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.

Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission.

Glial cells are increasingly recognized as active players that profoundly influence neuronal synaptic transmission by specialized signaling pathways. In particular, astrocytes have been shown recently to release small molecules, such as the amino acids l-glutamate and d-serine as "gliotransmitters," which directly control the efficacy of adjacent synapses. However, it is still controversial whether gliotransmitters are released from a cytosolic pool or by Ca(2+)-dependent exocytosis from secretory vesicles, i.e., by a mechanism similar to the release of synaptic vesicles in synapses. Here we report that rat cortical astrocytes contain storage vesicles that display morphological and biochemical features similar to neuronal synaptic vesicles. These vesicles share some, but not all, membrane proteins with synaptic vesicles, including the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) synaptobrevin 2, and contain both l-glutamate and d-serine. Furthermore, they show uptake of l-glutamate and d-serine that is driven by a proton electrochemical gradient. d-Serine uptake is associated with vesicle acidification and is dependent on chloride. Whereas l-serine is not transported, serine racemase, the synthesizing enzyme for d-serine, is anchored to the membrane of the vesicles, allowing local generation of d-serine. Finally, we reveal a previously unexpected mutual vesicular synergy between d-serine and l-glutamate filling in glia vesicles. We conclude that astrocytes contain vesicles capable of storing and releasing d-serine, l-glutamate, and most likely other neuromodulators in an activity-dependent manner.

Translating molecular advances in fragile X syndrome into therapy: a review.

Fragile X syndrome is an inherited disease with cognitive, behavioral, and neurologic manifestations, resulting from a single genetic mutation. A variety of treatments that target individual symptoms of fragile X syndrome are currently utilized with limited efficacy. Research in animal models has resulted in the development of potential novel pharmacologic treatments that target the underlying molecular defect in fragile X syndrome, rather than the resultant symptoms. This review describes recent advances in our understanding of the molecular basis of fragile X syndrome and summarizes the ongoing clinical research programs.

Introduction of snow and geomorphic disturbance variables into predictive models of alpine plant distribution in the Western Swiss Alps

Indirect topographic variables have been used successfully as surrogates for disturbance processes in plant species distribution models (SDM) in mountain environments. However, no SDM studies have directly tested the performance of disturbance variables. In this study, we developed two disturbance variables: a geomorphic index (GEO) and an index of snow redistribution by wind (SNOW). These were developed in order to assess how they improved both the fit and predictive power of presenceabsence SDM based on commonly used topoclimatic (TC) variables for 91 plants in the Western Swiss Alps. The individual contribution of the disturbance variables was compared to TC variables. Maps of models were prepared to spatially test the effect of disturbance variables. On average, disturbance variables significantly improved the fit but not the predictive power of the TC models and their individual contribution was weak (5.6% for GEO and 3.3% for SNOW). However their maximum individual contribution was important (24.7% and 20.7%). Finally, maps including disturbance variables (i) were significantly divergent from TC models in terms of predicted suitable surfaces and connectivity between potential habitats, and (ii) were interpreted as more ecologically relevant. Disturbance variables did not improve the transferability of models at the local scale in a complex mountain system, and the performance and contribution of these variables were highly species-specific. However, improved spatial projections and change in connectivity are important issues when preparing projections under climate change because the future range size of the species will determine the sensitivity to changing conditions.

Efficient lentiviral gene transfer into corneal stroma cells using a femtosecond laser.

We investigated a new procedure for gene transfer into the stroma of pig cornea for the delivery of therapeutic factors. A delimited space was created at 110 mum depth with a LDV femtosecond laser in pig corneas, and a HIV1-derived lentiviral vector expressing green fluorescent protein (GFP) (LV-CMV-GFP) was injected into the pocket. Corneas were subsequently dissected and kept in culture as explants. After 5 days, histological analysis of the explants revealed that the corneal pockets had closed and that the gene transfer procedure was efficient over the whole pocket area. Almost all the keratocytes were transduced in this area. Vector diffusion at right angles to the pocket's plane encompasses four (endothelium side) to 10 (epithelium side) layers of keratocytes. After 21 days, the level of transduction was similar to the results obtained after 5 days. The femtosecond laser technique allows a reliable injection and diffusion of lentiviral vectors to efficiently transduce stromal cells in a delimited area. Showing the efficacy of this procedure in vivo could represent an important step toward treatment or prevention of recurrent angiogenesis of the corneal stroma.

Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major.

Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases.

Le Briançonnais, terrain exotique dans les Alpes ?

New reconstructions of the Western Alps from late Early Jurassic till early Tertiary are proposed. These reconstructions use deep lithospheric data gathered through recent seismic surveys and tomographic studies carried out in the Alps. The present day position, under the Po plain, of the southern limit of the European plate (fig. 1), allows to define the former geometry of the Brianconnais peninsula. The Brianconnais domain is regarded as an exotic terrane formerly belonging to the European margin until Late Jurassic, then transported eastward during the drift of Iberia (fig. 5). Therefore, on a present day Western Alps cross section, a duplication of the European continental margin can be recognized (fig. 10). Stratigraphic and sedimentological data along a zone linking the Pyrenean fracture zone to the Brianconnais, can be related to a rifting event starting in Oxfordian time. This event is responsible for the Late Jurassic till mid-Cretaceous drift of Iberia opening, first the northern Atlantic, then the Gulf of Biscay. Simultaneously, the drift of the Brianconnais will open the Valais ocean and close the Piemontese ocean. The resulting oblique collision zone between the Brianconnais and the Apulian margin generates HP/LT metamorphism starting in Early Cretaceous. The eastward drift of the Brianconnais peninsula will eventually bring it in front of a more northerly segment of the former European margin. The thrusting of the Brianconnais unto that margin takes place in early Tertiary (fig. 9), following the subduction of the Valais ocean. The present nappe pile results not only from continent/continent frontal collision, but also from important lateral displacement of terranes, the most important one being the Brianconnais. The dilemma of `'en echelon'' oceanic domains in the Alps is an outcome of these translations. A solution is found when considering the opening of a Cretaceous Valais ocean across the European margin, running out eastward into the Piemontese ocean, where the drift is taken up along a former transform fault and compensated by subduction under the Apulian margin (fig. 8). In the Western Alps we are then dealing with two oceans, the Piemontese and the Valaisan and a duplicated European margin. In the Eastern Alps the single Piemontese ocean is cut by newly created oceanic crust. All these elements will be incorporated into the Penninic structural domain which does not represent a former unique paleogeographic area, it is a composite accretionary domain squeezed between Europe and Apulia.

Role of DC-SIGN in Lassa virus entry into human dendritic cells.

The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high mortality in humans. Antigen-presenting cells, in particular dendritic cells (DCs), are early and preferred targets of LASV, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary monocytes into DCs enhanced virus attachment and entry, concomitant with the upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived immature dendritic cells (MDDC) and can accelerate the capture of free virus. However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC-SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin, indicating the use of different endocytotic pathways. In sum, our data reveal that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role seems distinct from the function as an authentic entry receptor reported for phleboviruses.