Mechanism of HFR1 function in adaptive growth responses in "Arabidopsis thaliana"

AbstractPlants are sessile organisms, which have evolved an astonishing ability to sense changes in their environment. Depending on the surrounding conditions, such as changes in light and temperature, plants modulate the activity of important transcriptional regulators. The shade avoidance syndrome (SAS) is one important mechanism for shade-intolerant plants to adapt their growth in high vegetative density. In shaded conditions plants sense a diminished red/far-red ratio via the phytochrome system and respond with morphological changes such as elongation growth of stems and petioles. The Phytochrome Interacting Factors 4 and 5 (PIF4 and PIF5) are positive regulators of the SAS and required for a full response (Lorrain et al, 2008). They regulate the SAS by inducing the expression of shade avoidance marker genes such as PIL1, ATHB2, XTR7 and HFR1 (Hornitschek et al, 2009; Lorrain et al, 2008).I investigated the molecular mechanism underlying the regulation of the SAS by HFR1 (long Hypocotyl in FR light). Although HFR1 is a PIF-related bHLH transcription factor, we discovered that HFR1 is a non-DNA binding protein. Moreover, we revealed that HFR1 inhibits an exaggerated SAS by forming non-DNA binding heterodimers with PIF4 and PIF5 (Hornitschek et al, 2009). This negative feedback loop is an important mechanism to limit elongation growth also in elevated temperatures. HFR1 accumulation and activity are highly temperature-dependent and the increased activity of HFR1 at warmer temperatures also provides an important restraint on PIF4-driven elongation growth (Foreman et al, 2011).Finally we performed a genome-wide analysis to determine how PIF4 and PIF5 regulate growth in response to shade. We identified potential PIF5- target genes, which represent many well-known shade-responsive genes. Our analysis of gene expression also revealed a role of PIF4 and PIF5 in simulated sun possibly via the regulation of auxin sensitivity.RésuméLes plantes sont des organismes sessiles ayant développé une capacité surprenante à détecter des changements dans leur environnement. En fonction des conditions extérieures, telles que les variations de lumière ou de température, elles adaptent l'activité d'importants régulateurs transcriptionnels. Le syndrome d'évitement de l'ombre (SAS), est un mécanisme important pour les plantes intolérantes à l'ombre leur permettant d'adapter leur croissance lorsqu'elles se développent dans des conditions de végétations très denses. Dans ces conditions, les plantes détectent une réduction de la quantité relative de lumière rouge par rapport à la lumière rouge-lointain (rapport R/FR). Ce changement, perçu via le système des phytochromes, induit des modifications morphologiques telle qu'une élongation des tiges et des pétioles. Les protéines PIF4 et PIF5 (Phytochrome Interacting Factors) sont des régulateurs positifs du SAS et sont nécessaires pour une réponse complète (Lorrain et al, 2008). Ces facteurs de transcription régulent le SAS en induisant l'expression de gènes marqueurs de cette réponse tels que PIL1, ATHB2, XTR7 et HFR1 (Hornitschek et al, 2009; Lorrain et al, 2008).J'ai étudié les mécanismes moléculaires sous-jacents à la régulation du SAS par HFR1 (long Hypocotyl in FR light). HFR1 est un facteur de transcription type bHLH de la famille des PIF, quoique nous ayons découvert que HFR1 est une protéine ne se liant pas à Γ ADN. Nous avons montré que HFR1 inhibe un SAS exagéré en formant des heterodimères avec PIF4 et PIF5 (Hornitschek et al, 2009). Nous avons également montré que cette boucle de régulation négative est également un mécanisme important pour limiter la croissance de l'élongation dans des conditions de fortes températures. De plus l'accumulation et l'activité de HFR1 augmentent avec la température ce qui permet d'inhiber plus fortement l'effet activateur de PIF4 sur la croissance.Enfin, nous avons effectué une analyse génomique à large échelle afin de déterminer comment PIF4 et PIF5 régulent la croissance en réponse à l'ombre. Nous avons identifié les gènes cibles potentiels de PIF5, correspondant en partie à des gènes connus dans la réponse de l'évitement de l'ombre. Notre analyse de l'expression des gènes a également révélé un rôle important de PIF4 et PIF5 dans des conditions de croissance en plein soleil, probablement via la régulation de la sensibilité à l'auxine.

Farnesol-induced apoptosis in Candida albicans is mediated by Cdr1-p extrusion and depletion of intracellular glutathione.

Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent.

Persistent infection of arenaviruses : molecular mechanisms and pathogenesis

Arenaviruses are enveloped negative single strand RNA viruses that include a number of important human pathogens. The most prevalent human pathogen among the arenaviruses is the Old World arenavirus Lassa virus (LASV) which is endemic in West Africa from Senegal to Cameroon. LASV is the etiologic agent of a severe viral hemorrhagic fever named Lassa fever whose mortality rate can reach 30% in hospitalized patients. One of the hallmarks of fatal arenavirus infection in humans is the absence of an effective innate and adaptive immune response. In nature, arenaviruses are carried by rodents which represent the natural reservoirs as well as the vectors for transmission. In their natural rodent reservoir, arenaviruses have the ability to establish persistent infection without any overt signs and symptoms of pathology. We believe that the modulation of the host cell's innate immunity by arenaviruses is a key determinant for persistence in the natural host and for the pathogenesis in man. In this thesis, we studied the interaction of arenaviruses with two main branches of the host's innate anti-viral defense, the type I interferon (IFN) system and virus-induced mitochondrial apoptosis. The arenavirus nucleoprotein (NP) is responsible for the anti-IFN activity of arenaviruses. Specifically, NP blocks the activation and the nuclear translocation of the transcription factor interferon regulatory factor 3 (IRF3) which leads to type I IFN production. LASV and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) NPs contain a 3'-5'exoribonuclease domain in the C terminal part that has been linked to the anti-IFN activity of NP. In the first project, we sought to identify cellular component(s) of the type I IFN induction pathway targeted by the viral NP. Our study revealed that LCMV NP prevents the activation of IRF3 by blocking phosphorylation of the transcription factor. We found that LCMV NP specifically targets the IRF-activating kinase IKKs, and this specific binding is conserved within the Arenaviridae. We could also demonstrate that LCMV NP associates with the kinase domain of IKKs involving NP's C-terminal region. Lastly, we showed that the binding of LCMV NP inhibits the kinase activity of IKKs. This study allowed the discovery of a new cellular interacting partner of arenavirus NP. This newly described association may play a role in the anti-IFN activity of arenaviruses but potentially also in other aspects of arenavirus infection. For the second project, we investigated the ability of arenaviruses to avoid and/or suppress mitochondrial apoptosis. As persistent viruses, arenaviruses evolved a "hit and stay" survival strategy where the apoptosis of the host cell would be deleterious. We found that LCMV does not induce mitochondrial apoptosis at any time during infection. Specifically, no caspase activity, no cytochrome c release from the mitochondria as well as no cleavage of poly (ADP-ribose) polymerase (PARP) were detected during LCMV infection. Interestingly, we found that virus-induced mitochondrial apoptosis remains fully functional in LCMV infected cells, while the induction of type IIFN is blocked. Since both type IIFN production and virus- induced mitochondrial apoptosis critically depend on the pattern recognition receptor (PRR) RIG-I, we examined the role of RIG-I in apoptosis in LCMV infected cells. Notably, virus- induced mitochondrial apoptosis in LCMV infected cells was found to be independent of RIG- I and MDA5, but still depended on MAVS. Our study uncovered a novel mechanism by which arenaviruses alter the host cell's pro-apoptotic signaling pathway. This might represent a strategy arenaviruses developed to maintain this branch of the innate anti-viral defense in absence of type I IFN response. Taken together, these results allow a better understanding of the interaction of arenaviruses with the host cell's innate immunity, contributing to our knowledge about pathogenic properties of these important viruses. A better comprehension of arenavirus virulence may open new avenues for vaccine development and may suggest new antiviral targets for therapeutic intervention against arenavirus infections. - Les arenavirus sont des virus enveloppés à ARN simple brin qui comportent un grand nombre de pathogènes humains. Le pathogène humain le plus important parmi les arenavirus est le virus de Lassa qui est endémique en Afrique de l'Ouest, du Sénégal au Cameroun. Le virus de Lassa est l'agent étiologique d'une fièvre hémorragique sévère appelée fièvre de Lassa, et dont le taux de mortalité peut atteindre 30% chez les patients hospitalisés. L'une des caractéristiques principales des infections fatales à arenavirus chez l'Homme est l'absence de réponse immunitaire innée et adaptative. Dans la nature, les arenavirus sont hébergés par différentes espèces de rongeur, qui représentent à la fois les réservoirs naturels et les vecteurs de transmission des arenavirus. Dans leur hôte naturel, les arenavirus ont la capacité d'établir une infection persistante sans symptôme manifeste d'une quelconque pathologie. Nous pensons que la modulation de système immunitaire inné de la cellule hôte par les arenavirus est un paramètre clé pour la persistance au sein de l'hôte naturel, ainsi que pour la pathogenèse chez l'Homme. L'objectif de cette thèse était d'étudier l'interaction des arenavirus avec deux branches essentielles de la défense antivirale innée de la cellule hôte, le système interféron (IFN) de type I et l'apoptose. La nucléoprotéine virale (NP) est responsable de l'activité anti-IFN des arenavirus. Plus spécifiquement, la NP bloque 1'activation et la translocation nucléaire du facteur de transcription IRF3 qui conduit à la production des IFNs de type I. La NP du virus de Lassa et celle du virus de la chorioméningite lymphocytaire (LCMV), l'arénavirus prototypique, possèdent dans leur extrémité C-terminale un domaine 3'-5' exoribonucléase qui a été associé à l'activité anti-IFN de ces protéines. Dans un premier projet, nous avons cherché à identifier des composants cellulaires de la cascade de signalisation induisant la production d'IFNs de type I qui pourraient être ciblés par la NP virale. Nos recherches ont révélé que la NP de LCMV empêche 1'activation d'IRF3 en bloquant la phosphorylation du facteur de transcription. Nous avons découvert que la NP de LCMV cible spécifiquement la kinase IKKe, et que cette interaction spécifique est conservée à travers la famille des Arenaviridae. Notre étude a aussi permis de démontrer que la NP de LCMV interagit avec le domaine kinase d'IKKe et que l'extrémité C-terminale de la NP est impliquée. Pour finir, nous avons pu établir que l'association avec la NP de LCMV inhibe l'activité kinase d'IKKe. Cette première étude présente la découverte d'un nouveau facteur cellulaire d'interaction avec la NP des arenavirus. Cette association pourrait jouer un rôle dans l'activité anti-IFN des arénavirus, mais aussi potentiellement dans d'autres aspects des infections à arénavirus. Pour le second projet, nous nous sommes intéressés à la capacité des arénavirus à éviter et/ou supprimer l'apoptose mitochondriale. En tant que virus persistants, les arénavirus ont évolué vers une stratégie de survie "hit and stay" pour laquelle l'apoptose de la cellule hôte serait néfaste. Nous avons observé qu'à aucun moment durant l'infection LCMV n'induit l'apoptose mitochondriale. Spécifiquement, aucune activité de caspase, aucune libération mitochondriale de cytochrome c ainsi qu'aucun clivage de la polymerase poly(ADP-ribose) (PARP) n'a été détecté pendant l'infection à LCMV. Il est intéressant de noter que l'apoptose mitochondriale induite par les virus reste parfaitement fonctionnelle dans les cellules infectées par LCMV, alors que l'induction de la réponse IFN de type I est bloquée dans les mêmes cellules. La production des IFNs de type I et l'apoptose mitochondriale induite par les virus dépendent toutes deux du récepteur de reconnaissance de motifs moléculaires RIG-I. Nous avons, par conséquent, investigué le rôle de RIG-I dans l'apoptose qui a lieu dans les cellules infectées par LCMV lorsqu'on les surinfecte avec un autre virus pro-apoptotique. En particulier, l'apoptose mitochondriale induite par les surinfections s'est révélée indépendante de RIG-I et MDA5, mais dépendante de MAVS dans les cellules précédemment infectées par LCMV. Notre étude démontre ainsi l'existence d'un nouveau mécanisme par lequel les arénavirus altèrent la cascade de signalisation pro-apoptotique de la cellule hôte. Il est possible que les arénavirus aient développé une stratégie permettant de maintenir fonctionnelle cette branche de la défense antivirale innée en l'absence de réponse IFN de type I. En conclusion, ces résultats nous amènent à mieux comprendre l'interaction des arénavirus avec l'immunité innée de la cellule hôte, ce qui contribue aussi à améliorer notre connaissance des propriétés pathogéniques de ces virus. Une meilleure compréhension des facteurs de virulence des arénavirus permet, d'une part, le développement de vaccins et peut, d'autre part, servir de base pour la découverte de nouvelles cibles thérapeutiques utilisées dans le traitement des infections à arénavirus.

The mechanism of Hsp70 chaperones: (entropic) pulling the models together.

Hsp70s are conserved molecular chaperones that can prevent protein aggregation, actively unfold, solubilize aggregates, pull translocating proteins across membranes and remodel native proteins complexes. Disparate mechanisms have been proposed for the various modes of Hsp70 action: passive prevention of aggregation by kinetic partitioning, peptide-bond isomerase, Brownian ratcheting or active power-stroke pulling. Recently, we put forward a unifying mechanism named 'entropic pulling', which proposed that Hsp70 uses the energy of ATP hydrolysis to recruit a force of entropic origin to locally unfold aggregates or pull proteins across membranes. The entropic pulling mechanism reproduces the expected phenomenology that inspired the other disparate mechanisms and is, moreover, simple.

High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.

Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.

Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition.

OBJECTIVE: Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes. METHODS AND RESULTS: Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r2=0.27; P<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r2=0.39; P<0.0004) and LV mass index (r2=0.19; P=0.028), respectively. CONCLUSIONS: LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.

An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension.

AIMS: Connexins (Cxs) play a role in the contractility of the aorta wall. We investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and -independent hypertension. METHODS AND RESULTS: We subjected both wild-type (WT) mice and mice lacking Cx40 (Cx40(-/-)), to either a two-kidney, one-clip procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce renin-dependent and -independent hypertension, respectively. All hypertensive mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, and of Cx40 in EC (except in Cx40(-/-) mice). Cx43 was up-regulated, with no effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of hypertension. Blockade of the renin-angiotensin system of Cx40(-/-) mice normalized blood pressure and prevented both aortic thickening and Cx alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to physiologically relevant levels of angiotensin II (AngII) increased the levels of Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated kinase-dependent pathways and induced binding of the nuclear factor-kappa B (NF-kappaB) to the Cx43 gene promoter, increasing Cx43 expression. CONCLUSION: In both large and small arteries, hypertension differently regulates Cx expression in SMC and EC layers. Cx43 is selectively increased in renin-dependent hypertension via an AngII activation of the extracellular signal-regulated kinase and NF-kappaB pathways.

On the dual contrast enhancement mechanism in frequency-selective inversion-recovery magnetic resonance angiography (IRON-MRA)

The susceptibility of blood changes after administration of a paramagnetic contrast agent that shortens T(1). Concomitantly, the resonance frequency of the blood vessels shifts in a geometry-dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency-selective saturation prepulse prior to the imaging sequence. The dual origin of vascular enhancement depending first on off-resonance and second on T(1) lowering was investigated in vitro, together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented.

Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate MVA-C enhances immune responses against HIV-1 antigens.

Vaccinia virus (VACV) encodes an anti-apoptotic Bcl-2-like protein F1 that acts as an inhibitor of caspase-9 and of the Bak/Bax checkpoint but the role of this gene in immune responses is not known. Because dendritic cells that have phagocytosed apoptotic infected cells cross-present viral antigens to cytotoxic T cells inducing an antigen-specific immunity, we hypothesized that deletion of the viral anti-apoptotic F1L gene might have a profound effect on the capacity of poxvirus vectors to activate specific immune responses to virus-expressed recombinant antigens. This has been tested in a mouse model with an F1L deletion mutant of the HIV/AIDS vaccine candidate MVA-C that expresses Env and Gag-Pol-Nef antigens (MVA-C-ΔF1L). The viral gene F1L is not required for virus replication in cultured cells and its deletion in MVA-C induces extensive apoptosis and expression of immunomodulatory genes in infected cells. Analysis of the immune responses induced in BALB/c mice after DNA prime/MVA boost revealed that, in comparison with parental MVA-C, the mutant MVA-C-ΔF1L improves the magnitude of the HIV-1-specific CD8 T cell adaptive immune responses and impacts on the CD8 T cell memory phase by enhancing the magnitude of the response, reducing the contraction phase and changing the memory differentiation pattern. These findings reveal the immunomodulatory role of F1L and that the loss of this gene is a valid strategy for the optimization of MVA as vaccine vector.

Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover.

The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. Several tissues, including the thymus, lung, spleen, small intestine, large intestine, seminal vesicle, prostate, and uterus, clearly coexpress the two genes. Most tissues constitutively coexpressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune privileged. It may be, therefore, that the Fas system is implicated in both the regulation of physiological cell turnover and the protection of particular tissues against potential lymphocyte-mediated damage.

The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.

The caspase-3/p120 RasGAP module acts as a stress sensor that promotes pro-survival or pro-death signaling depending on the intensity and the duration of the stressful stimuli. Partial cleavage of p120 RasGAP generates a fragment, called fragment N, which protects stressed cells by activating Akt signaling. Akt family members regulate many cellular processes including proliferation, inhibition of apoptosis and metabolism. These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined. In this study, we investigated the individual contribution of each isoform in fragment N-mediated cell protection against Fas ligand induced cell death. To this end, DLD1 and HCT116 isogenic cell lines lacking specific Akt isoforms were used. It was found that fragment N could activate Akt1 and Akt2 but that only the former could mediate the protective activity of the RasGAP-derived fragment. Even overexpression of Akt2 or Akt3 could not rescue the inability of fragment N to protect cells lacking Akt1. These results demonstrate a strict Akt isoform requirement for the anti-apoptotic activity of fragment N.

PPAR beta/delta Agonists Modulate Platelet Function via a Mechanism Involving PPAR Receptors and Specific Association/Repression of PKC alpha-Brief Report

Objectives-Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) is a nuclear receptor found in platelets. PPAR beta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPAR beta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPAR beta/delta receptors and their intracellular signaling pathways in platelets are not known. Methods and Results-We have used mice lacking PPAR beta/delta (PPAR beta/delta(-/-)) to show the effects of the PPAR beta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPAR beta/delta, however GW501516 had no PPAR beta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKC alpha, which can mediate platelet activation, was bound and repressed by PPAR beta/delta after platelets were treated with GW501516. Conclusions-These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk. (Arterioscler Thromb Vasc Biol. 2009; 29: 1871-1873.)

Monitoring and failure mechanism interpretation of an unstable slope in Southern Switzerland based on terrestrial laser scanner

We present the application of terrestrial laser scanning (TLS) for the monitoring and characterization of an active landslide area in Val Canaria (Ticino, Southern Swiss Alps). At catchment scale, the study area is affected by a large Deep Seated Gravitational Slope Deformation (DSGSD) area presenting, in the lower boundary, several retrogressive landslides active since the 1990s. Due to its frequent landslide events this area was periodically monitored by TLS since 2006. Periodic acquisitions provided new information on 3D displacements at the bottom of slope and the detection of centimetre to decimetre level scale changes (e.g. rockfall and pre-failure deformations). In October 2009, a major slope collapse occured at the bottom of the most unstable area. Based on the comparison between TLS data before and after the collapse, we carried out a detailed failure mechanism analysis and volume calculation.

Nanoparticles for fingermark detection: an insight into the reaction mechanism

This publication presents one of the first uses of silicon oxide nanoparticles to detect fingermarks. The study is not confined to showing successful detection of fingermarks, but is focused on understanding the mechanisms involved in the fingermark detection process. To gain such an understanding, various chemical groups are grafted onto the nanoparticle surface, and parameters such as the pH of the solutions or zeta potential are varied to study their influence on the detection. An electrostatic interaction has been the generally accepted hypothesis of interaction between nanoparticles and fingermarks, but the results of this research challenge that hypothesis, showing that the interaction is chemically driven. Carboxyl groups grafted onto the nanoparticle surfaces react with amine groups of the fingermark secretion. This formation of amide linkage between carboxyl and amine groups has further been favoured by catalyzing the reaction with a compound of diimide type. The research strategy adopted here ought to be applicable to all detection techniques using nanoparticles. For most of them the nature of the interaction remains poorly understood.