Institute Estudios Avanzados

Caracas, Venezuela

Institute Estudios Avanzados

Caracas, Venezuela

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Garcia-Garcia V.,Institute Estudios Avanzados | Garcia-Garcia V.,Central University of Venezuela | Oldfield E.,University of Illinois at Urbana - Champaign | Benaim G.,Institute Estudios Avanzados | Benaim G.,Central University of Venezuela
Antimicrobial Agents and Chemotherapy | Year: 2016

We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca2+ homeostasis by releasing organelle Ca2+ into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate. Copyright © 2016, American Society for Microbiology. All Rights Reserved.


Torres K.,University Centroccidental Lisandro Alvarado | Valderrama E.,Hospital Antonio Maria Pineda UCLA | Sayegh M.,Institute Estudios Avanzados | Ramirez J.L.,Institute Estudios Avanzados | Chiurillo M.A.,University Centroccidental Lisandro Alvarado
Microbial Pathogenesis | Year: 2014

CagA and OipA are involved, among other virulence factors, in the ability of Helicobacter pylori to colonize the gastric mucosa and to modulate the host environment during the establishment of chronic infection. The number and type of EPIYA phosphorylation motifs and the presence and functional status of oipA have been involved in the induction of cellular transformations playing an important role in the development of H. pylori associated gastric diseases. This work determined the prevalence of the oipA virulence factor and EPIYA motif patterns in cagA-positive H.pylori gastric biopsies from chronic gastritis patients from the Central-Western region of Venezuela. DNA was extracted directly from gastric biopsies collected by upper endoscopy from 113 patients. The EPIYA motif genotyping and oipA gene functional status was determined by PCR and sequencing. Phylogenetic analysis with the 3' variable region of cagA sequences was performed. Only Western-type EPIYA variants were detected: ABC (68.14%), ABCC (29.20%) and ABCCC (2.66%). High prevalence of strains with the oipA gene (93.8%) and its functional status "ON" (83%) was observed. No significant association between EPIYA motif patterns or oipA functional status with the histological changes in the gastric mucosa was found. Our study demonstrated the absolute predominance of the Western-type cagA gene in a Venezuelan admixed population. This is the first report showing oipA status of H.pylori strains in Venezuela. Further studies with a larger number of samples and including other pathologies are necessary to continue evaluating the role of the H.pylori virulence factors in the prevalence of gastric diseases in our country. © 2014 Elsevier Ltd.


Chiurillo M.A.,University Centroccidental Lisandro Alvarado | Moran Y.,University Centroccidental Lisandro Alvarado | Canas M.,University Centroccidental Lisandro Alvarado | Valderrama E.,Hospital Antonio Maria Pineda UCLA | And 3 more authors.
International Journal of Infectious Diseases | Year: 2013

Background: Helicobacter pylori is a major cause of chronic gastritis and an established risk factor for gastric adenocarcinoma. This bacterium also exhibits an extraordinarily high genetic diversity. Methods: The genetic diversity of H. pylori strains from Venezuelan patients with chronic gastritis was evaluated by PCR-typing of vacA, cagA, iceA, and babA2 virulence-associated genes using DNA extracted directly from biopsies. The nucleotide sequence and prevalence of size variants of iceA1, iceA2, and babA2 PCR products were introduced in this analysis. Results: The frequency of vacA s1 was associated (p<0.01) with moderate/severe grades of atrophic gastritis. The cagA, iceA1, iceA2, and babA2 genotypes were found in 70.6%, 66.4%, 33.6%, and 92.3% of strains, respectively. The frequency of iceA2 and its subtype iceA2_D were higher (p<0.015) in cases with moderate/severe granulocytic inflammation. The most prevalent combined genotypes were vacA s1m1/. cagA/. iceA1/. babA2 (26.3%), vacA s2m2/. iceA1/. babA2 (19.5%), and vacA s1m1/. cagA/. iceA2/. babA2 (18.8%). Sequence analysis of iceA1, iceA2, and babA2 PCR-amplified fragments allowed us to define allelic variants and to increase the number of genotypes detected (from 19 to 62). A phylogenetic tree made with iceA1 sequences showed that the H. pylori strains analyzed here were grouped with those of Western origin. Conclusions: Our results show that patients from the western region of Venezuela have an elevated prevalence of infection with H. pylori strains carrying known virulence genotypes with high genetic diversity. This highlights the importance of identifying gene variants for an early detection of virulent genotypes. © 2013 International Society for Infectious Diseases.


Campelo R.,Institute Estudios Avanzados | Lozano I.D.,University of Granada | Figarella K.,Institute Estudios Avanzados | Osuna A.,University of Granada | And 2 more authors.
Infection and Immunity | Year: 2015

In its canonical role the reverse transcriptase telomerase recovers the telomeric repeats that are lost during DNA replication. Other locations and activities have been recently described for the telomerase protein subunit TERT in mammalian cells. In the present work, using biochemistry, molecular biology, and electron microscopy techniques, we found that in the human parasite Leishmania major, TERT (and telomerase activity) shared locations between the nuclear, mitochondrial, and cytoplasmic compartments. Also, some telomerase activity and TERT protein could be found in ~100-nm nanovesicles. In the mitochondrial compartment, TERT appears to be mainly associated with the kinetoplast DNA. When Leishmania cells were exposed to H2O2, TERT changed its relative abundance and activity between the nuclear and mitochondrial compartments, with the majority of activity residing in the mitochondrion. Finally, overexpression of TERT in Leishmania transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress. © 2015, American Society for Microbiology.


Forsyth P.,Institute Estudios Avanzados | Sevcik C.,Venezuelan Institute for Scientific Research | Marti nez R.,Venezuelan Institute for Scientific Research | Castillo C.,Institute Estudios Avanzados | D'Suze G.,Venezuelan Institute for Scientific Research
Journal of Insect Physiology | Year: 2012

We describe the effects of six bactridines (150nM) on cricket dorsal unpaired median (DUM) neurons. The addition of bactridine 2 to DUM neurons induced a large current component with a reversal potential more negative than -30mV, most evident at the end of the pulses. This current was completely suppressed when 1μM amiloride was applied before adding the bactridines. Since the amiloride sensitive current is able to distort the aim of our study, i.e. the effect of bactridines on sodium channels, all experiments were done in the presence of 1μM amiloride. Most bactridines induced voltage shifts of V1/2 of the Boltzmann inactivation voltage dependency curves in the hyperpolarizing direction. Bactridines 1, 4 and 6 reduced Na current peak by 65, 80 and 24% of the control, respectively. The sodium conductance blockage by bactridines was voltage independent at potentials >20mV. Bactridines effect on cricket DUM neurons does not correspond to neither α- nor β-toxins. Most bactridines shifted the inactivation curves in the hyperpolarizing direction without any effects on the activation m∞-like curves. Also bactridines differ from other NaScpTx in that they increased an amiloride-sensitive conductance in DUM neurons. Our result suggest that the α/β classification of sodium scorpion toxins is not all encompassing. The present work shows that bactridines target more than one site: insect voltage dependent Na channels and an amiloride-sensitive ionic pathway which is under study. © 2012 Elsevier Ltd.


Campelo R.,Institute Estudios Avanzados | Galindo M.M.,Institute Estudios Avanzados | Ramirez J.L.,Institute Estudios Avanzados
Acta Tropica | Year: 2011

High telomerase activity is always associated with actively dividing cells, however the detection of this activity in dividing Leishmania and Trypanosoma cruzi cells has always been disappointingly low. Recently, we have found that Leishmania major telomerase activity can be activated by heat, which combined with dilutions of the nuclear extracts produced an increase in activity comparable to cancer cells. Here we examined whether T. cruzi telomerase shares the same physicochemical properties of primer specificity and overall features of the L. major.Our studies revealed that no telomerase inhibitory factors were present in the nuclear lysates of T. cruzi however the enzyme was activated by heat and was very resilient to heat denaturation. We also showed the extension primer specificity, susceptibility to RNase-A and RNase-H digestion, and the effect of telomerase inhibitors. © 2011 Elsevier B.V.


Arguello E.,Simon Bolivar University of Venezuela | Silva R.,Simon Bolivar University of Venezuela | Castillo C.,Institute Estudios Avanzados | Huerta M.,Simon Bolivar University of Venezuela
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2012

In this paper we introduce a novel computational neuron-model, the Neuroid, which is based on three basic operations that are carried out by nerve cells to process the incoming information, such as comparison, and frequency pulse modulation-demodulation. The model was implemented using LabVIEW 10.0, in order to assign to each of these operations, an execution block (Virtual Instrument). The results of its implementation showed a very similar behavior to that exhibited by real neurons. Furthermore, due to its simplicity and low computational requirements, it is expected that the Neuroid can be used to create several software models of biological neural systems, either for research or teaching purposes. © 2012 IEEE.


Osorio M.,Institute Estudios Avanzados | Gamez E.,Institute Estudios Avanzados | Molina S.,Institute Estudios Avanzados | Infante D.,Institute Estudios Avanzados
Electronic Journal of Biotechnology | Year: 2012

Background: Cassava (Manihot esculenta Crantz) is a crop that is high in carbohydrates in the roots and in protein in the leaves, important for both human consumption and animal feed, and also has a significant industrial use for its starches. In this study we evaluated the genetic variability with molecular markers in different stages in micropropagated plants from somatic embryos of Venezuelan native clone 56. Results: Three markers were used: ISTR, AFLP and SSR, finding that ISTR showed the highest polymorphism among individuals tested. With AFLP a high similarity between the evaluated individuals was observed and with SSR total monomorphism was seen. Using cluster analysis it was found that individuals from an embryo labeled as fasciated at the beginning of the somatic embryogenesis process were grouped as independent of the other plants when analyzed at the acclimatization stage. The differences found with the different markers used are discussed. In field trials, micropropagated plants had a yield between 4 and 5 times the average yield of cassava in Venezuela. Conclusion: Despite variability in terms of DNA markers, somatic embryogenesis is suitable for mass propagation of highly performing cassava clones. © 2012 by Pontificia Universidad Católica de Valparáso, Chile.


Peigneur S.,Catholic University of Leuven | Sevcik C.,CNR Institute of Biophysics | Tytgat J.,Catholic University of Leuven | Castillo C.,Institute Estudios Avanzados | D'Suze G.,CNR Institute of Biophysics
FEBS Journal | Year: 2012

The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (Na V) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on Na V1.4, Bacts 4 and 6 on NaV1.3 and Bact 5 on Na V1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V1/2 of activation and inactivation of Na V1.3, NaV1.4 and NaV1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT/zF, changes in κ probably express changes in z, the valence, in a voltage-dependent manner. Changes in z may express toxin-induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a NaV1.2 voltage shift of the activation curves but no shift of the mutant NaV1.2 IFM/QQQ; peak INa was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure-function relationships and also as pharmacologically interesting peptides. Bactridines are scorpion toxins combining a dual functionality as antibacterial toxins and as selective voltage-gated sodium channel modulators. Bactridines possess different selectivities for neuronal and muscular NaV channels, with subtle differences in their effects on different channel isoforms. Bactridines emerge as potential research tools to understand sodium channel isoforms structure-function relationships, and also as pharmacologically interesting peptides. © 2012 The Authors Journal compilation © 2012 FEBS.


Arguello E.,Simon Bolivar University of Venezuela | Silva R.,Simon Bolivar University of Venezuela | Huerta M.,Simon Bolivar University of Venezuela | Castillo C.,Institute Estudios Avanzados
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2013

It is thought that using detailed neuron-models could lead to a better understanding of how the nervous system works. However, neural networks preserve their collective computational properties, regardless of the level of description used for modeling the main building block. In this paper, we built a Neuroid-based retina model. As a result of the implementation, the Neuroid was able to reproduce the essential features of the photoreceptor response to light. Likewise, the retina model responded to specific visual effects such as simultaneous contrast, Mach bands and Hermann grid. All of these suggest that the Neuroid comprises enough functional characteristics, such that we could focus not only on the most relevant computational aspects of nerve cells, but also in the collective capabilities of large-scale neural networks. © 2013 IEEE.

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