The continued interest in 2D carbon allotropes stems from their unique structural and electronic characteristics, which are crucial for diverse applications. This work theoretically introduces ...PHOTH-Graphene (PHOTH-G), a novel 2D planar carbon allotrope formed by 4-5-6-7-8 carbon rings. PHOTH-G emerges as a narrow band gap semiconducting material with low formation energy, demonstrating good stability under thermal and mechanical conditions. This material has slight mechanical anisotropy with Young modulus and Poisson ratios varying between 7.08-167.8 GPa and 0.21-0.96. PHOTH-G presents optical activity restricted to the visible range. Li atoms adsorbed on its surface have a migration barrier averaging 0.38 eV.
•Nanocrystals as high resolution three-photon excited luminescent nanothermometers.•Pump induced local heating as self-referenced photo-thermal agent.•Outstanding applications in the development of ...controlled hyperthermia.•Tm/Yb:NaNbO3 nanoparticles as self-monitored photo-thermal agents.
In this paper we report on Thulium/Ytterbium codoped sodium niobate (NaNbO3) colloidal nanocrystals as high resolution luminescent nanothermometers operating under three-photon excitation. The spectral shape of the Thulium (1G4→3H6) luminescence band at 480nm after 980nm (Ytterbium) excitation has been analyzed in detail in the biophysical temperature range. It has been found that the population re-distribution among the thermally coupled stark levels could be successfully used for ratiometric thermal sensing. The thermal sensitivity of the three photon excited luminescence has been successfully used to evaluate, in a single-beam experiment, the light induced thermal loading taking place in 940nm excited NaNbO3:Tm3+/Yb3+ nanocrystals.
The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz.
In this multicentre, open-label, randomised trial, 1216 ...antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log
10 decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression new Centers for Disease Control and Prevention grade C event or death, or change of allocated treatment). Analyses were by intention to treat.
Treatment failure occurred in 96 (43·6%) of 220 patients assigned nevirapine once daily, 169 (43·7%) of 387 assigned nevirapine twice daily, 151 (37·8%) of 400 assigned efavirenz, and 111 (53·1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5·9% (95% CI −0·9 to 12·8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0·193) or the increases in CD4-positive cells (p=0·800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine.
Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.
The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis treatment outcomes. Host-directed therapies (HDT) pose an ...complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozide's and Fluspirilene's efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.
Development of cavity ring-down spectroscopy (CRDS) has enabled real-time monitoring of carbon stable isotope ratios of carbon dioxide and methane in air. Here we demonstrate that CRDS can be adapted ...to assess aquatic carbon cycling processes from microbial to ecosystem scales. We first measured in situ isotopologue concentrations of dissolved CO2 (12CO2 and 13CO2) and CH4 (12CH4 and 13CH4) with CRDS via a closed loop gas equilibration device during a survey along an estuary and during a 40 h time series in a mangrove creek (ecosystem scale). A similar system was also connected to an in situ benthic chamber in a seagrass bed (community scale). Finally, a pulse-chase isotope enrichment experiment was conducted by measuring real-time release of 13CO2 after addition of 13C enriched phytoplankton to exposed intertidal sediments (microbial scale). Miller-Tans plots revealed complex transformation pathways and distinct isotopic source values of CO2 and CH4. Calculations of δ13C-DIC based on CRDS measured δ13C-CO2 and published fractionation factors were in excellent agreement with measured δ13C-DIC using isotope ratio mass spectroscopy (IRMS). The portable CRDS instrumentation used here can obtain real-time, high precision, continuous greenhouse gas data in lakes, rivers, estuaries and marine waters with less effort than conventional laboratory-based techniques.
Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new ...drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation-results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.
Abstract
Background
Dengue virus (DENV) and Zika virus (ZIKV) have a severe impact on human health worldwide. To understand the dynamics of these viruses in mosquito populations, it is necessary to ...maintain surveillance during non-epidemic years.
Methods
We aimed to assess the presence of DENV and ZIKV in Aedes aegypti females in the state of Sergipe, northeastern Brazil, during a non-epidemic year. The Ae. aegypti females collected were sectioned, and the heads and thorax were used to analyze the infection rate. Each female was first analyzed to detect Flavivirus using RT-PCR. Flavivirus-positive samples were further screened to detect ZIKV and DENV types 1, 2, 3 and 4.
Results
A total of 184 females were collected. ZIKV was identified in 5.4% of the sample and DENV in 7.1%, with the DENV-positive samples belonging to subtypes 2, 3 and 4. The presence of coinfected vectors was also observed. Of the four cities tested, only one was negative for all viruses.
Conclusions
These results show that the maintenance of vigilance during non-epidemic years can provide data on viruses circulating before the onset of outbreaks. This can enable the planning and implementation of local control measures to prevent the appearance of new outbreaks.
BMPOS Pylro, Victor S.; Morais, Daniel K.; de Oliveira, Francislon S. ...
Microbial ecology,
08/2016, Letnik:
72, Številka:
2
Journal Article
Recenzirano
Recent advances in science and technology are leading to a revision and re-orientation of methodologies, addressing old and current issues under a new perspective. Advances in next generation ...sequencing (NGS) are allowing comparative analysis of the abundance and diversity of whole microbial communities, generating a large amount of data and findings at a systems level. The current limitation for biologists has been the increasing demand for computational power and training required for processing of NGS data. Here, we describe the deployment of the Brazilian Microbiome Project Operating System (BMPOS), a flexible and user-friendly Linux distribution dedicated to microbiome studies. The Brazilian Microbiome Project (BMP) has developed data analyses pipelines for metagenomic studies (phylogenetic marker genes), conducted using the two main high-throughput sequencing platforms (Ion Torrent and Illumina MiSeq). The BMPOS is freely available and possesses the entire requirement of bioinformatics packages and databases to perform all the pipelines suggested by the BMP team. The BMPOS may be used as a bootable live USB stick or installed in any computer with at least 1 GHz CPU and 512 MB RAM, independent of the operating system previously installed. The BMPOS has proved to be effective for sequences processing, sequences clustering, alignment, taxonomic annotation, statistical analysis, and plotting of metagenomic data. The BMPOS has been used during several metagenomic analyses courses, being valuable as a tool for training, and an excellent starting point to anyone interested in performing metagenomic studies. The BMPOS and its documentation are available at http://www.brmicrobiome.org.
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