Functional interaction between Env oncogene from Jaagsiekte sheep retrovirus and tumor suppressor Sprouty2

<p>Abstract</p> <p>Background</p> <p>Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus capable of transforming target cells <it>in vitro </it>and <it>in vivo</it>. The Envelope <it>(Env) </it>gene from JSRV and from related retroviruses can induce oncogenic transformation, although the detailed mechanism is yet to be clearly understood. Host cell factors are envisaged to play a critical determining role in the regulation of <it>Env</it>-mediated cell transformation.</p> <p>Results</p> <p>JSRV <it>Env</it>-mediated transformation of a lung adenocarcinoma cell line induced rapid proliferation, anchorage-independent growth and tumor formation, but completely abrogated the migration ability. An analysis of the signaling scenario in the transformed cells suggested the involvement of the ERK pathway regulated by Sprouty2 in cell migration, and the PI3K-Akt and STAT3 pathways in proliferation and anchorage-independence. On the other hand, in a normal lung epithelial cell line, <it>Env</it>-mediated transformation only decreased the migration potential while the other functions remained unaltered. We observed that <it>Env </it>induced the expression of a tumor suppressor, Sprouty2, suggesting a correlation between <it>Env</it>-effect and Sprouty2 expression. Overexpression of Sprouty2 <it>per se </it>not only decreased the migratory potential and tumor formation potential of the target cells but also made them resistant to subsequent <it>Env</it>-mediated transformation. On the other hand, over expression of the functional mutants of Sprouty2 had no inhibitory effect, confirming the role of Sprouty2 as a tumor suppressor.</p> <p>Conclusions</p> <p>Our studies demonstrate that <it>Env </it>and Sprouty2 have a functional relationship, probably through shared signaling network. Sprouty2 functions as a tumor suppressor regulating oncogenic transformation of cells, and it therefore has the potential to be exploited as a therapeutic anti-cancer agent.</p

Sustainabilitas Arsitektur Masjid: Evaluasi Konsep “Simple Architecture” sebagai Implementasi Desain Arsitektur Berkelanjutan suatu Kawasan

Makalah ini membahas aspek-aspek “kesederhanaan” (simplicity) sebagai konsep desain bangunan masjid secara berkelanjutan (sustainable) sesuai konteks dengan mengambil studi kasus masjid kawasan Al-Irsyad Satya Kota Baru Parahyangan, Bandung. Masjid sebagai subyek arsitektur dan pusat ibadah menjadi ruang publik yang didesain dari elemen-elemen yang secara ideal mengandung nilai-nilai Islam dan bertujuan mendukung fungsinya. Desain masjid berkonsep simple atau “sederhana” digunakan sebagai alternatif kontemporer untuk mengoptimalisasi fungsi tersebut, meliputi struktur bangunan hingga biaya pemeliharaan (maintenance) sesuai prinsip keberlanjutan. Keterkaitan erat bangunan masjid dengan aktivitas masyarakat berpotensi melibatkan partisipasi masyarakat dan pengelola dalam menerapkan program sustainabilitas sesuai konteks lingkungannya. Metode yang digunakan dalam penelitian ini berbasis pendekatan Grounded Theory secara kualitatif melalui pengumpulan data dari kegiatan observasi, interview dan analisis program keberlanjutan kawasan. Penelitian menemukan keterkaitan konsep “sederhana” yang mendukung sustainabilitas desain sekaligus menggarisbawahi evaluasi konsep desain “sederhana” yang hadir serta faktor pemeliharaan/pengembangan masjid dan kawasan

A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting

<p>Abstract</p> <p>Objective</p> <p>To evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan.</p> <p>Methods</p> <p>This was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day) over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day) at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I) score, the Clinical Global Impression scale Severity (CGI-S) score, The Brief Psychiatry Rating Scale (BPRS), and the Quality of Life (QOL) scale, as well as Preference of Medicine (POM) ratings by patients and caregivers. Safety and tolerability were also assessed.</p> <p>Results</p> <p>A total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2%) completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs) were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3%) discontinued treatment due to AEs. No statistically significant changes were noted with respect to fasting plasma glucose, lipid profile, body weight, and body mass index after long-term treatment with aripiprazole.</p> <p>Conclusions</p> <p>Although the discontinuation rate was high, aripiprazole was found to be effective, safe and well tolerated in the long-term treatment of Taiwanese patients with schizophrenia who continued to receive treatment for 64 weeks.</p

Effect of Catalyst Morphology on the Quality of CVD Grown Graphene

The strong interest in graphene has motivated large effort in the scalable production of high-quality material. The potential of chemical vapor deposition on Cu foil to produce such graphene is impeded by lacking understanding of the relation between catalyst properties and graphene performance. We here present a systematic analysis of the catalyst morphology and its effect on electrical properties of graphene. We find that nanometer sized particles increase the density of bilayer regions but have no significant effect on carrier transport. Long wavelength roughness (waviness), on the other hand, generates defective graphitic regions that deteriorate carrier mobility. These findings shed light on the graphene formation process on Cu substrates and open a route to improve graphene quality for electronics applications

Utilization of IκB–EGFP Chimeric Gene as an Indicator to Identify Microbial Metabolites with NF-κB Inhibitor Activity

NF-κB regulates several important expressions, such as cytokine release, anti-apoptosis, adhesion molecule expression, and cell cycle processing. Several NF-κB inhibitors have been discovered as an anti-tumor or anti-inflammatory drug. The activity of NF-κB transcription factor is negatively regulated by IκB binding. In this study, IκB assay system was established and IκB–EGFP fusion protein was used as an indicator to monitor the effects of substances on the IκB degradation. The results indicated that the chosen hydroquinone could inhibit the IκB degradation and cause the cell de-attachment from the bottom of culture plate. In addition, this system could also monitor the IκB degradation of microbial metabolite of natural mixtures of propolis. Thus, the IκB assay system may be a good system for drug discovery related to microbial metabolite

Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas

The objective of this study is to examine the efficacy and tolerability of miglitol with respect to improving glycemic control in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment. This was a randomized, double-blinded, placebo-controlled, multicenter study. A total of 105 patients were randomized to receive 24 weeks of treatment with miglitol (n = 52; titrated from 50 mg to 100 mg 3 times daily) or placebo (n = 53). Concomitant sulfonylurea treatment and diet remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline at 24 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and postprandial serum insulin (PSI). The miglitol treatment group showed significantly greater reductions in HbA1c and PPG levels compared with the placebo group. With respect to adverse events, abdominal discomfort, diarrhea, and hypoglycemia occurred with similar frequency in both groups. Results of this study indicate that miglitol significantly improves metabolic control in Chinese patients with type 2 diabetes mellitus. Miglitol is safe and well tolerated, with the exception of abdominal discomfort. Therefore, miglitol may be a useful adjuvant therapy for Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment

BPR1K653, a Novel Aurora Kinase Inhibitor, Exhibits Potent Anti-Proliferative Activity in MDR1 (P-gp170)-Mediated Multidrug-Resistant Cancer Cells

Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells.BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats.BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments

Y-chromosomal STRs haplotypes in the Taiwanese Paiwan population

The distribution of Y-chromosomal short tandem repeat (Y-STR) haplotypes was determined in a population of Taiwanese Paiwan aboriginals. Using 17 Y-STR markers, a total of 135 haplotypes were observed, 102 of which were unique. The overall haplotype diversity for the 17 Y-STR loci tested was 0.9922 and the discrimination capacity was 0.6490. In addition, three novel intermediate alleles at the DYS448 locus were also found