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We discuss Tsallis holographic dark energy (THDE) model in higher dimension. An interacting dark energy model is proposed with Generalized Chaplygin Gas (GCG) in the framework of Compact Kaluza-Klein gravity. It is shown that a stable configuration can be found in the present epoch which is also compatible with the observed value of the density parameter. It is noted that dark energy (DE) might have evolved from a phantom phase in the past. Nature of dark energy is found to depend on the coupling parameter of the interaction. Classical stability consideration is also found to put an upper bound on the model parameter.

Solar cells based on hybrid perovskites have shown high efficiency while possessing simple processing methods. To gain a fundamental understanding of their properties on an atomic level, we investigate single crystals of CH 3 NH 3 PbI 3 with a narrow transition (~5 K) near 327 K. Temperature dependent structural measurements reveal a persistent tetragonal structure with smooth changes in the atomic displacement parameters (ADPs) on crossing T*. We show that the ADPs for I ions yield extended flat regions in the potential wells consistent with the measured large thermal expansion parameter. Molecular dynamics simulations reveal that this material exhibits significant asymmetries in the Pb-I pair distribution functions. We also show that the intrinsically enhanced freedom of motion of the iodine atoms enables large deformations. This flexibility (softness) of the atomic structure results in highly localized atomic relaxation about defects and hence accounts for both the high carrier mobility as well as the structural instability.

Hippocampal dysfunction in schizophrenia is widely acknowledged, yet the mechanism of such dysfunction remains debated. In this study we investigate the excitatory and inhibitory hippocampal neurotransmission using two complementary methodologies, proton magnetic resonance spectroscopy (MRS) and tissue biochemistry, sampling individuals with schizophrenia in vivo and postmortem hippocampal tissue in vitro . The results show significantly lower glutamate concentrations in hippocampus in schizophrenia, an in vivo finding mirrored by lower GluN1 protein levels selectively in the dentate gyrus (DG) in vitro . In a mouse model with a DG knockout of the GRIN1 gene, we further confirmed that a selective decrease in DG GluN1 is sufficient to decrease the glutamate concentrations in the whole hippocampus. Gamma-aminobutyric acid (GABA) concentrations and GAD67 protein were not significantly different in hippocampus in schizophrenia. Similarly, GABA concentrations in the hippocampi of mice with a DG knockout of the GRIN1 gene were not significantly different from wild type. These findings provide strong evidence implicating the excitatory system within hippocampus in the pathophysiology of schizophrenia, particularly indicating the DG as a site of pathology.

Mice with a mutation in the Clock gene ( Clock Δ19) have been identified as a model of mania; however, the mechanisms that underlie this phenotype, and the changes in the brain that are necessary for lithium’s effectiveness on these mice remain unclear. Here, we find that cholecystokinin ( Cck ) is a direct transcriptional target of CLOCK and levels of Cck are reduced in the ventral tegmental area (VTA) of Clock Δ19 mice. Selective knockdown of Cck expression via RNA interference in the VTA of wild-type mice produces a manic-like phenotype. Moreover, chronic treatment with lithium restores Cck expression to near wild-type and this increase is necessary for the therapeutic actions of lithium. The decrease in Cck expression in the Clock Δ19 mice appears to be due to a lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription, an effect reversed by lithium. Human postmortem tissue from bipolar subjects reveals a similar increase in Cck expression in the VTA with mood stabilizer treatment. These studies identify a key role for Cck in the development and treatment of mania, and describe some of the molecular mechanisms by which lithium may act as an effective antimanic agent.

Neuronal firing is a fundamental element of cerebral function; and, voltage-gated potassium (K + ) channels regulate that firing through the repolarization of action potentials. Kv3-type channels (Kv3.1–Kv3.4) represent a family of voltage-gated K + channels that have fast-spiking properties. Kv3.1 channel subunits are predominantly localized to cortical parvalbumin (PV)-positive, inhibitory interneurons. The firing properties of these interneurons participate in establishing the normal gamma oscillations and synchrony of cortical neuronal populations, thought to be the signature of higher information processing in human brain. Schizophrenia (SZ) is associated with abnormalities in cortical gamma synchrony and in information processing, particularly with dysfunction in working memory and executive function. Here, we report the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical areas, whereas Kv3.2 is abundantly represented in neo- and subcortical regions. In SZ cases, levels of Kv3.1b protein are decreased in the neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels are normal in antipsychotic-treated cases. Kv3.2 is not different in distribution or in level between normal and SZ cases, nor influenced by APD, in any region tested. The apparent increase in Kv3.1b protein levels by APDs in SZ neocortex was confirmed in laboratory rodents treated with chronic APDs. These findings show a decrease in Kv3.1b channel protein in SZ neocortex, a deficit that is restored by APDs. This alteration could be fundamentally involved in the cortical manifestations of SZ and in the therapeutic response to APDs.

CCAAT/enhancer-binding protein-δ (C/EBP-δ), a transcription factor, is elevated in carcinoma compared with that in normal tissue. This study reports a novel function of C/EBP-δ in lymphangiogenesis and tumor metastasis. Genetic deletion of C/EBP-δ in mice resulted in a significant reduction of lymphangiogenesis and pulmonary metastases, with a dramatic reduction of vascular endothelial growth factor-C (VEGF-C) and its cognate receptor VEGF receptor-3 (VEGFR3) in lymphatic endothelial cells (LECs). By contrast, no difference of VEGF-C in tumor tissues and bone marrow was observed between null and wild-type mice. Consistently, forced expression of C/EBP-δ increased VEGF-C and VEGFR3 expression in cultured LECs. These findings suggest a specific and important role of C/EBP-δ in the regulation of VEGFR3 signaling in LECs. Furthermore, expression of C/EBP-δ in cultured LECs significantly increased cell motility, and knockdown of C/EBP-δ inhibited cell motility and lymphatic vascular network formation in vitro . Forced expression of VEGF-C, but not recombinant VEGF-C, rescued the knockdown of C/EBP-δ-induced cell apoptosis, indicative of autonomous VEGF-C autocrine signaling essential for LEC survival. Moreover, hypoxia induces C/EBP-δ expression and C/EBP-δ regulates HIF-1α expression. Blocking HIF-1α activity totally blocked CEBP-δ-induced VEGF-C and VEGFR3 expression in LECs. Together, these findings uncover a new function of CEBP-δ in lymphangiogenesis through regulation of VEGFR3 signaling in LECs.

Clinical studies report associations between cannabis use during adolescence and later onset of schizophrenia. We examined the causal relationship between developmental cannabinoid administration and long-term behavioral and molecular alterations in mice. Mice were administered either WIN 55,212-2 (WIN), a cannabinoid receptor 1 (CB1) agonist or vehicle (Veh) during adolescence (postnatal day 30–35) or early adulthood (postnatal day 63–70). Behavioral testing was conducted after postnatal day 120 followed by biochemical assays. Adolescent cannabinoid treatment (ACU) leads to deficits in prepulse inhibition and fear conditioning in adulthood. Metabotropic glutamate receptors type 5 (mGluR5), a receptor critically involved in fear conditioning and endocannabinoid (eCB) signaling, is significantly reduced in the ACU mouse hippocampus. Next, we examined expression profiles of genes involved in eCB synthesis (diacylglycerol lipase (DGL)) and uptake (monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH)) in the experimental mice. We find evidence of increased MGL and FAAH in ACU mice, reflecting increases in eCB uptake and degradation. These data suggest that administration of cannabinoids during adolescence leads to a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations in sensorimotor gating and hippocampal-dependent learning and memory deficits. Further, these deficits are associated with a reduction in hippocampal mGluR5 and a sustained change in eCB turnover, suggesting reduced eCB signaling in the ACU hippocampus. These data suggest that significant cannabis use during adolescence may be a contributory causal factor in the development of certain features of schizophrenia and may offer mGluR5 as a potential therapeutic target.

We analyze the dynamics of squeezing in a ballistic quantum wire with Rashba spin-orbit interaction in the presence of both strong and weak magnetic fields and for different initial states of the system. Compared to the more standard measure of squeezing based on variances, we show that entropy squeezing is a more sensitive measure. Our results show that there is a strong relationship between the spin-orbit interaction and the strength of entropy squeezing. Furthermore, there is a relationship between the initial state and the number of squeezed components. This allows new knobs to control the strength and the component of entropy squeezing in a nanowire system.

BH3 interacting-domain death agonist (Bid) is a BH3-only pro-apoptotic member of the Bcl-2 family of proteins. Its function in apoptosis is associated with the proteolytic cleavage to the truncated form tBid, mainly by caspase-8. tBid translocates to mitochondria and assists Bax and Bak in induction of apoptosis. c-Jun N-terminal kinase (JNK)-dependent alternative processing of Bid to jBid was also reported. We have previously shown that the folate stress enzyme 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) activates JNK1 and JNK2 in cancer cells as a pro-apoptotic response. Here we report that in PC-3 prostate cancer cells, JNK1/2 phosphorylate Bid at Thr59 within the caspase cleavage site in response to ALDH1L1. In vitro , all three JNK isoforms, JNK 1–3, phosphorylated Thr59 of Bid with JNK1 being the least active. Thr59 phosphorylation protected Bid from cleavage by caspase-8, resulting in strong accumulation of the full-length protein and its translocation to mitochondria. Interestingly, although we did not observe jBid in response to ALDH1L1 in PC-3 cells, transient expression of Bid mutants lacking the caspase-8 cleavage site resulted in strong accumulation of jBid. Of note, a T59D mutant mimicking constitutive phosphorylation revealed more profound cleavage of Bid to jBid. JNK-driven Bid accumulation had a pro-apoptotic effect in our study: small interfering RNA silencing of either JNK1/2 or Bid prevented Bid phosphorylation and accumulation, and rescued ALDH1L1-expressing cells. As full-length Bid is a weaker apoptogen than tBid, we propose that the phosphorylation of Bid by JNKs, followed by the accumulation of the full-length protein, delays attainment of apoptosis, and allows the cell to evaluate the stress and make a decision regarding the response strategy. This mechanism perhaps can be modified by the alternative cleavage of phospho-T59 Bid to jBid at some conditions.

The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory’s (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest in assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.