New insight on bio-sensing by nano-fabricated memristors

We report here on a new insight for bio- sensing based on the memristive effect of functional- ized Schottky-barrier memristive silicon nanowire in dry environment. The device concept is discussed. Elec- trical measurements confirm the bio-detection by the narrowing of the memristive Ids − Vds hysteresis upon interaction of antigen with antibody-functionalized nanowire.

The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing.

PPARalpha and PPARbeta are expressed in the mouse epidermis during fetal development, but their expression progressively disappears after birth. However, the expression of PPARbeta is reactivated in adult mice upon proliferative stimuli, such as cutaneous injury. We show here that PPARbeta protects keratinocytes from growth factor deprivation, anoikis and TNF-alpha-induced apoptosis, by modulating both early and late apoptotic events via the Akt1 signaling pathway and DNA fragmentation, respectively. The control mechanisms involve direct transcriptional upregulation of ILK, PDK1, and ICAD-L. In accordance with the anti-apoptotic role of PPARbeta observed in vitro, the balance between proliferation and apoptosis is altered in the epidermis of wounded PPARbeta mutant mice, with increased keratinocyte proliferation and apoptosis. In addition, primary keratinocytes deleted for PPARbeta show defects in both cell-matrix and cell-cell contacts, and impaired cell migration. Together, these results suggest that the delayed wound closure observed in PPARbeta mutant mice involves the alteration of several key processes. Finally, comparison of PPARbeta and Akt1 knock-out mice reveals many similarities, and suggests that the ability of PPARbeta to modulate the Akt1 pathway has significant impact during skin wound healing.

Inverse metamorphic zonation in very low-grade Tibetan zone series of SE Zanskar and its tectonic consequences (NW India, Himalaya)

The metamorphism of the carbonate rocks of the SE Zanskar Tibetan zone has been studied by `'illite crystallinity'' and calcite-dolomite thermometry. The epizonal Zangla unit overlies the anchizonal Chumik unit. This discontinuous inverse zonation demonstrates a late to post-metamorphic thrust of the first unit over the second. The studied area underwent a complex tectonic history: - The tectonic units were stacked from the NE to the SW, generating recumbent folds, NE dipping thrusts and the regional metamorphism. The compressive movements were active under lower temperature conditions, resulting in late thrusts that disturbed the metamorphic zonation. The discontinuous inverse metamorphic zonation dates from this phase. - A NE vergent backfolding phase occurred at lower temperature conditions. It caused the uplift of more metamorphic levels. - A late extensional phase is revealed by the presence of NE dipping low angle normal faults, and a major high angle fault, the Sarchu fault. The low angle normal faults locally run along earlier thrusts (composite tectonic contacts). Their throw has been sufficient to reset a normal stratigraphic superposition (young layers overlying old ones), but insufficient to erase the inverse metamorphic relationship. However, the combined action of backfolding and normal faulting can locally lessen, or even cancel, the inverse metamorphic superposition. After deduction of the normal fault translation, the vertical component of the original thrust displacement through stratigraphy is 400 m, which is a value far too low to explain the temperature difference between the two units. The horizontal component of displacement is therefore far more important than the vertical one. The regional distribution of metamorphism within the Zangla unit points out to an anchizonal front and an epizonal inner part. This fact is in agreement with nappe tectonics.

Origin of the spectral shifts among the early intermediates of the rhodopsin photocycle.

A combined strategy based on the computation of absorption energies, using the ZINDO/S semiempirical method, for a statistically relevant number of thermally sampled configurations extracted from QM/MM trajectories is used to establish a one-to-one correspondence between the structures of the different early intermediates (dark, batho, BSI, lumi) involved in the initial steps of the rhodopsin photoactivation mechanism and their optical spectra. A systematic analysis of the results based on a correlation-based feature selection algorithm shows that the origin of the color shifts among these intermediates can be mainly ascribed to alterations in intrinsic properties of the chromophore structure, which are tuned by several residues located in the protein binding pocket. In addition to the expected electrostatic and dipolar effects caused by the charged residues (Glu113, Glu181) and to strong hydrogen bonding with Glu113, other interactions such as π-stacking with Ala117 and Thr118 backbone atoms, van der Waals contacts with Gly114 and Ala292, and CH/π weak interactions with Tyr268, Ala117, Thr118, and Ser186 side chains are found to make non-negligible contributions to the modulation of the color tuning among the different rhodopsin photointermediates.

A new perspective on the evolutionary history of western European Sorex araneus group revealed by paternal and maternal molecular markers.

The species of the common shrew (Sorex araneus) group are morphologically very similar, but have undergone a spectacular chromosomal evolution. We investigate here the evolutionary history of the Sorex araneus group distributed in western Europe. In particular, we clarify the position of a difficult species, S. granarius, using sex-specific (mtDNA and Y-chromosome) markers. The karyotype of S. granarius is generally considered similar to the common ancestor of the restricted group considered here. The mtDNA data (1.4 kb) confirms the close relationship between S. granarius and S. araneus sensu stricto (hereafter S. araneus s.s.), but the Y-chromosome (3.4 kb) produces a quite different picture: S. granarius is closely related to another species, S. coronatus. Comparison of mtDNA and Y-chromosome phylogenies suggests that the genetic and chromosomal evolution in this group are disconnected processes. The evolutionary history of the south-western European populations of the S. araneus group can only be understood considering secondary contacts between taxa after their divergence, implying genetic exchanges by means of hybridization and/or introgression.

Five years of sleep apnea treatment with a mandibular advancement device. Side effects and technical complications

Objective: To determine the variation in prevalence of temporomandibular disorders (TMD), other side effects, and technical complications during 5 years of sleep apnea treatment with a mandibular advancement device. Materials and Methods: Forty patients diagnosed with obstructive sleep apnea received an adjustable appliance at 70% of the maximum protrusion. The protrusion was then progressively increased. TMD (diagnosed according to the Research Diagnostic Criteria for TMD), overjet, overbite, occlusal contacts, subjective side effects, and technical complications were recorded before and a mean of 14, 21, and 58 months after treatment and analyzed by the Wilcoxon test (P Less-than .05). Results: Fifteen patients still used the oral appliance at the 5-year follow-up, and no significant variation in TMD prevalence was observed. Subjective side effects were common, and a significant reduction was found in overjet, overbite, and in the number of occlusal contacts. Furthermore, the patients made a mean of 2.5 unscheduled dental visits per year and a mean of 0.8 appliance repairs/relines per year by a dental technician. The most frequent unscheduled visits were needed during the first year and were a result of acrylic breakage on the lateral telescopic attachment, poor retention, and other adjustments to improve comfort. Conclusions: Five-year oral appliance treatment does not affect TMD prevalence but is associated with permanent occlusal changes in most sleep apnea patients during the first 2 years. Patients seek several unscheduled visits, mainly because of technical complications.

The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC) cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397) and Y(576/577)), Src (S(418)) and VE-cadherin (Y(658) and Y(731)), redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ(2) domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA-mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS-PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.

Comparison of two strategies to prevent varicella outbreaks in housing facilities for asylum seekers.

BACKGROUND: The proportion of adults with positive varicella serology is lower in populations from tropical countries. Therefore immigrants to countries with a temperate climate are at risk of acquiring varicella infection during adulthood. METHODS: We tested two different strategies to prevent varicella outbreaks in housing facilities for asylum seekers arriving in the Canton of Vaud, Switzerland. The first strategy consisted of a rapid response with isolation of the affected individuals and vaccination of the susceptible contacts. The second strategy consisted of a general vaccination upon arrival of all asylum seekers aged 15-39 years with no history of chickenpox. RESULTS: From May 2008 to January 2009 we applied the rapid response strategy. Eight hundred and fifty-eight asylum seekers arrived in the Canton and an attack rate of 2.8% (seven cases among 248 exposed asylum seekers) was observed. The mean cost was US$ 31.35 per asylum seeker. The general vaccination strategy was applied from February 2009 to May 2010, a period during which 966 asylum seekers were registered. This second strategy completely prevented any outbreak at a mean cost of US$ 83.85 per asylum seeker. CONCLUSIONS: Of the two analyzed interventions to prevent varicella outbreaks in housing facilities for asylum seekers, the general vaccination strategy was more effective, more sustainable, and ethically preferable, although more costly.

Kinship, ritual kinship and political milieus in an alpine Valley in 19th century

In my paper I will present some results about ritual kinship and political mobilization of popular groups in an alpine Valley: the Val de Bagnes, in the Swiss canton of Valais. There are two major reasons to choose the Val de Bagnes for our inquiry about social networks: the existence of sharp political and social conflicts during the 18th and the 19th century and the availability of almost systematic genealogical data between 1700 and 1900. The starting point of my research focuses on this question: what role did kinship and ritual kinship play in the political mobilization of popular groups and in the organization of competing factions? This question allows us to shed light on some other uses and meanings of ritual kinship in the local society. Was ritual kinship a significant instrument for economic cooperation? Or was it a channel for patronage or for privileged social contacts? The analysis highlights the importance of kinship and godparentage for the building of homogeneous social and political networks. If we consider transactions between individuals, the analysis of 19th century Val de Bagnes gives the impression of quite open networks. Men and women tried to diversify their relations in order to avoid strong dependency from powerful patrons. Nevertheless, when we consider the family networks, we can notice that most relations took place in a structured social space or a specific "milieu", were intense contacts enhanced trust, although political allegiances and social choices were not fully predictable on the basis of such preferential patterns. In a politically conflictual society, like 19th century Bagnes, ritual kinship interacted with kinship solidarities and ideological factors shaping dense social networks mostly based on a common political orientation. Such milieus sustained the building of political factions, which show surprising stability over time. In this sense, milieus are important factors to understand political and religious polarization in 19th century Switzerland.

Lésions de surcharge du membre inférieur chez le jeune footballeur

Résumé Le point de départ de ce travail est une passion pour le sport en général. L'intérêt s'est porté sur la répercussion du sport sur un organisme en croissance. Le football semble lié à une forte proportion de douleurs et de lésions des membres inférieurs. Après consultation de la littérature, il ressort qu'il n'existe pas d'étude spécifique sur les lésions de surcharge chez le jeune footballeur, bien que la mention du football comme facteur de risque des lésions de surcharge soit fréquente. Les lésions les plus souvent évoquées sont la maladie d'Osgood-Schlatter et la maladie de Sever. Un questionnaire a été élaboré, puis distribué aux juniors des clubs de football de Monthey et de Sion. Il comporte plusieurs volets tels que les données personnelles (poids, âge, taille, pied dominant), l'évolution de l'enfant au sein du club et les douleurs/lésions des membres inférieurs. Par la suite, les médecins traitants ont été contactés afin de préciser les diagnostics. 326 jeunes footballeurs ont participé à cette étude transversale. On recense 30 cas (9,7%) de pathologie de surcharge du membre inférieur dont 17 cas répondent au diagnostic d'ostéochondrose. 11 enfants ont été atteints de la maladie d'Osgood-Schlatter à un âge moyen de 12,3 ans (extrêmes 7 et 16 ans), elle est survenue après 4,7 ans d'entraînement en junior et la jambe de tir n'a pas d'influence sur le côté lésé. Dans ce groupe, 2 joueurs faisaient partie de la catégorie élite ce qui représente deux heures d'entraînement de plus par semaine que pour des jeunes d'âge équivalent. La maladie de Sever a affecté 6 jeunes entre 11 et 13 ans, soit à un âge moyen de 11,6 ans. Elle est apparue après une moyenne de 3,6 ans de football en junior. Le pied dominant n'a également que peu d'influence sur le côté lésé, par contre les lésions bilatérales sont plus fréquentes que dans le cadre de la maladie d'Osgood-Schlatter. Parmi ces joueurs, 4 sur 6 avaient un encadrement privilégié en élite avec une demi-heure d'entraînement supplémentaire par semaine par rapport à des jeunes d'âge équivalent. Le traitement de ces pathologies reste un arrêt ou du moins une modification de l'activité sportive. Il faut s'attacher à corriger les troubles statiques et reprendre l'entraînement en fonction des douleurs. Le moment où le jeune sportif concentre beaucoup d'espoirs correspond à une période de fragilité physique et psychologique. C'est pourquoi, il est important que les responsables des jeunes footballeurs, ainsi que les médecins qui les entourent soient conscients des facteurs de risque de chaque individu et inhérents à la pratique de ce sport.

Characterization of HbpR binding by site-directed mutagenesis of its DNA-binding site and by deletion of the effector domain.

In the presence of 2-hydroxybiphenyl, the enhancer binding protein, HbpR, activates the sigma54-dependent P(hbpC) promoter and controls the initial steps of 2-hydroxybiphenyl degradation in Pseudomonas azelaica. In the activation process, an oligomeric HbpR complex of unknown subunit composition binds to an operator region containing two imperfect palindromic sequences. Here, the HbpR-DNA binding interactions were investigated by site-directed mutagenesis of the operator region and by DNA-binding assays using purified HbpR. Mutations that disrupted the twofold symmetry in the palindromes did not affect the binding affinity of HbpR, but various mutations along a 60 bp region, and also outside the direct palindromic sequences, decreased the binding affinity. Footprints of HbpR on mutant operator fragments showed that a partial loss of binding contacts occurs, suggesting that the binding of one HbpR 'protomer' in the oligomeric complex is impaired whilst leaving the other contacts intact. An HbpR variant, devoid of its N-terminal sensing A-domain, was unable to activate transcription from the hbpC promoter while maintaining protection of the operator DNA in footprints. Wild-type HbpR was unable to activate transcription from the hbpC promoter when delta A-HbpR was expressed in the same cell, suggesting the formation of (repressing) hetero-oligomers. This model implies that HbpR can self-associate on its operator DNA without effector recognition or ATP binding. Furthermore, our findings suggest that the N-terminal sensing domain of HbpR is needed to activate the central ATPase domain rather than to repress a constitutively active C domain, as is the case for the related regulatory protein XylR.

A cartography of the Van der Waals territory

The distribution of distances from atoms of a particular element E to a probe atom X (oxygen in most cases), both bonded and intermolecular non-bonded contacts, has been analyzed. In general, the distribution is characterized by a maximum at short EX distances corresponding to chemical bonds, followed by a range of unpopulated distances the van der Waals gap and a second maximum at longer distances the van der Waals peak superimposed on a random distribution function that roughly follows a d3 dependence. The analysis of more than five million interatomic"non-bonded" distances has led to the proposal of a consistent set of van der Waals radii for most naturally occurring elements, and its applicability to other element pairs has been tested for a set of more than three million data, all of them compared to over one million bond distances.