Kyushu University

About: Kyushu University is a education organization based out in Fukuoka, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 68284 authors who have published 135190 publications receiving 3055928 citations. The organization is also known as: Kyūshū Daigaku.

Blockade of type β transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat

Abstract: We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could be therapeutically useful.

Positive allosteric systems designed on dynamic supramolecular scaffolds: toward switching and amplification of guest affinity and selectivity.

Abstract: Positive homotropic allosterism appears in important information transduction processes where chemical and physical signals are efficiently amplified. The phenomena are ubiquitous in nature, but the general methodology for the design of such allosteric systems is not yet established in an artificial system. This account reviews such artificial receptors that can bind guest ions and molecules in a positive allosteric manner and discusses what kinds of factors are indispensable as scaffolds in the design of this novel class of allosteric systems and what common factors are needed to realize the cooperativity. It has been shown that the scaffolds are mostly dynamic and are skillfully combined with the molecular recognition systems so that the subsequent guest binding can occur more favorably than the first guest binding. In addition, it has been suggested that positive homotropic allosterism can be utilized as a new strategy to attain high guest selectivity and guest affinity which cannot be attained by conv...

Producing Bulk Ultrafine-Grained Materials by Severe Plastic Deformation: Ten Years Later

Abstract: It is now well established that the processing of bulk solids through the application of severe plastic deformation (SPD) leads to exceptional grain refinement to the submicrometer or nanometer level. Extensive research over the last decade has demonstrated that SPD processing also produces unusual phase transformations and leads to the introduction of a range of nanostructural features, including nonequilibrium grain boundaries, deformation twins, dislocation substructures, vacancy agglomerates, and solute segregation and clustering. These many structural changes provide new opportunities for fine tuning the characteristics of SPD metals to attain major improvements in their physical, mechanical, chemical, and functional properties. This review provides a summary of some of these recent developments. Special emphasis is placed on the use of SPD processing in achieving increased electrical conductivity, superconductivity, and thermoelectricity, an improved hydrogen storage capability, materials for use in biomedical applications, and the fabrication of high-strength metal-matrix nanocomposites.

Skp2 targeting suppresses tumorigenesis by Arf-p53- independent cellular senescence

Abstract: Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19(Arf)-p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19(Arf)-p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.

SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses

Abstract: Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased T(H)2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T(H)2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.