8 research outputs found
Production of full-length cDNA sequences by sequencing and analysis of expressed sequence tags from Schistosoma mansoni
Determinação da concentração alveolar mínima do isofluorano em catetos (Tayassu tajacu)
Structural basis of the myotoxic inhibition of the Bothrops pirajai PrTX-I by the synthetic varespladib
Varespladib (LY315920) is a potent inhibitor of human group IIA phospholipase A2 (PLA2) originally developed to control inflammatory cascades of diseases associated with high or dysregulated levels of endogenous PLA2. Recently, varespladib was also found to inhibit snake venom PLA2 and PLA2-like toxins. Herein, ex vivo neuromuscular blocking activity assays were used to test the inhibitory activity of varespladib. The binding affinity between varespladib and a PLA2-like toxin was quantified and compared with other potential inhibitors for this class of proteins. Crystallographic and bioinformatic studies showed that varespladib binds to PrTX-I and BthTX-I into their hydrophobic channels, similarly to other previously characterized PLA2-like myotoxins. However, a new finding is that an additional varespladib binds to the MDiS region, a particular site that is related to muscle cell disruption by these toxins. The present results further advance the characterization of the molecular interactions of varespladib with PLA2-like myotoxins and provide additional evidence for this compound as a promising inhibitor candidate for different PLA2 and PLA2-like toxins.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
Production of full-length cDNA sequences by sequencing and analysis of expressed sequence tags from Schistosoma mansoni
The number of sequences generated by genome projects has increased
exponentially, but gene characterization has not followed at the same
rate. Sequencing and analysis of full-length cDNAs is an important step
in gene characterization that has been used nowadays by several
research groups. In this work, we have selected Schistosoma mansoni
clones for full-length sequencing, using an algorithm that investigates
the presence of the initial methionine in the parasite sequence based
on the positions of alignment start between two sequences. BLAST
searches to produce such alignments have been performed using parasite
expressed sequence tags produced by Minas Gerais Genome Network against
sequences from the database Eukaryotic Cluster of Orthologous
Groups(KOG). This procedure has allowed the selection of clones
representing 398 proteins which have not been deposited as S. mansoni
complete CDS in any public database. Dedicated sequencing of 96 of such
clones with reads from both 5' and 3' ends has been performed. These
reads have been assembled using PHRAP, resulting in the production of
33 full-length sequences that represent novel S. mansoni proteins.
These results shall contribute to construct a more complete view of the
biology of this important parasite
Identification and characterization of the first endogenous phospholipase A2 inhibitor from a non-venomous tropical snake, Boa constrictor (Serpentes: Boidae)
Prevalence and Relationship Between Dental Caries, Diet and Nutrition, Socioeconomic Status and Oral Hygiene Habits in Children Using Laser Fluorescence Device (Diagnodent)
Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients
Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART