emissions and global climate change. The best strategies to built-up carbon stocks in the soil are basically those that increase the input of organic matter to the soil, and/or decrease the rate of soil organic matter decomposition. Grain crop systems based on soil ploughing and harrowing lead to CO2 emissions combined with tremendous soil losses. In Brazil, no-tillage system was introduced to combat soil erosion by water and this soil management led to the build-up of soil carbon stocks with simultaneous high crop yields. However, the present procedure used to quantify carbon stocks in soils is laborious and of high cost. The use of infrared spectroscopy is very promising as an alternative low-cost method of soil carbon determination.

First record of the common bream (Abramis brama) introduced to the Iberian Peninsula

This is the first record of the common bream, Abramis brama (Linnaeus, 1758), introduced into the Iberian Peninsula. Eight individuals of this cyprinid fish species were captured (of a total of 978 fish) in the Boadella Reservoir (Catalonia, Spain) on August 18, 2004. This reservoir is only 14 km away from France, where the bream is native, and contains several exotic freshwater fish that are still not widespread in Spain. The further introduction of species and the illegal translocation of the bream by anglers to other Iberian river basins should be controlled by the Spanish administration

Persistent organic pollutants in two reservoirs along the Paraíba do Sul-Guandu River system, Rio de Janeiro, Brazil

Sediment contamination is evaluated by determining organic micropollutants (organochlorine compounds - OCs and polycyclic aromatic hydrocarbons - PAHs) in two important Brazilian water reservoirs. Trace levels of OCs were observed in the Santana reservoir (44.8 ng g-1 d.w. of p,p'-DDT), while in the Funil reservoir the levels were below detection level. Forty-eight percent of the found sigmaocs were polychlorinated biphenyls, 29% dichlorodiphenyltrichloroethane (DDT), 18% Drins, and 5% other pesticides (HCB, Heptachlor, Heptachlor-epoxide, gamma-HCH and a-Endosulfan). We observed lower levels of sigmaPAH in the Funil reservoir (1 to 275 ng g-1d.w.) than in the Santana reservoir (2.2 to 26.7 µg g-1 d.w.).