X-ray structures of Sap1 and Sap5: structural comparison of the secreted aspartic proteinases from Candida albicans.

Proteolytic activity is an important virulence factor for Candida albicans (C. albicans). It is attributed to the family of the secreted aspartic proteinases (Saps) from C. albicans with a minimum of 10 members. Saps show controlled expression and regulation for the individual stages of the infection process. Distinct isoenzymes can be responsible for adherence and tissue damage of local infections, while others cause systemic diseases. Earlier, only the structures of Sap2 and Sap3 were known. In our research, we have now succeeded in solving the X-ray crystal structures of the apoenzyme of Sap1 and Sap5 in complex with pepstatin A at 2.05 and 2.5 A resolution, respectively. With the structure of Sap1, we have completed the set of structures of isoenzyme subgroup Sap1-3. Of subgroup Sap4-6, the structure of the enzyme Sap5 is the first structure that has been described up to now. This facilitates comparison of structural details as well as inhibitor binding modes among the different subgroup members. Structural analysis reveals a highly conserved overall secondary structure of Sap1-3 and Sap5. However, Sap5 clearly differs from Sap1-3 by its electrostatic overall charge as well as through structural conformation of its entrance to the active site cleft. Design of inhibitors specific for Sap5 should concentrate on the S4 and S3 pockets, which significantly differ from Sap1-3 in size and electrostatic charge. Both Sap1 and Sap5 seem to play a major part in superficial Candida infections. Determination of the isoenzymes' structures can contribute to the development of new Sap-specific inhibitors for the treatment of superficial infections with a structure-based drug design program.

Conflict resolution and evolution of social structures in insect societies

In colonies of social Hymenoptera (which include all ants, as well as some wasp and bee species), only queens reproduce whereas workers generally perform other tasks. The evolution of worker's reproductive altruism can be explained by kin selection, which states that workers can indirectly transmit copies of their genes by helping the reproduction of relatives. The relatedness between queens and workers may however be low, particularly when there are multiple queens per colony, which limits the transmission of copies of workers genes and increases potential conflicts between colony members. In this thesis, we investigated the link between social structure variations and conflicts, and explored the mechanisms involved in variation of colony queen number in ants. According to kin selection, workers should rear the brood they are most related to. In social Hymenoptera, males are haploid whereas females (workers and queens) are diploid. As a result, workers can be up to three times more related to females than males in some colonies, where they should consequently favour the production of females. In contrast, queens are equally related to daughters and sons in all types of colonies and therefore should favour a balanced sex ratio. In a meta-analysis across all studies of social Hymenoptera, we showed that colony sex ratio is generally largely influenced by workers. Hence, the evolution of social structures where queens and workers are equally related to males and females may contribute to decrease the conflict between the two castes over colony sex ratio. Another conflict between queens and workers can occur over male production. Many species contain workers that still have the ability to lay haploid eggs. In some social structures, workers are on average more related to sons of queens than to sons of other workers. As a result, workers should eliminate worker-laid eggs to favour queen-laid eggs. We showed that in the ant Formica selysi, workers eliminate more worker-laid than queen-laid eggs, independently of colony social structure. These results therefore suggest that worker policing can evolve independently from relatedness, potentially because of costs of worker reproduction at the colony-level. Colony queen number is a key parameter that influences relatedness between group members. Queen body size is generally linked to the success of independent colony foundation by single queens and may influence the number of queens in the new colony. In the ant F. selysi, single-queen colonies produce larger queens than multiple-queen colonies. We showed that this association results from genes or maternal effects transmitted to the eggs. However, we also found that queens produced in colonies of the two social forms did not differ in their general ability to found new colonies independently. Queen body size may also influence queen dispersal ability and constrain small queens to be re-adopted in their original nest after mating at proximity. We tested the acceptance of new queens in another ant species, Formica paralugubris, which has numerous queens per colony. Our results show that workers do not discriminate between nestmate and foreign queens, and more generally accept new queens at a limited rate. To conclude, this thesis shows that mechanisms influencing variation in colony queen number and the influence of these changes on conflict resolution are complex. Data gathered in this thesis therefore constitute a solid background for further research on the evolution and the maintenance of complex organisations in insect societies.

The apical localization of transcribing RNA polymerases on supercoiled DNA prevents their rotation around the template.

The interaction of Escherichia coli RNA polymerase with supercoiled DNA was visualized by cryo-electron microscopy of vitrified samples and by classical electron microscopy methods. We observed that when E. coli RNA polymerase binds to a promoter on supercoiled DNA, this promoter becomes located at an apical loop of the interwound DNA molecule. During transcription RNA polymerase shifts the apical loop along the DNA, always remaining at the top of the moving loop. This relationship between RNA polymerase and the supercoiled template precludes circling of the RNA polymerase around the DNA and prevents the growing RNA transcript from becoming entangled with the template DNA.

Use of an in-house approach to study the three-dimensional structures of various outer membrane proteins: structure of the alcaligin outer membrane transporter FauA from Bordetella pertussis.

Bordetella pertussis is the bacterial agent of whooping cough in humans. Under iron-limiting conditions, it produces the siderophore alcaligin. Released to the extracellular environment, alcaligin chelates iron, which is then taken up as a ferric alcaligin complex via the FauA outer membrane transporter. FauA belongs to a family of TonB-dependent outer membrane transporters that function using energy derived from the proton motive force. Using an in-house protocol for membrane-protein expression, purification and crystallization, FauA was crystallized in its apo form together with three other TonB-dependent transporters from different organisms. Here, the protocol used to study FauA is described and its three-dimensional structure determined at 2.3 A resolution is discussed.

A 2D/3D image analysis system to track fluorescently labeled structures in rod-shaped cells: application to measure spindle pole asymmetry during mitosis.

BACKGROUND: The yeast Schizosaccharomyces pombe is frequently used as a model for studying the cell cycle. The cells are rod-shaped and divide by medial fission. The process of cell division, or cytokinesis, is controlled by a network of signaling proteins called the Septation Initiation Network (SIN); SIN proteins associate with the SPBs during nuclear division (mitosis). Some SIN proteins associate with both SPBs early in mitosis, and then display strongly asymmetric signal intensity at the SPBs in late mitosis, just before cytokinesis. This asymmetry is thought to be important for correct regulation of SIN signaling, and coordination of cytokinesis and mitosis. In order to study the dynamics of organelles or large protein complexes such as the spindle pole body (SPB), which have been labeled with a fluorescent protein tag in living cells, a number of the image analysis problems must be solved; the cell outline must be detected automatically, and the position and signal intensity associated with the structures of interest within the cell must be determined. RESULTS: We present a new 2D and 3D image analysis system that permits versatile and robust analysis of motile, fluorescently labeled structures in rod-shaped cells. We have designed an image analysis system that we have implemented as a user-friendly software package allowing the fast and robust image-analysis of large numbers of rod-shaped cells. We have developed new robust algorithms, which we combined with existing methodologies to facilitate fast and accurate analysis. Our software permits the detection and segmentation of rod-shaped cells in either static or dynamic (i.e. time lapse) multi-channel images. It enables tracking of two structures (for example SPBs) in two different image channels. For 2D or 3D static images, the locations of the structures are identified, and then intensity values are extracted together with several quantitative parameters, such as length, width, cell orientation, background fluorescence and the distance between the structures of interest. Furthermore, two kinds of kymographs of the tracked structures can be established, one representing the migration with respect to their relative position, the other representing their individual trajectories inside the cell. This software package, called "RodCellJ", allowed us to analyze a large number of S. pombe cells to understand the rules that govern SIN protein asymmetry. CONCLUSIONS: "RodCell" is freely available to the community as a package of several ImageJ plugins to simultaneously analyze the behavior of a large number of rod-shaped cells in an extensive manner. The integration of different image-processing techniques in a single package, as well as the development of novel algorithms does not only allow to speed up the analysis with respect to the usage of existing tools, but also accounts for higher accuracy. Its utility was demonstrated on both 2D and 3D static and dynamic images to study the septation initiation network of the yeast Schizosaccharomyces pombe. More generally, it can be used in any kind of biological context where fluorescent-protein labeled structures need to be analyzed in rod-shaped cells. AVAILABILITY: RodCellJ is freely available under http://bigwww.epfl.ch/algorithms.html, (after acceptance of the publication).

Selective neurodegeneration induced in rotation-mediated aggregate cell cultures by a transient switch to stationary culture conditions: a potential model to study ischemia-related pathogenic mechanisms.

Aggregating brain cell cultures at an advanced maturational stage (20-21 days in vitro) were subjected for 1-3 h to anaerobic (hypoxic) and/or stationary (ischemic) conditions. After restoration of the normal culture conditions, cell loss was estimated by measuring the release of lactate dehydrogenase as well as the irreversible decrease of cell type-specific enzyme activities, total protein and DNA content. Ischemia for 2 h induced significant neuronal cell death. Hypoxia combined with ischemia affected both neuronal and glial cells to different degrees (GABAergic neurons>cholinergic neurons>astrocytes). Hypoxic and ischemic conditions greatly stimulated the uptake of 2-deoxy-D-glucose, indicating increased glucose consumption. Furthermore, glucose restriction (5.5 mM instead of 25 mM) dramatically increased the susceptibility of neuronal and glial cells to hypoxic and ischemic conditions. Glucose media concentrations below 2 mM caused selective neuronal cell death in otherwise normal culture conditions. GABAergic neurons showed a particularly high sensitivity to glucose restriction, hypoxia, and ischemia. The pattern of ischemia-induced changes in vitro showed many similarities to in vivo findings, suggesting that aggregating brain cell cultures provide a useful in vitro model to study pathogenic mechanisms related to brain ischemia.

In vivo visualization of F-actin structures during the development of the moss Physcomitrella patens.

* The 'in planta' visualization of F-actin in all cells and in all developmental stages of a plant is a challenging problem. By using the soybean heat inducible Gmhsp17.3B promoter instead of a constitutive promoter, we have been able to label all cells in various developmental stages of the moss Physcomitrella patens, through a precise temperature tuning of the expression of green fluorescent protein (GFP)-talin. * A short moderate heat treatment was sufficient to induce proper labeling of the actin cytoskeleton and to allow the visualization of time-dependent organization of F-actin structures without impairment of cell viability. * In growing moss cells, dense converging arrays of F-actin structures were present at the growing tips of protonema cell, and at the localization of branching. Protonema and leaf cells contained a network of thick actin cables; during de-differentiation of leaf cells into new protonema filaments, the thick bundled actin network disappeared, and a new highly polarized F-actin network formed. * The controlled expression of GFP-talin through an inducible promoter improves significantly the 'in planta' imaging of actin.

The early Miocene rotation of the Corso-Sardinian block. New paleomagnetic constraints for the end of the motion

The paleomagnetic investigations carried out in the 70's on Oligo-Miocene volcanics of Sardinia have demonstrated that the island was turned by 35-30 degrees clockwise from 33 Ma up to 3-1-20.5 Ma and rotated counterclockwise in a few million years [De Jong et al., 1969, 1973; Bobier et Coulon, 1970; Coulon et al., 1974; Manzoni, 1974, 1975; Bellon rr nl.. 1977: Edel et Lortscher, 1977; Edel, 1979, 1980]. Since then, the end of the rotation fixed at 19 Ma by Montigny er al. [1981] was the subject of discussions and several studies associating paleomagnetism and radiometric dating were undertaken [Assorgia er al., 1994: Vigliotti et Langenheim, 1995: Deino et al., 1997; Gattacceca rt Deino, 1999]. This is a contribution to this debate that is hampered by thr important secular variation recorded in the volcanics. The only way to get our of this problem is to sample series of successive flows as completely as possible, and to reduce the effect of secular variation by the calculation of means. Sampling was performed north of Bonorva in 5 pyroclastic flows that belong to the upper ignimbritic series SI2 according to Coulon rr nl. [1974] or LBLS according to Assorgia et al. [1997] (fig. I). Ar-40/Ar-39 dating of biotites from the debris flow (MDF) has yielded an age or 18.35 +/- 0.03 Ma [Dubois, 2000]. Five of the investigated sites are located beneath the debris flow ITV, TVB, TVD, SPM85, SPM86), one site was cured in the matrix of the debris flow (MDF) and one in 4 metric blocks included in the flow (DFC). Another site was sampled in the upper ash flow (PDM) that marks the end of the pyroclastic activity, just before the marine transgression. According to micropaleontological and radiometric dating this transgression has occurred between 18.35 and 17.6 Ma [Dubois, 2000]. After removal of a soft viscous component, the thermal demagnetization generally shows a univectorial behaviour of the remanent magnetization (fig. 2a). The maximum unblocking temperatures of 580-620 degrees (tab. I) and a rapid saturation below 100 mT (fig. 3) indicate that the carrier of the characteristic magnetization is magnetite. The exception comes: from the upper site PDM in which were found two characteristic components, one with a normal polarity and low unblocking temperatures up to 350 degreesC and one with a reversed polarity and maximum unblocking temperatures at 580-600 degreesC of magnetite. After calculation of a mean direction for each flow, the mean << Al >> direction 4 degrees /57 degrees (alpha (95) = 13 degrees) computed with the mean directions for the 5 flows may be considered as weakly affected by secular variation. But the results require a more careful examination. The declinations are N to NNW beneath the debris flow. NNW in the debris flow. and NNE (or SSW) above the debris flow, The elongated distribution of the directions obtained at sites TVB and TVD. scattered from the mean direction of TV to the mean direction of MDF is interpreted as due to partial overprinting during the debris How volcanic episode, The low temperature component PDMa is likely related to the alteration seen on thin sections and is also viewed as an overprint. As NNE/SSW directions occur as well below (mean direction << B >> : 5 degrees /58 degrees) as above the debris flow (PDMb : 200 degrees/-58 degrees). the NNW directions (<< C >> : 337 degrees /64 degrees) associated with the debris flow volcanism may be interpreted as resulting from a magnetic field excursion. According to the polarity scale of Cande and Kent [1992, 1995] and the radiometric age of MDF, the directions with normal polarity (TV, TVB, TVD, SPM85. SPM86a. MDF. DFC) may represent the period 5En. while the directions with reversed polarity PDMb and SPM86b were likely acquired during the period 5Dr. Using the mean << Al >> direction, the mean << B >>, or the PDM direction (tab. I). the deviation in declination with the direction of stable Europe 6.4 degrees /58.7 degrees (alpha (95) = 8 degrees) for a selection of 4 middle Tertiary poles by Besse et Courtillot [1991] or 7 degrees /56 degrees (alpha (95) = 3 degrees) for 19 poles listed by Edel [1980] can be considered as negligible. Using the results from the uppermost ignimbritic layer of Anglona also emplaced around 18.3 Ma [Odin rt al.. 1994]. the mean direction << E >> (3 degrees /51.5 degrees) leads to the same conclusion. On the contrary, when taking into account all dated results available for the period 5En (mean direction << D >> 353 degrees /56 degrees for 45 sites) (tab. II). the deviation 13 degrees is much more significant. As the rotation of Sardinia started around 21-20.5 Ma. the assumption of a constant velocity of rotation and the deviations of the Sardinia directions with respect to the stable Europe direction locate the end of the motion between 18.3 and 17.2 or 16.7 Ma (fig. 4). During the interval 18.35-17.5 Ma, the marine transgression took place. At the same period a NE-SW shortening interpreted as resulting from the collision of Sardinia with Apulia affected different parts of the island [Letouzey et al., 1982]. Consequently, the new paleomagnetic results and the tectono-sedimentary evolution are in favour of an end of the rotation at 17.5-18 Ma.

High-resolution seismic images of potentially seismogenic structures beneath the northwest Canterbury Plains, New Zealand

The transpressional boundary between the Australian and Pacific plates in the central South Island of New Zealand comprises the Alpine Fault and a broad region of distributed strain concentrated in the Southern Alps but encompassing regions further to the east, including the northwest Canterbury Plains. Low to moderate levels of seismicity (e. g., 2 > M 5 events since 1974 and 2 > M 4.0 in 2009) and Holocene sediments offset or disrupted along rare exposed active fault segments are evidence for ongoing tectonism in the northwest plains, the surface topography of which is remarkably flat and even. Because the geology underlying the late Quaternary alluvial fan deposits that carpet most of the plains is not established, the detailed tectonic evolution of this region and the potential for larger earthquakes is only poorly understood. To address these issues, we have processed and interpreted high-resolution (2.5 m subsurface sampling interval) seismic data acquired along lines strategically located relative to extensive rock exposures to the north, west, and southwest and rare exposures to the east. Geological information provided by these rock exposures offer important constraints on the interpretation of the seismic data. The processed seismic reflection sections image a variably thick layer of generally undisturbed younger (i.e., < 24 ka) Quaternary alluvial sediments unconformably overlying an older (> 59 ka) Quaternary sedimentary sequence that shows evidence of moderate faulting and folding during and subsequent to deposition. These Quaternary units are in unconformable contact with Late Cretaceous-Tertiary interbedded sedimentary and volcanic rocks that are highly faulted, folded, and tilted. The lowest imaged unit is largely reflection-free Permian Triassic basement rocks. Quaternary-age deformation has affected all the rocks underlying the younger alluvial sediments, and there is evidence for ongoing deformation. Eight primary and numerous secondary faults as well as a major anticlinal fold are revealed on the seismic sections. Folded sedimentary and volcanic units are observed in the hanging walls and footwalls of most faults. Five of the primary faults represent plausible extensions of mapped faults, three of which are active. The major anticlinal fold is the probable continuation of known active structure. A magnitude 7.1 earthquake occurred on 4 September 2010 near the southeastern edge of our study area. This predominantly right-lateral strike-slip event and numerous aftershocks (ten with magnitudes >= 5 within one week of the main event) highlight the primary message of our paper: that the generally flat and topographically featureless Canterbury Plains is underlain by a network of active faults that have the potential to generate significant earthquakes.

Sex differences: From mental rotation to object location memory, an ERP study

Sex differences in cognition have been largely investigated. The most consistent sex differences favoring females are observed in object location memory involving the left hemisphere whereas the most consistent sex differences favoring males are observed in tasks that require mental rotation involving the right hemisphere. Here we used a task involving these two abilities to see the impact of mental rotation on object location memory. To that end we used a combination of behavioral and event-related potential (ERP) electroencephalography (EEG) measures.A computer screen displayed a square frame of 4 pairs of images (a "teddy" bear, a shoe, an umbrella and a lamp) randomly arranged around a central fixation cross. After a 10-second interval for memorization, images disappeared and were replaced by a test frame with no image but a random pair of two locations marked in black. In addition, this test frame was randomly displayed either in the original orientation (0° rotation) or in the rotated one (90° clockwise - CW - or 90° counterclockwise - CCW). Preceding the test frame, an arrow indicating the presence or the absence of rotation of the frame was displayed on the screen. The task of the participants (15 females and 15 males) was to determine if two marked locations corresponded or not to a pair of identical images. Each response was followed by feedback.Findings showed no significant sex differences in the performance of the original orientation. In comparison with this position, the rotation of the frame produced an equal decrease of male and female performance. In addition, this decrease was significantly higher when the rotation of the frame was in a CCW direction. We further assessed the ERP when the arrow indicated the direction of rotation as stimulus-onset, during four time windows representing major components C1, P1, N1 and N2. Although no sex differences were observed in performance, brain activities differed according to sex. Enhanced amplitudes were found for the CCW compared to CW rotation over the right posterior areas for the P1, N1 and N2 components for men as well as for women. Major topographical differences related to sex were measured for the CW rotation condition as marked lateralized amplitude: left-hemisphere amplitude larger than right one was measured during P1 time range for men. These similar patterns prolonged from P1 to N1 for women. Early distinctions were found in interaction with sex between CCW and CW waveform amplitudes, expressing over anterior electrode sites during C1 time range (0-50 ms post-stimulus).In conclusion (i) women do not outperform men in object location memory in this study (absence of rotation condition); (ii) mental rotation, in particular the direction of rotation, influences performance on object location memory; (iii) CCW rotation is associated with activity in the right parietal hemisphere whereas the CW rotation involves the left parietal hemisphere; (iv) this last effect is less pronounced in males, which could explain why greater involvement of right parietal areas in men and of bilateral posterior areas in women is generally reported in mental rotation tasks; and (v) the early distinctions between both directions of rotation located over anterior sites could be related to sex differences in their respective involvement of control mechanisms.

The effect of femoral component rotation on the five-year outcome of cemented mobile bearing total knee arthroplasty.

PURPOSE: Performing total knee replacement, accurate alignment and neutral rotation of the femoral component are widely believed to be crucial for the ultimate success. Contrary to absolute bone referenced alignment, using a ligament balancing technique does not automatically rotate the femoral component parallel to the transepicondylar axis. In this context we established the hypothesis that rotational alignment of the femoral component parallel to the transepicondylar axis (0° ± 3°) results in better outcome than alignment outside of this range. METHODS: We analysed 204 primary cemented mobile bearing total knee replacements five years postoperatively. Femoral component rotation was measured on axial radiographs using the condylar twist angle (CTA). Knee society score, range of motion as well as subjective rating documented outcome. RESULTS: In 96 knees the femoral component rotation was within the range 0 ± 3° (neutral rotation group), and in 108 knees the five-year postoperative rotational alignment of the femoral component was outside of this range (outlier group). Postoperative CTA showed a mean of 2.8° (±3.4°) internal rotation (IR) with a range between 6° external rotation (ER) and 15° IR (CI 95). No difference with regard to subjective and objective outcome could be detected. CONCLUSION: The present work shows that there is a large given natural variability in optimal rotational orientation, in this study between 6° ER and 15° IR, with numerous co-factors determining correct positioning of the femoral component. Further studies substantiating pre- and postoperative determinants are required to complete the understanding of resulting biomechanics in primary TKA.

Geological transect across the Northwestern Himalaya in eastern Ladakh and Lahul (A model for the continental collision of India and Asia)

The detailed geological mapping and structural study of a complete transect across the northwestern Himalaya allow to describe the tectonic evolution of the north Indian continental margin during the Tethys ocean opening and the Himalayan Orogeny. The Late Paleozoic Tethys rifting is associated with several tectonomagmatic events. In Upper Lahul and SE Zanskar, this extensional phase is recorded by Lower Carboniferous synsedimentary transtensional faults, a Lower Permian stratigraphic unconformity, a Lower Permian granitic intrusion and middle Permian basaltic extrusions (Panjal Traps). In eastern Ladakh, a Permian listric normal fault is also related to this phase. The scarcity of synsedimentary faults and the gradual increase of the Permian syn-rift sediment thickness towards the NE suggest a flexural type margin. The collision of India and Asia is characterized by a succession of contrasting orogenic phases. South of the Suture Zone, the initiation of the SW vergent Nyimaling-Tsarap Nappe corresponds to an early phase of continental underthrusting. To the S, in Lahul, an opposite underthrusting within the Indian plate is recorded by the NE vergent Tandi Syncline. This structure is associated with the newly defined Shikar Beh Nappe, now partly eroded, which is responsible for the high grade (amphibolite facies) regional metamorphism of South Lahul. The main thrusting of the Nyimaling-Tsarap Nappe followed the formation of the Shikar Beh Nappe. The Nyimaling-Tsarap Nappe developed by ductile shear of the upper part of the subducted Indian continental margin and is responsible for the progressive regional metamorphism of SE Zanskar, reaching amphibolite facies below the frontal part of the nappe, near Sarchu. In Upper Lahul, the frontal parts of the Nyimaling-Tsarap and Shikar Beh nappes are separated by a zone of low grade metamorphic rocks (pumpellyite-actinolite facies to lower greenschist facies). At high structural level, the Nyimaling-Tsarap Nappe is characterized by imbricate structures, which grade into a large ductile shear zone with depth. The related crustal shortening is about 87 km. The root zone and the frontal part of this nappe have been subsequently affected by two zones of dextral transpression and underthrusting: the Nyimaling Shear Zone and the Sarchu Shear Zone. These shear zones are interpreted as consequences of the counterclockwise rotation of the continental underthrusting direction of India relative to Asia, which occurred some 45 and 36 Ma ago, according to plate tectonic models. Later, a phase of NE vergent `'backfolding'' developed on these two zones of dextral transpression, creating isoclinal folds in SE Zanskar and more open folds in the Nyimaling Dome and in the Indus Molasse sediments. During a late stage of the Himalayan Orogeny, the frontal part of the Nyimaling-Tsarap Nappe underwent an extension of about 15 km. This phase is represented by two types of structures, responsible for the tectonic unroofing of the amphibolite facies rocks of the Sarchu area: the Sarchu high angle Normal Fault, cutting a first set of low angle normal faults, which have been created by reactivation of older thrust planes related to the Nyimaling-Tsarap Nappe.

Phylogenetic structures of the Holarctic Sorex araneus group and its relationships with S-samniticus, as inferred from mtDNA sequences

The shrews of the Sorex araneus group, characterized by the sexual chromosome complex XY1, Y2 have been intensively studied by morphological, karyotypical, and biochemical analyses. Nevertheless, the phylogenetic relationships among the species belonging to the araneus complex are still under debate, as different approaches gave often contradictory results. In this paper, partial nucleotide sequences of the mitochondrial DNA cytochrome b gene (1011 bp) were determined for 6 species of the araneus group from Eurasia and North America. We also included in the data set the sequences of Sorex samniticus, whose relationships with the araneus group remain controversial. Three other species representing two major karyological groups were also examined. Both parsimony and distance trees strongly support the monophyly of the araneus group. Sorex sumniticus is significantly more closely related to the araneus complex than to the other species included in the analysis. Based on the branching pattern within the araneus group, an attempt has been made to reconstruct the colonization history of the Holarctic region.

Intégration de méthodes de data mining dans le renseignement criminel : analyse par des structures issues de la théorie des graphes dans le profilage des stupéfiants

Data mining can be defined as the extraction of previously unknown and potentially useful information from large datasets. The main principle is to devise computer programs that run through databases and automatically seek deterministic patterns. It is applied in different fields of application, e.g., remote sensing, biometry, speech recognition, but has seldom been applied to forensic case data. The intrinsic difficulty related to the use of such data lies in its heterogeneity, which comes from the many different sources of information. The aim of this study is to highlight potential uses of pattern recognition that would provide relevant results from a criminal intelligence point of view. The role of data mining within a global crime analysis methodology is to detect all types of structures in a dataset. Once filtered and interpreted, those structures can point to previously unseen criminal activities. The interpretation of patterns for intelligence purposes is the final stage of the process. It allows the researcher to validate the whole methodology and to refine each step if necessary. An application to cutting agents found in illicit drug seizures was performed. A combinatorial approach was done, using the presence and the absence of products. Methods coming from the graph theory field were used to extract patterns in data constituted by links between products and place and date of seizure. A data mining process completed using graphing techniques is called ``graph mining''. Patterns were detected that had to be interpreted and compared with preliminary knowledge to establish their relevancy. The illicit drug profiling process is actually an intelligence process that uses preliminary illicit drug classes to classify new samples. Methods proposed in this study could be used \textit{a priori} to compare structures from preliminary and post-detection patterns. This new knowledge of a repeated structure may provide valuable complementary information to profiling and become a source of intelligence.

Structural development of the Tso Morari ultra-high pressure nappe of the Ladakh Himalaya

A continental subduction-related and multistage exhumation process for the Tso Morari ultra-high pressure nappe is proposed. The model is constrained by published thermo-barometry and age data, combined with new geological and tectonic maps. Additionally, observations on the structural and metamorphic evolution of the Tso Morari area and the North Himalayan nappes are presented. The northern margin of the Indian continental crust was subducted to a depth of >90 km below Asia after continental collision some 55 Ma ago. The underthrusting was accompanied by the detachment and accretion of Late Proterozoic to Early Eocene sediments, creating the North Himalayan accretionary wedge, in front of the active Asian margin and the 103-50 Ma Ladakh arc batholith. The basic dikes in the Ordovician Tso Morari granite were transformed to eclogites with crystallization of coesite, some 53 Ma ago at a depth of >90 kin (>27 kbar) and temperatures of 500 to 600 degrees C. The detachment and extrusion of the low density Tso Morari nappe, composed of 70% of the Tso Morari granite and 30% of graywackes with some eclogitic dikes, occurred by ductile pure and simple shear deformation. It was pushed by buoyancy forces and by squeezing between the underthrusted Indian lithosphere and the Asian mantle wedge. The extruding Tso Morari nappe reached a depth of 35 km at the base of the North Himalayan accretionary wedge some 48 Ma ago. There the whole nappe stack recrystallized under amphibolite facies conditions of a Barrovian regional metamorphism with a metamorphic field gradient of 20 degrees C/km. An intense schistosity with a W-E oriented stretching lineation L, and top-to-the E shear criteria and crystallization of oriented sillimanite needles after kyanite, testify to the Tso Morari nappe extrusion and pressure drop. The whole nappe stack, comprising from the base to top the Tso Morari, Tetraogal, Karzok and Mata-Nyimaling-Tsarap nappes, was overprinted by new schistosities with a first N-directed and a second NE-directed stretching lineation L-2 and L-3 reaching the base of the North Himalayan accretionary wedge. They are characterized by top-to-the S and SW shear criteria. This structural overprint was related to an early N- and a younger NE-directed underthrusting of the Indian plate below Asia that was accompanied by anticlockwise rotation of India. The warping of the Tso Morari dome started already some 48 Ma ago with the formation of an extruding nappe at depth. The Tso Morari dome reached a depth of 15 km about 40 Ma ago in the eastern Kiagar La region and 30 Ma ago in the western Nuruchan region. The extrusion rate was of about 3 cm/yr between 53 and 48 Ma, followed by an uplift rate of 1.2 mm/yr between 48 and 30 Ma and of only 0.5 mm/yr after 30 Ma. Geomorphology observations show that the Tso Morari dome is still affected by faults, open regional dome, and basin and pull-apart structures, in a zone of active dextral transpression parallel to the Indus Suture zone.