cGMP favors the interaction between APP and BACE1 by inhibiting Rab5 GTPase activity

We previously demonstrated that cyclic guanosine monophosphate (cGMP) stimulates amyloid precursor protein (APP) and beta-secretase (BACE1) approximation in neuronal endo-lysosomal compartments, thus boosting the production of amyloid-\u3b2 (A\u3b2) peptides and enhancing synaptic plasticity and memory. Here, we further investigated the mechanism by which cGMP regulates the subcellular localization of APP and BACE1, finding that the cyclic nucleotide inhibits the activity of Rab5, a small GTPase associated with the plasma membrane and early endosomes. Accordingly, we also found that expression of a dominant-negative Rab5 mutant increases both APP-BACE1 approximation and A\u3b2 extracellular levels, therefore mimicking the effects induced by cGMP. These results reveal a functional correlation between the cGMP/A\uf062 pathway and the activity of Rab5 that may contribute to the understanding of Alzheimer\u2019s disease pathophysiology

Selective inhibition of phosphodiesterase 4D increases tau phosphorylation at Ser214 residue

Tau is a protein that normally participates in the assembly and stability of microtubules. However, it can form intraneuronal hyperphosphorylated aggregates that are hallmarks of Alzheimer's disease and other neurodegenerative disorders known as tauopathies. Tau can be phosphorylated by multiple kinases at several sites. Among such kinases, the cAMP-dependent protein kinase A (PKA) phosphorylates tau at Ser214 (pTAU-S214), an event that was shown to reduce the pathological assembly of the protein. Given that the neuronal cAMP/PKA-activated cascade is involved in synaptic plasticity and memory, and that cAMP-enhancing strategies demonstrated promising therapeutic potential for the treatment of cognitive deficits, we investigated the impact of cAMP on pTAU-S214 in N2a cells and rat hippocampal slices. Our results confirm that the activation of adenylyl cyclase increases pTAU-S214 in both model systems and, more interestingly, this effect is mimicked by GEBR-7b, a phosphodiesterase 4D inhibitor with proven pro-cognitive efficacy in rodents

Fungal communities isolated from dead apple leaves from orchards in Quebec

Le champignon causant la tavelure du pommier, Venturia inaequalis, hiverne dans les feuilles mortes de pommier (Malus pumila) sous forme de pseudothèces. Les objectifs de cette étude étaient de monter une collection de champignons afin de vérifier subséquemment leur résistance au froid et leur potentiel antagoniste contre V. inaequalis et d'acquérir des connaissances sur la microflore des feuilles mortes de pommiers. Des champignons ont été isolés sur des feuilles mortes de pommiers récoltées au printemps et à l'automne de 1993. Au total, 345 isolats fongiques provenant de 49 genres ont été identifiés. Quinze genres sont rapportés pour la première fois comme colonisateurs des feuilles de pommiers en Amérique du Nord.Venturia inaequalis, the causal agent of apple scab, overwinters in apple (Malus pumila) leaves on the orchard floor by producing pseudothecia. The objectives of this survey were to make a collection of fungi to be subsequently tested for their potential as psychrophile biocontrol agents against V. inaequalis and to acquire knowledge on the diversity of the microflora of dead apple leaves. Fungi were recovered from dead apple leaves collected in the spring and fall of 1993. A total of 345 isolates from 49 genera were identified. Fifteen gene were not previously recorded as colonizers of apple leaves in North America

Metallic Nanopillars: Selective Plasmonic Platforms Based on Nanopillars to Enhance Vibrational Sum-Frequency Generation Spectroscopy (Advanced Optical Materials 3/2013)

Molecules adsorbed on metallic nanopillars give an enhanced vibrational sum-frequency generation (SFG) signal when a localized surface plasmon resonance is excited. The metallic nanopillars, created on page 244 by D. Lis et al., possess two plasmon modes that can be selectively excited by either incident visible or generated SFG polarized laser beams. Depending on which mode is excited, the molecules adsorb either onto the vertical nanopillar wall, on top of it, or on the flat substrate. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Investigating the amyloid-beta enhancing effect of cGMP in neuro2a cells

Long-term potentiation (LTP) and the process of memory formation require activation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Notably, recent evidence indicated that both cyclic nucleotides boost the production of amyloid-beta (A\u3b2) peptides. In particular, cAMP was shown to favor hippocampal LTP by stimulating the synthesis of the amyloid precursor protein APP, whereas cGMP was found to enhance LTP and to improve memory by increasing A\u3b2 levels without affecting the expression of APP. The results of the present study substantiate that cGMP has a role in the endocytic pathway of APP and suggest a scenario where the cyclic nucleotide enhances the production of A\u3b2 by favoring the trafficking of APP from the cell cortex to the endolysosomal compartment

A high resolution electron energy loss spectroscopy study of the adsorption of benzylic amide macrocycle on Au(111)

The adsorption from the gas phase of a macrocyclic molecule composed of benzylic amide (–CONH–CH2–C6H4–) groups on Au(111) at 300 K has been studied using high resolution electron energy loss spectroscopy. The film order and vibrational properties were explored as a function of coverage, method of adlayer deposition and annealing. Beyond a critical coverage, a template effect strongly influences the macrocycle’s orientation with respect to the substrate. In the case of ordered films (domain size > 80 Å), the intensity of the out-of-plane C–H deformation mode relative to the in-plane C–H stretch indicates that an adsorption geometry with the plane of the phenyl rings largely parallel to the Au(111) surface is favoured in the submonolayer to monolayer coverage regime. Upon consideration of solid state X-ray diffraction data, this flat-lying molecular orientation, which is accompanied by chemisorption via the carbonyl function, must involve considerable distortion of the adsorbed macro cycle from its crystal structure.

Method for enhancing a sum frequency generation signal

The present invention is related to a method for spatially selecting an enhanced sum frequency generation signal comprising the steps of: - providing an adsorption substrate com prising a flat surface and metallic nanorods fixed onto the flat surface, said nanorods having an aspect ratio higher th an 1, preferably higher than 1,2 and exhibiting longitudinal and transverse plasmon modes, the excitation frequency of the longitudinal and transverse plasmon modes being different; - adsorbing molecules of interest at the surface of the adsorption substrate; - illuminating said adsorption substrate with a first and a second coherent light source which overlap on said adsorption substrate; - measuring the sum frequency light generated from the interaction between the first and the second coherent light source at the interface between the substrate and the adsorbed material, wherein the frequency of the first light source or the sum of the frequency of the first light source with the frequency of the second light source corresponds to the resonance frequency of either the transverse or the longitudinal surface plasmon mode of the nanorods, thereby selecting the signal arising from either the sidewalls of the nanorods or the end surfaces of the nanorods