Plasma Membrane-Associated Restriction Factors and Their Counteraction by HIV-1 Accessory Proteins.

The plasma membrane is a site of conflict between host defenses and many viruses. One aspect of this conflict is the host's attempt to eliminate infected cells using innate and adaptive cell-mediated immune mechanisms that recognize features of the plasma membrane characteristic of viral infection. Another is the expression of plasma membrane-associated proteins, so-called restriction factors, which inhibit enveloped virions directly. HIV-1 encodes two countermeasures to these host defenses: The membrane-associated accessory proteins Vpu and Nef. In addition to inhibiting cell-mediated immune-surveillance, Vpu and Nef counteract membrane-associated restriction factors. These include BST-2, which traps newly formed virions at the plasma membrane unless counteracted by Vpu, and SERINC5, which decreases the infectivity of virions unless counteracted by Nef. Here we review key features of these two antiviral proteins, and we review Vpu and Nef, which deplete them from the plasma membrane by co-opting specific cellular proteins and pathways of membrane trafficking and protein-degradation. We also discuss other plasma membrane proteins modulated by HIV-1, particularly CD4, which, if not opposed in infected cells by Vpu and Nef, inhibits viral infectivity and increases the sensitivity of the viral envelope glycoprotein to host immunity

Withania somnifera against glutamate excitotoxicity and neuronal cell loss in a scopolamine-induced rat model of Alzheimer’s disease

Alzheimer’s disease, a chronic and progressive neurodegenerative disorder with no prevention and cure, affecting nearly 50 million people worldwide. Glutamate is the principal excitatory neurotransmitter in the central nervous system involved in 50% of basic brain functions, especially cortical and hippocampal regions, like memory, cognition, and learning. The glutamate-mediated toxicity is termed as excitotoxicity. The present study was aimed to determine whether the methanolic and water extracts of root from the medicinal plant, Withania somnifera, could decrease the glutamate excitotoxicity and its related neuronal cell loss in a scopolamine-induced animal model of Alzheimer's disease. The rats were randomly divided into different groups of 5 in each: normal control - treated orally with saline; AD model - injected intra peritoneally with scopolamine (2 mg/Kg body wt) alone to induce Alzheimer's disease; AD model rats treated orally with the methanolic extract (AD+ME-WS) (300 mg/Kg body wt), water extract (AD+WE-WS) (300 mg/Kg body wt), and donepezil hydrochloride, a standard control (AD+DZ) (5 mg/Kg body wt) for 30 consecutive days. Increased glutamate (Glu) levels and decreased glutamate dehydrogenase (GDH) activity were reversed with Withania somnifera root extracts in both the cerebral cortex and hippocampus regions in scopolamine-induced Alzheimer's disease model rat brain. The histopathological studies of the same treatment also showed protection against neuronal cell loss in both regions. These results support the idea that these extracts could be effective for the reduction of brain damage by preventing glutamate excitotoxicity generated neuronal cell loss in the scopolamine-induced Alzheimer's disease model. DOI: http://dx.doi.org/10.5281/zenodo.442677

Accurate molecular energies by extrapolation of atomic energies using an analytic quantum mechanical model

Using a new analytic quantum mechanical method based on Slater's Xalpha method, we show that a fairly accurate estimate of the total energy of a molecule can be obtained from the exact energies of its constituent atoms. The mean absolute error in the total energies thus determined for the G2 set of 56 molecules is about 16 kcal/mol, comparable to or better than some popular pure and hybrid density functional models.Comment: 5 pages, REVTE

Metal-insulator transitions in tetrahedral semiconductors under lattice change

Although most insulators are expected to undergo insulator to metal transition on lattice compression, tetrahedral semiconductors Si, GaAs and InSb can become metallic on compression as well as by expansion. We focus on the transition by expansion which is rather peculiar; in all cases the direct gap at $\Gamma$ point closes on expansion and thereafter a zero-gap state persists over a wide range of lattice constant. The solids become metallic at an expansion of 13 % to 15 % when an electron fermi surface around L-point and a hole fermi surface at $\Gamma$-point develop. We provide an understanding of this behavior in terms of arguments based on symmetry and simple tight-binding considerations. We also report results on the critical behavior of conductivity in the metal phase and the static dielectric constant in the insulating phase and find common behaviour. We consider the possibility of excitonic phases and distortions which might intervene between insulating and metallic phases.Comment: 12 pages, 8 figure

Rat Brain Biogenic Amine Levels during Acute and Subacute Phosphamidon Treatment with Reference to Behavioral Tolerance

Organophosphate (OP) pesticides exert their toxic effects by cholinesterase inhibition and the consequent prolongation of the undesirable effects of accumulation of acetylcholine. However, sustained cholinesterase inhibition through sustained sub-acute administration of organophosphates leads to disappearance of the initial signs of toxicity, termed behavioral tolerance. The present study examines if the levels of amine neurotransmitter substances in rat brain regions are altered during acute and sub-acute treatment with an organophosphate pesticide. Phosphamidon under different time intervals was used with due reference to behavioral tolerance. Acute (1 day) and sub-acute (1 day, 7 days, 15 days) doses of phosphamidon were administered by oral intubation. Different brain regions were isolated at specific time intervals. The levels of epinephrine (EP), nor-epinephrine (NE), dopamine (DA) and serotonin (5-HT) and the activity levels of the enzyme monoamine oxidase (MAO) were determined at the specified time intervals under both acute and sub-acute dose treatments. The amine levels showed differential variations in different brain regions during acute and sub-acutetreatments, implying regional changes in catecholamine and serotonin levels during the development of OP-induced behavioral tolerance. Monoamine oxidase activity was in general inhibited in all the brain regions under both acute and sub-acute treatments. The results indicate the involvement of noncholinergic mechanisms during behavioral tolerance.  Key words: Behavioral tolerance, Biogenic amines, Phosphamidon, Ratbrai

Decisison Useful Financial Reporting Information Characteristics: An Empirical Validation of the Proposed FASB/IASB International Accounting Model

As part of a future international accounting standard, the USA Financial Accounting Standards Board and UK International Accounting Standards Board recently updated their description of the financial reporting information characteristics that determine its decision usefulness for end users. Yet the relationships inherent in the description have not been empirically validated. If invalid, the description may globally misguide future professional information efforts for a multitude of business users and decisions. A causal model is created of decision-useful financial reporting information characteristics from the description, then evaluated using partial least squares and survey data from business information users as defined by the international standard. The model significantly predicted user perceptions of key information constructs (Decision Usefulness [76%], Relevance [62%], and Faithful Representativeness [57%]; R2 values, p\u3c0.01). However, theoretically and practically important constructs (Verifiability, Completeness, Faithful Representativeness) did not significantly contribute to the model

An Expert System Approach to Audit Planning and Evaluation in the Belief-Function Framework

This is the author's final draft. The publisher's version is available from: