Regulation of human immunodeficiency virus type 1 gene transcription by nuclear receptors in human brain cells.

Infection of cells of the central nervous system by the human immunodeficiency virus type-1 (HIV-1) leads to HIV-1-associated neuropathology. Recent studies have demonstrated the importance of long terminal repeat (LTR) binding sites in determining the pathogenicity of HIV. Here we have investigated the presence and the functional role of transcription factors that have the potential to interact, directly or indirectly, with the nuclear receptor-responsive element in the LTR of HIV-1, in different human cell lines of the brain. Cotransfection experiments showed that in oligodendroglioma TC-620 cells, the retinoic acid receptor and the retinoid X receptor activate LTR-driven transcription in the absence of ligand. Addition of all-trans- or 9-cis-retinoic acid reverses this effect. In contrast, in astrocytoma, neuronal, and microglial cells, no significant effect of the retinoid acid pathway was detected. This retinoid response is mediated by distinct molecular interactions in the lymphotropic LAI and the neurotropic JR-CSF HIV-1 strains. Moreover, retinoid receptors were found to antagonize the chicken ovalbumin upstream promoter transcription factor- as well as the c-JUN-mediated LTR transactivation. Our findings demonstrate the importance of the retinoic acid signaling pathway and of cross-coupling interactions in the repression of HIV-1 LTR gene expression.journal articleresearch support, non-u.s. gov't1996 Sep 13importe

Crystal Structure of T7 Gene 4 Ring Helicase Indicates a Mechanism for Sequential Hydrolysis of Nucleotides

AbstractWe have determined the crystal structure of an active, hexameric fragment of the gene 4 helicase from bacteriophage T7. The structure reveals how subunit contacts stabilize the hexamer. Deviation from expected six-fold symmetry of the hexamer indicates that the structure is of an intermediate on the catalytic pathway. The structural consequences of the asymmetry suggest a “binding change” mechanism to explain how cooperative binding and hydrolysis of nucleotides are coupled to conformational changes in the ring that most likely accompany duplex unwinding. The structure of a complex with a nonhydrolyzable ATP analog provides additional evidence for this hypothesis, with only four of the six possible nucleotide binding sites being occupied in this conformation of the hexamer. This model suggests a mechanism for DNA translocation

Impact of Professional Student Mentored Research Fellowship on Medical Education and Academic Medicine Career Path

CONTEXT: This study explores the long-term impact of the Professional Student Mentored Research Fellowship (PSMRF) program at the University of Kentucky College of Medicine (UKCOM) on medical students\u27 research productivity and career paths. METHODS: Demographic characteristics, academic profiles, number of publications and residency placements from 2007 to 2012 were used to assess 119 PSMRF graduates against a comparison cohort of 898 UKCOM (non-PSMRF) students. RESULTS: PSMRF students had higher MCAT scores at admission (31.5 ± 0.6 vs. 30.6 ± 0.2, p = 0.007) and achieved higher USMLE Step 1 scores (228 ± 4.2 vs. 223 ± 1.5, p = 0.03) than comparison group. PSMRF students were more likely to publish PubMed-indexed papers (36.7% vs. 17.9%, p \u3c 0.0001), achieve AOA status (19.3% vs. 8.5%, p = 0.0002) and match to top 25 US News and World Report residency programs (23.4% vs. 12.1%, p = 0.008). A greater proportion of PSMRF fellows matched to top tier competitive specialties (23% vs. 14.2%, p = 0.07), however this difference was not statistically significant. CONCLUSIONS: The PSMRF program shows a significant increase in enrollment, as well as positive associations with indicators of success in medical school and subsequent quality of residency program

Effect of Buffer Layer selection on Perovskite-Based Solar Cell Efficiency: A Simulation Study Using OghmaNano Software

This simulation paper investigates the impact of incorporating three different buffer layers (CZTSE, CZTS, and CZS) on the efficiency of two different types of perovskite absorber layers (MAPbCl3 and MAGeI3) in a solar cell using the OghmaNano software. The absorber thickness is optimized for maximum efficiency, and then each type of buffer layer is optimized for further efficiency gains. Results show that MAGeI3 has higher efficiency values compared to MAPbCl3. Moreover, the CZS buffer layer demonstrates a remarkable increase in efficiency compared to CZTS and CZTSe buffer layers, with a difference of up to 23.35% for MAPbCl3 and 6.8% for MAGeI3. This study highlights the importance of buffer layer selection and optimization for achieving higher solar cell efficiency

Association between malnutrition in children living in favelas, maternal nutritional status, and environmental factors

OBJECTIVE: To investigate the association of malnutrition in children living in substandard settlements (slums) of Maceió, AL, Brazil, with maternal nutritional status and environmental conditions. METHODS: Cross-sectional study involving a probability sample of 2,075 mothers (18 to 45 years) and their children (4 months to 6 years), living in the slums of the city of Maceió. First, we conducted a cluster analysis with the purpose of choosing the settlements and the administrative region of the city of Maceió with the lowest human development index. After this analysis, the 7th Administrative Region was designated for the study, including its 23 substandard settlements. Socioeconomic, demographic, anthropometric, and maternal and child health data were collected by means of household survey. The statistical analysis included the odds ratio of a child to be malnourished, and the univariate regression was used to check which maternal variables were associated with this malnutrition. RESULTS: Chronic malnutrition (-2 standard deviations/height for age) was found in 8.6% of children and was associated with mother's age and educational level, type of residence, number of rooms, flooring, water supply, and low birth weight (< 2,500 g) in children aged < 24 months. We also found an association between child malnutrition and maternal height. Such association was not observed regarding body mass index. CONCLUSIONS: The high prevalence of malnutrition observed in these settlements was related to social and environmental conditions and short maternal height, who had weight deficit or weight excess.OBJETIVO: Investigar a associação da desnutrição em crianças residentes em assentamentos subnormais (favelas) de Maceió (AL) com o estado nutricional materno e as condições socioambientais. MÉTODOS: Estudo transversal, envolvendo amostra probabilística de 2.075 mães (18 a 45 anos) e respectivos filhos (4 meses a 6 anos), moradoras nas favelas da cidade de Maceió (AL). Para escolha dos assentamentos, procedeu-se primeiramente a uma análise de clusters para eleger a região administrativa da cidade de Maceió com menor índice de desenvolvimento humano. Após essa análise, a 7ª Região Administrativa foi a designada para o estudo, com seus 23 assentamentos subnormais. Os dados socioeconômicos, demográficos, antropométricos e de saúde materno-infantil foram coletados através de inquérito domiciliar. A estatística analisou a razão de chances de uma criança ser desnutrida, e a regressão univariada foi usada para verificar quais variáveis maternas estariam associadas a essa desnutrição. RESULTADOS: A desnutrição crônica (-2 desvios padrão/altura por idade) esteve presente em 8,6% das crianças e associou-se com idade e escolaridade materna, tipo de residência, número de cômodos, revestimento de piso, origem da água e baixo peso ao nascer (< 2.500 g) em crianças com idade < 24 meses. Encontrou-se também associação entre desnutrição infantil e baixa estatura materna, que não foi observada para índice de massa corporal. CONCLUSÕES: A alta prevalência de desnutrição infantil observada nesses assentamentos esteve relacionada às condições socioambientais e à baixa estatura das mães, que apresentaram déficit ou excesso de peso.Secretaria Estadual de Saúde de AlagoasUniversidade Federal de Alagoas Faculdade de NutriçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de FisiologiaUNIFESP, Depto. de FisiologiaSciEL

The Structure of β-Carbonic Anhydrase from the Carboxysomal Shell Reveals a Distinct Subclass with One Active Site for the Price of Two

CsoSCA (formerly CsoS3) is a bacterial carbonic anhydrase localized in the shell of a cellular microcompartment called the carboxysome, where it converts HCO-3 to CO2 for use in carbon fixation by ribulose-bisphosphate carboxylase/oxygenase (RuBisCO). CsoSCA lacks significant sequence similarity to any of the four known classes of carbonic anhydrase (α, β, γ, or δ), and so it was initially classified as belonging to a new class, ϵ. The crystal structure of CsoSCA from Halothiobacillus neapolitanus reveals that it is actually a representative member of a new subclass of β-carbonic anhydrases, distinguished by a lack of active site pairing. Whereas a typical β-carbonic anhydrase maintains a pair of active sites organized within a two-fold symmetric homodimer or pair of fused, homologous domains, the two domains in CsoSCA have diverged to the point that only one domain in the pair retains a viable active site. We suggest that this defunct and somewhat diminished domain has evolved a new function, specific to its carboxysomal environment. Despite the level of sequence divergence that separates CsoSCA from the other two subclasses of β-carbonic anhydrases, there is a remarkable level of structural similarity among active site regions, which suggests a common catalytic mechanism for the interconversion of HCO-3 and CO2. Crystal packing analysis suggests that CsoSCA exists within the carboxysome shell either as a homodimer or as extended filaments

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis

Background. Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods. This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. Results. Renal and patient survivals were better in the group A (P \u3c 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P \u3c 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients\u27 morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). Conclusions. Renal transplantation in patients with has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies

Structural Analysis of CsoS1A and the Protein Shell of the \u3ci\u3eHalothiobacillus neapolitanus\u3c/i\u3e Carboxysome

The carboxysome is a bacterial organelle that functions to enhance the efficiency of CO2 fixation by encapsulating the enzymes ribulose bisphosphate carboxylase/ oxygenase (RuBisCO) and carbonic anhydrase. The outer shell of the carboxysome is reminiscent of a viral capsid, being constructed from many copies of a few small proteins. Here we describe the structure of the shell protein CsoS1A from the chemoautotrophic bacterium Halothiobacillus neapolitanus. The CsoS1A protein forms hexameric units that pack tightly together to form a molecular layer, which is perforated by narrow pores. Sulfate ions, soaked into crystals of CsoS1A, are observed in the pores of the molecular layer, supporting the idea that the pores could be the conduit for negatively charged metabolites such as bicarbonate, which must cross the shell. The problem of diffusion across a semiporous protein shell is discussed, with the conclusion that the shell is sufficiently porous to allow adequate transport of small molecules. The molecular layer formed by CsoS1A is similar to the recently observed layers formed by cyanobacterial carboxysome shell proteins. This similarity supports the argument that the layers observed represent the natural structure of the facets of the carboxysome shell. Insights into carboxysome function are provided by comparisons of the carboxysome shell to viral capsids, and a comparison of its pores to the pores of transmembrane protein channels

Analytical methods applied to diverse types of Brazilian propolis

Propolis is a bee product, composed mainly of plant resins and beeswax, therefore its chemical composition varies due to the geographic and plant origins of these resins, as well as the species of bee. Brazil is an important supplier of propolis on the world market and, although green colored propolis from the southeast is the most known and studied, several other types of propolis from Apis mellifera and native stingless bees (also called cerumen) can be found. Propolis is usually consumed as an extract, so the type of solvent and extractive procedures employed further affect its composition. Methods used for the extraction; analysis the percentage of resins, wax and insoluble material in crude propolis; determination of phenolic, flavonoid, amino acid and heavy metal contents are reviewed herein. Different chromatographic methods applied to the separation, identification and quantification of Brazilian propolis components and their relative strengths are discussed; as well as direct insertion mass spectrometry fingerprinting

Electrospray Ionization Mass Spectrometry Fingerprinting Of Propolis.

Crude ethanolic extracts of propolis, a natural resin, have been directly analysed using electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) in the negative ion mode. European, North American and African samples have been analyzed, but emphasis has been given to Brazilian propolis which displays diverse and region-dependent chemical composition. ESI-MS provides characteristic fingerprint mass spectra, with propolis samples being divided into well-defined groups directly related to their geographical origins. Chemometric multivariate analysis statistically demonstrates the reliability of the ESI-MS fingerprinting method for propolis. On-line ESI-MS/MS tandem mass spectrometry of characteristic [M - H](-) ion markers provides an additional dimension of fingerprinting selectivity, while structurally characterizing the ESI-MS marker components of propolis. By comparison with standards, eight such markers have been identified: para-coumaric acid, 3-methoxy-4-hydroxycinnamaldehyde, 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran, 3-prenyl-4-hydroxycinnamic acid, chrysin, pinocembrin, 3,5-diprenyl-4-hydroxycinnamic acid and dicaffeoylquinic acid. The negative mode ESI-MS fingerprinting method is capable of discerning distinct composition patterns to typify, to screen the sample origin and to reveal characteristic details of the more polar and acidic chemical components of propolis samples from different regions of the world.129739-4