Hepatitis C virus infection in Brazilian long-distance truck drivers

Hepatitis C virus (HCV) infection is a global public health problem. Long-distance truck drivers live apart from their family for long periods of time, a lifestyle that favors at-risk behaviors such as unprotected sex with multiple partners and illicit drug use. As data concerning HCV infection in this population are still rare, this paper aims to investigate the prevalence, genotypes/subtypes, and the factors associated with HCV infection in long-distance truck drivers in Brazil. A cross-sectional survey was carried out with 641 Brazilian long-truck drivers who were recruited at a major truck stop located at kilometer 1,296 of the BR-153 highway, which is considered to be one of the longest roads in Brazil. All individuals were interviewed, and their serum samples were tested for the presence of antibodies to HCV (anti-HCV) by ELISA and immunoblot. Anti-HCV positive samples were tested for HCV RNA by PCR amplification of the 5' NC and NS5B regions and were genotyped using the LiPA assay and nucleotide sequencing, respectively. Factors associated with HCV infection were identified with logistic regression. The prevalence of HCV infection was 1.4% (95% CI: 0.7-2.8). History of blood transfusion, sharing of personal hygiene tools, illicit drug use and HBV status were factors independently associated with HCV infection in the study population. HCV RNA was detected in 8/9 anti-HCV positive samples, in which genotypes 1 (n = 3), 2 (n = 2), and 3 (n = 3) were determined by LiPA. Using phylogenetic tree analysis of the NS5B region, subtypes 1a (n = 1), 1b (n = 2), 2b (n = 2) and 3a (n = 3) were identified. These data show that the prevalence of HCV infection among Brazilian truck drivers was similar to that observed for the general population. History of blood transfusion, sharing of personal hygiene tools, illicit drug use and HBV status were predictors of HCV infection. The HCV genotypes/subtypes identified in the study population are consistent with those circulating in Brazil

Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function

There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders. Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MSE). Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides. The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1b immunohistochemistry, and tumor necrosis factor (TNF)-a and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (Po0.05). Higher hepatic TNF-a (Po0.001) and IL-10 (Po0.01) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells (presumably Kupffer cells) were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA-I mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity

SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds

Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Tuning the energetics and tailoring the optical properties of silver clusters confined in zeolites

The integration of metal atoms and clusters in well-defined dielectric cavities is a powerful strategy to impart new properties to them that depend on the size and geometry of the confined space as well as on metal-host electrostatic interactions. Here, we unravel the dependence of the electronic properties of metal clusters on space confinement by studying the ionization potential of silver clusters embedded in four different zeolite environments over a range of silver concentrations. Extensive characterization reveals a strong influence of silver loading and host environment on the cluster ionization potential, which is also correlated to the cluster's optical and structural properties. Through fine-tuning of the zeolite host environment, we demonstrate photoluminescence quantum yields approaching unity. This work extends our understanding of structure property relationships of small metal clusters and applies this understanding to develop highly photoluminescent materials with potential applications in optoelectronics and bioimaging

Prevalence of antimicrobial resistance in enteric Escherichia coli from domestic pets and assessment of associated risk markers using a generalized linear mixed model

Antimicrobial resistance (AMR) is a growing global public health problem, which is caused by the use of antimicrobials in both human and animal medical practice. The objectives of the present cross-sectional study were as follows: (1) to determine the prevalence of resistance in Escherichia coli isolated from the feces of pets from the Porto region of Portugal against 19 antimicrobial agents and (2) to assess the individual, clinical and environmental characteristics associated with each pet as risk markers for the AMR of the E. coli isolates. From September 2009 to May 2012, rectal swabs were collected from pets selected using a systematic random procedure from the ordinary population of animals attending the Veterinary Hospital of Porto University. A total of 78 dogs and 22 cats were sampled with the objective of isolating E. coli. The animals’ owners, who allowed the collection of fecal samples from their pets, answered a questionnaire to collect information about the markers that could influence the AMR of the enteric E. coli. Chromocult tryptone bile X-glucuronide agar was used for E. coli isolation, and the disk diffusion method was used to determine the antimicrobial susceptibility. The data were analyzed using a multilevel, univariable and multivariable generalized linear mixed model (GLMM). Several (49.7%) of the 396 isolates obtained in this study were multidrug-resistant. The E. coli isolates exhibited resistance to the antimicrobial agent's ampicillin (51.3%), cephalothin (46.7%), tetracycline (45.2%) and streptomycin (43.4%). Previous quinolone treatment was the main risk marker for the presence of AMR for 12 (ampicillin, cephalothin, ceftazidime, cefotaxime, nalidixic acid, ciprofloxacin, gentamicin, tetracycline, streptomycin, chloramphenicol, trimethoprim–sulfamethoxazole and aztreonam) of the 15 antimicrobials assessed. Coprophagic habits were also positively associated with an increased risk of AMR for six drugs, ampicillin, amoxicillin–clavulanic acid, cephamycin, ciprofloxacin, streptomycin, and trimethoprim–sulfamethoxazole. In summary, pets with a record of one or more previous quinolone treatments and exhibiting coprophagic habits were at an increased risk of harboring multidrug-resistant E. coli strains in their feces compared to pets without these characteristics. AMR is a serious global problem, and assessing the risk markers for the presence of drug-resistant bacteria in pets, a very close source of resistance determinants to humans, is essential for the implementation of safe handling procedures for companion animals and for the prudent selection of antimicrobial compounds in veterinary practice

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe