Draft Genome Sequence of Streptomyces incarnatus NRRL8089, which Produces the Nucleoside Antibiotic Sinefungin

A draft genome sequence of Streptomyces incarnatus NRRL8089, which produces the nucleoside antibiotic sinefungin, is described here. The genome contains 8,897,465 bp in 76 contigs and 8,266 predicted genes. Interestingly, the genome encodes an open reading frame for selenocysteine-containing formate dehydrogenase-O and the selenoprotein biosynthetic gene cluster selABCD

Pengaruh Pemberian Momentum Pada Artificial Neural Network Backpropagation

Salah satu algoritma Artificial Neural Network (ANN) yang biasa digunakan adalah algoritmabackpropagation dengan pola model gradient descent pada proses pembelajarannya. Akan tetapi,gradient descent memiliki kelemahan yaitu tidak mudah digunakan dan terkadang lambat dalampengkonvergenan solusinya. Untuk mengatasi kelemahan tersebut dilakukan suatu modifikasi yaitudengan memberikan momentum pada Perubahan bobotnya. Pada proses prediksi surface roughnesspada CNC Milling menggunakan ANN Backpropagation dengan momentum pada Perubahan bobotini, nilai rata-rata persentase error yang dihasilkan pada masing-masing nilai momentum yangdiberikan adalah tidak banyak mengalami Perubahan. Namun jika nilai momentum yang diberikanmendekati nilai maksimal momentum yaitu mendekati nilai satu maka akan menyebabkanterjadinya overshoot. Pemberian momentum pada Perubahan bobot menyebabkan Perubahan yangcukup besar yaitu pada waktu prosesnya, semakin besar nilai momentum yang diberikan makasemakin cepat pula waktu proses yang dibutuhkan. Hal ini berarti jika ingin waktu prosesprediksinya menjadi cepat maka gunakan nilai momentum yang besar, namun sebaiknya kurangdari 0.9

Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet

Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver

Clinical and Biological Overlap between Schizophrenia, Autism Spectrum Disorder, and Trauma and Stress-Related Disorders: The Three-Tree Model of SCZ-ASD-TSRD

There is significant overlap in the clinical and neurobiological profiles of schizophrenia (SCZ), autism spectrum disorder (ASD), and trauma- and stress-related disorders (TSRDs); moreover, they often co-occur as comorbid disorders. Although current international classification criteria and those in the psychiatry/psychology field recognize such comorbidities, the assessment and treatment of these patients are provided as independent disorders. In this chapter, we summarize the current understanding of the attributes shared by the three disorders and discuss the possible contributors to the development of SCZ, ASD, and TSRD, which include environmental, genetic, and biological factors. We also propose a three-tree model that represents the clinical and biological relationships among the three diseases as a new perspective for assessing and treating these disorders. A comprehensive understanding of these disorders will enable improvements in medical care for patients with these illnesses

Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway

Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling

悪性褐色細胞腫患者の生存と化学療法の効果

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Switching and Emergence of CTL Epitopes in HIV-1 Infection

Background Human Leukocyte Antigen (HLA) class I restricted Cytotoxic T Lymphocytes (CTLs) exert substantial evolutionary pressure on HIV-1, as evidenced by the reproducible selection of HLA-restricted immune escape mutations in the viral genome. An escape mutation from tyrosine to phenylalanine at the 135th amino acid (Y135F) of the HIV-1 nef gene is frequently observed in patients with HLA-A*24:02, an HLA Class I allele expressed in ~70% of Japanese persons. The selection of CTL escape mutations could theoretically result in the de novo creation of novel epitopes, however, the extent to which such dynamic “CTL epitope switching” occurs in HIV-1 remains incompletely known. Results Two overlapping epitopes in HIV-1 nef, Nef126-10 and Nef134-10, elicit the most frequent CTL responses restricted by HLA-A*24:02. Thirty-five of 46 (76%) HLA-A*24:02-positive patients harbored the Y135F mutation in their plasma HIV-1 RNA. Nef codon 135 plays a crucial role in both epitopes, as it represents the C-terminal anchor for Nef126-10 and the N-terminal anchor for Nef134-10. While the majority of patients with 135F exhibited CTL responses to Nef126-10, none harboring the “wild-type” (global HIV-1 subtype B consensus) Y135 did so, suggesting that Nef126-10 is not efficiently presented in persons harboring Y135. Consistent with this, peptide binding and limiting dilution experiments confirmed F, but not Y, as a suitable C-terminal anchor for HLA-A*24:02. Moreover, experiments utilizing antigen specific CTL clones to recognize endogenously-expressed peptides with or without Y135F indicated that this mutation disrupted the antigen expression of Nef134-10. Critically, the selection of Y135F also launched the expression of Nef126-10, indicating that the latter epitope is created as a result of escape within the former. Conclusions Our data represent the first example of the de novo creation of a novel overlapping CTL epitope as a direct result of HLA-driven immune escape in a neighboring epitope. The robust targeting of Nef126-10 following transmission (or in vivo selection) of HIV-1 containing Y135F may explain in part the previously reported stable plasma viral loads over time in the Japanese population, despite the high prevalence of both HLA-A*24:02 and Nef-Y135F in circulating HIV-1 sequences