c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.

Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD

Neutron Stars in a Varying Speed of Light Theory

We study neutron stars in a varying speed of light (VSL) theory of gravity in which the local speed of light depends upon the value of a scalar field $\phi$. We find that the masses and radii of the stars are strongly dependent on the strength of the coupling between $\phi$ and the matter field and that for certain choices of coupling parameters, the maximum neutron star mass can be arbitrarily small. We also discuss the phenomenon of cosmological evolution of VSL stars (analogous to the gravitational evolution in scalar-tensor theories) and we derive a relation showing how the fractional change in the energy of a star is related to the change in the cosmological value of the scalar field.Comment: 15 pages, 2 figures. Added solutions with a more realistic equation of state. To be published in PR

The value of the spineless monkey orange tree (Strychnos madagascariensis) for conservation of northern sportive lemurs (Lepilemur milanoii and L. ankaranensis)

Tree hollows provide shelters for a large number of forest-dependent vertebrate species worldwide. In  Madagascar, where high historical and ongoing rates of deforestation and forest degradation are  responsible for a major environmental crisis, reduced availability of tree hollows may lead to declines in hollow-dwelling species such as sportive lemurs, one of the most species-rich groups of lemurs. The identification of native tree species used by hollow-dwelling lemurs may facilitate targeted management interventions to maintain or improve habitat quality for these lemurs. During an extensive survey of sportive lemurs in northern Madagascar, we identified one tree species, Strychnos madagascariensis (Loganiaceae), the spineless monkey orange tree, as a principal sleeping site of two species of northern sportive lemurs, Lepilemur ankaranensis and L. milanoii (Lepilemuridae). This tree species represented 32.5% (n=150) of the 458 sleeping sites recorded. This result suggests that S. madagascariensis may be valuable for the conservation of hollow-dwelling lemurs. De nombreux vertébrés forestiers à travers le monde trouvent refuge dans des cavités et des trous  d’arbres. À Madagascar, les taux de déforestation historiques et actuels sont responsables d’une crise environnementale majeure. Dans ce contexte, une disponibilité réduite d’arbres pourvus de cavités  pourrait entrainer le déclin des espèces dépendant de ces abris comme par exemple les lépilemurs, un des groupes de lémuriens les plus riches en espèces. L’identification des espèces d’arbres indigènes creusés de trous et utilisés par les lémuriens pourrait faciliter la mise en place d’actions de conservation ayant pour but de maintenir ou améliorer l’habitat de ces lémuriens. Au cours d’une étude réalisée dans le Nord de Madagascar, nous avons observé que Strychnos madagascariensis  (Loganiaceae) était   fréquemment utilisé comme site dortoir par les deux espèces de lépilemurs présentes, Lepilemur   ankaranensis and L. milanoii (Lepilemuridae). Cette espèce d’arbre concernait 32,5% (n = 150) des 458  sites dortoirs enregistrés. Ce résultat suggère que S. madagascariensis pourrait être important pour la  conservation des lémuriens dépendant de sites dortoirs

Forest type influences population densities of nocturnal lemurs in Manompana, Northeastern Madagascar

Forest loss, fragmentation, and anthropization threaten the survival of forest species all over the world. Shifting agriculture is one of these threatening processes in Madagascar. However, when its cycle is halted and the land is left to regenerate, the resulting growth of secondary forest may provide a viable habitat for folivorous and omnivorous lemur species. We aimed to identify the response of nocturnal lemurs to different successional stages of regenerating secondary, degraded mature, and mature forest across a mosaic-type landscape. We surveyed four nocturnal lemur species (Avahi laniger, Microcebus cf. simmonsi, Allocebus trichotis, and Daubentonia madagascariensis) in four forest types of varying habitat disturbance in northeastern Madagascar. We estimated densities in mature and regenerating secondary forest for the eastern woolly lemur (Avahi laniger) and mouse lemur (Microcebus cf. simmonsi), two sympatric species with folivorous and omnivorous diets respectively. We did not estimate densities of Allocebus trichotis and Daubentonia madagascariensis owing to small sample size; however, we observed both species exclusively in mature forest. We found higher population densities of A. laniger and M. cf. simmonsi in secondary than in mature forest, showing the potential of regenerating secondary forest for lemur conservation. Several environmental factors influenced the detectability of the two lemur species. While observer and habitat type influenced detection of the eastern woolly lemur, canopy height and vine density influenced detection of mouse lemurs. Understanding how different species with different diets interact with anthropogenically impacted habitat will aid future management decisions for the conservation of primate species

Pathogenic Aβ A2V versus protective Aβ A2T mutation : early stage aggregation and membrane interaction

We investigated the effects of punctual A-to-V and A-to-T mutations in the amyloid precursor protein APP, corresponding to position 2 of A\u3b21\u201342. Those mutations had opposite effects on the onset and progression of Alzheimer disease, the former inducing early AD pathology and the latter protecting against the onset of the disease. We applied Static and Dynamic Light Scattering and Circular Dichroism, to study the different mutants in the early stages of the aggregation process, essential for the disease. Comparative results showed that the aggregation pathways differ in the kinetics and extent of the process, in the size of the aggregates and in the evolution of the secondary structure, resulting in fibrils of different morphology, as seen by AFM. Mutated peptides had comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering, all of them displayed disordering effects on the internal structure of mixed phospholipids-gangliosides model membranes

The Molecular Assembly of Amyloid A beta Controls Its Neurotoxicity and Binding to Cellular Proteins

Accumulation of beta-sheet-rich peptide (A beta) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. A beta species are potent neurotoxins, however the molecular mechanism responsible for A beta toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of A beta 1-40 and A beta 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that A beta toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as A beta receptors in N2a cells, triggering a multi factorial toxicity

Estimation des densités et tailles de population du Microcèbe Roux du Nord de (Microcebus tavaratra) dans la région Loky-Manambato (Daraina)

La région Loky-Manambato dans le Nord de Madagascar, est connue pour abriter le propithèque à couronne dorée (Propithecus tattersalli), un lémurien emblématique et endémique de la région. Néanmoins cette région composée d’une dizaine de fragments forestiers de taille moyenne et encore relativement peu étudiés, abrite aussi le microcèbe roux du nord (Microcebus tavaratra). Malgré la gestion des forêts de cette région par l’ONG Fanamby depuis 2005, aucune étude n’avait encore été menée dans chacun des fragments forestiers de la région pour déterminer la présence et quantifier la taille des populations de microcèbes de chacun d’entre eux. Lors de notre étude nous avons tenté d’estimer les densités et les tailles des populations de M. tavaratra dans neuf des dix principaux fragments forestiers de la région. Dans ce but nous avons utilisé la méthode de «line transect distance-sampling». Nos résultats montrent que les densités de microcèbes sont relativement élevées, et varient de 28 à 325 ind/km² entre fragments forestiers de la région. Desétudes plus approfondies des données collectées seront nécessaires pour déterminer les variables environnementales responsables des différences de densité observées.FCT grant: (SFRH/BD/64875/2009); l’Institut Français de la Biodiversité, GDRI Madagascar, “Laboratoire d’Excellence” (LABEX) TULIP: (ANR -10-LABX-41)

Daraina sportive lemur (Lepilemur milanoii) density and population size estimates in most of its distribution range: the Loky-Manambato region.

The population of the Daraina sportive lemur (Lepilemur milanoii) is believed to be mostly confined to the Loky-Manambato region (Louis et al., 2006). Very little is known about L. milanoii and it is classified as “Data Deficient” by the IUCN (IUCN, 2013; Schwitzer et al., 2013). Despite the management of the area by the NGO Fanamby since 2005, no study had been conducted to determine the presence and the abundance of L. milanoii in the main forest fragments of the region. During the 2011 dry season we surveyed the ten main forest fragments of the Loky-Manambato region and estimated L. milanoii densities and population sizes using line transect distance sampling (Buckland, 2001) and the DISTANCE software (Thomas et al., 2010). The results suggest that sportive lemur densities are reasonably high in the region, but with important discrepancies between forest fragments, with densities ranging from 49.8 ind./km² in Antsaharaingy to 590.5 ind./km² in Ampondrabe. For the region Loky-Manambato we were able to estimate a population size of 52,000 individuals. This is the first estimate for the total population size and we argue that similar studies should be repeated to monitor environmental changes and anthropogenic pressures (hunting, deforestation, mining, etc.).FCT grant: (SFRH/BD/64875/2009); the Groupement de Recherche International (GDRI); "Laboratoire d’Excellence" (LABEX) entitled TULIP : (ANR-10-LABX-41); Rufford Small Grant Foundation grant: (10941-1)

Molecular cloning and functional characterization of brefeldin A-ADP-ribosylated substrate. A novel protein involved in the maintenance of the Golgi structure.

Brefeldin A (BFA) is a fungal metabolite that disassembles the Golgi apparatus into tubular networks and causes the dissociation of coatomer proteins from Golgi membranes. We have previously shown that an additional effect of BFA is to stimulate the ADP-ribosylation of two cytosolic proteins of 38 and 50 kDa (brefeldin A-ADP-riboslyated substrate (BARS)) and that this effect greatly facilitates the Golgi-disassembling activity of the toxin. In this study, BARS has been purified from rat brain cytosol and microsequenced, and the BARS cDNA has been cloned. BARS shares high homology with two known proteins, C-terminal-binding protein 1 (CtBP1) and CtBP2. It is therefore a third member of the CtBP family. The role of BARS in Golgi disassembly by BFA was verified in permeabilized cells. In the presence of dialyzed cytosol that had been previously depleted of BARS or treated with an anti-BARS antibody, BFA potently disassembled the Golgi. However, in cytosol complemented with purified BARS, or even in control cytosols containing physiological levels of BARS, the action of BFA on Golgi disassembly was strongly inhibited. These results suggest that BARS exerts a negative control on Golgi tubulation, with important consequences for the structure and function of the Golgi complex

On spontaneous scalarization

We study in the physical frame the phenomenon of spontaneous scalarization that occurs in scalar-tensor theories of gravity for compact objects. We discuss the fact that the phenomenon occurs exactly in the regime where the Newtonian analysis indicates it should not. Finally we discuss the way the phenomenon depends on the equation of state used to describe the nuclear matter.Comment: 41 pages, RevTex, 10 ps figures, submitted to Phys. Rev.