<Emphasis Type="Italic">lin-12</Emphasis> Notch functions in the adult nervous system of <Emphasis Type="Italic">C. elegans</Emphasis>

Background  

Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion.     

Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain

Background  

The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus).     

Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants

Background  

Amyloid precursor protein (APP) is enzymatically cleaved by γ-secretase to form two peptide products, either Aβ40 or the more neurotoxic Aβ42. The Aβ42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD). The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains.     

Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

Background  

Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.     

Signalling crosstalk in FGF2-mediated protection of endothelial cells from HIV-gp120

Background  

The blood brain barrier (BBB) is the first line of defence of the central nervous system (CNS) against circulating pathogens, such as HIV. The cytotoxic HIV protein, gp120, damages endothelial cells of the BBB, thereby compromising its integrity, which may lead to migration of HIV-infected cells into the brain. Fibroblast growth factor 2 (FGF2), produced primarily by astrocytes, promotes endothelial cell fitness and angiogenesis. We hypothesized that treatment of human umbilical vein endothelial cells (HUVEC) with FGF2 would protect the cells from gp120-mediated toxicity via endothelial cell survival signalling.     

GABA<Subscript>A</Subscript>receptor γ2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines

Background  

Gamma-aminobutyric acid type A receptors (GABA_A-Rs) are the major inhibitory receptors in the mammalian brain and are modulated by a number of sedative/hypnotic drugs including benzodiazepines and anesthetics. The significance of specific GABA_A-Rs subunits with respect to behavior and in vivo drug responses is incompletely understood. The γ2 subunit is highly expressed throughout the brain. Global γ2 knockout mice are insensitive to the hypnotic effects of diazepam and die perinatally. Heterozygous γ2 global knockout mice are viable and have increased anxiety-like behaviors. To further investigate the role of the γ2 subunit in behavior and whole animal drug action, we used gene targeting to create a novel mouse line with attenuated γ2 expression, i.e., γ2 knockdown mice.     

Human neuronal stargazin-like proteins, γ2, γ3 and γ4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.

Background  

Stargazin (γ₂) and the closely related γ₃, and γ₄ transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC) γ subunits and transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA) receptor regulatory proteins (TARPs). In this investigation, we examined the distribution patterns of the stargazin-like proteins γ₂, γ₃, and γ₄ in the human central nervous system (CNS). In addition, we investigated whether human γ₂ or γ₄ could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes.     

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

Background  

Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity.     

Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC), BDNF, and TrkB mRNA expression in the rat tongue

Background  

In rodents, dietary Na⁺ deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na⁺ stimulation. However, in the rat taste bud cells Na⁺ deprivation increases the number of amiloride sensitive epithelial Na⁺ channels (ENaC), which are considered as the "receptor" of the Na⁺ component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ) in taste buds were observed from rats fed with diets containing either 0.03% (Na⁺ deprivation) or 1% (control) NaCl for 15 days, by using in situ hybridization and real-time quantitative RT-PCR (qRT-PCR). Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na⁺ deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined.     

Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction

Background  

Taste receptor cells are responsible for transducing chemical stimuli into electrical signals that lead to the sense of taste. An important second messenger in taste transduction is IP₃, which is involved in both bitter and sweet transduction pathways. Several components of the bitter transduction pathway have been identified, including the T2R/TRB taste receptors, phospholipase C β2, and the G protein subunits α-gustducin, β3, and γ13. However, the identity of the IP₃ receptor subtype in this pathway is not known. In the present study we used immunocytochemistry on rodent taste tissue to identify the IP₃ receptors expressed in taste cells and to examine taste bud expression patterns for IP₃R3.     

New insight into the role of the β3 subunit of the GABA<Subscript>A</Subscript>-R in development,behavior, body weight regulation,and anesthesia revealed by conditional gene knockout

Background  

The β3 subunit of the γ-aminobutyric acid type A receptor (GABA_A-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.     

Quartic gauge couplings and the radiation zero in?pp→l±νγγ?events at the LHC

We report a study of the process pp→l^±νγγ at CERN’s Large Hadron Collider, using a leading order partonic-level event generator interfaced to the Pythia program for showering and hadronisation and a with a generic detector simulation. The process is sensitive to possible anomalous quartic gauge boson couplings of the form WWγγ. It is shown how unitarity-safe limits may be placed on these anomalous couplings by applying a binned maximum likelihood fit to the distribution of the two-photon invariant mass, M _γγ, below a cutoff of ∼1 TeV. Assuming 30 fb⁻¹ of integrated luminosity, the expected limits are two orders of magnitude tighter than those available from LEP. It is also demonstrated how the Standard Model radiation zero feature of the q [`(q)]^￠?W\upgamma\upgamma\bar{\mathrm{q}}^{\prime}\to\mathrm {W}\upgamma\upgamma process may be observed in the difference between the two-photon and charged lepton pseudo-rapidities.     

Effect of top quark spin on the unparticle couplings in $\gamma\gamma \to t\bar{t}$

We investigate the potential of γ γ collisions to probe scalar unparticle couplings via top–antitop quark pair production. We find 95% confidence level limits on the unparticle couplings with an integrated luminosity of 500 fb⁻¹ and an energy of  TeV. We investigate the effect of the top quark spin polarization on the unparticle couplings. It is shown that spin polarization of the top quark leads to a significant improvement in the sensitivity limits.     

Age-related waning of in vitro Interferon-γ levels against r32kDaBCG in BCG vaccinated children

Background  

Mycobacterium bovis BCG vaccine has displayed inconsistent efficacy in different trials conducted in various geographical regions. Nevertheless, it significantly reduces the risk of severe childhood tuberculosis and continues to be used to prevent tuberculosis in many countries. Many studies revealed that efficacy of vaccine wanes with age. Most of the studies were based on in vivo and in vitro responses to tuberculin. With the advent of newer tests such as in vitro interferon-γ assays and identification of potent immunogenic mycobacterial proteins there is a need to corroborate the observations. This study aims at ascertaining the need for a booster at a later age as indicated by in vitro release of IFN-γ while evaluating Ag85A as an antigen.     

Unparticle searches through gamma–gamma scattering

We investigate the effects of unparticles on γγ→γγ scattering for the photon collider mode of the future multi-TeV e⁺e^- linear collider. We show the effects of unparticles on the differential, and total scattering cross sections for different polarization configurations. Considering 1-loop standard model background contributions from the charged fermions and W^± bosons to the cross section, we calculate the upper limits on the unparticle couplings λ₀ to the photons for various values of the scaling dimension d (1<d<2) at = 0.5–5 TeV.     

Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls

Background  

The exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC) and 40 healthy subjects (HC) and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures.