Publications by authors named "Jose L Ramírez"

54 Publications

Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens.

Science 2010 Oct;330(6000):88-90

Department of Entomology, Iowa State University, Ames, IA 50011, USA.

The mosquito Culex quinquefasciatus poses a substantial threat to human and veterinary health as a primary vector of West Nile virus (WNV), the filarial worm Wuchereria bancrofti, and an avian malaria parasite. Comparative phylogenomics revealed an expanded canonical C. quinquefasciatus immune gene repertoire compared with those of Aedes aegypti and Anopheles gambiae. Transcriptomic analysis of C. quinquefasciatus genes responsive to WNV, W. bancrofti, and non-native bacteria facilitated an unprecedented meta-analysis of 25 vector-pathogen interactions involving arboviruses, filarial worms, bacteria, and malaria parasites, revealing common and distinct responses to these pathogen types in three mosquito genera. Our findings provide support for the hypothesis that mosquito-borne pathogens have evolved to evade innate immune responses in three vector mosquito species of major medical importance.
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http://dx.doi.org/10.1126/science.1193162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104938PMC
October 2010

Allotriploid genotypic assignment in abalone larvae by detection of microsatellite-recombinant genotypes.

J Hered 2010 Jul-Aug;101(4):476-90. Epub 2010 Mar 10.

Centro de Investigaciones Biológicas del Noroeste SC, Aquaculture Program, Aquaculture Genetics and Breeding Laboratory, Mar Bermejo 195, La Paz BCS 23090, Mexico.

Abalone species are different from most mollusks utilized in aquaculture as they are known to hybridize in laboratory-induced matings. Allotriploidization of hybrid abalone has not yet been studied, and methodology useful in verifying the genotypic condition of such allotriploids do not exist. Genotypic verification of hybridization and allotriploidization in a cross of Haliotis fulgens and Haliotis rufescens was performed utilizing 6 crossamplifying microsatellite loci. Five H. rufescens spawns were used in this experiment, dividing each spawn into control and experimental hybrid groups and further into diploids and triploids. Two microsatellite loci developed for H. fulgens and H. rufescens allowed for the genotypic identification of hybrids within diploid and triploids. To further verify the percentage of allotriploids within the genotypic hybrids in the triploid hybrid groups, microsatellite loci originally developed in Haliotis corrugata and Haliotis kamtschatkana were tested for crossamplification in H. fulgens and H. rufescens. Of 21 loci, 4 were chosen for this study based on their crossamplification, heterozygosity in the females, and centromere recombination frequencies. Allotriploids in triploid-hybrid larvae were then detected by identifying larvae with recombinant genotypes at any of those loci. One family had low success verification associated with reduced recombination frequencies for all loci in that family. These results demonstrate that allotriploid verification at larval stages is feasible but depends on the number of loci available, their crossamplification in the species, and their recombination frequencies.
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http://dx.doi.org/10.1093/jhered/esq027DOI Listing
October 2010

The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes.

Dev Comp Immunol 2010 Jun 19;34(6):625-9. Epub 2010 Jan 19.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205-2179, USA.

Dengue virus has become one of the most important arboviral pathogens affecting the world today. The virus is transmitted among humans by the mosquitoes Aedes aegypti and Ae. albopictus. Like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. We have previously demonstrated the involvement of the Toll pathway in the anti-dengue defense at 7 days after infection. In the present study, we have investigated the activity of this immune signaling pathway against different dengue virus serotypes at the early stages of infection in laboratory and field-derived mosquito strains. Our studies corroborate the importance of the Toll pathway in the anti-dengue defense repertoire at 3 days after an infectious blood meal, when new virions are released from the midgut for dissemination and infection of other mosquito tissues. These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes.
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http://dx.doi.org/10.1016/j.dci.2010.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917001PMC
June 2010

Structure-activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding.

J Med Chem 2010 Jan;53(1):18-36

deCODE Chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, USA.

The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.
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http://dx.doi.org/10.1021/jm9005912DOI Listing
January 2010

Machine learning techniques for the automated classification of adhesin-like proteins in the human protozoan parasite Trypanosoma cruzi.

IEEE/ACM Trans Comput Biol Bioinform 2009 Oct-Dec;6(4):695-702

Computer Science Department, Escuela Politécnica Superior, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

This paper reports on the evaluation of different machine learning techniques for the automated classification of coding gene sequences obtained from several organisms in terms of their functional role as adhesins. Diverse, biologically-meaningful, sequence-based features were extracted from the sequences and used as inputs to the in silico prediction models. Another contribution of this work is the generation of potentially novel and testable predictions about the surface protein DGF-1 family in Trypanosoma cruzi. Finally, these techniques are potentially useful for the automated annotation of known adhesin-like proteins from the trans-sialidase surface protein family in T. cruzi, the etiological agent of Chagas disease.
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http://dx.doi.org/10.1109/TCBB.2008.125DOI Listing
February 2010

Mosquito infection responses to developing filarial worms.

PLoS Negl Trop Dis 2009 Oct 13;3(10):e529. Epub 2009 Oct 13.

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (approximately 13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed.
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http://dx.doi.org/10.1371/journal.pntd.0000529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752998PMC
October 2009

Discovery of insect and human dengue virus host factors.

Nature 2009 Apr;458(7241):1047-50

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.
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http://dx.doi.org/10.1038/nature07967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462662PMC
April 2009

Challenges and approaches for mosquito targeted malaria control.

Curr Mol Med 2009 Mar;9(2):116-30

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205-2179, USA.

Malaria is one of today's most serious diseases with an enormous socioeconomic impact. While anti-malarial drugs have existed for some time and vaccines development may be underway, the most successful malaria eradication programs have thus far relied on attacking the mosquito vector that spreads the disease causing agent Plasmodium. Here we will review past, current and future perspectives of malaria vector control strategies and how these approaches have taken a promising turn thanks recent advances in functional genomics and molecular biology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925229PMC
http://dx.doi.org/10.2174/156652409787581600DOI Listing
March 2009

Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding.

ACS Chem Biol 2009 Feb;4(2):115-26

deCODE Chemistry, Woodridge, Illinois 60517, USA.

Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents.
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http://dx.doi.org/10.1021/cb8002094DOI Listing
February 2009

Fate of a genetically modified bacterium in foregut of glassy-winged sharpshooter (Hemiptera: Cicadellidae).

J Econ Entomol 2008 Oct;101(5):1519-25

University of California, Department of Entomology, Riverside, CA 92521-0314, USA.

Symbiotic control is a new strategy being investigated to prevent the spread of insect-transmitted pathogens by reducing vector competence. We are developing this strategy to reduce the spread of Xylella fastidiosa by Homalodisca vitripennis (Germar) [formerly Homalodisca coagulata (Say)] (Hemiptera: Cicadellidae), the glassy-winged sharpshooter. In this study, the fate of a transformed symbiotic bacterium, Alcaligenes xylosoxidans variety denitriicans (S1Axd), in the foregut of glassy-winged sharpshooter when fed on citrus (Citrus spp.) and grape (Vitris spp.) was assessed. TaqMan-based quantitative real-time polymerase chain reaction (PCR) was used to detect and quantify bacterial cells remaining in the foregut at 0, 2, 4, 9, and 12 d after acquisition. S1Axd titer dropped rapidly by 2 d after acquisition, but in spite of this, at end of the 12-d experimental period, 45 and 38% of the glassy-winged sharpshooters retained the transformed bacteria, when fed on grape and citrus, respectively.
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http://dx.doi.org/10.1603/0022-0493(2008)101[1519:foagmb]2.0.co;2DOI Listing
October 2008

The Aedes aegypti toll pathway controls dengue virus infection.

PLoS Pathog 2008 Jul 4;4(7):e1000098. Epub 2008 Jul 4.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference-based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi)-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway-associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway.
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http://dx.doi.org/10.1371/journal.ppat.1000098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435278PMC
July 2008

Detection of the bacterium, Xylella fastidiosa, in saliva of glassy-winged sharpshooter, Homalodisca vitripennis.

J Insect Sci 2008 ;8:1-7

Department of Entomology, University of California Riverside, USA.

Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), the glassy-winged sharpshooter, is one of the most important vectors of the bacterium, Xylella fastidiosa subsp. piercei (Xanthomonadales: Xanthomonadaceae) that causes Pierce's Disease in grapevines in California. In the present study we report a new method for studying pathogen transmission or probing behavior of H. vitripennis. When confined, H. vitripennis attempt to probe the surface of sterile containers 48 hours post-acquisition of X. f. piercei. The saliva deposited during attempted feeding probes was found to contain X. f. piercei. We observed no correlation between X. f. piercei titers in the foregut of H. vitripennis that fed on Xylella-infected grapevines and the presence of this bacterium in the deposited saliva. The infection rate after a 48 h post-acquisition feeding on healthy citrus and grapevines was observed to be 77% for H. vitripennis that fed on grapevines and 81% for H. vitripennis that fed on citrus, with no difference in the number of positive probing sites from H. vitripennis that fed on either grapevine or citrus. This method is amenable for individual assessment of X. f. piercei-infecuvity, with samples less likely to be affected by tissue contamination that is usually present in whole body extracts.
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http://dx.doi.org/10.1673/031.008.3401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061605PMC
May 2010

An induced mass spawn of the hermaphroditic lion-paw scallop, Nodipecten subnodosus: genetic assignment of maternal and paternal parentage.

J Hered 2008 Jul-Aug;99(4):337-48. Epub 2008 Mar 11.

Genomic Variation Laboratory, Department of Animal Science, University of California, One Shields Avenue, Davis, CA 95616, USA.

The Pacific lion-paw scallop is commonly propagated for aquaculture by induced mass spawns of few individuals. Parentage of a mass spawn of this species has not been evaluated nor has the maternal and paternal contribution of each of these functional hermaphrodites to the progeny. Genotypes of 6 spawners and 374 resulting progeny at 6 microsatellite loci were coupled with mitochondrial DNA sequencing to assign maternal and paternal parentage. After the identification of a high proportion of null alleles (9.7%), microsatellite data revealed that 51.7% of the progenies were full siblings, with a significant, unequal contribution of the 6 spawners to the progeny. Three progenies were the result of self-fertilization. All spawners contributed paternally (though unequally); however, 2 spawners were the maternal parents of all but 7 progenies resulting in a variance effective population size of 3.52. DNA sequencing confirmed 4 microsatellite mutations within 4476 alleles scored, all in the paternal germ line. With minor exception, the loci conformed to Mendelian rules of segregation when null alleles were accounted for, and 2 loci were found to be linked. These results lend insight to the genetic composition of induced mass spawns and provide a basis for the development of more effective spawning techniques.
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http://dx.doi.org/10.1093/jhered/esn012DOI Listing
September 2008

Usefulness of 12 Y-STRs for forensic genetics evaluation in two populations from Venezuela.

Leg Med (Tokyo) 2008 Mar 5;10(2):107-12. Epub 2007 Nov 5.

Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

The distribution of allele frequencies and haplotypes for 12 STRs loci, (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438 and DYS439) on the Y-chromosome from two Venezuelan populations were determined in 173 DNA samples of unrelated males living in Caracas (62) and Maracaibo (111). Some parameters of forensic importance were calculated. AMOVA and genetic distances between these populations were estimated. The results confirmed Y-STR genotypes as useful markers for forensic genetics analysis.
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http://dx.doi.org/10.1016/j.legalmed.2007.08.005DOI Listing
March 2008

In silico, biologically-inspired modelling of genomic variation generation in surface proteins of Trypanosoma cruzi.

Kinetoplastid Biol Dis 2007 Jul 10;6. Epub 2007 Jul 10.

Computer Science Research Institute and School of Computing and Mathematics, University of Ulster, Jordanstown, BT37 OQB, Northern Ireland, UK.

Background: Protozoan parasites improve the likelihood of invading or adapting to the host through their capacity to present a large repertoire of surface molecules. The understanding of the mechanisms underlying the generation of antigenic diversity is crucial to aid in the development of therapies and the study of evolution. Despite advances driven by molecular biology and genomics, there is a need to gain a deeper understanding of key properties that may facilitate variation generation, models for explaining the role of genomic re-arrangements and the characterisation of surface protein families on the basis of their capacity to generate variation. Computer models may be implemented to explore, visualise and estimate the variation generation capacity of gene families in a dynamic fashion. In this paper we report the dynamic simulation of genomic variation using real T. cruzi coding sequences as inputs to a computational simulation system. The effects of random, multiple-point mutations and gene conversions on genomic variation generation were quantitatively estimated and visualised. Simulations were also implemented to investigate the potential role of pseudogenes as a source of antigenic variation in T. cruzi.

Results: Computational models of variation generation were applied to real coding sequences from surface proteins in T. cruzi: trans-sialidase-like proteins and putative surface protein dispersed gene family-1. In the simulations the sequences self-replicated, mutated and re-arranged during thousands of generations. Simulations were implemented for different mutation rates to estimate the relative robustness of the protein families in the face of DNA multiple-point mutations and sequence re-arrangements. The gene super-families and families showed distinguishing evolutionary responses, which may be used to characterise them on the basis of their capacity to generate variability. The simulations showed that sequences from T. cruzi nuclear genes tend to be relatively more robust against random, multiple-point mutations than those obtained from surface protein genes. Simulations also showed that a gene conversion model may act as an effective variation generation mechanism. Differential variation responses can be used to characterise the sequence groups under study. For example, unlike other families, sequences from the DGF1 family have the capacity to maximise variation at the amino acid level under relatively low mutation rates and through gene conversion. However, in relation to the other protein families, they exhibit more robust behaviour in response to more severe modifications through intra-family genomic sequence exchange. Independent simulations indicate that DGF1 pseudogenes might play a role in the generation of greater genomic variation in the DFG1 gene family through gene conversion under different experimental conditions.

Conclusion: Digital, dynamic simulations may be implemented to characterise gene families on the basis of their capacity to generate variation in the face of genomic perturbations. Such simulations may be useful to explore antigenic variation mechanisms and hypotheses about robustness at the genomic level. This investigation illustrated how sequences derived from surface protein genes and computer simulations can be used to investigate variation generation mechanisms. Such in silico experiments of self-replicating sequences undergoing random mutations and genomic re-arrangements can offer insights into the diversity generation potential of the genes under study. Biologically-inspired simulations may support the study of genomic variation mechanisms in pathogens whose genomes have been recently sequenced.
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http://dx.doi.org/10.1186/1475-9292-6-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1965468PMC
July 2007

Endoscopic approach for mandibular orthognathic surgery.

Facial Plast Surg Clin North Am 2006 Feb;14(1):45-50

Massachusetts General Hospital, Warren Building, Suite 1201, Boston MA 02114, USA.

The field of minimally invasive surgery is defined as the combination of surgical innovation with modern technology. This article describes the history of surgery and newer developments in endoscopic surgery for mandibular orthognathic surgery.
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http://dx.doi.org/10.1016/j.fsc.2005.11.003DOI Listing
February 2006

Trypanosoma rangeli expresses a gene of the group II trans-sialidase superfamily.

Mol Biochem Parasitol 2005 Jul 9;142(1):133-6. Epub 2005 Apr 9.

Decanato de Medicina, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Estado Lara, Venezuela.

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http://dx.doi.org/10.1016/j.molbiopara.2005.03.012DOI Listing
July 2005

Agonist-induced up-regulation of human somatostatin receptor type 1 is regulated by beta-arrestin-1 and requires an essential serine residue in the receptor C-tail.

Biochim Biophys Acta 2005 May 22;1669(2):182-92. Epub 2005 Feb 22.

Fraser Laboratories, Room M3-15, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.

We have previously shown that the human somatostatin receptor type 1 (hSSTR1) does not undergo agonist-induced internalization, but is instead up-regulated at the membrane upon prolonged somatostatin (SST) exposure. The deletion of the carboxyterminal C-tail of the receptor completely abolishes up-regulation. To identify molecular signals that mediate hSSTR1 up-regulation, we created mutant receptors with progressive C-tail deletions. Up-regulation was found to be absent in mutants lacking residues Lys359-Ser360-Arg361. Moreover, point mutation of Ser360 to Ala completely abolished up-regulation. The coexpression of wild type hSSTR1 with V53D, a dominant negative mutant of beta-arrestin-1, completely blocked hSSTR1 up-regulation. Further analysis demonstrated that calcium-calmodulin (CaM) dependent kinases were essential for the SST-induced up-regulation response. Like wild type receptors, all mutants failed to internalize after agonist exposure and were able to inhibit forskolin-stimulated cAMP accumulation. Taking these data together, we suggest that SST-induced hSSTR1 up-regulation is critically dependent upon a specific Lys-Ser-Arg sequence in the C-tail of the receptor, with Ser360 being essential. Up-regulation also requires the participation of CaM protein kinases and interactions with beta-arrestins. In contrast, coupling to adenyl cyclase (AC) and internalization occur independently of molecular signals in the receptor's C-tail.
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http://dx.doi.org/10.1016/j.bbamem.2005.02.004DOI Listing
May 2005

Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas.

Mol Cell Endocrinol 2004 Jun;221(1-2):105-19

Fraser Laboratories, Departments of Medicine, Royal Victoria Hospital, McGill University, Montreal, Que., Canada H3A 1A1.

The actions of somatostatin (SST) are mediated through five somatostatin receptor subtypes, termed SSTR1-5. Although SSTRs commonly display an overlapping pattern of tissue distribution, subtype-selective responses have been shown to occur in the same tissue. In the present study, we have investigated the changes in SSTR subtypes at the cellular and molecular level in both the brain and the pancreatic islets of mice deficient in SSTR5 (SSTR5KO). Expression levels of insulin and glucagon were also determined in the pancreas of these mice. Semi-quantitative RT-PCR and Western blot analysis showed significant increases in the expression of SSTR2 and 3 with a corresponding reduction in SSTR4 in the brains of female SSTR5KOs, while no changes were observed in male KOs. Strikingly, SST mRNA and SST-like immunoreactivity (SST-LI) were reduced in the brain of male KO animals but not in their female counterparts. In male SSTR5KO islets, there was an increase in the number of cells immunoreactive for SSTR1-3, whereas in female islets only SSTR3 expression was increased. Pancreatic SST-LI and SST mRNA, as well as immunoreactivity for insulin were reduced in male but not in female KO mice. These data indicate that deficiency of SSTR5 leads to subtype-selective sexually dimorphic changes in the expression of both brain and pancreatic SSTRs.
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http://dx.doi.org/10.1016/j.mce.2004.02.001DOI Listing
June 2004

[Prenatal and postnatal effects of dengue infection during pregnancy].

Biomedica 2003 Dec;23(4):416-23

Instituto Colombiano de Medicina Tropical, Medellín, Colombia.

The risk of dengue virus infection during pregnancy has increased due to the current rash of frequent and severe dengue epidemics. The effects of dengue virus in the fetus and newborn children have been studied only superficially and with contradictory results. Therefore, a retrospective cohort study was conducted in Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus infection acquired during pregnancy. Twenty-two babies born from mothers who suffered dengue during the epidemics of 1998 were compared with babies from non-infected mothers. In the exposed cohort, three premature births occurred, three children suffered from fetal anomalies and four children were born with low weight. In the non-exposed children, none of these problems were found. Psychomotor development was normal in both groups. Only the low weight subgroup was statistically significant (Fisher test, p = 0.045). These results suggested that the children from women with dengue during pregnancy present low weight, greater frequency of premature birth and increased fetal distress. A larger sample is necessary to confirm these results.
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December 2003

Brain somatostatin receptors are up-regulated in somatostatin-deficient mice.

Mol Endocrinol 2002 Aug;16(8):1951-63

Fraser Laboratories, Department of Medicine, McGill University and Royal Victoria Hospital, Montréal, Québec, Canada, H3A 1A1.

The peptide somatostatin (SST) is widely synthesized in the brain and periphery and acts through a family of five receptors (SSTR1-5) to exert numerous effects. A gene product related to SST, cortistatin (CST), also interacts with SSTR1-5. Here we have investigated the regulation of SSTR1-5 and of CST in SST knockout (SSTKO) mice. The five SSTRs were quantitated individually by subtype-selective binding analysis, by immunocytochemistry, and by mRNA measurement and showed, in the brain of SSTKO mice, up-regulation of subtypes 1, 2, 4, and 5, and down-regulation of SSTR3. Peripheral tissues displayed both subtype- and tissue-specific changes in SSTR1-5 mRNA levels of expression. Lack of SST did not up-regulate normal CST expression in brain nor did it induce its expression in the periphery. SST-like immunoreactivity, however, was induced in the proximal midgut in SSTKO animals, suggesting intestinal expression of a novel SST-like gene.
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http://dx.doi.org/10.1210/me.2002-0068DOI Listing
August 2002

Comparative study of Trypanosoma rangeli and Trypanosoma cruzi telomeres.

Mol Biochem Parasitol 2002 Apr;120(2):305-8

Instituto de Biologia Experimental, Universidad Central de Venezuela, Apartado 47525, 1041-A Caracas, Venezuela.

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http://dx.doi.org/10.1016/s0166-6851(02)00005-1DOI Listing
April 2002

A diverse assemblage of Anacardiaceae from Oligocene sediments, Tepexi de Rodriguez, Puebla, Mexico.

Am J Bot 2002 Mar;89(3):535-45

Facultad de Ciencias, Departamento de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Del. Coyoacan, 04510 México D.F..

Among the plants collected from the Pie de Vaca Formation of the Oligocene, of Tepexi de Rodríguez, Puebla, México are five plants of Anacardiaceae, Haplorhus medranoensis, Rhus toxicodendron, Rhus sp., Comocladia intermedia, and Pistacia marquezii represented by their leaves and/or leaflets. The past and present diversity and geographic distribution of one of these genera, Rhus, demonstrate its capability to adapt and diversify in a wide variety of environments. Leaf architecture characters of this taxon overlap with those of other genera in the family, suggesting a high degree of phenotypic plasticity. The presence in the Pie de Vaca Formation of a type of Pistacia with leaf architecture characters similar to those of Asian plants further supports a long history of exchange between low-latitude North America and Asia. Links between low-latitude North and South America and the Caribbean are suggested by the presence of Comocladia and Haplorhus. Whereas Comocladia highlights the long history of regional endemics in the area, Haplorhus, today an endemic monotypic genus of Peru, suggests exchange mechanisms between North and South America. The morphologic characters of these taxa, and those of Pseudosmodingium (Anacardiaceae), some Rosaceae, Leguminosae, and Berberidaceae, suggest that the Pie de Vaca community was established and evolved in harsh environmental conditions. The Pie de Vaca flora thus provides significant new insights into the biogeographic relationships of the low latitude vegetation of North America.
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http://dx.doi.org/10.3732/ajb.89.3.535DOI Listing
March 2002

Somatostatin stimulates GH secretion in two porcine somatotrope subpopulations through a cAMP-dependent pathway.

Endocrinology 2002 Mar;143(3):889-97

Department of Cell Biology, Physiology, and Immunology, University of Cordoba, E-14071 Cordoba, Spain.

Somatostatin (SRIF) inhibits GH release from rat somatotropes by reducing adenylate cyclase (AC) activity and the free cytosolic calcium concentration ([Ca(2+)](i)). In contrast, we have reported that SRIF can stimulate GH release in vitro from pig somatotropes. Specifically, 10(-7) and 10(-15) M SRIF stimulate GH release from a subpopulation of high density (HD) somatotropes isolated by Percoll gradient centrifugation, whereas in low density (LD) somatotropes only 10(-15) M SRIF induces such an effect. To ascertain the signaling pathways underlying this phenomenon, we assessed SRIF effects on second messengers in cultured LD and HD cells by measuring cAMP, IP turnover, and [Ca(2+)](i). Likewise, contribution of the corresponding signaling pathways to SRIF-induced GH release was evaluated by blocking AC, PLC, extracellular Ca(2+) influx, or intracellular Ca(2+) mobilization. Both 10(-7) and 10(-15) M SRIF increased cAMP, IP turnover, and [Ca(2+)](i) in HD cells. Conversely, in LD cells 10(-7) M SRIF reduced [Ca(2+)](i), but did not alter cAMP or IP, and 10(-15) M SRIF was without effect. Interestingly, SRIF-stimulated GH release was abolished in both subpopulations by AC blockade, but not by PLC inhibition. Furthermore, SRIF-induced GH release was not reduced by blockade of extracellular Ca(2+) influx through voltage-sensitive channels or by depletion of thapsigargin-sensitive intracellular Ca(2+) stores. Therefore, SRIF stimulates GH secretion from cultured porcine somatotrope subpopulations through an AC/cAMP pathway-dependent mechanism that is seemingly independent of net increases in IP turnover or [Ca(2+)](i). These novel actions challenge classic views of SRIF as a mere inhibitor for somatotropes and suggest that it may exert a more complex, dual function in the control of porcine GH release, wherein molecular heterogeneity of somatotropes would play a critical role.
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http://dx.doi.org/10.1210/endo.143.3.8685DOI Listing
March 2002