GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein

GABA(A) receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1alpha (PP1alpha) in facilitating GABA(A) receptor phospho-dependent regulation using PRIP-1(-/-) mice. In wild-type animals, robust phosphorylation and functional modulation of GABA(A) receptors containing beta3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1(-/-) mice. PRIP-1(-/-) mice exhibited enhanced PP1alpha activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABA(A) receptor beta subunits, and moreover, these proteins were found to be PP1alpha substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1alpha-PRIP-1 complexes, providing a local mechanism for the activation of PP1alpha. Together, these results suggest an essential role for PRIP-1 in controlling GABA(A) receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors

Nonrelativistic Superconformal M2-Brane Theory

We investigate the low energy physics of particles in the symmetric phase of the N=6 mass-deformed ABJM theory in terms of the superconformal nonrelativistic field theory with 14 supercharges. They describe the certain kind of excitations on M2 branes in the background of external four-form flux. We study the nonrelativistic superconformal algebra and their representations by using the operator-state correspondence with the related harmonic oscillator Hamiltonian. We find the unitarity bounds on the scaling dimension and particle number of any local operator, and comment on subtleties in computing the superconformal Witten index that counts the chiral operators.Comment: 34 pages, 1 figure, latex, some minor corrections, remarks on flux-charge composite operators, bps bound changed, charge-flux operator reargue

Prognostic Significance of Angiogenesis by Chalkley Counting in Node Negative Cancer of the Ampulla of Vater

Angiogenesis is essential for tumor growth and metastasis. Currently, the Chalkley assay with CD34 immunostaining is the proposed standard method for angiogenesis quantification in solid tumor sections. The purpose of this study was to evaluate the expression of CD34 and its prognostic significance using the Chalkley method in node negative carcinoma of the ampulla of Vater. Between January 1997 and December 2006, 56 node negative patients who had curative resection for carcinoma of the ampulla of Vater were retrospectively reviewed. The Chalkley count was expressed as the mean value of the three counts for each tumor and further divided into two groups according to the mean value of the Chalkley count: low < 4 or high ≥ 4. The mean Chalkley count value was 4.0 (± 3.1). In the low Chalkley group, the 1- and 3-yr recurrence rates were 18.3%, 47.6% respectively; in the high Chalkley group, the 1- and 3-yr recurrence rates were 26.5% and 60.6% respectively. Only high Chalkley count had statistical significance as a factor in recurrence of node negative ampulla of Vater carcinoma. Assessment of angiogenesis may have an important role in the prognostic evaluation of node negative cancer of the ampulla of Vater

Aspects of Non-minimal Gauge Mediation

A large class of non-minimal gauge mediation models, such as (semi-)direct gauge mediation, predict a hierarchy between the masses of the supersymmetric standard model gauginos and those of scalar particles. We perform a comprehensive study of these non-minimal gauge mediation models, including mass calculations in semi-direct gauge mediation, to illustrate these features, and discuss the phenomenology of the models. We point out that the cosmological gravitino problem places stringent constraints on mass splittings, when the Bino is the NLSP. However, the GUT relation of the gaugino masses is broken unlike the case of minimal gauge mediation, and an NLSP other than the Bino (especially the gluino NLSP) becomes possible, relaxing the cosmological constraints. We also discuss the collider signals of the models.Comment: 56 pages, 8 figures; v2:minor corrections, references added; v3:minor correction

Phosphodiesterase 4D Gene and Risk of Noncardiogenic Ischemic Stroke in a Korean Population

Recently published studies from different populations provide apparently conflicting evidence on the association between the phosphodiesterase 4D (PDE4D) gene and ischemic stroke. The relationship between a representative PDE4D genotype and ischemic stroke was explored in a case-control study of 205 consecutive Korean patients with noncardiogenic ischemic stroke and 103 healthy controls who were neurologically and radiologically proven to be stroke-free. We selected and genotyped a PDE4D single nucleotide polymorphism (SNP 41, rs152312) as a candidate marker for susceptibility to ischemic stroke because SNP 41 has shown the most significant association with stroke in both a meta-analysis and the original Icelandic study of the PDE4D gene. No significant difference was observed between the cases and controls in the distribution of the PDE4D SNP 41 genotypes. The results from the adjusted conditional logistic regression analysis (adjusted for age, hypertension, diabetes and smoking status) showed no significant association between PDE4D SNP 41 genotypes and an increased risk of noncardiogenic ischemic stroke. The PDE4D gene is not a major risk factor for noncardiogenic ischemic stroke in a Korean population, which supports the recent evidence suggesting that the causative genetic variants of ischemic stroke may differ across populations

FBXW7 E3 ubiquitin ligase: degrading, not degrading, or being degraded

https://deepblue.lib.umich.edu/bitstream/2027.42/152265/1/13238_2019_Article_652.pd

Catalytic ozone oxidation of benzene at low temperature over MnOx/Al-SBA-16 catalyst

The low-temperature catalytic ozone oxidation of benzene was investigated. In this study, Al-SBA-16 (Si/Al = 20) that has a three-dimensional cubic Im3m structure and a high specific surface area was used for catalytic ozone oxidation for the first time. Two different Mn precursors, i.e., Mn acetate and Mn nitrate, were used to synthesize Mn-impregnated Al-SBA-16 catalysts. The characteristics of these two catalysts were investigated by instrumental analyses using the Brunauer-Emmett-Teller method, X-ray diffraction, X-ray photoelectron spectroscopy, and temperature-programmed reduction. A higher catalytic activity was exhibited when Mn acetate was used as the Mn precursor, which is attributed to high Mn dispersion and a high degree of reduction of Mn oxides formed by Mn acetate than those formed by Mn nitrate

Cks1 Is Required for Tumor Cell Proliferation but Not Sufficient to Induce Hematopoietic Malignancies

The Cks1 component of the SCFSkp2 complex is necessary for p27Kip1 ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27Kip1 levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27Kip1 levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27Kip1. To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo

Protective Immunity Against Challenge Infection with Trichinella spiralis in the Rat

Protective immunity and immune response were studied in rats after primarily infection with Trichinella spiralis. The parameters measured include serum antibody isotype responses, mesenteric lymph node (MLN) cell and spleen cell proliferation responses in vitro, and the levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-10 as markers of the T-helper (Th) subset. Protective immunity was assessed by the degree of expulsion of adult worms from the rat intestine. Protective immunity against adult worms after challenge infection was 99.80%. Although IFN-γ, IL-2, IL-4 and IL-10 in both the MLNs and spleen were detected, IFN-γ and IL-2 levels were higher in the spleen than in the MLNs, and IL-4 and an increased amount of IL-10 was released in the MLNs as compared to the spleen. The levels of the specific immunoglobulins (Ig) G, IgM, IgG1 and IgG2a on week 6 after primary infection, and on day 7 after challenge infection, were higher as compared to levels in uninfected rats that only received a challenge infection (P ? 0.001), whereas the antibody level of IgG1 was significantly elevated from that of IgG2a (P ? 0.001). These results demonstrate that Th1 type responses predominated. In addition, as Th2 type cytokines were also produced, it is proposed that the protective immunity by primary infection was also related to the Th1 type responses

Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2

INTRODUCTION: Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. METHODS: 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression of markers in duplicate tumor and stroma cores. PRINCIPAL FINDINGS: In univariate analyses, low tumor cell expression of Ang-4 (P = 0.046) and low stromal expressions of Ang-4 (P = 0.009) and Ang-2 (P = 0.017) were individually associated with a poor survival. In the multivariate analysis, low stromal Ang-2 (HR 1.88; CI 95% 1.15-3.08) and Ang-4 (HR 1.47, CI 95% 1.02-2.11, P = 0.04) expressions were independently associated with a poor prognosis. In patients with high tumor cell expression of Ang-2, a concomitantly high tumor VEGF-A expression mediated a dramatic survival reduction (P<0.001). In the multivariate analysis of patients with high Ang-2 expression, high tumor VEGF-A expression appeared an independent poor prognosticator (HR 6.43; CI 95% 2.46-16.8; P<0.001). CONCLUSIONS: In tumor cells, only Ang-4 expression has prognostic impact in NSCLC. In tumor stroma, Ang-4 and Ang-2 are independently associated with survival. The prognostic impact of tumor cell VEGF-A in NSCLC appears strongly associated with a concomitantly high tumor cell expression of Ang-2