Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells.

Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE: Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection.

Growth of Crassostrea gasar cultured in marine and estuary environments in Brazilian waters

The objective of this work was to evaluate the growth of the mangrove oyster Crassostrea gasar cultured in marine and estuarine environments. Oysters were cultured for 11 months in a longline system in two study sites - São Francisco do Sul and Florianópolis -, in the state of Santa Catarina, Southern Brazil. Water chlorophyll-α concentration, temperature, and salinity were measured weekly. The oysters were measured monthly (shell size and weight gain) to assess growth. At the end of the culture period, the average wet flesh weight, dry flesh weight, and shell weight were determined, as well as the distribution of oysters per size class. Six nonlinear models (logistic, exponential, Gompertz, Brody, Richards, and Von Bertalanffy) were adjusted to the oyster growth data set. Final mean shell sizes were higher in São Francisco do Sul than in Florianópolis. In addition, oysters cultured in São Francisco do Sul were more uniformly distributed in the four size classes than those cultured in Florianópolis. The highest average values of wet flesh weight and shell weight were observed in São Francisco do Sul, whereas dry flesh weight did not differ between the sites. The estuary environment is more promising for the cultivation of oysters.

Investigating the relationship between pollination strategies and the size-advantage model in zoophilous plants using the reproductive biology of Arum cylindraceum and other European Arum species as case studies

The size-advantage model (SAM) explains the temporal variation of energetic investment on reproductive structures (i.e. male and female gametes and reproductive organs) in long-lived hermaphroditic plants and animals. It proposes that an increase in the resources available to an organism induces a higher relative investment on the most energetically costly sexual structures. In plants, pollination interactions are known to play an important role in the evolution of floral features. Because the SAM directly concerns flower characters, pollinators are expected to have a strong influence on the application of the model. This hypothesis, however, has never been tested. Here, we investigate whether the identity and diversity of pollinators can be used as a proxy to predict the application of the SAM in exclusive zoophilous plants. We present a new approach to unravel the dynamics of the model and test it on several widespread Arum (Araceae) species. By identifying the species composition, abundance and spatial variation of arthropods trapped in inflorescences, we show that some species (i.e. A. cylindraceum and A. italicum) display a generalist reproductive strategy, relying on the exploitation of a low number of dipterans, in contrast to the pattern seen in the specialist A. maculatum (pollinated specifically by two fly species only). Based on the model presented here, the application of the SAM is predicted for the first two and not expected in the latter species, those predictions being further confirmed by allometric measures. We here demonstrate that while an increase in the female zone occurs in larger inflorescences of generalist species, this does not happen in species demonstrating specific pollinators. This is the first time that this theory is both proposed and empirically tested in zoophilous plants. Its overall biological importance is discussed through its application in other non-Arum systems.

Effect of neighborhood and plot size on experiments with multiple-harvest oleraceous crops

The objective of this work was to determine the efficiency of the Papadakis method on the quality evaluation of experiments with multiple-harvest oleraceous crops, and on the estimate of the covariate and the ideal plot size. Data from nine uniformity trials (five with bean pod, two with zucchini, and two with sweet pepper) and from one experiment with treatments (with sweet pepper) were used. Through the uniformity trials, the best way to calculate the covariate was defined and the optimal plot size was calculated. In the experiment with treatments, analyses of variance and covariance were performed, in which the covariate was calculated by the Papadakis method, and experimental precision was evaluated based on four statistics. The use of analysis of covariance with the covariate obtained by the Papadakis method increases the quality of experiments with multiple-harvest oleraceous crops and allows the use of smaller plot sizes. The best covariate is the one that considers a neighboring plot of each side of the reference plot.

Population genomics of eusocial insects: the costs of a vertebrate-like effective population size

The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life-history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome-wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA-seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes - a marker of the effective population size - in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels.

Testis size, sperm characteristics and testosterone concentrations in four species of shrews (Mammalia, Soricidae).

The aim of this study was to establish and compare the sperm characteristics in four shrew species in the context of the sperm competition hypothesis. As expected, the large relative testis size in promiscuous species was associated with a high number of cauda epididymal spermatozoa and a high concentration of circulating testosterone. In addition, in Sorex and Neomys, species with high intensity of sperm competition, the spermatozoa stored in cauda epididymis were characterized by high percentage of progressive motility whereas in Crocidura and Suncus, the cauda epididymal spermatozoa were motile but with very low percentage of progressive motility. This capability is achieved only following the passage through the vas gland, a specialized region for sperm storage located along the vas deferens in these shrew species. The hypothesis that sperm competition is positively correlated with spermatozoa length could not be confirmed. In Crocidura and Suncus, the total sperm length is increased by the large sperm head due to a big acrosome. This trait, specific to the subfamily Crocidurinae, may results from a selective pressure independent of the context of sperm competition, related to a specific, but as yet unclear role, for the acrosome during the fertilization.

Size and fat content of gynes in relation to the mode of colony founding in ants (Hymenoptera; Formicidae)

In ants, there are two main processes of colony founding, the independent and the dependent modes. In the first case young queens start colony founding without the help of workers, whereas in the second case they are accompanied by workers. To determine the relation between the mode of colony founding and the physiology of queens, we collected mature gynes of 24 ant species. Mature gynes of species utilizing independent colony founding had a far higher relative fat content than gynes of species employing dependent colony founding. These fat reserves are stored during the period of maturation, i.e. between the time of emergence and mating, and serve as fuel during the time of colony founding to nurture the queen and the brood. Gynes of species founding independently but non claustrally were found to have a relative fat content intermediate between the values found for gynes founding independently and those founding dependently. This suggests that such gynes rely partially on their fat reserves and partially on the energy provided by prey they collect to nurture themselves and the first brood during the time of colony founding. Study of the fat content of mature gynes of all species has shown that it gives a good indication of the mode of colony founding.

The class basis of the cleavage between the New Left and the radical right: An analysis for Austria, Denmark, Norway and Switzerland

This chapter argues that the electoral competition between the New Left and the Radical Right is best understood as a cultural divide anchored in different class constituencies. Based on individual-level data from the European Social Survey, we analyze the links between voters' class position, their economic and cultural preferences and their party choice for four small and affluent European countries. We find a striking similarity in the class pattern across countries. Everywhere, the New Left attracts disproportionate support from socio-cultural professionals and presents a clear-cut middle-class profile, whereas the Radical Right is most successful among production and service workers and receives least support from professionals. In general, the Radical Right depends on the votes of lowereducated men and older citizens and has turned into a new type of working-class party. However, its success within the working-class is not due to economic, but to cultural issues. The voters of the Radical Right collide with those of the New Left over a cultural conflict of identity and community - and not over questions of redistribution. A full-grown cleavage has thus emerged in the four countries under study, separating a libertarian-universalistic pole from an authoritarian-communitarian pole and going along with a process of class realignment.

On the transcriptional role of NLRC5 and the function of NLRC5-driven MHC class I expression in the immune system

Major histocompatibility complex (MHC) molecules are of crucial importance for the immune system to recognize and defend the body against external attacks. Foreign antigens are presented by specialized cells, called antigen presenting cells, to T lymphocytes in the context of MHC molecules, thereby inducing T cell activation. In addition, MHC molecules are essential for Natural Killer (NK) cell biology, playing a role in NK cell education and activation. Recently, the NOD-like receptor (NLR) family member NLRC5 (NLR caspase recruitment domain containing protein 5) was found to act as transcriptional regulator of MHC class I, in particular in T and NK cells. Its role in MHC class I expression is however minor in dendritic cells (DCs). This raised the question of whether inflammatory conditions, which augment the levels of NLRC5 in DCs, could increase its contribution to MHC class I expression. Our work shows that MHC class I transcript and intracellular levels depend on NLRC5, while its role in MHC class I surface expression is instead negligible. We describe however a general salvage mechanism that enables cells with low intracellular MHC class I levels to nevertheless maintain relatively high MHC class I on the cell surface. In addition, we lack a thorough understanding of NLRC5 target gene specificity and mechanism of action. Our work delineates the unique consensus sequence in MHC class I promoters required for NLRC5 recruitment and pinpoints conserved features conferring its specificity. Furthermore, through genome-wide analyses, we confirm that NLRC5 regulates classical MHC class I genes and identify novel target genes all encoding non-classical MHC class I molecules exerting an array of functions in immunity and tolerance. We finally asked why a dedicated factor co-regulates MHC class I expression specifically in T and NK lymphocytes. We show that deregulated NLRC5 expression affects the education of NK cells and alters the crosstalk between T and NK cells, leading to NK cell-mediated killing of T lymphocytes. Altogether this thesis work brings insights into molecular and physiological aspects of NLRC5 function, which might help understand certain aspects of immune responses and disorders. -- Les molécules du complexe majeur d'histocompatibilité (CMH) sont essentielles au système immunitaire pour l'initiation de la réponse immunitaire. En effet, l'activation des lymphocytes T nécessite la reconnaissance d'un antigène étranger présenté par les cellules présentatrices d'antigènes sur une molécule du CMH. Les molécules du CMH ont également un rôle fondamental pour la fonction des cellules Natural Killer (NK) puisqu'elles sont nécessaires à leur processus d'éducation et d'activation. Récemment, NLRC5 (NLR caspase recruitment domain containing protein 5), un membre de la famille des récepteurs de type NOD (NLRs), a été décrit comme un facteur de transactivation de l'expression des gènes du CMH de classe I. A l'état basai, cette fonction transcriptionnelle est essentielle dans les lymphocytes T et NK, alors que ce rôle reste mineur pour l'expression des molécules du CMH de classe I dans les cellules dendritiques (DCs). Dans des conditions inflammatoires, l'expression de NLRC5 augmente dans les DCs. Notre travail démontre que, dans ces conditions, les transcrits et les niveaux intracellulaires des molécules du CMH de classe I augmentent aussi d'une façon dépendante de NLRC5. A contrario, le rôle de NLRC5 sur les niveaux de molécules de surface reste minoritaire. Cette observation nous a conduits à l'identification d'un mécanisme général de compensation qui permet aux cellules de maintenir des niveaux relativement élevés de molécules de CMH de class I à leur surface malgré de faibles niveaux intracellulaires. De plus, il semblait nécessaire de s'orienter vers une approche plus globale afin de déterminer l'étendue de la fonction transcriptionnelle de NLRC5. Par une approche du génome entier, nous avons pu décrire une séquence consensus conservée présente dans les promoteurs des gènes du CMH de classe I, sur laquelle NLRC5 est spécifiquement recruté. Nous avons pu également identifier de nouveaux gènes cibles codant pour des molécules de CMH de classe I non classiques impliqués dans l'immunité et la tolérance. Finalement, nous nous sommes demandé quel est l'intérêt d'avoir un facteur transcriptionnel, en l'occurrence NLRC5, qui orchestre l'expression du CMH de classe I dans les lymphocytes T et NK. Nous montrons que la dérégulation de l'expression de NLRC5 affecte l'éducation des cellules NK et conduit à la mort cellulaire des lymphocytes T médiée par les cellules NK. Dans l'ensemble ce travail de thèse contribue à la caractérisation du rôle de NLRC5, tant au niveau moléculaire que physiologique, ce qui présente un intérêt dans le cadre de la compréhension de certains aspects physiopathologique de la réponse immunitaire.

Experimental and clinical radiofrequency ablation: proposal for standardized description of coagulation size and geometry.

BACKGROUND: Radiofrequency (RF) ablation is used to obtain local control of unresectable tumors in liver, kidney, prostate, and other organs. Accurate data on expected size and geometry of coagulation zones are essential for physicians to prevent collateral damage and local tumor recurrence. The aim of this study was to develop a standardized terminology to describe the size and geometry of these zones for experimental and clinical RF. METHODS: In a first step, the essential geometric parameters to accurately describe the coagulation zones and the spatial relationship between the coagulation zones and the electrodes were defined. In a second step, standard terms were assigned to each parameter. RESULTS: The proposed terms for single-electrode RF ablation include axial diameter, front margin, coagulation center, maximal and minimal radius, maximal and minimal transverse diameter, ellipticity index, and regularity index. In addition a subjective description of the general shape and regularity is recommended. CONCLUSIONS: Adoption of the proposed standardized description method may help to fill in the many gaps in our current knowledge of the size and geometry of RF coagulation zones.

Image-Based Coral Reef Classification and Thematic Mapping

This paper presents a novel image classification scheme for benthic coral reef images that can be applied to both single image and composite mosaic datasets. The proposed method can be configured to the characteristics (e.g., the size of the dataset, number of classes, resolution of the samples, color information availability, class types, etc.) of individual datasets. The proposed method uses completed local binary pattern (CLBP), grey level co-occurrence matrix (GLCM), Gabor filter response, and opponent angle and hue channel color histograms as feature descriptors. For classification, either k-nearest neighbor (KNN), neural network (NN), support vector machine (SVM) or probability density weighted mean distance (PDWMD) is used. The combination of features and classifiers that attains the best results is presented together with the guidelines for selection. The accuracy and efficiency of our proposed method are compared with other state-of-the-art techniques using three benthic and three texture datasets. The proposed method achieves the highest overall classification accuracy of any of the tested methods and has moderate execution time. Finally, the proposed classification scheme is applied to a large-scale image mosaic of the Red Sea to create a completely classified thematic map of the reef benthos

Relationships of basal metabolic rate, relative testis size and cycle length of spermatogenesis in shrews (Mammalia, Soricidae).

The aim of the present study was to determinate the cycle length of spermatogenesis in three species of shrew, Suncus murinus, Sorex coronatus and Sorex minutus, and to assess the relative influence of variation in basal metabolic rate (BMR) and mating system (level of sperm competition) on the observed rate of spermatogenesis, including data of shrew species studied before (Sorex araneus, Crocidura russula and Neomys fodiens). The dynamics of sperm production were determined by tracing 5-bromodeoxyuridine in the DNA of germ cells. As a continuous scaling of mating systems is not evident, the level of sperm competition was evaluated by the significantly correlated relative testis size (RTS). The cycle durations estimated by linear regression were 14.3 days (RTS 0.3%) in Suncus murinus, 9.0 days (RTS 0.5%) in Sorex coronatus and 8.5 days (RTS 2.8%) in Sorex minutus. In regression and multiple regression analyses including all six studied species of shrew, cycle length was significantly correlated with BMR (r2=0.73) and RTS (r2=0.77). Sperm competition as an ultimate factor obviously leads to a reduction in the time of spermatogenesis in order to increase sperm production. BMR may act in the same way, independently or as a proximate factor, revealed by the covariation, but other factors (related to testes size and thus to mating system) may also be involved.