Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia,Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.     

Integrating sequence and structural biology with DAS

Background  

The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence.     

Identification and Characterization of Polymorphisms in piRNA Regions

piRNAs are a class of noncoding RNAs that perform functions in epigenetic regulation and silencing of transposable elements, a mechanism conserved among most mammals. At present, there are more than 30,000 known piRNAs in humans, of which more than 80% are derived from intergenic regions, and approximately 20% are derived from the introns and exons of pre-mRNAs. It was observed that the expression of the piRNA profile is specific in several organs, suggesting that they play functional roles in different tissues. In addition, some studies suggest that changes in regions that encode piRNAs may have an impact on their function. To evaluate the conservation of these regions and explore the existence of a seed region, SNP and INDEL variant rates were investigated in several genomic regions and compared to piRNA region variant rates. Thus, data analysis, data collection, cleaning, treatment, and exploration were implemented using the R programming language with the help of the RStudio platform. We found that piRNA regions are highly conserved after considering INDELs and do not seem to present an identifiable seed region after considering SNPs and INDEL variants. These findings may contribute to future studies attempting to determine how polymorphisms in piRNA regions can impact diseases.     

Glycosylation sites and site-specific glycosylation in human Tamm- Horsfall glycoprotein

The N-glycosylation sites of human Tamm-Horsfall glycoprotein from one healthy male donor have been characterized, based on an approach using endoproteinase Glu-C (V-8 protease, Staphylococcus aureus ) digestion and a combination of chromatographic techniques, automated Edman sequencing, and fast atom bombardment mass spectrometry. Seven out of the eight potential N-glycosylation sites, namely, Asn52, Asn56, Asn208, Asn251, Asn298, Asn372, and Asn489, turned out to be glycosylated, and the potential glycosylation site at Asn14, being close to the N-terminus, is not used. The carbohydrate microheterogeneity on three of the glycosylation sites was studied in more detail by high-pH anion-exchange chromatographic profiling and 500 MHz1H-NMR spectroscopy. Glycosylation site Asn489 contains mainly di- and tri-charged oligosaccharides which comprise, among others, the GalNAc4 S (beta1-4)GlcNAc terminal sequence. Only glycosylation site Asn251 bears oligomannose-type carbohydrate chains ranging from Man5GlcNAc2to Man8GlcNAc2, in addition to a small amount of complex- type structures. Profiling of the carbohydrate moieties of Asn208 indicates a large heterogeneity, similar to that established for native human Tamm-Horsfall glycoprotein, namely, multiply charged complex-type carbohydrate structures, terminated by sulfate groups, sialic acid residues, and/or the Sda-determinant.      

Agroforestry coffee soils increase the insect‐suppressive potential offered by entomopathogenic fungi over full‐sun soils: A case proposing a “bait survival technique”

Entomopathogenic fungi are important natural enemies of insects. However, there is little information on the insect‐suppressive potential of these fungi and possible effects of farming management on this. Meanwhile, changes in natural landscapes due to agricultural intensification have caused considerable biodiversity loss and consequent decay of ecosystem services. However, the adoption of practices such as agroforestry in agroecosystems can foster abiotic and biotic conditions that conserve biodiversity, consequently restoring the provision of ecosystems services. Here, we assessed the effect of management systems (agroforestry or full‐sun) on the pest‐suppressive potential of entomopathogenic fungi in Brazilian coffee plantations. We used the insect bait method coupled with survival analyses to assess the speed of kill by entomopathogenic fungi and their presence in soil samples from both farming systems. We found that insects exposed to agroforestry soils died more quickly than insects exposed to full‐sun soils. Of the fungi isolated from the bait insects, Metarhizium was found most frequently, followed by Beauveria. Meanwhile, Fusarium was frequently isolated as primary or secondary infections. We propose that the differential survival of insects is indicative of a greater suppressive potential by entomopathogenic fungi in agroforestry, and that this could be promoted by the diversified landscape, microclimatic stability, and reduced soil disturbance in agroforestry systems. Furthermore, our results provide a useful demonstration of the potential use of the insect bait method to investigate pest‐suppressive potential through bait insect mortality, and we term this the “bait survival technique.”     

Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis

Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.     

Improvement of the energy supply and contractile function in normal and ischemic rat hearts by dietary orotic acid

AimsAs cardiac performance is closely related to its energy supply, our study investigated the effect of the orotic acid cardioprotective agent on the pathways of energy supply, in both conditions of normal flow and ischemia.Main methodsMale Wistar rats were fed during nine days with a balanced diet only or supplemented with 1% orotic acid.Key findingsDietary administration of orotic acid increased the cardiac utilization of fatty acids, activity of the lipoprotein lipase, expression of the gene of peroxisome proliferator-activated receptor α and its target enzymes. In addition, orotic acid increased the myocardial uptake and incorporation of glucose, glycogen content and level of GLUT4, concentration of glycolytic metabolites and lactate production in both experimental conditions, baseline and after regional ischemia.SignificanceThus, in orotic acid hearts there was a simultaneous stimulus of fatty acid oxidation and glycolytic pathway, reflected in increased energetic content even in pre-ischemia. The analysis of the cardiac contractility index showed a positive inotropic effect of orotic acid due, at least in part, to the increased availability of energy. The result allows us to suggest that the metabolic changes induced by orotic acid result in appreciable alterations on myocardial contractile function.     

Positive and purifying selection influence the evolution of doublesex in the Anastrepha fraterculus species group

The gene doublesex (dsx) is considered to be under strong selective constraint along its evolutionary history because of its central role in somatic sex differentiation in insects. However, previous studies of dsx used global estimates of evolutionary rates to investigate its molecular evolution, which potentially miss signals of adaptive changes in generally conserved genes. In this work, we investigated the molecular evolution of dsx in the Anastrepha fraterculus species group (Diptera, Tephritidae), and test the hypothesis that this gene evolved solely by purifying selection using divergence-based and population-based methods. In the first approach, we compared sequences from Anastrepha and other Tephritidae with other Muscomorpha species, analyzed variation in nonsynonymous to synonymous rate ratios (dN/dS) in the Tephritidae, and investigated radical and conservative changes in amino acid physicochemical properties. We show a general selective constraint on dsx, but with signs of positive selection mainly in the common region. Such changes were localized in alpha-helices previously reported to be involved in dimer formation in the OD2 domain and near the C-terminal of the OD1 domain. In the population-based approach, we amplified a region of 540 bp that spanned almost all of the region common to both sexes from 32 different sites in Brazil. We investigated patterns of selection using neutrality tests based on the frequency spectrum and locations of synonymous and nonsynonymous mutations in a haplotype network. As in the divergence-based approach, these analyses showed that dsx has evolved under an overall selective constraint, but with some events of positive selection. In contrast to previous studies, our analyses indicate that even though dsx has indeed evolved as a conserved gene, the common region of dsx has also experienced bouts of positive selection, perhaps driven by sexual selection, during its evolution.