Developmental functions of the P120-catenin sub-family

AbstractFor more than a decade, cell, developmental and cancer investigators have brought about a wide interest in the biology of catenin proteins, an attraction being their varied functions within differing cellular compartments. While the diversity of catenin localizations and roles has been intriguing, it has also posed a challenge to the clear interpretation of loss- or gain-of-function developmental phenotypes. The most deeply studied member of the larger catenin family is beta-catenin, whose contributions span areas including cell adhesion and intracellular signaling/ transcriptional control. More recently, attention has been directed towards p120-catenin, which in conjunction with the p120-catenin sub-family members ARVCF- and delta-catenins, are the subjects of this review. Although the requirement for vertebrate versus invertebrate p120-catenin are at variance, vertebrate p120-catenin sub-family members may each inter-link cadherin, cytoskeletal and gene regulatory functions in embryogenesis and disease

Complications of nephrotic syndrome

Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS

Non-practising entities (NPEs) and patent remedies for future infringement

This research establishes a new patent remedy (injunction) system against future infringements in such a way as to discourage trolling behaviours of non-practising entities (NPEs) without chilling inventors’ incentives to innovate. For this research target, this thesis reviewed the general characteristics of NPEs in the current and past patent system, the current patent remedy laws in different countries (the US, UK and Germany), the patent holdups caused by NPEs’ patent enforcement against manufacturers, and various solutions which have been proposed so far. In doing so, it addresses important findings that the major cause of NPE problems stems from the inherent uncertainty nature of patent, that the courts’ discretion of whether to grant or deny an injunction needs to be clearly defined, and that the new injunction system should skilfully balance the short-term as well as the long-term transaction costs which are caused by NPEs’ patent enforcements. Considering these findings, this thesis proposes a new injunction model, alias a ‘three-tiered remedy system.’ Unlike the present two-tiered system, it divides the remedies into three different types: (1) granting an unqualified injunction against wilful infringers; (2) granting a suspended injunction against innocent infringers; and (3) denying injunctions in exceptional circumstances. The most differentiated feature of this model is to award a suspended injunction as a default remedy in order to mitigate the patent holdup arising from the uncertainty problem of patent. Since the suspension period is determined in proportion to the required time for designing around the infringed patent, this new model can provide a very useful solution to mitigate the harmful effect of NPEs’ patent enforcement without jeopardizing the integrity of exclusive right of patent at the same time

The Light and Period Variations of the Eclipsing Binary AA Ursae Majoris

We present new multiband CCD photometry for AA UMa made on 8 nights between January and March 2009; the $R$ light curves are the first ever compiled. Historical light curves, as well as ours, display partial eclipses and inverse O'Connell effects with Max I fainter than Max II. Among possible spot models, a cool spot on either of the component stars and its variability with time permit good light-curve representations for the system. A total of 194 eclipse timings over 81 yrs, including our five timings, were used for ephemeris computations. We found that the orbital period of the system has varied due to a periodic oscillation overlaid on an upward parabolic variation. The continuous period increase at a fractional rate of $+$1.3$\times$10$^{-10}$ is consistent with that calculated from the W-D code and can be interpreted as a thermal mass transfer from the less to the more massive secondary star at a rate of 6.6$\times$10$^{-8}$ M$_\odot$ yr$^{-1}$. The periodic component is in satisfactory accord with a light-time effect due to an unseen companion with a period of 28.2 yrs, a semi-amplitude of 0.007 d, and a minimum mass of $M_3 \sin i_3$=0.25 $M_\odot$ but this period variation could also arise from magnetic activity.Comment: 23 pages, including 5 figures and 8 tables, accepted for publication in PAS

Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

Visfatin Induces Sickness Responses in the Brain

BACKGROUND/OBJECTIVE: Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity. METHODOLOGY: Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated. PRINCIPAL FINDINGS: Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity. CONCLUSIONS: Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain