Immune correlates of vaccine protection against HIV-1 acquisition.

The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4(+) T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition.

Parallel declines in species and genetic diversity driven by anthropogenic disturbance: a multispecies approach in a French Atlantic dune system.

Numerous studies assess the correlation between genetic and species diversities, but the processes underlying the observed patterns have only received limited attention. For instance, varying levels of habitat disturbance across a region may locally reduce both diversities due to extinctions, and increased genetic drift during population bottlenecks and founder events. We investigated the regional distribution of genetic and species diversities of a coastal sand dune plant community along 240 kilometers of coastline with the aim to test for a correlation between the two diversity levels. We further quantify and tease apart the respective contributions of natural and anthropogenic disturbance factors to the observed patterns. We detected significant positive correlation between both variables. We further revealed a negative impact of urbanization: Sites with a high amount of recreational infrastructure within 10 km coastline had significantly lowered genetic and species diversities. On the other hand, a measure of natural habitat disturbance had no effect. This study shows that parallel variation of genetic and species diversities across a region can be traced back to human landscape alteration, provides arguments for a more resolute dune protection, and may help to design priority conservation areas.

Genetic and antigenic analysis of Babesia bigemina isolates from five geographical regions of Brazil

A molecular epidemiological study was performed with Babesia bigemina isolates from five geographical regions of Brazil. The genetic analysis was done with random amplification of polymorphic DNA (RAPD), repetitive extragenic palindromic elements-polymerase chain reaction (REP-PCR) and enterobacterial repetitive intergenic consensus sequences-polymerase chain reaction (ERIC-PCR) that showed genetic polymorphism between these isolates and generated fingerprinting. In RAPD, ILO872 and ILO876 primers were able to detect at least one fingerprinting for each B. bigemina isolate. The amplification of B. bigemina DNA fragments by REP-PCR and ERIC-PCR gave evidence for the presence in this haemoprotozoan of the sequences described previously in microorganisms of the bacterial kingdom. For the first time it was demonstrated that both techniques can be used for genetic analysis of a protozoan parasite, although the ERIC-PCR was more discriminatory than REP-PCR. The dendogram with similarity coefficient among isolates showed two clusters and one subcluster. The Northeastern and Mid-Western isolates showed the greatest genetic diversity, while the Southeastern and Southern isolates were the closest. The antigenic analysis was done through indirect fluorescent antibody technique and Western blotting using a panel of monoclonal antibodies directed against epitopes on the merozoite membrane surface, rhoptries and membrane of infected erythrocytes. As expected, the merozoite variable surface antigens, major surface antigen (MSA)-1 and MSA-2 showed antigenic diversity. However, B cell epitopes on rhoptries and infected erythrocytes were conserved among all isolates studied. In this study it was possible to identify variable and conserved antigens, which had already been described as potential immunogens. Considering that an attenuated Babesia clone used as immunogen selected populations capable of evading the immunity induced by this vaccine, it is necessary to evaluate more deeply the cross-protection conferred by genetically more distant Brazilian B. bigemina isolates and make an evaluation of the polymorphism degree of variable antigens such as MSA-1 and MSA-2.

Protecting Genetic Information: A Comparison of Normative Approaches

The increasing use of genetic information has emerged as an important concern worldwide as scientific and technological advances continue to advance at lightening speed and as governments struggle to develop appropriate policy frameworks. While most countries clearly recognize that genetic information warrants some form of privacy protection, the underlying rationale for providing that protection and the approach which is ultimately adopted vary significantly across the board. As a result, a medley of laws, policy statements and guidelines currently exist to protect genetic information, each with its inherent assumptions, concepts and terminology.

Droits de propriété intellectuelle et protection des plantes: approches, limites et perspectives

Le droit de la propriété intellectuelle présente, depuis quelques années, un intérêt particulier à l'évolution de la recherche sur les plantes. Ceci s'est traduit, au plan international, par l'adoption de plusieurs instruments visant à assurer une meilleure protection des investissements consentis dans ce domaine. Il s'agit notamment de la Convention de l'UPOV, qui s'inscrit dans une logique de protection par la voie sui generis avec la possibilité de délivrance de certificat d'obtention végétale aux sélectionneurs; de l'Accord ADPIC, qui, en plus de recommander un système sui generis efficace, ouvre l'option de protection par brevet ou en définitive par le cumul des deux systèmes; de la Convention sur la Diversité Biologique (CDB) et du Traité de la FAO portant sur les ressources phytogénétiques pour l'alimentation et l'agriculture, qui, favorables aux deux précédentes formes de protection, demandent que soient prises en compte des considérations relatives aux droits souverains des pays sur leurs ressources végétales, au partage des bénéfices, etc. Au plan régional, on distingue, entre autres, l'initiative de l'Afrique, visant à assurer la protection des plantes suivant une logique partagée entre l'alignement sur les normes internationales existantes (Accord de Bangui) ou l'institution d'une autre législation originale qui reflète les réalités et préoccupations du continent (Loi modèle). Il apparaît donc qu'il existe plusieurs instruments pour cerner la même réalité. Ceci est forcément la source de quelques difficultés qui sont d'ordre conceptuel, socioéconomique, environnemental et juridique. Pour les pallier, il est important que certaines conditions soient satisfaites afin d'harmoniser les points de vue entre les différents acteurs concernés par la question et d'assurer une appropriation conséquente des instruments adoptés.

Investigating the role of potential genetic markers that can predict risk for steroid refractory inflammatory bowel disease

Contexte - La variation interindividuelle de la réponse aux corticostéroïdes (CS) est un problème important chez les patients atteints de maladies inflammatoires d’intestin. Ce problème est bien plus accentué chez les enfants avec la prévalence de la corticodépendance extrêmement (~40 %) élevée. La maladie réfractaire au CS a des répercussions sur le développement et le bien-être physique et psychologique des patients et impose des coûts médicaux élevés, particulièrement avec la maladie active comparativement à la maladie en rémission, le coût étant 2-3 fois plus élevé en ambulatoire et 20 fois plus élevé en hôpital. Il est ainsi primordial de déterminer les marqueurs prédictifs de la réponse aux CS. Les efforts précédents de découvrir les marqueurs cliniques et démographiques ont été équivoques, ce qui souligne davantage le besoin de marqueurs moléculaires. L'action des CS se base sur des processus complexes déterminés génétiquement. Deux gènes, le ABCB1, appartenant à la famille des transporteurs transmembraneaux, et le NR3C1, encodant le récepteur glucocorticoïde, sont des éléments importants des voies métaboliques. Nous avons postulé que les variations dans ces gènes ont un rôle dans la variabilité observée de la réponse aux CS et pourraient servir en tant que les marqueurs prédictifs. Objectifs - Nous avons visé à: (1) examiner le fardeau de la maladie réfractaire aux CS chez les enfants avec la maladie de Crohn (MC) et le rôle des caractéristiques cliniques et démographiques potentiellement liés à la réponse; (2) étudier l'association entre les variantes d'ADN de gène ABCB1 et la réponse aux CS; (3) étudier les associations entre les variantes d'ADN de gène NR3C1 et la réponse aux CS. Méthodes - Afin d’atteindre ces objectifs, nous avons mené une étude de cohorte des patients recrutés dans deux cliniques pédiatriques tertiaires de gastroentérologie à l’Ottawa (CHEO) et à Montréal (HSJ). Les patients avec la MC ont été diagnostiqués avant l'âge de 18 ans selon les critères standard radiologiques, endoscopiques et histopathologiques. La corticorésistance et la corticodépendance ont été définies en adaptant les critères reconnus. L’ADN, acquise soit du sang ou de la salive, était génotypée pour des variations à travers de gènes ABCB1 et NR3C1 sélectionnées à l’aide de la méthodologie de tag-SNP. La fréquence de la corticorésistance et la corticodépendance a été estimée assumant une distribution binomiale. Les associations entre les variables cliniques/démographiques et la réponse aux CS ont été examinées en utilisant la régression logistique en ajustant pour des variables potentielles de confusion. Les associations entre variantes génétiques de ABCB1 et NR3C1 et la réponse aux CS ont été examinées en utilisant la régression logistique assumant différents modèles de la transmission. Les associations multimarqueurs ont été examinées en utilisant l'analyse de haplotypes. Les variantes nongénotypées ont été imputées en utilisant les données de HAPMAP et les associations avec SNPs imputés ont été examinées en utilisant des méthodes standard. Résultats - Parmi 645 patients avec la MC, 364 (56.2%) ont reçu CS. La majorité de patients étaient des hommes (54.9 %); présentaient la maladie de l’iléocôlon (51.7%) ou la maladie inflammatoire (84.6%) au diagnostic et étaient les Caucasiens (95.6 %). Huit pourcents de patients étaient corticorésistants et 40.9% - corticodépendants. Le plus bas âge au diagnostic (OR=1.34, 95% CI: 1.03-3.01, p=0.040), la maladie cœxistante de la région digestive supérieure (OR=1.35, 95% CI: 95% CI: 1.06-3.07, p=0.031) et l’usage simultané des immunomodulateurs (OR=0.35, 95% CI: 0.16-0.75, p=0.007) ont été associés avec la corticodépendance. Un total de 27 marqueurs génotypés à travers de ABCB1 (n=14) et NR3C1 (n=13) ont été en l'Équilibre de Hardy-Weinberg, à l’exception d’un dans le gène NR3C1 (rs258751, exclu). Dans ABCB1, l'allèle rare de rs2032583 (OR=0.56, 95% CI: 0.34-0.95, p=0.029) et génotype hétérozygote (OR=0.52, 95% CI: 0.28-0.95 p=0.035) ont été négativement associes avec la dépendance de CS. Un haplotype à 3 marqueurs, comprenant le SNP fonctionnel rs1045642 a été associé avec la dépendance de CS (p empirique=0.004). 24 SNPs imputés introniques et six haplotypes ont été significativement associés avec la dépendance de CS. Aucune de ces associations n'a cependant maintenu la signification après des corrections pour des comparaisons multiples. Dans NR3C1, trois SNPs: rs10482682 (OR=1.43, 95% CI: 0.99-2.08, p=0.047), rs6196 (OR=0.55, 95% CI: 0.31-0.95, p=0.024), et rs2963155 (OR=0.64, 95% CI: 0.42-0.98, p=0.039), ont été associés sous un modèle additif, tandis que rs4912911 (OR=0.37, 95% CI: 0.13-1.00, p=0.03) et rs2963156 (OR=0.32, 95% CI: 0.07-1.12, p=0.047) - sous un modèle récessif. Deux haplotypes incluant ces 5 SNPs (AAACA et GGGCG) ont été significativement (p=0.006 et 0.01 empiriques) associés avec la corticodépendance. 19 SNPs imputés ont été associés avec la dépendance de CS. Deux haplotypes multimarqueurs (p=0.001), incluant les SNPs génotypés et imputés, ont été associés avec la dépendance de CS. Conclusion - Nos études suggèrent que le fardeau de la corticodépendance est élevé parmi les enfants avec le CD. Les enfants plus jeunes au diagnostic et ceux avec la maladie coexistante de la région supérieure ainsi que ceux avec des variations dans les gènes ABCB1 et NR3C1 étaient plus susceptibles de devenir corticodépendants.

La discrimination génétique et l’assurance-vie : les mesures de protection actuelles suffisent-elles?

"De plus en plus, la recherche en génétique s'attarde à identifier les mutations de gènes qui prédisposent les porteurs de ces mutations à des maladies complexes. La recherche tente également d'établir un lien entre le développement de la maladie pour certains porteurs en fonction de leur contexte socio-économique et de leur interaction avec l'environnement. Compte tenu de ces nombreux facteurs d'analyse, l'interprétation des caractéristiques génétiques d'un individu et du risque qui en découle s'avère particulièrement complexe. Or, cette complexité croissante se produit alors même que l'accès aux données génétiques se banalise et qu'il est maintenant possible pour quiconque d'obtenir une analyse personnalisée de son génome via l'internet. La discrimination génétique n'est pas définie en droit canadien ; il est généralement acquis que, dans le contexte de l'assurance-vie, celle-ci est susceptible d'avoir des conséquences désastreuses. Cependant, nous ne croyons pas que l'information d'ordre génétique doive être l'objet d'une approche exceptionnelle causant accrocs au droit général des assurances. D'autant plus, les conséquences du risque de discrimination génétique semblent davantage relevées de la crainte que de l'exercice d'une discrimination réelle. Dans ce contexte, il s'avère nécessaire d'évaluer les mesures de protection contre la discrimination génétique dans le contexte de l'assurance-vie. Pour ce faire, nous abordons, d'une part, les normes d'application générale en matière de protection contre la discrimination; normes parmi lesquelles la Charte des droits et libertés de la personne offre une protection intéressante. D'autre part, nous nous intéressons aux normes visant la discrimination spécifiquement génétique, notamment le nouvel Genetic Information Nondiscrimination Act et l'affaire Audet c. Industrielle-Alliance. Enfin, nous proposons des mesures minimales qui sauraient s'avérer utile pour préserver un juste équilibre."

Plant genetic diversity, irrigation and nutrient cycling in traditional mountain oases of northern Oman

Little is known about plant biodiversity, irrigation management and nutrient fluxes as criteria to assess the sustainability of traditional irrigation agriculture in eastern Arabia. Therefore interdisciplinary studies were conducted over 4 yrs on flood-irrigated fields dominated by wheat (Triticum spp.), alfalfa (Medicago sativa L.) and date palm (Phoenix dactylifera L.) in two mountain oases of northern Oman. In both oases wheat landraces consisted of varietal mixtures comprising T. aestivum and T. durum of which at least two botanical varieties were new to science. During irrigation cycles of 6-9 days on an alfalfa-planted soil, volumetric water contents ranged from 30-13%. For cropland, partial oasis balances (comprising inputs of manure, mineral fertilizers, N2-fixation and irrigation water, and outputs of harvested products) were similar for both oases, with per hectare annual surpluses of 131 kg N, 37 kg P and 84 kg K at Balad Seet and of 136 kg N, 16 kg P and 66 kg K at Maqta. Respective palm grove surpluses, in contrast were with 303 kg N, 38 kg P, and 173 kg K ha^-1 yr^-1 much higher at Balad Seet than with 84 kg N, 14 kg P and 91 kg K ha^-1 yr^-1 at Maqta. The results show that the sustainability of these irrigated landuse systems depends on a high quality of the irrigation water with low Na but high CaCO3, intensive recycling of manure and an elaborate terrace structure with a well tailored water management system that allows adequate drainage.

Low genetic diversity in a marine nature reserve: re-evaluating diversity criteria in reserve design

Little consideration has been given to the genetic composition of populations associated with marine reserves, as reserve designation is generally to protect specific species, communities or habitats. Nevertheless, it is important to conserve genetic diversity since it provides the raw material for the maintenance of species diversity over longer, evolutionary time-scales and may also confer the basis for adaptation to environmental change. Many current marine reserves are small in size and isolated to some degree (e.g. sea loughs and offshore islands). While such features enable easier management, they may have important implications for the genetic structure of protected populations, the ability of populations to recover from local catastrophes and the potential for marine reserves to act as sources of propagules for surrounding areas. Here, we present a case study demonstrating genetic differentiation, isolation, inbreeding and reduced genetic diversity in populations of the dogwhelk Nucella lapillus in Lough Hyne Marine Nature Reserve (an isolated sea lough in southern Ireland), compared with populations on the local adjacent open coast and populations in England, Wales and France. Our study demonstrates that this sea lough is isolated from open coast populations, and highlights that there may be long-term genetic consequences of selecting reserves on the basis of isolation and ease of protection.

Natural disaster accounting bias and its equivalence across genetic resource stocks

Two sources of bias arise in conventional loss predictions in the wake of natural disasters. One source of bias stems from neglect of accounting for animal genetic resource loss. A second source of bias stems from failure to identify, in addition to the direct effects of such loss, the indirect effects arising from implications impacting animal-human interactions. We argue that, in some contexts, the magnitude of bias imputed by neglecting animal genetic resource stocks is substantial. We show, in addition, and contrary to popular belief, that the biases attributable to losses in distinct genetic resource stocks are very likely to be the same. We derive the formal equivalence across the distinct resource stocks by deriving an envelope result in a model that forms the mainstay of enquiry in subsistence farming and we validate the theory, empirically, in a World-Society-for-the-Protection-of-Animals application

Genetic diversity at the Dhn3 locus in Turkish Hordeum spontaneum populations with comparative structural analyses

We analysed Hordeum spontaneum accessions from 21 different locations to understand the genetic diversity of HsDhn3 alleles and effects of single base mutations on the intrinsically disordered structure of the resulting polypeptide (HsDHN3). HsDHN3 was found to be YSK2-type with a low-frequency 6-aa deletion in the beginning of Exon 1. There is relatively high diversity in the intron region of HsDhn3 compared to the two exon regions. We have found subtle differences in K segments led to changes in amino acids chemical properties. Predictions for protein interaction profiles suggest the presence of a protein-binding site in HsDHN3 that coincides with the K1 segment. Comparison of DHN3 to closely related cereals showed that all of them contain a nuclear localization signal sequence flanking to the K1 segment and a novel conserved region located between the S and K1 segments [E(D/T)DGMGGR]. We found that H. vulgare, H. spontaneum, and Triticum urartu DHN3s have a greater number of phosphorylation sites for protein kinase C than other cereal species, which may be related to stress adaptation. Our results show that the nature and extent of mutations in the conserved segments of K1 and K2 are likely to be key factors in protection of cells.

PODOCARPUS SP.PL. REFUGIA IN BRAZIL`S ATLANTIC FOREST: ANALYSING THE PAST TO IMPROVE FUTURE PROTECTION

The Atlantic rainforest has the second highest biodiversity in Brazil. It has been shrinking rapidly in area as a result of intensive deforestation, and only 7% of the original cover now remains, as isolated patches or in ecological reserves. In order to obtain new information on the distribution of the Atlantic rainforest during the Quaternary, we examined herbarium data to locate relevant populations and extracted DNA from fresh leaves from 26 populations. The present-day distribution of endemic Podocarpus populations shows that they are widely dispersed across eastern Brazil, and that the expansion of Podocarpus recorded in single Amazonian pollen records may have originated from either western or eastern populations. Genetic analysis enabled us to determine the boundaries of their regional expansion: northern and central populations of P. sellowii appeared between 5 degrees and 15 degrees S some 16,000 years ago; populations of P lambertii or sellowii have appeared between 15 degrees and 23 degrees S at different times since the last glaciation at least; and P lambertii appeared between 23 degrees and 30 degrees S during the recent expansion of Araucaria forests. The combination of botanical, pollen, and molecular analyses proved to be a rapid means of inferring distribution boundaries for sparse populations and their regional evolution within tropical ecosystems. Today the rainforest refugia we identified have become hotspots that are crucial to the survival of the Atlantic forest under unfavourable climatic conditions and, as such, offer the only possible opportunity for this type of forest to expand in the event of future climate change.

Genetic variation and population structure of the endangered Hyacinth Macaw (Anodorhynchus hyacinthinus): implications for conservation

The Hyacinth Macaw (Anodorhynchus hyacinthinus) is one of 14 endangered species in the family Psittacidae occurring in Brazil, with an estimated total population of 6,500 specimens. We used nuclear molecular markers (single locus minisatellites and microsatellites) and 472 bp of the mitochondrial DNA control region to characterize levels of genetic variability in this species and to assess the degree of gene flow among three nesting sites in Brazil (Pantanal do Abobral, Pantanal de Miranda and Piaui). The origin of five apprehended specimens was also investigated. The results suggest that, in comparison to other species of parrots, Hyacinth Macaws possess relatively lower genetic variation and that individuals from two different localities within the Pantanal (Abobral and Miranda) belong to a unique interbreeding population and are genetically distinct at nuclear level from birds from the state of Piaui. The analyses of the five apprehended birds suggest that the Pantanal is not the source of birds for illegal trade, but their precise origin could not be assigned. The low genetic variability detected in the Hyacinth Macaw does not seem to pose a threat to the survival of this species. Nevertheless, habitat destruction and nest poaching are the most important factors negatively affecting their populations in the wild. The observed genetic structure emphasizes the need of protection of Hyacinth Macaws from different regions in order to maintain the genetic diversity of this species.

Oxidative stress protection of Trypanosomes requires selenophosphate synthase

Selenoproteins are characterized by the incorporation of at least one amino acid selenocysteine (Sec-U) encoded by in-frame UGA stop codons. These proteins, as well as the components of the Sec synthesis pathway, are present in members of the bacteria, archaea and eukaryote domains. Although not a ubiquitous pathway in all organisms, it was also identified in several protozoa, including the Kinetoplastida. Genetic evidence has indicated that the pathway is non-essential to the survival of Trypanosoma growing in non-stressed conditions. By analyzing the effects of RNA interference of the Trypanosoma brucei selenophosphate synthetase SPS2, we found a requirement under sub-optimal growth conditions. The present work shows that SPS2 is involved in oxidative stress protection of the parasite and its absence severely hampers the parasite survival in the presence of an oxidizing environment that results in an apoptotic-like phenotype and cell death. (C) 2011 Elsevier B.V. All rights reserved.

Allocation of protective devices in distribution circuits using nonlinear programming models and genetic algorithms

The optimized allocation of protective devices in strategic points of the circuit improves the quality of the energy supply and the system reliability index. This paper presents a nonlinear integer programming (NLIP) model with binary variables, to deal with the problem of protective device allocation in the main feeder and all branches of an overhead distribution circuit, to improve the reliability index and to provide customers with service of high quality and reliability. The constraints considered in the problem take into account technical and economical limitations, such as coordination problems of serial protective devices, available equipment, the importance of the feeder and the circuit topology. The use of genetic algorithms (GAs) is proposed to solve this problem, using a binary representation that does (1) or does not (0) show allocation of protective devices (reclosers, sectionalizers and fuses) in predefined points of the circuit. Results are presented for a real circuit (134 busses), with the possibility of protective device allocation in 29 points. Also the ability of the algorithm in finding good solutions while improving significantly the indicators of reliability is shown. (C) 2003 Elsevier B.V. All rights reserved.