Papel do ferro no mecanismo fungicida mediado pelo óxido nítrico de macrófagos murinos ativados com IFN-gama contra conídias do Paracoccidioides brasiliensis

Iron is an essential growth element of virtually all microorganisms and its restriction is one of the mechanisms used by macrophages to control microbial multiplication. Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis, an important systemic mycosis in Latin America, is inhibited in its conidia-to-yeast conversion in the absence of iron. We studied the participation of iron in the nitric oxide (NO)-mediated fungicidal mechanism against conidia. Peritoneal murine macrophages activated with 50U/mL of IFN-gamma or treated with 35 µM Deferoxamine (DEX) and infected with P. brasiliensis conidia, were co-cultured and incubated for 96 h in the presence of different concentrations of holotransferrin (HOLO) and FeS0(4). The supernatants were withdrawn in order to assess NO2 production by the Griess method. The monolayers were fixed, stained and observed microscopically. The percentage of the conidia-to-yeast transition was estimated by counting 200 intracellular propagules. IFN-gamma-activated or DEX-treated Mthetas presented marked inhibition of the conidia-to-yeast conversion (19 and 56%, respectively) in comparison with non-activated or untreated Mthetas (80%). IFN-gamma-activated macrophages produced high NO levels in comparison with the controls. Additionally, when the activated or treated-macrophages were supplemented with iron donors (HOLO or FeSO4), the inhibitory action was reversed, although NO production remained intact. These results suggest that the NO-mediated fungicidal mechanism exerted by IFN-gamma-activated macrophages against P. brasiliensis conidia, is dependent of an iron interaction.O ferro é elemento essencial para o crescimento de microrganismos e sua limitação é um dos mecanismos usados por macrófagos para controlar a multiplicação microbiana. Paracoccidioides brasiliensis, o agente da paracoccidioidomicose, uma das micoses sistêmicas mais importantes na América Latina, é inibido em sua conversão de conídia-à-levedura na ausência do ferro. Estudamos a participação do ferro no mecanismo fungicida mediado pelo óxido nítrico (NO) na sua interação com as conídias do fungo. Macrófagos peritoneais murinos ativados com 50U/mL de IFN-gama ou tratados com 35 µM Deferoxamina (DEX) e infectados com conídias do P. brasiliensis foram co-cultivados e incubados por 96 h na presença de concentrações diferentes de holotransferrina (HOLO) e FeS0(4). Os sobrenadantes foram retirados a fim de avaliar a produção de NO2 pelo método de Griess. Os macrófagos eram fixados, corados e observados ao microscópio. A porcentagem da transição de conídia-à-levedura foi estimada contando 200 propágulos intracelulares. Os macrófagos ativados com citocina ou tratados com DEX apresentaram inibição marcada da conversão de conídia-à-levedura (19 e 56%, respectivamente) em comparação com macrófagos controle (80%). Os macrófagos ativados com IFN-gama produziram elevação nos níveis de NO em comparação com macrófagos não-tratados ou não-activados. Adicionalmente, quando as monocapas ativadas ou tratadas foram suplementadas com doadores do ferro (HOLO ou FeSO4), a ação inibitória foi revertida embora a produção de NO permanecesse intacto. Estes resultados sugerem que o mecanismo fungicida mediado pelo NO exercido por macrófagos ativados com IFN-gama contra conídias do P. brasiliensis é dependente de uma interação do ferro

Sensor for Distance Measurement Using Pixel Grey-Level Information

An alternative method for distance measurement is presented, based on a radiometric approach to the image formation process. The proposed methodology uses images from an infrared emitting diode (IRED) to estimate the distance between the camera and the IRED. Camera output grey-level intensities are a function of the accumulated image irradiance, which is also related by inverse distance square law to the distance between the camera and the IRED. Analyzing camera-IRED distance, magnitudes that affected image grey-level intensities, and therefore accumulated image irradiance, were integrated into a differential model which was calibrated and used for distance estimation over a 200 to 600 cm range. In a preliminary model, the camera and the emitter were aligned

Empty substrate integrated waveguide technology for E plane high-frequency and high-performance circuits

Substrate integrated circuits (SIC) have attracted much attention in the last years because of their great potential of low cost, easy manufacturing, integration in a circuit board, and higher-quality factor than planar circuits. A first suite of SIC where the waves propagate through dielectric have been first developed, based on the well-known substrate integrated waveguide (SIW) and related technological implementations. One step further has been made with a new suite of empty substrate integrated waveguides, where the waves propagate through air, thus reducing the associated losses. This is the case of the empty substrate integrated waveguide (ESIW) or the air-filled substrate integrated waveguide (air-filled SIW). However, all these SIC are H plane structures, so classical H plane solutions in rectangular waveguides have already been mapped to most of these new SIC. In this paper a novel E plane empty substrate integrated waveguide (ESIW-E) is presented. This structure allows to easily map classical E plane solutions in rectangular waveguide to this new substrate integrated solution. It is similar to the ESIW, although more layers are needed to build the structure. A wideband transition (covering the frequency range between 33 GHz and 50 GHz) from microstrip to ESIW-E is designed and manufactured. Measurements are successfully compared with simulation, proving the validity of this new SIC. A broadband high-frequency phase shifter (for operation from 35 GHz to 47 GHz) is successfully implemented in ESIW-E, thus proving the good performance of this new SIC in a practical application.This work was supported by the Ministerio de Economía y Competitividad, Spanish Goverment, under research projects TEC2013-47037-C5-3-R, TEC2013-47037-C5-1-R, AYA2013-49759-EXP, and CSD2010-00064

The Spanish Infrared Camera onboard the EUSO-BALLOON (CNES) flight on August 24, 2014

The EUSO-Balloon (CNES) campaign was held during Summer 2014 with a launch on August 24. In the gondola, next to the Photo Detector Module (PDM), a completely isolated Infrared camera was allocated. Also, a helicopter which shooted flashers flew below the balloon. We have retrieved the Cloud Top Height (CTH) with the IR camera, and also the optical depth of the nonclear atmosphere have been inferred with two approaches: The first one is with the comparison of the brightness temperature of the cloud and the real temperature obtained after the pertinent corrections. The second one is by measuring the detected signal from the helicopter flashers by the IR Camera, considering the energy of the flashers and the location of the helicopter

Emerging Disease Burdens and the Poor in Cities of the Developing World

Patterns of future urban growth, combined with advances in the treatment of traditional scourges of communicable diseases, will cause a shift in the burden of disease toward category 2 (noncommunicable) and 3 (injury) conditions over the next 30 years. Communicable diseases, particularly HIV/AIDs, will continue to be the most important killers among the poor. However, new risks will emerge for several reasons. First, the marked sprawl of cities in the developing world will make access to care more difficult. Second, increasing motor vehicles and the likelihood of inadequate infrastructure will make air pollution and accidents in road traffic more common than in the past. Third, impoverished urban populations have already shown a propensity toward undernourishment, and its obverse, obesity, is already emerging as a major risk. Also, the large projected increase in slums suggests that violence and homicide will become a more important burden of health, and very large hazards will be created by fire-prone, insubstantial dwellings that will house nearly two billion people by 2030. In addition, decentralized governance will exacerbate the tensions and discontinuities that have plagued the management of health issues on the urban fringe over the past decade. Accordingly, public health agencies will need to adjust to the regional and country-specific factors to address the changing profile of risk. This analysis suggests that four factors – levels of poverty, speed of city growth, sprawl in cities, and degree of decentralization – will have importance in shaping health strategies. These factors vary in pace and intensity by region, suggesting that health care strategies for Category II and III conditions will need to be differentiated by region of the world. Also, interventions will have to rely increasingly on actors outside the ranks of public health specialists

Synthesis and preliminary pharmacological evaluation of methoxilated indoles with possible dopaminergic central action

Compounds 5-7 were synthesized from 4-tetralones with o-iodoanilines by a radical nucleophilic substitution or SRN1 reaction, and were pharmacologically evaluated in order to establish their possible antagonistic action on the central dopaminergic receptors. Behavioural parameters, such as stereotypy in rats were measured after intracerebroventricular administration of these compounds at doses of 10 μg/5 μL. Our results demonstrate that compounds 5-7 do not affect stereotypy behaviour. However, they inhibit the apomorphine-induced stereotypy behaviour, suggesting the involvement of the central dopaminergic system. Also we observe that there is a concordance between the behavioural profiles induced by our compounds and those reported for clozapine 8 and ziprasidone 9. It is plausible to suggest that compounds 5-7 could be acting as potential atypical antipsychotic agents. Quantum calculations performed on the basis of a comparative conformational study of their structures indicate a stereoelectronic similarity between the basic nuclei of compounds 4 and 5-7. In addition Molecular Dynamics (MD) simulations performed on compounds 5-7 at the binding site of dopamine D2 receptor suggest that these compounds could interact with the human D2 dopamine receptors.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The atmospheric science of JEM-EUSO

An Atmospheric Monitoring System (AMS) is critical suite of instruments for JEM-EUSO whose aim is to detect Ultra-High Energy Cosmic Rays (UHECR) and (EHECR) from Space. The AMS comprises an advanced space qualified infrared camera and a LIDAR with cross checks provided by a ground-based and airborne Global Light System Stations. Moreover the Slow Data Mode of JEM-EUSO has been proven crucial for the UV background analysis by comparing the UV and IR images. It will also contribute to the investigation of atmospheric effects seen in the data from the GLS or even to our understanding of Space Weather

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population

Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population