Excitatory amino acid transporters in physiology and disorders of the central nervous system

Excitatory amino acid transporters (EAATs) encompass a class of five transporters with distinct expression in neurons and glia of the central nervous system (CNS). EAATs are mainly recognized for their role in uptake of the amino acid glutamate, the major excitatory neurotransmitter. EAATs-mediated clearance of glutamate released by neurons is vital to maintain proper glutamatergic signalling and to prevent toxic accumulation of this amino acid in the extracellular space. In addition, some EAATs also act as chloride channels or mediate the uptake of cysteine, required to produce the reactive oxygen speciesscavenger glutathione. Given their central role in glutamate homeostasis in the brain, as well as their additional activities, it comes as no surprise that EAAT dysfunctions have been implicated in numerous acute or chronic diseases of the CNS, including ischemic stroke and epilepsy, cerebellar ataxias, amyotrophic lateral sclerosis, Alzheimer´s disease and Huntington´s disease. Here we review the studies in cellular and animal models, as well as in humans that highlight the roles of EAATs in the pathogenesis of these devastating disorders. We also discuss the mechanisms regulating EAATs expression and intracellular trafficking and new exciting possibilities to modulate EAATs and to provide neuroprotection in course of pathologies affecting the CNS

Productivity and economic evaluation of Willow (Salix alba L.) based silvopastoral agroforestry system in Kashmir valley

Performance of two fodder crops namely, sorghum (Sorghum vulgare L.) and maize (Zea mays L.) was investigated with Willow (Salix alba L.) to evaluate productivity and economics of the silvopastoral agroforestry system in Kashmir valley. The experiment was laid out by planting two year old willows at 2.0m × 2.0m spacing and dividing the main plot into sub-plots of size 8m × 2m each with 5 replications in randomized block design (RDB). The intercrops of sorghum and maize were maintained at 20cm × 10 cm spacing and supplied with recommended doses of fertilizers. The economics of the willow plantation intercropped with fodder crops was compared with sole willow farming by the benefit-cost ratio and net present worth. The study revealed the differential behaviour of Salix alba regarding growth parameters (height, diameter and girth) by different intercrops and various fodder intercrops with respect to yield, above ground biomass, dry matter production and soil nutrient status (pH, organic carbon, available nitrogen, phosphorus and potassium). The willow based silvopastoral system was estimated to have benefit-cost ratio of 2.71 with maize and 2.68 with sorghum, while as sole crop the willows accrued a benefit-cost ratio of 2.66. The study is useful in discovering growth of willows, productivity of fodder crops and soil nutrient status under various silvopastoral agroforestry systems for maximizing economic gains. The findings envisaged evidences in favour of adopting willow based silvopastoral agroforestry instead of sole tree farming and the knowledge of interactions will be helpful in proper management of the system for sustained multiple productions

Practical tools for third order cosmological perturbations

We discuss cosmological perturbation theory at third order, deriving the gauge transformation rules for metric and matter perturbations, and constructing third order gauge invariant quantities. We present the Einstein tensor components, the evolution equations for a perfect fluid, and the Klein-Gordon equation at third order, including scalar, vector and tensor perturbations. In doing so, we also give all second order tensor components and evolution equations in full, exhilarating generality.Comment: 17 pages, revtex4; v2: corresponds to version published in JCA

Generalized Assisted Inflation

We obtain a new class of exact cosmological solutions for multi-scalar fields with exponential potentials. We generalize the assisted inflation solutions previously obtained, and demonstrate how they are modified when there exist cross-couplings between the fields, such as occur in supergravity inspired cosmological models.Comment: 5 page

SORCS1 and SORCS3 control energy balance and orexigenic peptide production

SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin-related kinase B to attenuate signaling by brain-derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti-related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight. Our findings highlight a novel concept in regulation of the melanocortin system and the role played by trafficking receptors SORCS1 and SORCS3 in this process

Multiple field inflation

Inflation offers a simple model for very early evolution of our Universe and the origin of primordial perturbations on large scales. Over the last 25 years we have become familiar with the predictions of single-field models, but inflation with more than one light scalar field can alter preconceptions about the inflationary dynamics and our predictions for the primordial perturbations. I will discuss how future observational data could distinguish between inflation driven by one field, or many fields. As an example, I briefly review the curvaton as an alternative to the inflaton scenario for the origin of structure.Comment: 27 pages, no figures. To appear in proceedings of 22nd IAP Colloquium, Inflation +25, Paris, June 200

SorCS2 facilitates release of endostatin from astrocytes and controls post-stroke angiogenesis

SorCS2 is an intracellular sorting receptor of the VPS10P domain receptor gene family recently implicated in oxidative stress response. Here, we interrogated the relevance of stress-related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy brain, expression of SorCS2 was massively induced in astrocytes surrounding the ischemic core in mice following stroke. Post-stroke induction was likely a result of increased levels of transforming growth factor β1 in damaged brain tissue, inducing Sorcs2 gene transcription in astrocytes but not neurons. Induced astrocytic expression of SorCS2 was also seen in stroke patients, substantiating the clinical relevance of this observation. In astrocytes in vitro and in the mouse brain in vivo, SorCS2 specifically controlled release of endostatin, a factor linked to post-stroke angiogenesis. The ability of astrocytes to release endostatin acutely after stroke was lost in mice deficient for SorCS2, resulting in a blunted endostatin response which coincided with impaired vascularization of the ischemic brain. Our findings identified activated astrocytes as a source for endostatin in modulation of post-stroke angiogenesis, and the importance of the sorting receptor SorCS2 in this brain stress response

Large non-Gaussianity from two-component hybrid inflation

We study the generation of non-Gaussianity in models of hybrid inflation with two inflaton fields, (2-brid inflation). We analyse the region in the parameter and the initial condition space where a large non-Gaussianity may be generated during slow-roll inflation which is generally characterised by a large f_NL, tau_NL and a small g_NL. For certain parameter values we can satisfy tau_NL>>f_NL^2. The bispectrum is of the local type but may have a significant scale dependence. We show that the loop corrections to the power spectrum and bispectrum are suppressed during inflation, if one assume that the fields follow a classical background trajectory. We also include the effect of the waterfall field, which can lead to a significant change in the observables after the waterfall field is destabilised, depending on the couplings between the waterfall and inflaton fields.Comment: 16 pages, 6 figures; v2: comments and references added, typos corrected, matches published versio

Affleck-Dine baryogenesis with modulated reheating

Modulated reheating scenario is one of the most attractive models that predict possible detections of not only the primordial non-Gaussianity but also the tensor fluctuation through future CMB observations such as the Planck satellite, the PolarBeaR and the LiteBIRD satellite experiments. We study the baryonic-isocurvature fluctuations in the Affleck-Dine baryogenesis with the modulated reheating scenario. We show that the Affleck-Dine baryogenesis can be consistent with the modulated reheating scenario with respect to the current observational constraint on the baryonic-isocurvature fluctuations.Comment: 7 page