1,721,014 research outputs found
Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism.
No full textPED/PEA-15 is a 15 kDa ubiquitously expressed protein implicated in a number of fundamental cellular functions, including apoptosis, proliferation and glucose metabolism. PED/PEA-15 lacks enzymatic function and mainly serves as a molecular adaptor. PED/PEA-15 is an endogenous substrate for protein kinase C (PKC), calcium/calmodulin-dependent protein kinase II (CAM kinase II) and Akt. In particular, PKC phosphorylates PED/PEA-15 at Ser104 and CAM kinase II or Akt at Ser116, modifying its stability. Evidence obtained over the past ten years has indicated that PED/PEA-15 regulates cell survival by interfering with both intrinsic and extrinsic apoptotic pathways. In addition, it may also control cell proliferation, by interfering with ERK1/2-mediated pathways. Indeed, PED/PEA-15 has been identified as an ERK1/2 interactor, which modifies its subcellular localization and targeting to a specific subset of substrates. Increased PED/PEA-15 levels may affect tumorigenesis and cancer progression as well as sensitivity to anti-cancer agents. Moreover, PED/PEA-15 affects astrocyte motility and increases susceptibility to skin carcinogenesis in vivo. PED/PEA-15 expression is regulated at the transcriptional and the post-translational levels. Increased PED/PEA-15 expression has been identified in individuals with type 2 diabetes early during the natural history of the disease. Evidence generated over the past ten years indicated that this defect contributes to altering glucose tolerance by impairing insulin action and insulin secretion and might play a role in the development of diabetes-associated neurological disorders. Strategies are being devised to target key signaling events in PED/PEA-15 action aiming at improving glucose tolerance and at facilitating cancer cell death
PED/PEA-15 MODULATES COXSACKIE AND ADENOVIRUS RECEPTOR (CAR) EXPRESSION AND ADENOVIRAL INFECTIVITY VIA ERK-MEDIATED SIGNALS IN GLIOMA CELLS.
No full textAbstract Aims: Glioblastoma multiforme (GBM) is the most aggressive human brain tumour, and is highly resistant to chemo and radiotherapy. Selective replicating oncolytic viruses represent a novel approach for the treatment of neoplastic diseases. Coxsackie and Adenovirus Receptor (CAR) is the primary receptor for adenoviruses, and loss or reduction of CAR greatly decreases adenoviral entry. Understanding the mechanisms regulating CAR expression and localisation will contribute to increase the efficacy of oncolytic adenoviruses. Results. Two glioma cell lines (U343MG and U373MG) were infected with the oncolytic adenovirus dl922-947. U373MG cells were more susceptible to cell death following viral infection, compared to U343MG cells. The enhanced sensitivity was paralleled by increased adenoviral entry and CAR mRNA and protein levels in U373MG cells. In addition, U373MG cells displayed decreased ERK1/2 nuclear/cytosolic ratio, compared to U343MG cells. Intracellular content of PED/PEA-15, an ERK1/2 interacting protein, was also augumented in these cells. Both ERK2 overexpression and genetic silencing of PED/PEA-15 by antisense oligonucleotides increased ERK nuclear accumulation and reduced CAR expression and adenoviral entry. Conclusions: Our data indicate that dl922-947 could represent an useful tool for the treatment of GBM and that PED/PEA-15 modulates CAR expression and adenoviral entry, by sequestering ERK1/2
GLUTAMIC ACID DECARBOXYLASE ANTIBODIES IN IDIOPATHIC GENERALIZED EPILEPSY AND TYPE 1 DIABETES.
No full textGlutamic acid decarboxylase antibodies in idiopathic generalized epilepsy and type 1 diabetes.
No full textAutoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: A study on 233 patients.
No full textAutoantibodies to glutamic acid decarboxylase (GADA) have been associated to a wide range of neurologic conditions, including epilepsy. However, the spectrum of epileptic conditions associated with GADA is not completely established. We aimed to determine the occurrence of GADA in a large series of patients with different epilepsy types. Moreover, we assessed whether specific subgroups of patients are associated to GAD autoimmunity. METHODS: GADA were measured by radioimmunoassay in a series of consecutive unselected epileptic patients observed over a 2-years-period. Patients with neuromuscular features, acute or subacute encephalopathic course, cognitive deterioration or psychiatric symptoms were excluded. RESULTS: Two hundred thirty-three patients (121 women, mean age: 29.3 years; range: 6-78) were recruited. There were eighty-three (35.6%) patients with idiopathic (66 generalized, 17 focal) epilepsy; fifty-nine (25.3%) with cryptogenic (52 focal, 7 generalized) epilepsy, and ninety-one (39.0%) with symptomatic (75 focal, 16 generalized) epilepsy. GADA were detected in six (2.58%) patients. Two had idiopathic generalized epilepsy associated with diabetes mellitus type 1 (DM1); the other four patients suffered from cryptogenic temporal epilepsy and no history or signs of DM1. GADA positive patients could not be distinguished by seizure frequency or number of AEDs. However, in these cases, the mean epilepsy duration (8.5+/-5.0 years) was shorter compared to the other 48 GADA-negative patients with cryptogenic focal epilepsy (17.3+/-9.6) (p<0.0001). CONCLUSIONS: We confirm that GAD autoimmunity may be associated with some forms of epilepsy. The preferential identification in patients with cryptogenic temporal epilepsy deserves particularly further investigation
Prostate health index vs percent free prostate-specific antigen for prostate cancer detection in men with "gray" prostate-specific antigen levels at first biopsy: systematic review and meta-analysis
No full textThe most promising approach to improve the specificity of prostate-specific antigen (PSA) test relies on the measurement of different molecular isoforms of PSA in serum. Currently, in men with a total PSA (tPSA) level between 2 and 10 ng/mL, measurement of %fPSA (free to total PSA ratio x100) is used as reflex testing to better distinguish between malignant and benign prostate disease. Recently, Beckman Coulter developed the prostate health index (PHI) and several studies suggested that this test may improve the diagnostic ability of %fPSA. We performed a meta-analysis to evaluate the usefulness of PHI compared with %fPSA in the detection of prostate cancer (PCa) at first biopsy in men with tPSA "gray" levels of 2-10 ng/mL. Data on sensitivity and specificity were extracted from 8 eligible studies. Only observational studies comparing the diagnostic ability of PHI and %fPSA in tPSA range of 2-10 ng/mL were included. A total of 8 studies involving 2969 patients with a tPSA range of 20 ng/mL undergoing first biopsy were included in this meta-analysis. Biopsy-confirmed PCa was detected in 1287 (43.3%) men. Selected studies determined both PHI and %fPSA as a reflex test. The areas under curve (AUCs) of PHI and %fPSA were 0.74 (95% confidence interval (CI), 0.70-0.77) and 0.63 (95% CI, 0.58-0.67), respectively. Meta-regression analysis confirmed the superiority of PHI which showed, compared with %fPSA, a relative diagnostic odds ratio of 2.81 (95% CI, 2.19-3.6; P < 0.0001). In conclusion, PHI instead of %fPSA as a reflex test in men with tPSA "gray" levels is a better predictor of positive first biopsy and can offer a reduction in unnecessary biopsies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease
No full textBisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health
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