Magneto-resistance in a lithography defined single constrained domain wall spin valve

We have measured domain wall magnetoresistance in a single lithographically constrained domain wall. An H-shaped Ni nano-bridge was fabricated by e-beam lithography with the two sides being single magnetic do- mains showing independent magnetic switching. The connection between the sides constraining the domain wall when the sides line up anti-parallel. The magneto-resistance curve clearly identifies the magnetic con- figurations that are expected from a spin valve-like structure. The value of the magneto-resistance at room temperature is around 0.1% or 0.4 ­. This value is shown to be in agreement with a theoretical formulation based on spin accumulation. Micromagnetic simulations show it is possible to reduce the size of the domain wall further by shortening the length of the bridge

Spherically symmetric ADM gravity with variable G and Lambda(c)

This paper investigates the Arnowitt--Deser--Misner (hereafter ADM) form of spherically symmetric gravity with variable Newton parameter G and cosmological term Lambda(c). The Newton parameter is here treated as a dynamical variable, rather than being merely an external parameter as in previous work on closely related topics. The resulting Hamilton equations are obtained; interestingly, a static solution exists, that reduces to Schwarzschild geometry in the limit of constant G, describing a Newton parameter ruled by a nonlinear differential equation in the radial variable r. A remarkable limiting case is the one for which the Newton parameter obeys an almost linear growth law at large r. An exact solution for G as a function of r is also obtained in the case of vanishing cosmological constant. Some observational implications of these solutions are obtained and briefly discussed.Comment: 16 pages, 2 figures. The presentation has been improved in all section

Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death.

Autophagy has recently elicited significant attention as a mechanism that either protects or promotes cell death, although different autophagy pathways, and the cellular context in which they occur, remain to be elucidated. We report a thorough cellular and biochemical characterization of a novel selective autophagy that works as a protective cell response. This new selective autophagy is activated in pancreatic acinar cells during pancreatitis-induced vesicular transport alteration to sequester and degrade potentially deleterious activated zymogen granules. We have coined the term “zymophagy” to refer to this process. The autophagy-related protein VMP1, the ubiquitin-protease USP9x, and the ubiquitin-binding protein p62 mediate zymophagy. Moreover, VMP1 interacts with USP9x, indicating that there is a close cooperation between the autophagy pathway and the ubiquitin recognition machinery required for selective autophagosome formation. Zymophagy is activated by experimental pancreatitis in genetically engineered mice and cultured pancreatic acinar cells and by acute pancreatitis in humans. Furthermore, zymophagy has pathophysiological relevance by controlling pancreatitis-induced intracellular zymogen activation and helping to prevent cell death. Together, these data reveal a novel selective form of autophagy mediated by the VMP1-USP9x-p62 pathway, as a cellular protective response.Fil: Grasso, Daniel Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ropolo, Alejandro Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lo Ré, Andrea Emilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Boggio, Verónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Molejon, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iovanna, Juan L.. Inserm; FranciaFil: Gonzalez, Claudio D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Urrutia, Raúl. Mayo Clinic; Estados UnidosFil: Vaccaro, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study

<p>Abstract</p> <p>Background</p> <p>Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel.</p> <p>Patients/methods</p> <p>In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT) and the inhibition of platelet aggregation (IPA) by light transmission aggregometry (LTA). Arachidonic acid (0.625 mmol/L) and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L) were used as platelet agonists.</p> <p>Results</p> <p>Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis) were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32). Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L.</p> <p>Conclusion</p> <p>In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L.</p

Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease

Several epidemiological studies have shown that cigarette smoking might alter the incidence of Alzheimer’s disease. However, inconsistent results have been reported regarding the risk of Alzheimer’s disease among smokers. Previous studies in experimental animal models have reported that administration of some cigarette components (for example, nicotine) alters amyloid-b aggregation, providing a possible link. However, extrapolation of these findings towards the in vivo scenario is not straightforward as smoke inhalation involves a number of other components. Here, we analysed the effect of smoking under more relevant conditions. We exposed transgenic mouse models of Alzheimer’s disease to cigarette smoke and analysed the neuropathological alterations in comparison with animals not subjected to smoke inhalation. Our results showed that smoking increases the severity of some abnormalities typical of Alzheimer’s disease, including amyloidogenesis, neuroinflammation and tau phosphorylation. Our findings suggest that cigarette smoking may increase Alzheimer’s disease onset and exacerbate its features and thus, may constitute an important environmental risk factor for Alzheimer’s disease

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

<p>Abstract</p> <p>Background</p> <p>High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro.</p> <p>Methods</p> <p>Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM).</p> <p>Results</p> <p/> <p>In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→_{35 min}were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→_{35 min}with no effect on PTG but were independent of rFVIIa concentration.</p> <p>Conclusion</p> <p/> <p>Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications.</p

A Network of Physiological Interactions Modulating GI Homeostasis: Probiotics, Inflammasome, mTOR

The gastrointestinal surface is in constant interaction with various exogenous molecules. Exogenous components are discriminated in the GI context, as good, in case of nutrients and fibers, and bad, when they negatively affect host integrity. During this tolerogenic process, they also train the host’s immune system. The immune system is a morpho-physiologic unit driven by immune cells with the assistance of commensal organisms. Several species of commensal microorganisms have been used for centuries as probiotics due to their beneficial effects on human health. Lowering local levels of pro-inflammatory cytokines has a systemic effect, which is one of the fundamental characteristics associated with probiotics. Still, the primary mechanisms wiring those regulatory circuits as a unit remain unclear. Modulation of the innate immune system, via regulation of inflammasome assembly is emerging as a critical driver of this interaction. Stimulation of toll like receptors (TLR) and inner cell sensors like NLRP3 connect probiotics with essential host systems. In this context, the mTOR-regulated circuits, an intricate network modulating a cascade of protein phosphorylations, could be an important channel connecting host metabolism and probiotics crosstalk

Unified treatment of spin torques using a coupled magnetisation dynamics and three-dimensional spin current solver

A three-dimensional spin current solver based on a generalised spin drift-diffusion description, including the bulk and interfacial spin Hall effects, is integrated with a magnetisation dynamics solver. The resulting model is shown to simultaneously reproduce the spin-orbit torques generated using the spin Hall effect, spin pumping torques generated by magnetisation dynamics in multilayers, as well as the spin transfer torques acting on magnetisation regions with spatial gradients, whilst field-like and spin-like torques are reproduced in a spin valve geometry. Two approaches to modelling interfaces are analysed, one based on the spin mixing conductance and the other based on continuity of spin currents where the spin dephasing length governs the absorption of transverse spin components. In both cases analytical formulas are derived for the spin-orbit torques in a heavy metal / ferromagnet bilayer geometry, showing in general both field-like and damping-like torques are generated. The limitations of the analytical approach are discussed, showing that even in a simple bilayer geometry, due to the non-uniformity of the spin currents, a full three-dimensional treatment is required. The model is further applied to the analysis of the spin Hall angle in Pt by reproducing published experimental ferromagnetic resonance data in the bilayer geometry