- Malaria, Antimicrobial Peptides, Insect Immune System, Ecología De Parasitos Y Vectores, Biotechnology, Cognitive Sciences, and 17 moreStem Cell Research, Molecular and cellular biology, Bioinformatics, Molecular Biology, Biochemistry, Immunology, Cytotoxicity, Phospholipase A2, Amino Acid Sequence, Electronic Transport In Molecules, Bioorganic and medicinal Chemistry, Chemistry, Microbiology, Organic Chemistry, Biochimie, Medical Biotechnology, and Gene expression and regulationedit
Malaria transmission depends on the parasites' successful invasion of the mosquito. This is achieved by the ookinete, a motile zygote that forms in the blood bolus after the mosquito takes an infectious blood meal. The ookinete invades... more
Malaria transmission depends on the parasites' successful invasion of the mosquito. This is achieved by the ookinete, a motile zygote that forms in the blood bolus after the mosquito takes an infectious blood meal. The ookinete invades the midgut epithelium and strongly attaches to the basal lamina, differentiating into an oocyst that produces the vertebrate-invasive sporozoites. Despite their importance, the ookinete and the oocyst are the least studied stages of the parasite. Much of what we know about the ookinete comes from in vitro experiments, which are hindered by the concomitant contamination with blood cells and other parasite stages. Although methods to purify them exist, they vary in terms of yield, costs, and difficulty to perform. A method for ookinete purification taking advantage of their adhesive properties was herein developed. The method consists of covering any culture-suitable surface with extracellular matrix gel, after which the ookinete culture is incubated on the gel to allow for ookinete attachment. The contaminant cells are then simply washed away. This procedure results in purer and less stressed ookinete preparations, which, by the nature of the method, are ready for oocyst production. Furthermore, it allows for micro-purifications using only 1 μl of blood, opening the possibility to make axenic ookinete cultures without sacrificing mice
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Dengue virus has shown a complex pattern of transmission across Latin America over the last two decades. In an attempt to explain the permanence of the disease in regions subjected to drought seasons lasting over six months, various... more
Dengue virus has shown a complex pattern of transmission across Latin America over the last two decades. In an attempt to explain the permanence of the disease in regions subjected to drought seasons lasting over six months, various hypotheses have been proposed. These include transovarial transmission, forest reservoirs and asymptomatic human virus carriers. Dengue virus is endemic in Mexico, a country in which half of the population is seropositive. Seropositivity is a risk factor for Dengue Hemorrhagic Fever upon a second encounter with the dengue virus. Since Dengue Hemorrhagic Fever can cause death, it is important to develop epidemiological mathematical tools that enable policy makers to predict regions potentially at risk for a dengue epidemic. We formulated a mathematical model of dengue transmission, considering both human behavior and environmental conditions pertinent to the transmission of the disease. When data on past human population density, temperature and rainfall were entered into this model, it provided an accurate picture of the actual spread of dengue over recent years in four states (representing two climactic conditions) in Mexico.
The immune response of Anopheles mosquitoes to Plasmodium invasion has been extensively studied and shown to be mediated mainly by the nitric oxide synthase (NOS), dual oxidase (DUOX), phenoloxidase (PO), and antimicrobial peptides... more
The immune response of Anopheles mosquitoes to Plasmodium invasion has been extensively studied and shown to be mediated mainly by the nitric oxide synthase (NOS), dual oxidase (DUOX), phenoloxidase (PO), and antimicrobial peptides activity. Here, we studied the correlation between a heat shock insult, transcription of immune response genes, and subsequent susceptibility to Plasmodium berghei infection in Anopheles albimanus. We found that transcript levels of many immune genes were drastically affected by the thermal stress, either positively or negatively. Furthermore, the transcription of genes associated with modifications of nucleic acid methylation was affected, suggesting an increment in both DNA and RNA methylation. The heat shock increased PO and NOS activity in the hemolymph, as well as the transcription of several immune genes. As consequence, we observed that heat shock increased the resistance of mosquitoes to Plasmodium invasion. The data provided here could help the understanding of infection transmission under the ever more common heat waves.
Agave marmorata Roezl is an endemic succulent specie from the Oaxaca-Puebla area of Mexico. This plant is a medicinal recourse and contain a rich variety of saponins-type compounds with mul- tiples biological effects. Some of them have... more
Agave marmorata Roezl is an endemic succulent specie from the Oaxaca-Puebla area of Mexico. This plant is a medicinal recourse and contain a rich variety of saponins-type compounds with mul- tiples biological effects. Some of them have been shown to be anticancer, antibacterial, or having anti-inflammatory and immu- noregulation effects. This paper is the first scientific report to describe the pharmacological activity and chemistry of the sap- onin smilagenin-3-O-[b-D-glucopyranosyl (1!2)-b-D-galactopyra- noside] (1), isolated from Agave marmorata Roezl. Saponin (1) displayed immunomodulating activity when assayed on cultured macrophages. It inhibits NO production (EC50 1⁄4 5.6mg/ml, Emax 1⁄4 101%), as well as NF-jB expression (EC50 1⁄4 0.086mg/ml, Emax 1⁄4 90%). Using bioinformatic molecular docking, we identified a new smilagenin- PI3K kinase interaction site.
The cuticular hydrocarbon (CHC) profile reflects the insect’s physiological states. These states include age, sex, reproductive stage, or gravidity. Environmental factors such as diet, relative humidity, or exposure to insecticides also... more
The cuticular hydrocarbon (CHC) profile reflects the insect’s physiological states. These states include age, sex, reproductive stage, or gravidity. Environmental factors such as diet, relative humidity, or exposure to insecticides also affect the CHCs composition in mosquitoes. In this work, the CHC profile was analyzed in two Anopheles albimanus phenotypes with different degrees of susceptibility to Plasmodium: the susceptible-White and resistant-Brown phenotypes. The effects of the CHC profile were considered under a carbon-rich diet (sugar), a protein-rich diet (blood), and an infectious challenge (blood containing Plasmodium berghei ookinetes). The CHCs were analyzed by gas chromatography coupled with either mass spectrometry or flame ionization detection, identifying 19 CHCs with chain lengths ranging from 20 to 37 carbons. The qualitative and quantitative changes observed in the CHCs composition were dependent on the diet and parasite challenge, and independent of the phenotype. The exception was the challenge condition, where significant differences in the CHC profile between the phenotypes were observed. Interestingly, the White Plasmoidum-challenged mosquitoes had a 68% increased abundance in the CHCs compared with the blood-fed mosquitoes. In contrast, the Brown strain showed an increased abundance only in 6.25% of the CHCs, with an overall decrease of the rest of the CHCs. Since the lipid metabolism in Anopheles mosquitoes has been shown crucial for Plasmodium development, the changes in the CHC profiles associated with infection could have multiple effects on mosquito fitness and impacts on disease transmission.
Epigenetic mechanisms such as DNA methylation and histone post-translational modifications are fundamental for the phenotypic plasticity of insects during their interaction with the environment. In response to environmental cues, the... more
Epigenetic mechanisms such as DNA methylation and histone post-translational modifications are fundamental for the phenotypic plasticity of insects during their interaction with the environment. In response to environmental cues, the methylation pattern in DNA is dynamically remodeled to achieve an epigenetic control of gene expression. DNA methylation is the focus of study in insects for its evolutionarily conserved character; however, there is scant knowledge about the epigenetic regulation in vector mosquitoes, especially during their infection by parasites. The aim of the present study was to evaluate the participation of DNA methylation in the immune response of Anopheles albimanus to a Plasmodium infection. For this, we first investigated the presence of a fully functional DNA methylation system in A. albimanus by assessing its potential role in larval development. Subsequently, we evaluated the transcriptional response to Plasmodium berghei of two mosquito phenotypes with different degrees of susceptibility to the parasite, in a scenario where their global DNA methylation had been pharmacologically inhibited. Our study revealed that A. albimanus has a functional DNA methylation system that is essential to larval viability, and that is also responsive to feeding and parasite challenges. The pharmacological erasure of the methylome with azacytidine or decitabine abolished the divergent responses of both mosquito phenotypes, leading to a transcriptionally similar response upon parasite challenge. This response was more specific, and the infection load in both phenotypes was lowered. Our findings suggest that DNA methylation may constitute a key factor in vector competence, and a promising target for preventing malaria transmission.
Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this... more
Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this behavior is intriguing. Here, we explore the effect of various parameters on likelihood of new serotype emergence. In order to determine the time scales of such an event, we used a Timed Markov Transmission Model to explore the influences of sylvatic versus peri-urban transmission, viral mutation rate, and vertical transmission on the probabilities of novel serotype emergence. We found that around 1 000 years are required for a new serotype to emerge, consistent with phylogenetic analysis of extant dengue serotypes. Furthermore, we show that likelihood of establishing chains of mosquito-human-mosquito infection, known as consolidation, is the primary factor which constrains novel serotype emergence. Our work illustrates the restrictions on and provides a mechanistic explanation for the low probability of novel dengue virus serotype emergence and the low number of observed DENV serotypes.
Phospholipase A2 (PLA2) cleaves the ester bond at position 2 of the glycerol moiety of phospholipids, and is widely distributed in mammals, reptiles and arthropods [1]. Recently, the old classification of PLA2 into three groups [2] was... more
Phospholipase A2 (PLA2) cleaves the ester bond at position 2 of the glycerol moiety of phospholipids, and is widely distributed in mammals, reptiles and arthropods [1]. Recently, the old classification of PLA2 into three groups [2] was expanded according to some ...
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2,4-Dichlorophenoxyacetic acid (2,4-D) and nitrate are agricultural contaminants found in rural ground water. It is not known whether levels found in groundwater pose a human or environmental health risk, nor is the mechanism of toxicity... more
2,4-Dichlorophenoxyacetic acid (2,4-D) and nitrate are agricultural contaminants found in rural ground water. It is not known whether levels found in groundwater pose a human or environmental health risk, nor is the mechanism of toxicity at the molecular/cellular level understood. ...
Research Interests: Biochemistry, Groundwater, Environmental Health, Biology, Cytotoxicity, and 15 moreDNA repair, Gene expression, Humans, Hepatocellular Carcinoma, Ground Water, Cell Viability, Herbicides, Hierarchical Clustering, In Vitro Toxicology, Cdna Microarray, Cell Proliferation, Level, Cell Survival, Cell Cycle Control, and Gene expression profiling
Research Interests: Biology, Biological Chemistry, Medicine, Biological Sciences, DNA, and 15 moreHumans, Animals, Biological, Phosphorylation, Plasmids, Immunoprecipitation, CHEMICAL SCIENCES, Cell nucleus, Oocytes, Cytoplasm, DNA binding proteins, Gene Expression Regulation, Dimerization, Immunoblotting, and Medical and Health Sciences
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Since Hsp90 is a known modulator of HSF1 activity, we examined the effects of two pharmacological inhibitors of Hsp90, novobiocin and geldanamycin, on HSF1 DNA-binding activity in the Xenopus oocyte model system. Novobiocin exhibits... more
Since Hsp90 is a known modulator of HSF1 activity, we examined the effects of two pharmacological inhibitors of Hsp90, novobiocin and geldanamycin, on HSF1 DNA-binding activity in the Xenopus oocyte model system. Novobiocin exhibits antiproliferative activity in culture cells and interacts with a C-terminal ATP-binding pocket on Hsp90, inhibiting Hsp90 autophosphorylation. Treatment of oocytes with novobiocin followed by heat shock results in a dose-dependent decrease in HSF1 DNA-binding and transcriptional activity. Immunoprecipitation experiments demonstrate novobiocin does not alter HSF1 activity through dissociation of Hsp90 from either monomeric or trimerized HSF1, suggesting that the effect of novobiocin on HSF1 is mediated through alterations in Hsp90 autophosphorylation. Geldanamycin binds the N-terminal ATPase site of Hsp90 and inhibits chaperone activity. Geldanamycin treatment of oocytes resulted in a dose-dependent increase in stability of active HSF1 trimers during subm...
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Cecropin 3 (Ccrp3) is an antimicrobial peptide from Anopheles albimanus, which is expressed during Plasmodium berghei infection. Here, we report that synthetic Ccrp3, aside from antibacterial activity, also shows cardio regulatory... more
Cecropin 3 (Ccrp3) is an antimicrobial peptide from Anopheles albimanus, which is expressed during Plasmodium berghei infection. Here, we report that synthetic Ccrp3, aside from antibacterial activity, also shows cardio regulatory functions. In rats, Ccrp3 significantly diminishes blood pressure as well as the heartbeat frequency at nanomolar concentration. Ccrp3 affect the rat cardiac muscle mitochondria, inducing uncoupling of oxidative phosphorylation, oxygen consumption and transport of Ca(2). Ccrp3 treatment of the mitochondria causes mitochondrial damage promoting oxidative stress, causing overproduction of reactive oxygen species (ROS) and inhibition of superoxide dismutase. At nM concentration, Ccrp3 inhibits superoxide dismutase activity through direct interaction, diminishing by its enzymatic activity. Ccrp3 induces the release of the pro-apoptotic marker Bax from the mitochondria. Altogether, these results suggest that Ccrp3 pro-oxidative activity on cardiac muscle mitochondria could be responsible for triggering the heartbeat frequency and blood pressure lowering observed the Ccrp3 injected rats.
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Research Interests: Biology, Biological Chemistry, Medicine, Biological Sciences, DNA, and 15 moreHumans, Animals, Biological, Phosphorylation, Plasmids, Immunoprecipitation, CHEMICAL SCIENCES, Cell nucleus, Oocytes, Cytoplasm, DNA binding proteins, Gene Expression Regulation, Dimerization, Immunoblotting, and Medical and Health Sciences
... Invest. Clin. 49, 4958. Brazón, J., D'Suze, G., D'Errico, ML, Arocha-Piñango, CL, Guerrero, B., 2009. Discreplasminin, a plasmin inhibitor isoltated from Tityus discrepans scorpion venom. Arch. Toxicol. ... FEBS Lett. 460,... more
... Invest. Clin. 49, 4958. Brazón, J., D'Suze, G., D'Errico, ML, Arocha-Piñango, CL, Guerrero, B., 2009. Discreplasminin, a plasmin inhibitor isoltated from Tityus discrepans scorpion venom. Arch. Toxicol. ... FEBS Lett. 460, 447450. Condrea, E., Yang, CC, Rosenberg, P., 1981. ...
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is the main vector of Dengue Virus, carrying the virus during the whole mosquito life post-infection. Few mosquito fitness costs have been associated to the virus infection, thereby allowing for a swift dissemination. In order to diminish... more
is the main vector of Dengue Virus, carrying the virus during the whole mosquito life post-infection. Few mosquito fitness costs have been associated to the virus infection, thereby allowing for a swift dissemination. In order to diminish the mosquito population, public health agency use persistent chemicals with environmental impact for disease control. Most countries barely use biological controls, if at all. With the purpose of developing novel Dengue control strategies, a detailed understanding of the unexplored virus-vector interactions is urgently needed. Damage induced (through tissue injury or bacterial invasion) DNA duplication (endoreplication) has been described in insects during epithelial cells renewal. Here, we delved into the mosquito midgut tissue ability to synthesize DNA ; postulating that Dengue virus infection could trigger a protective endoreplication mechanism in some mosquito cells. We hypothesized that the orthologue of the gene (not previously annotated in t...