The Influence Of Job Insecurity On Career Commitment And Attitude In Multinational Corporations

As the perception of lifelong work shifts into lifelong career in the job insecurity market, the career development of employees through professional and competitive career management has become more important than being loyal to a lifelong work. Furthermore, in the case of multinational corporations, such as differentiation from the head office policy, cultural differences in labor relations, and the liquidity of business withdrawal, such a feature has a higher possibility of job insecurity than general companies. Therefore, the purpose of this study is to verify empirically how job insecurity influences career commitment and career attitude through individual, job and career characteristics as intermediation with the members of multinational corporations as objectives. For this purpose, a total of 366 questionnaire data that targeted 27 multinational corporations were collected and analyzed. The result shows that the job insecurity of multinational corporations affects individual characteristic rather than job or career characteristic, and it is confirmed that individual characteristic has an effect on career commitment and career attitude. In the end, multinational corporations, unlike ordinary domestic companies, need active organizational career development program that corresponds to an open corporate culture as well as innovative and open systems and policies that balance both internal and external networking activities in terms of human resource management of corporations

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Alternative Embryo Transfer on Day 3 or Day 5 for Reducing the Risk of Multiple Gestations

Purpose: This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos. Methods: All zygotes were cocultured with cumulus cells in 10 ¹l of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro. Results: The number of embryos transferred in period II was 2.9 ± 0.6, while that in period I was 3.7 ± 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%). Conclusions: We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations

Transcriptomic Analysis of High Fat Diet Fed Mouse Brain Cortex

High fat diet can lead to metabolic diseases such as obesity and diabetes known to be chronic inflammatory diseases with high prevalence worldwide. Recent studies have reported cognitive dysfunction in obese patients is caused by a high fat diet. Accordingly, such dysfunction is called “type 3 diabetes” or “diabetic dementia.” Although dysregulation of protein-coding genes has been extensively studied, profiling of non-coding RNAs including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) has not been reported yet. Therefore, the objective of this study was to obtain profiles of diverse RNAs and determine their patterns of alteration in high fat fed brain cortex compared to normal brain cortex. To investigate regulatory roles of both coding and non-coding RNAs in high fat diet brain, we performed RNA sequencing of ribosomal RNA-depleted RNAs and identified genome-wide lncRNAs and circRNAs expression and co-expression patterns of mRNAs in high fat diet mouse brain cortex. Our results showed expression levels of mRNAs related to neurogenesis, synapse, and calcium signaling were highly changed in high fat diet fed cortex. In addition, numerous differentially expressed lncRNAs and circRNAs were identified. Our study provides valuable expression profiles and potential function of both coding and non-coding RNAs in high fat diet fed brain cortex

NFATc1 regulates the transcription of DNA damage-induced apoptosis suppressor

AbstractDNA damage induced apoptosis suppressor (DDIAS), or human Noxin (hNoxin), is strongly expressed in lung cancers. DDIAS knockdown induced apoptosis in non-small cell lung carcinoma A549 cells in response to DNA damage, indicating DDIAS as a potential therapeutic target in lung cancer. To understand the transcriptional regulation of DDIAS, we determined the transcription start site, promoter region, and transcription factor. We found that DDIAS transcription begins at nucleotide 212 upstream of the DDIAS translation start site. We cloned the DDIAS promoter region and identified NFAT2 as a major transcription factor (Im et al., 2016 [1]). We demonstrated that NFATc1 regulates DDIAS expression in both pancreatic cancer Panc-1 cells and lung cancer cells

Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells

Background: In breast cancer, the HER2/neu oncoprotein, which belongs to the epidermal growth factor receptor family, may trigger activation of the phosphoinositide-3 kinase (PI3K)/Akt pathway, which controls cell proliferation, survival, migration, and invasion. In this study, we examined the question of whether or not adenine nucleotide translocase 2 (ANT2) short hairpin RNA (shRNA)-mediated down-regulation of HER2/neu and inhibitory effects on the PI3K/Akt signaling pathway suppressed migration and invasiveness of breast cancer cells. Methods: We utilized an ANT2 vector-based RNA interference approach to inhibition of ANT2 expression, and the HER2/neu-overexpressing human breast cancer cell line, SK-BR3, was used throughout the study. Results: In this study, ANT2 shRNA decreased HER2/neu protein levels by promoting degradation of HER2/neu protein through dissociation from heat shock protein 90 (HSP90). As a result, ANT2 shRNA induced inhibitory effects on the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling by ANT2 shRNA caused down-regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells. Conclusions: These results indicate that knock-down of ANT2 by shRNA down-regulates HER2/neu through suppression of HSP90`s function and inhibits the PI3K/Akt signaling pathway, resulting ultimately in suppressed migration and invasion of breast cancer cells.Wang S, 2009, MOL CANCER, V8, DOI 10.1186/1476-4598-8-81MAHMUT Y, 2009, CANC METASTASIS REV, V28, P15Jang JY, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr1857Ono M, 2006, CLIN CANCER RES, V12, P7242, DOI 10.1158/1078-0432.CCR-06-0646Stirling PC, 2006, NAT STRUCT MOL BIOL, V13, P865, DOI 10.1038/nsmb1153Le Bras M, 2006, CANCER RES, V66, P9143, DOI 10.1158/0008-5472.CAN-05-4407Scaltriti M, 2006, CLIN CANCER RES, V12, P5268, DOI 10.1158/1078-0432.CCR-06-1554ERIC I, 2006, AM J PHYSIOL-CELL PH, V291, P579Romond EH, 2005, NEW ENGL J MED, V353, P1673Piccart-Gebhart MJ, 2005, NEW ENGL J MED, V353, P1659Chevrollier A, 2005, J BIOENERG BIOMEMBR, V37, P307, DOI 10.1007/s10863-005-8642-5Meares GP, 2004, FEBS LETT, V574, P181, DOI 10.1016/j.febslet.2004.08.026Sreedhar AS, 2004, FEBS LETT, V562, P11Citri A, 2004, CELL CYCLE, V3, P51Luciakova K, 2003, J BIOL CHEM, V278, P30624, DOI 10.1074/jbc.M303530200Rao JS, 2003, NAT REV CANCER, V3, P489, DOI 10.1038/nrc1121Val JFF, 2002, CANCER GENET CYTOGEN, V138, P69GARCIARUIZ C, 2002, J BIOL CHEM, V277, P16396Slamon DJ, 2001, NEW ENGL J MED, V344, P783Prenzel N, 2001, ENDOCR-RELAT CANCER, V8, P11Braun S, 2001, CANCER RES, V61, P1890Xu WP, 2001, J BIOL CHEM, V276, P3702Sternlicht MD, 2001, ANNU REV CELL DEV BI, V17, P463Greenlee RT, 2001, CA-CANCER J CLIN, V51, P15Fang JM, 2000, P NATL ACAD SCI USA, V97, P3884Clynes RA, 2000, NAT MED, V6, P443Zhou BP, 2000, J BIOL CHEM, V275, P8027Menard S, 2000, J CELL PHYSIOL, V182, P150Cobleigh MA, 1999, J CLIN ONCOL, V17, P2639Pegram MD, 1998, J CLIN ONCOL, V16, P2659Fiore C, 1998, BIOCHIMIE, V80, P137WOLFGANG HS, 1998, J CELL BIOL, V143, P901Werb Z, 1997, CELL, V91, P439Baselga J, 1996, J CLIN ONCOL, V14, P737CORNELIUS LA, 1995, J INVEST DERMATOL, V105, P170HANEMAAIJER R, 1993, BIOCHEM J, V296, P803UNEMORI EN, 1990, J BIOL CHEM, V265, P445MIGNATTI P, 1989, J CELL BIOL, V108, P671SLAMON DJ, 1987, SCIENCE, V235, P177

Soybeans Ameliolate Diabetic Nephropathy in Rats

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented