Differential Proteins Expression Distinguished Between Patients With Infectious and Noninfectious Uveitis.

PURPOSE: We investigated the aqueous humor proteome and associated plasma proteome in patients with infectious or noninfectious uveitis. METHODS: AH and plasma were obtained from 28 patients with infectious uveitis (IU), 29 patients with noninfectious uveitis (NIU) and 35 healthy controls undergoing cataract surgery. The proteins profile was analyzed by SomaScan technology. RESULTS: We found 1844 and 2484 proteins up-regulated and 124 and 161 proteins down-regulated in the AH from IU and NIU groups, respectively. In the plasma, three proteins were up-regulated in NIU patients, and one and five proteins were down-regulated in the IU and NIU patients, respectively. The results of pathway enrichment analysis for both IU and NIU groups were related mostly to inflammatory and regulatory processes. CONCLUSION: SomaScan was able to detect novel AH and plasma protein biomarkers in IU and NIU patients. Also, the unique proteins found in both AH and plasma suggest a protein signature that could distinguish between infectious and noninfectious uveitis.

Setting New Routes for Antifungal Drug Discovery Against Pathogenic Fungi.

Fungal diseases are life-threatening to human health and responsible for millions of deaths around the world. Fungal pathogens lead to a high number of morbidity and mortality. Current antifungal treatment comprises drugs, such as azoles, echinocandins, and polyenes and the cure is not guaranteed. In addition, such drugs are related to severe side effects and the treatment lasts for an extended period. Thus, setting new routes for the discovery of effective and safe antifungal drugs should be a priority within the health care system. The discovery of alternative and efficient antifungal drugs showing fewer side effects is time-consuming and remains a challenge. Natural products can be a source of antifungals and used in combinatorial therapy. The most important natural products are antifungal peptides, antifungal lectins, antifungal plants, and fungi secondary metabolites. Several proteins, enzymes, and metabolic pathways could be targets for the discovery of efficient inhibitor compounds and recently, heat shock proteins, calcineurin, salinomycin, the trehalose biosynthetic pathway, and the glyoxylate cycle have been investigated in several fungal species. HSP protein inhibitors and echinocandins have been shown to have a fungicidal effect against azole-resistant fungi strains. Transcriptomic and proteomic approaches have advanced antifungal drug discovery and pointed to new important specific-pathogen targets. Certain enzymes, such as those from the glyoxylate cycle, have been a target of antifungal compounds in several fungi species. Natural and synthetic compounds inhibited the activity of such enzymes and reduced the ability of fungal cells to transit from mycelium to yeast, proving to be promisor antifungal agents. Finally, computational biology has developed effective approaches, setting new routes for early antifungal drug discovery since normal approaches take several years from discovery to clinical use. Thus, the development of new antifungal strategies might reduce the therapeutic time and increase the quality of life of patients.

Solid state characterization and theoretical study of non-linear optical properties of a Fluoro-N-Acylhydrazide derivative.

In this work we determine the linear and non-linear optical properties of a Fluoro-N-Acylhydrazide derivative (FBHZ), using a combined supermolecule approach and an iterative scheme of electrostatic polarization, where the atoms of neighbouring molecules are represented by point charges. Our results for non-linear optics (NLO) are comparable to those found experimentally, suggesting that FBHZ constitutes an attractive object for future studies and for use as an interesting material for third-order NLO applications. The dynamic electrical properties of FBHZ in different solvent media are reported. Its molecular properties are closely related to supramolecular features; accordingly, we analysed all its crystal structure properties via intermolecular interactions in the solid state, using X-ray crystallography data and Hirshfeld surface (HS), including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and hot-stage microscopy (HSM), where the results reveal crystal stability in respect to temperature variation.

Signaling transcript profile of the asexual intraerythrocytic development cycle of Plasmodium falciparum induced by melatonin and cAMP.

According to the World Health Organization (WHO), Plasmodium falciparum is the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP. Therefore, we performed RNA sequencing (RNA-Seq) analysis in P. falciparum erythrocytic stages (ring, trophozoite and schizont) treated with MEL and cAMP. To investigate the expression profile of P. falciparum genes regulated by MEL and cAMP, we performed RNA-Seq analysis in three P. falciparum strains (control, 3D7; protein kinase 7 knockout, PfPK7-; and PfPK7 complement, PfPK7C). In the 3D7 strain, 38 genes were differentially expressed upon MEL treatment; however, none of the genes in the trophozoite (T) stage PfPK7- knockout parasites were differentially expressed upon MEL treatment for 5 hours compared to untreated controls, suggesting that PfPK7 may be involved in the signaling leading to differential gene expression. Moreover, we found that MEL modified the mRNA expression of genes encoding membrane proteins, zinc ion-binding proteins and nucleic acid-binding proteins, which might influence numerous functions in the parasite. The RNA-Seq data following treatment with cAMP show that this molecule modulates different genes throughout the intraerythrocytic cycle, namely, 75, 101 and 141 genes, respectively, in the ring (R), T and schizont (S) stages. Our results highlight P. falciparum's perception of the external milieu through the signaling molecules MEL and cAMP, which are able to drive to changes in gene expression in the parasite.

Long non-coding RNA INXS is a critical mediator of BCL-XS induced apoptosis.

BCL-X mRNA alternative splicing generates pro-apoptotic BCL-XS or anti-apoptotic BCL-XL gene products and the mechanism that regulates splice shifting is incompletely understood. We identified and characterized a long non-coding RNA (lncRNA) named INXS, transcribed from the opposite genomic strand of BCL-X, that was 5- to 9-fold less abundant in tumor cell lines from kidney, liver, breast and prostate and in kidney tumor tissues compared with non-tumors. INXS is an unspliced 1903 nt-long RNA, is transcribed by RNA polymerase II, 5'-capped, nuclear enriched and binds Sam68 splicing-modulator. Three apoptosis-inducing agents increased INXS lncRNA endogenous expression in the 786-O kidney tumor cell line, increased BCL-XS/BCL-XL mRNA ratio and activated caspases 3, 7 and 9. These effects were abrogated in the presence of INXS knockdown. Similarly, ectopic INXS overexpression caused a shift in splicing toward BCL-XS and activation of caspases, thus leading to apoptosis. BCL-XS protein accumulation was detected upon INXS overexpression. In a mouse xenograft model, intra-tumor injections of an INXS-expressing plasmid caused a marked reduction in tumor weight, and an increase in BCL-XS isoform, as determined in the excised tumors. We revealed an endogenous lncRNA that induces apoptosis, suggesting that INXS is a possible target to be explored in cancer therapies.

Ecology of anopheline mosquitoes (Diptera: Culicidae) in the Central Atlantic Forest Biodiversity Corridor, southeastern Brazil.

Knowledge of the fauna composition of anopheline mosquitoes, their ecological aspects and behavior, and influence of climatic variables on their population dynamics can help in understanding the transmission of Plasmodium parasites and thus develop more efficient strategies for the control of malaria. In the Central Atlantic Forest Biodiversity Corridor, southeastern Brazil, foci of introduced malaria have been reported among people returning from the Amazon region, north Brazil. Our objective was to evaluate and compare the anopheline fauna from a preserved environment and an adjacent peridomiciliary modified environment at the Central Atlantic Forest Biodiversity Corridor. We collected anopheline mosquitoes on a monthly basis from June 2004 to May 2006 from both these environments to understand the ecological aspects and their association with the occurrence of malaria. We captured 5,491 anopheline mosquitoes belonging to two subgenera and 11 species and studied the correlations between anopheline mosquito species and climatic variables. We considered Anopheles darlingi (Root) as the principal malaria vector and Anopheles albitarsis s. l. (Arribalzaga) as the secondary vector.

An examination of morphometric variations in a neotropical toad population (Proceratophrys cristiceps, Amphibia, Anura, Cycloramphidae).

The species Proceratophrys cristiceps belongs to the genus Proceratophrys within the family Cycloramphidae. These amphibians are found exclusively in South America in the morphoclimatic domain of the semi-arid depression zones in northeastern Brazil known as the Caatinga. We examined intrapopulational variation using univariate and multivariate statistics with traditional and geometric morphometrics, which supported the existence of two morphotypes of this species. Our results indicated significant degrees of variation in skeletal characteristics between some natural populations of this species. Careful analyses of variability levels are fundamental to avoid taxonomic errors, principally in populations that demonstrate characteristics intimately associated with their area of occurrence, as is the case of Proceratophrys cristiceps.

Ototoxicidade / Ototoxicity

Faz-se um estudo clínico apoiados em revisäo bibliográfica da Ototoxicidade, procurando uma análise das alteraçöes histopatológicas e características clínicas; ressalta-se a importância do tratamento preventivo como forma ideal para o controle da patologia

Glomus jugular: descriçäo de um caso clínico / Glomus jugulare: report of a clinical case

Descreve-se um caso de Glomus Jugularis, diagnosticado no Serviço de Otorrinolaringologia da Santa Casa da Misericórdia de Mirassol, sendo que para este intento foi realizado um minucioso exame clínico, teste audiológico, radiografias contrastadas e de todos os achados clínicos e terapêuticos do caso com a bibliografia consultada, buscando dar maiores subsídios ao conhecimento deste tipo de patologia tumoral

Fístula perilinfática / Perilymphatic fistula

Apresenta-se uma revisäo da literatura sobre fístula perilinfática, e fazem-se consideraçöes sobe o diagnóstico e tratamento

Obstruçäo nasal provocada por alteraçöes sistêmicas / Nasal obstruction induced by systemic changes

É analisada uma das queixas mais freqüentes das rinopatías: a obstruçäo nasal. A avaliaçäo clínico-terapêutica é feita através de uma revisäo da fisiologia nasal e à análise clínica do sintoma. Säo feitas consideraçöes quanto ao tratamento