Nanostructure des particules polymériques : aspects physiques, chimiques et biologiques

Les nanotechnologies appliquées aux sciences pharmaceutiques ont pour but d’améliorer l’administration de molécules actives par l’intermédiaire de transporteurs nanométriques. Parmi les différents types de véhicules proposés pour atteindre ce but, on retrouve les nanoparticules polymériques (NP) constituées de copolymères “en bloc”. Ces copolymères permettent à la fois l’encapsulation de molécules actives et confèrent à la particule certaines propriétés de surface (dont l’hydrophilicité) nécessaires à ses interactions avec les milieux biologiques. L’architecture retenue pour ces copolymères est une structure constituée le plus fréquemment de blocs hydrophiles de poly(éthylène glycol) (PEG) associés de façon linéaire à des blocs hydrophobes de type polyesters. Le PEG est le polymère de choix pour conférer une couronne hydrophile aux NPs et son l’efficacité est directement liée à son organisation et sa densité de surface. Néanmoins, malgré les succès limités en clinique de ces copolymères linéaires, peu de travaux se sont attardés à explorer les effets sur la structure des NPs d’architectures alternatives, tels que les copolymères en peigne ou en brosse. Durant ce travail, plusieurs stratégies ont été mises au point pour la synthèse de copolymères en peigne, possédant un squelette polymérique polyesters-co-éther et des chaines de PEG liées sur les groupes pendants disponibles (groupement hydroxyle ou alcyne). Dans la première partie de ce travail, des réactions d’estérification par acylation et de couplage sur des groupes pendants alcool ont permis le greffage de chaîne de PEG. Cette méthode génère des copolymères en peigne (PEG-g-PLA) possédant de 5 à 50% en poids de PEG, en faisant varier le nombre de chaînes branchées sur un squelette de poly(lactique) (PLA). Les propriétés structurales des NPs produites ont été étudiées par DLS, mesure de charge et MET. Une transition critique se situant autour de 15% de PEG (poids/poids) est observée avec un changement de morphologie, d’une particule solide à une particule molle (“nanoagrégat polymére”). La méthode de greffage ainsi que l’addition probable de chaine de PEG en bout de chaîne principale semblent également avoir un rôle dans les changements observés. L’organisation des chaînes de PEG-g-PLA à la surface a été étudiée par RMN et XPS, méthodes permettant de quantifier la densité de surface en chaînes de PEG. Ainsi deux propriétés clés que sont la résistance à l’agrégation en conditions saline ainsi que la résistance à la liaison aux protéines (étudiée par isothermes d’adsorption et microcalorimétrie) ont été reliées à la densité de surface de PEG et à l’architecture des polymères. Dans une seconde partie de ce travail, le greffage des chaînes de PEG a été réalisé de façon directe par cyclo-adition catalysée par le cuivre de mPEG-N3 sur les groupes pendants alcyne. Cette nouvelle stratégie a été pensée dans le but de comprendre la contribution possible des chaines de PEG greffées à l’extrémité de la chaine de PLA. Cette librairie de PEG-g-PLA, en plus d’être composée de PEG-g-PLA avec différentes densités de greffage, comporte des PEG-g-PLA avec des PEG de différent poids moléculaire (750, 2000 et 5000). Les chaines de PEG sont seulement greffées sur les groupes pendants. Les NPs ont été produites par différentes méthodes de nanoprécipitation, incluant la nanoprécipitation « flash » et une méthode en microfluidique. Plusieurs variables de formulation telles que la concentration du polymère et la vitesse de mélange ont été étudiées afin d’observer leur effet sur les caractéristiques structurales et de surface des NPs. Les tailles et les potentiels de charges sont peu affectés par le contenu en PEG (% poids/poids) et la longueur des chaînes de PEG. Les images de MET montrent des objets sphériques solides et l'on n’observe pas d’objets de type agrégat polymériques, malgré des contenus en PEG comparable à la première bibliothèque de polymère. Une explication possible est l’absence sur ces copolymères en peigne de chaine de PEG greffée en bout de la chaîne principale. Comme attendu, les tailles diminuent avec la concentration du polymère dans la phase organique et avec la diminution du temps de mélange des deux phases, pour les différentes méthodes de préparation. Finalement, la densité de surface des chaînes de PEG a été quantifiée par RMN du proton et XPS et ne dépendent pas de la méthode de préparation. Dans la troisième partie de ce travail, nous avons étudié le rôle de l’architecture du polymère sur les propriétés d’encapsulation et de libération de la curcumine. La curcumine a été choisie comme modèle dans le but de développer une plateforme de livraison de molécules actives pour traiter les maladies du système nerveux central impliquant le stress oxydatif. Les NPs chargées en curcumine, montrent la même transition de taille et de morphologie lorsque le contenu en PEG dépasse 15% (poids/poids). Le taux de chargement en molécule active, l’efficacité de changement et les cinétiques de libérations ainsi que les coefficients de diffusion de la curcumine montrent une dépendance à l’architecture des polymères. Les NPs ne présentent pas de toxicité et n’induisent pas de stress oxydatif lorsque testés in vitro sur une lignée cellulaire neuronale. En revanche, les NPs chargées en curcumine préviennent le stress oxydatif induit dans ces cellules neuronales. La magnitude de cet effet est reliée à l’architecture du polymère et à l’organisation de la NP. En résumé, ce travail a permis de mettre en évidence quelques propriétés intéressantes des copolymères en peigne et la relation intime entre l’architecture des polymères et les propriétés physico-chimiques des NPs. De plus les résultats obtenus permettent de proposer de nouvelles approches pour le design des nanotransporteurs polymériques de molécules actives.

Physiological and Genetic Diversity Studies on Regeneration of Santalum Album L.

S. album L. is the source of highly priced and fragrant heartwood which on steam distillation yields on an average 57 per cent oil of high perfumery value. Global demand for sandalwood is about 5000-6000 tons/year and that of oil is 100 tons/year. Heartwood of sandal is estimated to fetch up to Rs. 3.7 million/ton and wood oil Rs.70,000-100,000/ kg in the international market. Sandal heartwood prices have increased from Rs. 365/ton in 1900 to Rs. 6.5 lakhs/ton in 1999-2000 and to Rs. 37 lakhs/ton in 2007. Substantial decline in sandalwood production has occurred from 3176 tons/year during 1960-‘ 65 to 1500 tons/year in 1997-98, and to 500 tons/year in 2007.Depletion of sandal resources is attributed to several factors, both natural and anthropogenic. Low seed setting, poor seed germination, seedling mortality, lack of haustorial connection with host plant roots, recurrent annual fires in natural sandal forests, lopping of trees for fodder, excessive grazing, hacking, encroachments, seedling diseases and spread of sandal spike disease are the major problems facing sandal. While these factors hinder sandal regeneration in forest areas, the situation is accelerated by human activities of chronic overexploitation and illicit felling.Deterioration of natural sandal populations due to illicit felling, encroachments and diseases has an adverse effect on genetic diversity of the species. The loss of genetic diversity has aggravated during recent years due to extensive logging, changing landuse patterns and poor natural regeneration. The consequent genetic erosion is of serious concern affecting tree improvement programme in sandal. Conservation as well as mass propagation are the two strategies to be given due importance. To initiate any conservation programme, precise knowledge of the factors influencing regeneration and survival of the species is essential. Hence, the present study was undertaken with the objective of investigating the autotrophic and parasitic phase of sandal seedlings growth, the effects of shade on morphology, chlorophyll concentration and chlorophyll fluorescence of sandal seedlings, genetic diversity in sandal seed stands using ISSR markers, and the diversity of fungal isolates causing sandal seedling wilt using RAPD markers. All these factors directly influence regeneration and survival of sandal seedlings in natural forests and plantations.

Molecular Biological investigations on viral diseases affecting farmed penaeid shrimps in Kerala

This thesis covers various aspects of viral diseases affecting shrimp aquaculture. The research component of this thesis can be divided into four areas. The areas covered are: I) A study to determine the prevalence of WSSV among the crustaceans in the Vembanad estuary, the shrimp aquaculture farms surrounding the estuary, and the sea off Cochin coast, India using two , sets of nested PCR primers. 2) An investigation to compare the sequence of six major structural proteins of WSSV; vp28, vp26, vp 19, vp68, vp281, vp466 from different geographical locations with that of an isolate from India. 3) Simultaneous occurrence of HPV, IHHNV, MBV and WSSV in postlarvae of P. monodon from hatcheries in India was monitored by Polymerase Chain Reaction. 4) A real time PCR procedure was developed for the quantitative analysis of WSSV infection. The viral load of postlarvae from hatcheries in Kerala meant for aquaculture was also determined using the quantitative PCR.

Biochemical & Pharmacological evaluation of liver oils of selected deep sea sharks and chimaeras of the Indian EEZ

With a seacoast of 8,1 18 km, an exclusive economic zone (EEZ) of 2 million square km, and with an area of about 30,000 square km under aquaculture, lndia produces close to six million tonnes of fish, over 4 per cent of the world fish production. While the marine waters upto 50m depth have been fully exploited, those beyond, remain unexplored. There is an ever increasing demand for fishery resources as food. The coastal fishery resources of the country are dwindling at a rapid pace and it becomes highly imperative that we search for alternate fishery resources for food. The option we have is to hunt for marine fishery resources. Studies pertaining to proximate composition, amino acid and fatty acid composition are essential to understand the nutraceutical values of these deep sea fishery resources. The present study was aimed to carry out proximate composition of deep sea fishery resources obtained during cruises onboard the FORV Sarise Sampada, to identify fishery resources which have appreciable lipid content and thereby analyse the bioactive potentials of marine lipids, to study the amino acid profile of these fishery resources, to understand the contents of SPA, MUFA and PUFA and to calculate the n3/n6 fatty acid contents. Though the presence of nutraceuticals was identified in the marine fishery resources their use as potential food resources deserve further investigation. So the study were carried out to calculate the hepatosomatic indices of sharks & chimaeras and conduct biochemical characterisation of liver oils of Apristurus indicus, Cenlrophorus scalprams, Centroselachus crepidater, Neoharriotta raleighana, and Harriotta pinnata obtained during cruises onboard the FORV Sugar Sampada.Therapeutic use of shark liver oil is evident from its use for centuries as a remedy to heal wounds and fight flu (Neil er al. 2006). Japanese seamen called it 'samedava' or "cure all". Shark liver oil is being promoted worldwide as a dietary supplement to boost the immune system, fight infections, to treat cancer and to lessen the side effects of conventional cancer treatment. These days more emphasis is laid on the nutritive benefits of shark liver oils especially on the omega 3 polyunsaturated fatty acids ( PUFAs) (Anandan er al. 2007) and alkylglycerols (AKGs) (Pugliese er al. I998) contained in them due to the high rise of inflammatory disorders such as arthritis, asthma and neurodegenerative diseases like Alzheimer’s, Parkinson’s and Schizophrenia. So the present study also evaluate the pharmacological properties with respect to analgesic, anti-inflammatory, anti pyretic and anti-ulcer effects of four different liver oils of sharks belonging to the Indian EEZ and to identify the components of oil responsible for these activities.The analgesic and anti-inflammatory activities of liver oils from Neoharriotra raleighana (NR), Centrosymnus crepidater (CC), Apristurus indicus (AI), and Centrophorus sculpratus (CS) sharks caught from the Arabian Sea and the Indian Ocean were compared. The main objectives also include determination of the cholesterol lowering effects of liver oils of Neoharriotra raleighana (NR) and Centrophorus sculpratus (CS) on the high fat diet induced dyslipidemia and to compare the impact of four isolipidemic diets, on levels of serum diagnostic marker enzymes, on lipid profile of blood and liver and antioxidant status of heart in male Albino rats. And also to study the efficacy of Centrophorus sculpratus (CS) liver oil against Complete Freund’s Adjuvant-induced arthritis and to compare the anti-inflammatory activity of this oil with a traditionally used anti-inflammatory substance gingerol (oleoresin extracted from ginger.). The results of the present study indicated that both (Centrophorus sculpratus liver oils as well as gingerol extracts proved to be effective natural remedies against CFA-induced arthritis in Albino rats.

Studies on some aspects of the reproductive physiology of the female grey mullet mugil cephalus l.

Aquaculture is the dynamic pursuit of production of organisms from water a process analogous to agriculture on land. The field of aquaculture is an emerging bioindustry, based upon the culture and husbandry of economically utilizable aquatic organisms. Of late, there has been a global upsurge for aquaculture, the main reasons for which include the requirement of protein source for the increasing world population, the decision by various world nations to increase the fish yield by developing unutilized or partially utilized water bodies and depletion of natural stock which is evident in recent years due to excessive exploitation .The present study has been taken up on the reproductive physiology of the female grey mullet, M. cephalus. The thesis is presented in seven chapters. In the present study, variations in the major biochemical parameters namely, moisture, proteins, lipids, carbohydrates cholesterol, carotenoid, ash, calcium and iron in four tissues E. muscle, liver, ovary and bloodserum of cephalus have been analysed at different maturity stages.

Studies on the microbial diseases of dendrobium hybrid (orchids)

There is no baseline data available at present on the nature of various diseases that occur in a orchid population, under cultivation, in any commercial orchid farm maintained by small scale entrepreneurs who invest considerable amount of money, effort and time. The available data on type of disease symptoms, causative agent, , nature of pathogens, as to bacteria or ftmgi or any other biological agents, and their source, appropriate and effective control measures could not be devised, for large scale implementation and effective management, although arbitrary methods are being practiced by very few farms. Further influence of seasonal variations and environmental factors on disease outbreak is also not scientifically documented and statistically verified as to their authenticity. In this context, the primary objective of the present study was to create a data bank on the following aspects 1. Occurrence of different disease symptoms in Dendrobium hybrid over a period of one year covering all seasons 2. Variations in the environmental parameters at the orchid farms 3. Variations in the characteristics of water used for irrigation in the selected orchid farm 4. Microbial population associated with the various disease symptoms 5. Isolation and identification of bacteria isolated from diseased plants 6. Statistical treatment of the quantitative data and evolving statistical model

Molecular genetic profiling of functional genes of pearl oyster, Pinctada fucata

There are a number of genes involved in the regulation of functional process in marine bivalves. In the case of pearl oyster, some of these genes have major role in the immune/defence function and biomineralization process involved in the pearl formation in them. As secondary filter feeders, pearl oysters are exposed to various kinds of stressors like bacteria, viruses, pesticides, industrial wastes, toxic metals and petroleum derivatives, making susceptible to diseases. Environmental changes and ambient stress also affect non-specific immunity, making the organisms vulnerable to infections. These stressors can trigger various cellular responses in the animals in their efforts to counteract the ill effects of the stress on them. These include the expression of defence related genes which encode factors such as antioxidant genes, pattern recognition receptor proteins etc. One of the strategies to combat these problems is to get insight into the disease resistance genes, and use them for disease control and health management. Similarly, although it is known that formation of pearl in molluscs is mediated by specialized proteins which are in turn regulated by specific genes encoding them, there is a paucity of sufficient information on these genes.In view of the above facts, studies on the defence related and pearl forming genes of the pearl oyster assumes importance from the point of view of both sustainable fishery management and aquaculture. At present, there is total lack of sufficient knowledge on the functional genes and their expressions in the Indian pearl oyster Pinctada fucata. Hence this work was taken up to identify and characterize the defence related and pearl forming genes, and study their expression through molecular means, in the Indian pearl oyster Pinctada fucata which are economically important for aquaculture at the southeast coast of India. The present study has successfully carried out the molecular identification, characterization and expression analysis of defence related antioxidant enzyme genes and pattern recognition proteins genes which play vital role in the defence against biotic and abiotic stressors. Antioxidant enzyme genes viz., Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidise (GPX) and glutathione-S-transferase (GST) were studied. Concerted approaches using the various molecular tools like polymerase chain reaction (PCR), random amplification of cDNA ends (RACE), molecular cloning and sequencing have resulted in the identification and characterization of full length sequences (924 bp) of the Cu/Zn SOD, most important antioxidant enzyme gene. BLAST search in NCBI confirmed the identity of the gene as Cu/Zn SOD. The presence of the characteristic amino acid sequences such as copper/zinc binding residues, family signature sequences and signal peptides were found out. Multiple sequence alignment comparison and phylogenetic analysis of the nucleotide and amino acid sequences using bioinformatics tools like BioEdit,MEGA etc revealed that the sequences were found to contain regions of diversity as well as homogeneity. Close evolutionary relationship between P. fucata and other aquatic invertebrates was revealed from the phylogenetic tree constructed using SOD amino acid sequence of P. fucata and other invertebrates as well as vertebrates

Genetic Programming meets Model-Driven Development

Genetic programming is known to provide good solutions for many problems like the evolution of network protocols and distributed algorithms. In such cases it is most likely a hardwired module of a design framework that assists the engineer to optimize specific aspects of the system to be developed. It provides its results in a fixed format through an internal interface. In this paper we show how the utility of genetic programming can be increased remarkably by isolating it as a component and integrating it into the model-driven software development process. Our genetic programming framework produces XMI-encoded UML models that can easily be loaded into widely available modeling tools which in turn posses code generation as well as additional analysis and test capabilities. We use the evolution of a distributed election algorithm as an example to illustrate how genetic programming can be combined with model-driven development. This example clearly illustrates the advantages of our approach – the generation of source code in different programming languages.

"Genetic Diversity and Selection in Three Plasmodium vivax Merozoite Surface Protein 7 (Pvmsp-7) Genes in a Colombian Population"

A completely effective vaccine for malaria (one of the major infectious diseases worldwide) is not yet available; different membrane proteins involved in parasite-host interactions have been proposed as candidates for designing it. It has been found that proteins encoded by the merozoite surface protein (msp)-7 multigene family are antibody targets in natural infection; the nucleotide diversity of three Pvmsp-7 genes was thus analyzed in a Colombian parasite population. By contrast with P. falciparum msp-7 loci and ancestral P. vivax msp-7 genes, specie-specific duplicates of the latter specie display high genetic variability, generated by single nucleotide polymorphisms, repeat regions, and recombination. At least three major allele types are present in Pvmsp-7C, Pvmsp-7H and Pvmsp-7I and positive selection seems to be operating on the central region of these msp-7 genes. Although this region has high genetic polymorphism, the C-terminus (Pfam domain ID: PF12948) is conserved and could be an important candidate when designing a subunit-based antimalarial vaccine.

Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1 ¨ ∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

Introducing polyautoimmunity: secondary autoimmune diseases no longer exist

Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases.

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.

Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis

Background: Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs. Methods and Findings: The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25-1.92; p-value, 0.001). Conclusion: Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.

Genetic diversity and selection in three plasmodium vivax merozoite surface protein 7 (pvmsp-7) genes in a colombian population

A completely effective vaccine for malaria (one of the major infectious diseases worldwide) is not yet available; different membrane proteins involved in parasite-host interactions have been proposed as candidates for designing it. It has been found that proteins encoded by the merozoite surface protein (msp)-7 multigene family are antibody targets in natural infection; the nucleotide diversity of three Pvmsp-7 genes was thus analyzed in a Colombian parasite population. By contrast with P. falciparum msp-7 loci and ancestral P. vivax msp-7 genes, specie-specific duplicates of the latter specie display high genetic variability, generated by single nucleotide polymorphisms, repeat regions, and recombination. At least three major allele types are present in Pvmsp-7C, Pvmsp-7H and Pvmsp-7I and positive selection seems to be operating on the central region of these msp-7 genes. Although this region has high genetic polymorphism, the C-terminus (Pfam domain ID: PF12948) is conserved and could be an important candidate when designing a subunit-based antimalarial vaccine.

Búsqueda de selección en el polimorfismo 677C>T (c.665C>T) del gen de la metilentetrahidrofolato reductasa (MTHFR) en una población Colombiana

Se realizó un estudio genético – poblacional en dos grupos etarios de población colombiana con la finalidad de evaluar las diferencias genéticas relacionadas con el polimorfismo MTHFR 677CT en busca de eventos genéticos que soporten la persistencia de este polimorfismo en la especie humana debido que este ha sido asociado con múltiples enfermedades. De esta manera se genotipificaron los individuos, se analizaron los genotipos, frecuencias alélicas y se realizaron diferentes pruebas genéticas-poblacionales. Contrario a lo observado en poblaciones Colombianas revisadas se identificó la ausencia del Equilibrio Hardy-Weinberg en el grupo de los niños y estructuras poblacionales entre los adultos lo que sugiere diferentes historias demográficas y culturales entre estos dos grupos poblacionales al tiempo, lo que soporta la hipótesis de un evento de selección sobre el polimorfismo en nuestra población. De igual manera nuestros datos fueron analizados junto con estudios previos a nivel nacional y mundial lo cual sustenta que el posible evento selectivo es debido a que el aporte de ácido fólico se ha incrementado durante las últimas dos décadas como consecuencia de las campañas de fortificación de las harinas y suplementación a las embarazadas con ácido fólico, por lo tanto aquí se propone un modelo de selección que se ajusta a los datos encontrados en este trabajo se establece una relación entre los patrones nutricionales de la especie humana a través de la historia que explica las diferencias en frecuencias de este polimorfismo a nivel espacial y temporal.