Bayesian estimation of speciation and extinction from incomplete fossil occurrence data.

The temporal dynamics of species diversity are shaped by variations in the rates of speciation and extinction, and there is a long history of inferring these rates using first and last appearances of taxa in the fossil record. Understanding diversity dynamics critically depends on unbiased estimates of the unobserved times of speciation and extinction for all lineages, but the inference of these parameters is challenging due to the complex nature of the available data. Here, we present a new probabilistic framework to jointly estimate species-specific times of speciation and extinction and the rates of the underlying birth-death process based on the fossil record. The rates are allowed to vary through time independently of each other, and the probability of preservation and sampling is explicitly incorporated in the model to estimate the true lifespan of each lineage. We implement a Bayesian algorithm to assess the presence of rate shifts by exploring alternative diversification models. Tests on a range of simulated data sets reveal the accuracy and robustness of our approach against violations of the underlying assumptions and various degrees of data incompleteness. Finally, we demonstrate the application of our method with the diversification of the mammal family Rhinocerotidae and reveal a complex history of repeated and independent temporal shifts of both speciation and extinction rates, leading to the expansion and subsequent decline of the group. The estimated parameters of the birth-death process implemented here are directly comparable with those obtained from dated molecular phylogenies. Thus, our model represents a step towards integrating phylogenetic and fossil information to infer macroevolutionary processes.

Plastid genome characterisation in Brassica and Brassicaceae using a new set of nine SSRs.

We report a new set of nine primer pairs specifically developed for amplification of Brassica plastid SSR markers. The wide utility of these markers is demonstrated for haplotype identification and detection of polymorphism in B. napus, B. nigra, B. oleracea, B. rapa and in related genera Arabidopsis, Camelina, Raphanus and Sinapis. Eleven gene regions (ndhB-rps7 spacer, rbcL-accD spacer, rpl16 intron, rps16 intron, atpB-rbcL spacer, trnE-trnT spacer, trnL intron, trnL-trnF spacer, trnM-atpE spacer, trnR-rpoC2 spacer, ycf3-psaA spacer) were sequenced from a range of Brassica and related genera for SSR detection and primer design. Other sequences were obtained from GenBank/EMBL. Eight out of nine selected SSR loci showed polymorphism when amplified using the new primers and a combined analysis detected variation within and between Brassica species, with the number of alleles detected per locus ranging from 5 (loci MF-6, MF-1) to 11 (locus MF-7). The combined SSR data were used in a neighbour-joining analysis (SMM, D (DM) distances) to group the samples based on the presence and absence of alleles. The analysis was generally able to separate plastid types into taxon-specific groups. Multi-allelic haplotypes were plotted onto the neighbour joining tree. A total number of 28 haplotypes were detected and these differentiated 22 of the 41 accessions screened from all other accessions. None of these haplotypes was shared by more than one species and some were not characteristic of their predicted type. We interpret our results with respect to taxon differentiation, hybridisation and introgression patterns relating to the 'Triangle of U'.

Source-wavelet estimation during full-waveform inversion of ground-penetrating radar data

A major issue in the application of waveform inversion methods to crosshole ground-penetrating radar (GPR) data is the accurate estimation of the source wavelet. Here, we explore the viability and robustness of incorporating this step into a recently published time-domain inversion procedure through an iterative deconvolution approach. Our results indicate that, at least in non-dispersive electrical environments, such an approach provides remarkably accurate and robust estimates of the source wavelet even in the presence of strong heterogeneity of both the dielectric permittivity and electrical conductivity. Our results also indicate that the proposed source wavelet estimation approach is relatively insensitive to ambient noise and to the phase characteristics of the starting wavelet. Finally, there appears to be little to no trade-off between the wavelet estimation and the tomographic imaging procedures.

Deep crustal electromagnetic structure of Bhuj earthquake region (India) and its implications

The existence of fluids and partial melt in the lower crust of the seismically active Kutch rift basin (on the western continental margin of India) owing to underplating has been proposed in previous geological and geophysical studies. This hypothesis is examined using magnetotelluric (MT) data acquired at 23 stations along two profiles across Kutch Mainland Uplift and Wagad Uplift. A detailed upper crustal structure is also presented using twodimensional inversion of MT data in the Bhuj earthquake (2001) area. The prominent boundaries of reflection in the upper crust at 5, 10 and 20 km obtained in previous seismic reflection profiles correlate with conductive structures in our models. The MT study reveals 1-2 km thick Mesozoic sediments under the Deccan trap cover. The Deccan trap thickness in this region varies from a few meters to 1.5 km. The basement is shallow on the northern side compared to the south and is in good agreement with geological models as well as drilling information. The models for these profiles indicate that the thickness of sediments would further increase southwards into the Gulf of Kutch. Significant findings of the present study indicate 1) the hypocentre region of the earthquake is devoid of fluids, 2) absence of melt (that is emplaced during rifting as suggested from the passive seismological studies) in the lower crust and 3) a low resistive zone in the depth range of 5-20 km. The present MT study rules out fluidsand melt (magma) as the causative factors that triggered the Bhuj earthquake. The estimated porosity value of 0.02% will explain 100-500 ohm·m resistivity values observed in the lower crust. Based on the seismic velocities and geochemical studies, presence of garnet is inferred. The lower crust consists of basalts - probably generated by partial melting of metasomatised garnet peridotite at deeper depths in the lithosphere - and their composition might be modified by reaction with the spinel peridotites.

Comparison of human and rhesus macaque T-cell responses elicited by boosting with NYVAC encoding human immunodeficiency virus type 1 clade C immunogens.

Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4(+) and CD8(+) T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-gamma, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-gamma T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

Stratigraphie, morphodynamique, paléoenvironnements des terrains sédimentaires meubles à forte déclivité du domaine périglaciaire alpin

Dans le contexte d'un climat de plus en plus chaud, une étude « géosystémique » de la répartition du pergélisol dans l'ensemble d'un versant périglaciaire alpin, de la paroi rocheuse jusqu'au glacier rocheux, s'avère primordiale. S'insérant dans cette problématique, ce travail de thèse vise comme objectif général l'étude des versants d'éboulis situés à l'intérieur de la ceinture du pergélisol discontinu selon deux volets de recherche différents : une étude de la stratigraphie et de la répartition du pergélisol dans les éboulis de haute altitude et des processus qui lui sont associés ; une reconstitution de l'histoire paléoenvironnementale du domaine périglaciaire alpin pendant le Tardiglaciaire et l'Holocène. La stratigraphie et la répartition spatiale du pergélisol a été étudiée dans cinq éboulis des Alpes Valaisannes (Suisse), dont trois ont fait l'objet de forages profonds, grâce à la prospection géophysique de détail effectuée à l'aide de méthodes thermiques, de résistivité, sismiques et nucléaires. Les mesures effectuées ont permis de mettre en évidence que, dans les cinq éboulis étudiés, la répartition du pergélisol est discontinue et aucun des versants n'est intégralement occupé par du pergélisol. En particulier, il a été possible de prouver de manière directe que, dans un éboulis, le pergélisol est présent dans les parties inférieures du versant et absent dans les parties supérieures. Trois facteurs de contrôle principaux de la répartition du pergélisol déterminée au sein des éboulis étudiés ont été individualisés, pouvant agir seuls ou de manière combinée : la ventilation ascendante, l'augmentation de la granulométrie en direction de l'aval et la redistribution de la neige par le vent et les avalanches. Parmi ceux-ci, la relation ventilation-granulométrie semble être le facteur de contrôle principal permettant d'expliquer la présence de pergélisol dans les parties inférieures d'un éboulis et son absence dans les parties supérieures. Enfin, l'analyse de la structure des éboulis périglaciaires de haute altitude a permis de montrer que la stratigraphie du pergélisol peut être un élément important pour l'interprétation de la signification paléoclimatique de ce type de formes. Pour le deuxième volet de la recherche, grâce aux datations relatives effectuées à l'aide de l'utilisation conjointe de la méthode paléogéographique et du marteau de Schmidt, il a été possible de définir la chrono-stratigraphie du retrait glaciaire et du développement des glaciers rocheux et des versants d'éboulis des quatre régions des Alpes suisses étudiées (régions du Mont Gelé - Mont Fort, des Fontanesses et de Chamosentse, dans les Alpes Valaisannes, et Massif de la Cima di Gana Bianca, dans les Alpes Tessinoises). La compilation de toutes les datations effectuées a permis de montrer que la plupart des glaciers rocheux actifs étudiés se seraient développés soit juste avant et/ou pendant l'Optimum Climatique Holocène de 9.5-6.3 ka cal BP, soit au plus tard juste après cet évènement climatique majeur du dernier interglaciaire. Parmi les glaciers rocheux fossiles datés, la plupart aurait commencé à se former dans la deuxième moitié du Tardiglaciaire et se serait inactivé dans la première partie de l'Optimum Climatique Holocène. Pour les éboulis étudiés, les datations effectuées ont permis d'observer que leur surface date de la période entre le Boréal et l'Atlantique récent, indiquant que les taux d'éboulisation après la fin de l'Optimum Climatique Holocène ont dû être faibles, et que l'intervalle entre l'âge maximal et l'âge minimal est dans la plupart des cas relativement court (4-6 millénaires), indiquant que les taux d'éboulisation durant la période de formation des éboulis ont dû être importants. Grâce au calcul des taux d'érosion des parois rocheuses sur la base du volume de matériaux rocheux pour quatre des éboulis étudiés, il a été possible mettre en évidence l'existence d'une « éboulisation parapériglaciaire » liée à la dégradation du pergélisol dans les parois rocheuses, fonctionnant principalement durant les périodes de réchauffement climatique rapide comme cela a été le cas au début du Bølling, du Préboréal à la fin de l'Atlantique récent et, peut-être, à partir des années 1980. - In the context of a warmer climate, a « geosystemical » study of the permafrost distribution in a whole alpine periglacial hillslope, from the rockwall to the rockglacier, is of great importance. With respect to this problem, the general objective of this PhD thesis is the global study of talus slopes located within the alpine periglacial belt following two different research axes: the analysis of the internal structure and of the permafrost distribution of high altitude talus slopes and of the related processes; the reconstruction of the palaeoenvironmental history of the alpine periglacial belt during the Lateglacial and the Holocene. The stratigraphy and the permafrost distribution were studied in five talus slopes of the Valais Alps (Switzerland) with the analysis of borehole data (on three of the five talus slopes) and other methods of permafrost prospecting: Electrical Resistivity Tomography (ERT), Refraction Seismic Tomography (RST) and nuclear well logging. The collected data shows that, in all of the studied talus slopes, permafrost distribution is discontinuous and that neither of the hillslopes is integrally characterised by permafrost. In particular, this data proves by direct investigations that, in talus slopes, permafrost is present in the lower parts of the hillslope, whereas it is absent in the upper parts. Permafrost distribution in alpine talus slopes is depending of the combination of almost three controlling factors, whose respective importance is variable: the chimney effect, the increase of grain size downslope and the redistribution of snow by avalanches. Depending on the size of the talus and on topographical and geomorphological heterogeneities, various cases are possible: one dominant controlling factor or the combination of various factors. Nevertheless, it would be an error to consider each controlling factor independently, without considering their relationships. Between these controlling factors, the relationship chimney effect/grain size seems to be the most important factor controlling the presence of permafrost in the lowest part of periglacial talus slopes, and its absence in the upper parts. Finally, the analysis of the talus structure shows that the permafrost stratigraphy may be an important element of interpretation of the palaeoclimatic significance of an alpine talus slope. The second research axe focused on the establishment of a chronology of the Lateglacial glacier retreat and the dating of rockglaciers and talus slopes development in four studied regions of the Swiss Alps (Mont Gelé - Mont Fort, Fontanesses and Chamosentse regions, in the Valais Alps, and the Cima di Gana Bianca Massif, in the Ticino Alps). The compilation of the dates acquired through the combination of the palaeogeographical method and of the Schmidt hammer indicates that most of the investigated active rockglaciers started to evolve during the early phases of the Holocene or, at the latest, after the early-to-mid Holocene Climatic Optimum (ending around 6.3 ka cal BP). For the dated relict rockglaciers, most of them started to evolve in the second half of the Lateglacial, and probably became inactive at the beginning of the Holocene Climatic Optimum. For the investigated talus slopes, the relative dating carried out allowed to show that their surface date from the period included between the Boreal and the end of the Atlantic, pointing out that the rockwall retreat after the end of the Holocene Climatic Optimum was weak, and that the interval between maximal and minimal ages is in most cases relatively short (4-6 millennia). Therefore, the rockwall retreat during the development period of the talus slopes must has been considerable. Thanks to the calculation of rockwall erosion rates based on the volume of talus accumulations for four of the investigated hillslopes, it was possible to find evidences of the existence of "paraperiglacial rockfall phases" related to the permafrost degradation in rockwalls. These phases coincide with rapid climate warming periods, as at the beginning of the Bølling, during the Preboreal or, maybe, since 1980.

Stable isotopes in lake Geneva carbonate sediments and molluscs: Review and new data

New isotopic results on bulk carbonate and mollusc (gastropods and bivalves) samples from Lake Geneva (Switzerland), spanning the period from the Oldest Dryas to the present day, are compared with pre-existing stable isotope data. According to preliminary calibration of modern samples, Lake Geneva endogenic calcite precipitates at or near oxygen isotopic equilibrium with ambient water, confirming the potential of this large lake to record paleoenvironmental and paleoclimatic changes. The onset of endogenic calcite precipitation at the beginning of the Allerod biozone is clearly indicated by the oxygen isotopic signature of bulk carbonate. A large change in delta(13)C values occurs during the Preboreal. This carbon shift is likely to be due to a change in bioproductivity and/or to a `'catchment effect'', the contribution of biogenic CO2 from the catchment area to the dissolved inorganic carbon reservoir of the lake water becoming significant only during the Preboreal. Gastropods are confirmed as valuable for studies of changes in paleotemperature and in paleowater isotopic composition, despite the presence of a vital effect. Mineralogical evidence indicates an increased detrital influence upon sedimentation since the Subboreal time period. On the other hand, stable isotope measurements of Subatlantic carbonate sediments show values comparable to those of pure endogenic calcite and of gastropods (taking into account the vital effect). This apparent disagreement still remains difficult to explain.

PchR-box recognition by the AraC-type regulator PchR of Pseudomonas aeruginosa requires the siderophore pyochelin as an effector.

Under iron limitation, the opportunistic human pathogen Pseudomonas aeruginosa produces the siderophore pyochelin. When secreted into the extracellular environment, pyochelin complexes ferric ions and delivers them, via the outer membrane receptor FptA, to the bacterial cytoplasm. Extracellular pyochelin also acts as a signalling molecule, inducing the expression of pyochelin biosynthesis and uptake genes by a mechanism involving the AraC-type regulator PchR. We have identified a 32 bp conserved sequence element (PchR-box) in promoter regions of pyochelin-controlled genes and we show that the PchR-box in the pchR-pchDCBA intergenic region is essential for the induction of the pyochelin biosynthetic operon pchDCBA and the repression of the divergently transcribed pchR gene. PchR was purified as a fusion with maltose-binding protein (MBP). Mobility shift assays demonstrated specific binding of MBP-PchR to the PchR-box in the presence, but not in the absence of pyochelin and iron. PchR-box mutations that interfered with pyochelin-dependent regulation in vivo, also affected pyochelin-dependent PchR-box recognition in vitro. We conclude that pyochelin, probably in its iron-loaded state, is the intracellular effector required for PchR-mediated regulation. The fact that extracellular pyochelin triggers this regulation suggests that the siderophore can enter the cytoplasm.

Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs.

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease. Tolerance to self-antigens is achieved through thymic deletion of highly autoreactive conventional T (Tconv) cells and generation of FoxP3(+) regulatory T (Treg) cells. The main costimulatory molecule, CD28, augments the negative selection of Tconv cells and promotes the generation of FoxP3(+) Treg cells. The role of its antagonistic homolog CTLA-4, however, remains a topic of debate. To address this topic, we investigated the thymic development of T cells in the presence and absence of CTLA-4 in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1-9. We reveal that CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells generated and broadens the repertoire of peripheral Tconv cells. T-cell repertoire alteration after deletion of CTLA-4 results from changes in TCR Vα and Jα segment selection as well as CDR3α composition in Tconv and Treg cells. CTLA-4, therefore, regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance.

Full-waveform inversion of cross-hole ground-penetrating radar data to characterize a gravel aquifer close to the Thur River, Switzerland

Cross-hole radar tomography is a useful tool for mapping shallow subsurface electrical properties viz. dielectric permittivity and electrical conductivity. Common practice is to invert cross-hole radar data with ray-based tomographic algorithms using first arrival traveltimes and first cycle amplitudes. However, the resolution of conventional standard ray-based inversion schemes for cross-hole ground-penetrating radar (GPR) is limited because only a fraction of the information contained in the radar data is used. The resolution can be improved significantly by using a full-waveform inversion that considers the entire waveform, or significant parts thereof. A recently developed 2D time-domain vectorial full-waveform crosshole radar inversion code has been modified in the present study by allowing optimized acquisition setups that reduce the acquisition time and computational costs significantly. This is achieved by minimizing the number of transmitter points and maximizing the number of receiver positions. The improved algorithm was employed to invert cross-hole GPR data acquired within a gravel aquifer (4-10 m depth) in the Thur valley, Switzerland. The simulated traces of the final model obtained by the full-waveform inversion fit the observed traces very well in the lower part of the section and reasonably well in the upper part of the section. Compared to the ray-based inversion, the results from the full-waveform inversion show significantly higher resolution images. At either side, 2.5 m distance away from the cross-hole plane, borehole logs were acquired. There is a good correspondence between the conductivity tomograms and the natural gamma logs at the boundary of the gravel layer and the underlying lacustrine clay deposits. Using existing petrophysical models, the inversion results and neutron-neutron logs are converted to porosity. Without any additional calibration, the values obtained for the converted neutron-neutron logs and permittivity results are very close and similar vertical variations can be observed. The full-waveform inversion provides in both cases additional information about the subsurface. Due to the presence of the water table and associated refracted/reflected waves, the upper traces are not well fitted and the upper 2 m in the permittivity and conductivity tomograms are not reliably reconstructed because the unsaturated zone is not incorporated into the inversion domain.

Lymphoid stroma in health and disease

Summary Secondary lymphoid organs (SLOB), such as lymph nodes and spleen, are the sites where primary immune responses are initiated. T lymphocytes patrol through the blood and SLOs on the search for pathogens which are presented to them as antigens by dendritic cells. Stromal cells in the Tzone - so called T zone fibroblastic reticular cells (TRCs) -are critical in organizing the migration of T cells and dendritic cells by producing the chemoattractants CCL19 and CCL21 and by forming a network which T cells use as a guidance system. They also form a system of small channels or conduits that allow rapid transport of small antigen molecules or cytokines from the subcapsular sinus to high endothelial venules. The phenotype and function of TRCs have otherwise remained largely unknown. We found a critical role for lymph node access in CD4+ and CD8+ T cell homeostasis and identified TRCs within these organs as the major source of interleukin-7 (IL-7). IL-7 is an essential survival factor for naïve T lymphocytes of which the cellular source in the periphery had been poorly defined. In vitro, TRC were able to prevent the death of naïve T but not of B lymphocytes by secreting IL-7 and the CCR7 ligand CCL 19. Using gene-targeted mice, we show anon-redundant function of CCL19 in T cell homeostasis. The data suggest that TRCs regulate T cell numbers by providing a limited reservoir of survival factors for which T cells have to compete. They help to maintain a diverse T cell repertoire granting full immunocompetence. To determine whether TRCs also play a role in pathology, we characterized so-called tertiary lymphoid organs (TLOs) that often develop at sites of chronic inflammation. We show that TLOs resemble lymph nodes or Peyer's patches not only with regard to lymphoid cells. TLOs formed extensive TRC networks and a functional conduit system in all three marine inflammation models tested. In one model we dissected the cells and signals leading to the formation of these structures. We showed that they critically depend on the presence of lymphotoxin and lymphoid tissue inducer cells. TRCs in TLOs also produce CCL19, GCL21 and possibly IL-7 which are all involved in the development of TLOs. Stromal cells therefore play a central role in the onset and perpetuation of chronic inflammatory diseases and could be an interesting target for therapy. Résumé Le système immunitaire est la défense de notre corps contre toutes sortes d'infections et de tumeurs. II est constitué de différentes populations de lymphocytes qui patrouillent constamment le corps à la recherche de pathogène. Parmi eux, les lymphocytes T et B passent régulièrement dans les organes lymphoïdes secondaires (SLO) qui sont les sites d'initiation de la réponse immunitaire. Les lymphocytes T sont recrutés du sang aux SLO où ils cherchent leur antigène respectif présenté par des cellules dendritiques. Des cellules stromales dans la zone T -nommées fibroblastic reticular cells' (TRC) -sécrètent des chimiokines CCL19 et CCL21 et ainsi facilitent les rencontres entre lymphocytes T et cellules dendritiques. De plus, elles forment un réseau que les lymphocytes T utilisent comme système de guidage. Ce réseau forme des petits canaux (ou conduits) qui permettent le transport rapide, d'antigène soluble ou de cytokines, de la lymphe aux veinules à endothelium épais (HEV). Le phénotype ainsi que les autres fonctions des TRCs demeurent encore à ce jour inconnus. Nous avons trouvé que l'accès des lymphocytes T CD4+ et CD8+ aux ganglions joue un rôle central pour l'homéostasie. Interleukin-7 (IL-7) est un facteur de survie essentiel pour les lymphocytes T naïfs dont la source cellulaire dans la périphérie était mal définie. Nous avons identifié les TRCs dans les ganglions comme source principale d'interleukin-7 (IL-7). In vitro, les TRCs étaient capable de prévenir la mort des lymphocytes T mais pas celle de lymphocytes B grâce à la sécrétion d'IL-7 et de CCL19. En utilisant des souris déficientes du gène CCL19, nous avons observé que l'homéostasie des lymphocytes T dépend aussi de CCL19 in vivo. Les données suggèrent que les TRCs aident à maintenir un répertoire large et diversifié de cellules T et ainsi l'immunocompétence. Pour déterminer si les TRCs pourraient jouer un rote également dans la pathologie, nous avons caractérisé des organes lymphoïdes tertiaires (TLOs) souvent associés avec l'inflammation chronique. Les TLOs ressemblent à des ganglions ou des plaques de Peyer pas seulement en ce qui concerne la présence de lymphocytes. Nous avons constaté que les TLOs forment des réseaux de TRC et un système fonctionnel de conduits. La formation de ces structures est fortement diminuée dans l'absence du signal lymphotoxin ou des cellules connues comme ymphoid tissue-inducer tells: Les TRCs dans les TLOs produisent les chimiokines CCL19, CCL21 et possiblement aussi IL-7 qui sont impliquées dans le développement des TLOs. Les cellules stromales jouent donc un rôle central dans l'initation et la perpétuation des maladies inflamatoires chroniques et pourraient être une cible intéressante pour la thérapie.

Comparing 'visual' effect size indices for single-case designs

Effect size indices are indispensable for carrying out meta-analyses and can also be seen as an alternative for making decisions about the effectiveness of a treatment in an individual applied study. The desirable features of the procedures for quantifying the magnitude of intervention effect include educational/clinical meaningfulness, calculus easiness, insensitivity to autocorrelation, low false alarm and low miss rates. Three effect size indices related to visual analysis are compared according to the aforementioned criteria. The comparison is made by means of data sets with known parameters: degree of serial dependence, presence or absence of general trend, changes in level and/or in slope. The percent of nonoverlapping data showed the highest discrimination between data sets with and without intervention effect. In cases when autocorrelation or trend is present, the percentage of data points exceeding the median may be a better option to quantify the effectiveness of a psychological treatment.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: role of Renin genes.

Several studies have demonstrated that mice are polymorphic for the number of renin genes, with some inbred strains harboring one gene (Ren-1(c)) and other strains containing two genes (Ren-1(d) and Ren-2). In this study, the effects of 1% salt and deoxycorticosterone acetate (DOCA)/salt were investigated in one- and two-renin gene mice, for elucidation of the role of renin in the modulation of BP, cardiac, and renal responses to salt and DOCA. The results demonstrated that, under baseline conditions, mice with two renin genes exhibited 10-fold higher plasma renin activity, 100-fold higher plasma renin concentrations, elevated BP (which was angiotensin II-dependent), and an increased cardiac weight index, compared with one-renin gene mice (all P &lt; 0.01). The presence of two renin genes markedly increased the BP, cardiac, and renal responses to salt. The number of renin genes also modulated the responses to DOCA/salt. In one-renin gene mice, DOCA/salt induced significant renal and cardiac hypertrophy (P &lt; 0.01) even in the absence of any increase in BP. Treatment with losartan, an angiotensin II AT(1) receptor antagonist, decreased BP in two-renin gene mice but not in one-renin gene mice. However, losartan prevented the development of cardiac hypertrophy in both groups of mice. In conclusion, these data demonstrate that renin genes are important determinants of BP and of the responses to salt and DOCA in mice. The results confirm that the Ren-2 gene, which controls renin production mainly in the submaxillary gland, is physiologically active in mice and is not subject to the usual negative feedback control. Finally, these data provide further evidence that mineralocorticoids promote cardiac hypertrophy even in the absence of BP changes. This hypertrophic process is mediated in part by the activation of angiotensin II AT(1) receptors.