Acidic pH shock induces the expressions of a wide range of stress-response genes

<p>Abstract</p> <p>Background</p> <p>Environmental signals usually enhance secondary metabolite production in <it>Streptomycetes </it>by initiating complex signal transduction system. It is known that different sigma factors respond to different types of stresses, respectively in <it>Streptomyces </it>strains, which have a number of unique signal transduction mechanisms depending on the types of environmental shock. In this study, we wanted to know how a pH shock would affect the expression of various sigma factors and shock-related proteins in <it>S. coelicolor </it>A3(2).</p> <p>Results</p> <p>According to the results of transcriptional and proteomic analyses, the major number of sigma factor genes were upregulated by an acidic pH shock. Well-studied sigma factor genes of <it>sigH </it>(heat shock), <it>sigR </it>(oxidative stress), <it>sigB </it>(osmotic shock), and <it>hrdD </it>that play a major role in the secondary metabolism, were all strongly upregulated by the pH shock. A number of heat shock proteins including the DnaK family and chaperones such as GroEL2 were also observed to be upregulated by the pH shock, while their repressor of <it>hspR </it>was strongly downregulated. Oxidative stress-related proteins such as thioredoxin, catalase, superoxide dismutase, peroxidase, and osmotic shock-related protein such as vesicle synthases were also upregulated in overall.</p> <p>Conclusion</p> <p>From these observations, an acidic pH shock was considered to be one of the strongest stresses to influence a wide range of sigma factors and shock-related proteins including general stress response proteins. The upregulation of the sigma factors and shock proteins already found to be related to actinorhodin biosynthesis was considered to have contributed to enhanced actinorhodin productivity by mediating the pH shock signal to regulators or biosynthesis genes for actinorhodin production.</p

More than 7-year survival of a patient following repeat hepatectomy for total 20 colon cancer liver metastases

A 54-year-old man was transferred with sigmoid colon cancer combined with multiple bilobar liver metastases. Nine metastases were in the left lobe and 5 metastases were in the right lobe. After low anterior resection, all 9 lesions in the left lobe were completely removed by wedge resections. Because the remnant liver volume after multiple wedge resection of the left lobe was not sufficient to perform a right hepatectomy simultaneously, we planned a two-stage hepatectomy. Right portal vein embolization was performed one week after the first liver operation. A right hepatectomy was safely performed 22 days after the first hepatectomy. A recurrent mass developed in the segment III 18 months after the right hepatectomy. Radiofrequency ablation (RFA) was performed to remove that lesion. Five other metastases developed 18 months after RFA whereby multiple wedge resections were performed. The patient has survived for more than 7 years after the first liver operation

Anti-biofouling Coating by Wrinkled, Dual-roughness Structures of Diamond-like Carbon (DLC)

The textured surface with superhydrophobic nature was explored for an anti-biofouling template. Hierarchical structures composed of the nano-scale wrinkle covering on micro-scale polymer pillar patterns were fabricated by combining the deposition of a thin coating layer of biocompatible diamond-like carbon (DLC) and the replica molding of poly-(dimethylsiloxane) (PDMS) micro-pillars. The as-prepared surfaces were shown to have extreme hydrophobicity (static contact angle > 160 degrees) owing to low surface energy (24.2 mN/m) and dual-roughness structures of the DLC coating. It was explored that the hierarchical surfaces showed poor adhesion of the Calf Pulmonary Artery Endothelial (CPAE) cells for cultures of 7 days suggesting that the 3-dimensional (3-D) patterned superhydrophobic DLC coating exhibits excellent anti-biofouling properties against non-specific cell adhesion. In particular, the reduced filopodia extension during cell growth was caused by disconnected focal adhesions on the pillar pattern. This limited cell adhesion could prevent undesired growth and proliferation of biological species on the surface of biomedical devices such as stents, implants or even injection syringes.This work was supported by Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2007-000-20675-0), the Micro Thermal System Research Center of Seoul National University, and the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (Grant KRF-J03003). This work was supported in part by a grant (06K1501-01610) from the CNMT under the 21st Century Frontier R&D Programs of MEST of Korea (MWM, KRL)

Vascular effects of estrogen in type II diabetic postmenopausal women

AbstractOBJECTIVESWe assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women.BACKGROUNDThere is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen.METHODSWe administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design.RESULTSCompared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 ± 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 ± 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 ± 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 ± 48% and lower glycosylated hemoglobin levels by 3 ± 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 ± 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 ± 46% and 5 ± 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 ± 31% (p = 0.043).CONCLUSIONSThe effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels

Direct Reprogramming of Rat Neural Precursor Cells and Fibroblasts into Pluripotent Stem Cells

Background: Given the usefulness of rats as an experimental system, an efficient method for generating rat induced pluripotent stem (iPS) cells would provide researchers with a powerful tool for studying human physiology and disease. Here, we report direct reprogramming of rat neural precursor (NP) cells and rat embryonic fibroblasts (REF) into iPS cells by retroviral transduction using either three (Oct3/4, Sox2, and Klf4), four (Oct3/4, Sox2, Klf4, and c-Myc), or five (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) genes. Methodology and Principal Findings: iPS cells were generated from both NP and REF using only three (Oct3/4, Sox2, and Klf4) genes without c-Myc. Two factors were found to be critical for efficient derivation and maintenance of rat iPS cells: the use of rat instead of mouse feeders, and the use of small molecules specifically inhibiting mitogen-activated protein kinase and glycogen synthase kinase 3 pathways. In contrast, introduction of embryonic stem cell (ESC) extracts induced partial reprogramming, but failed to generate iPS cells. However, when combined with retroviral transduction, this method generated iPS cells with significantly higher efficiency. Morphology, gene expression, and epigenetic status confirmed that these rat iPS cells exhibited ESC-like properties, including the ability to differentiate into all three germ layers both in vitro and in teratomas. In particular, we found that these rat iPS cells could differentiate to midbrain-like dopamine neurons with a high efficiency. Conclusions/Significance: Given the usefulness of rats as an experimental system, our optimized method would be useful for generating rat iPS cells from diverse tissues and provide researchers with a powerful tool for studying human physiology and disease

A Long-Term Treatment Outcome of Abdominal Sacrocolpopexy

Purpose: The aim of this study was to evaluate the long-term treatment outcome and major complication rates of abdominal sacrocolpopexy (ASC). Materials and Methods: This retrospective study included 57 Korean women who underwent ASC with mesh for symptomatic uterine or vault prolapse and attended follow-up visits for at least 5 years. Forty-seven women with urodynamic stress incontinence concomitantly received a modified Burch colposuspension. The long-term anatomical and functional outcomes and complication rates were assessed. Results: The median follow-up was 66 months (range 60-108). Overall anatomical success rates (no recurrence of any prolapse ≥ stage II according to the pelvic organ prolapse-quantification system) were 86.0%. Urinary urgency and voiding dysfunction were significantly improved after surgery, however, recurrent stress urinary incontinence developed in 44.7 % (21/47) of cases and half of them developed within 1-3 months post-op. Bowel function (constipation and fecal incontinence) and sexual function (sexual activity and dyspareunia) did not significantly change after surgery. Major complication requiring reoperation or intensive care developed in 12 (21.0%) cases. Conclusion: ASC provides durable pelvic support, however, it may be ineffective for alleviating pelvic floor dysfunction except for urinary urgency and voiding dysfunction, and it contains major complication risk that cannot be overlooked