The tumour-suppressive function of CLU is explained by its localisation and interaction with HSP60

The product of the CLU gene promotes or inhibits tumourigenesis in a context-dependent manner. It has been hypothesised that different CLU isoforms have different and even opposing biological functions, but this theory has not been experimentally validated. Here we show that molecules involved in survival pathways are differentially modulated by the intracellular or secreted forms of CLU. Secreted CLU, which is selectively increased after transformation, activates the survival factor AKT, whereas intracellular CLU inhibits the activity of the oncogenic transcription factor nuclear factor kappa B. Furthermore, intracellular CLU is inactivated by the pro-proliferative and pro-survival activity of the chaperone protein HSP60 in neuroblastoma cells by forming a physical complex. Thus, localisation is key for CLU physiology, explaining the wide range of effects in cell survival and transformation

Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers

Recent studies have suggested that epigenetic inactivation of tumour-related genes by promoter methylation participates in the development of gastric cancer. We newly identified the frequently aberrant promoter methylation of alpha-1B-adrenergic receptor (ADRA1B) in colorectal cancer by methylation-sensitive representational difference analysis (MS-RDA) and examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumours showed ADRA1B promoter methylation. In contrast, ADRA1B promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRA1B promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription–PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRA1B promoter is frequently methylated in gastric cancer. Our results suggest that the ADRA1B gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer

CUP-1 Is a Novel Protein Involved in Dietary Cholesterol Uptake in Caenorhabditis elegans

Sterols transport and distribution are essential processes in all multicellular organisms. Survival of the nematode Caenorhabditis elegans depends on dietary absorption of sterols present in the environment. However the general mechanisms associated to sterol uptake in nematodes are poorly understood. In the present work we provide evidence showing that a previously uncharacterized transmembrane protein, designated Cholesterol Uptake Protein-1 (CUP-1), is involved in dietary cholesterol uptake in C. elegans. Animals lacking CUP-1 showed hypersensitivity to cholesterol limitation and were unable to uptake cholesterol. A CUP-1-GFP fusion protein colocalized with cholesterol-rich vesicles, endosomes and lysosomes as well as the plasma membrane. Additionally, by FRET imaging, a direct interaction was found between the cholesterol analog DHE and the transmembrane “cholesterol recognition/interaction amino acid consensus” (CRAC) motif present in C. elegans CUP-1. In-silico analysis identified two mammalian homologues of CUP-1. Most interestingly, CRAC motifs are conserved in mammalian CUP-1 homologous. Our results suggest a role of CUP-1 in cholesterol uptake in C. elegans and open up the possibility for the existence of a new class of proteins involved in sterol absorption in mammals

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model

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Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic

Perceived managerial and leadership effectiveness in a Korean context: An indigenous qualitative study

Multinational corporations (MNCs) across the world have sent an increasing number of managers abroad to leverage unprecedented opportunities in the era of globalization. However, their failure rate has been above 33% for decades, resulting in substantial costs (Puck, Kittler, & Wright, 2008). One of the primary reasons for this failure is a lack of understanding of the national and organizational cultures within the host countries (Festing & Maletzky, 2011). For example, while a number of MNCs have entered the Korean market, several such as Yahoo, Motorola, and Walmart have failed and withdrawn due to the companies’ lack of adjustment to the Korean cultural context (Choe, 2006; Woo, 2013). In spite of the significance of culturally embedded practices, most researchers who have explored management and leadership in Asian countries, whether they were Western or indigenous researchers, have implemented studies using extant Western management and leadership theories derived within the Western cultural context (Leung, 2007; Tsui, 2006). Numerous scholars have claimed that this could be problematic because the findings of such studies may not be applicable to non-Western countries (Li, 2012; Liden & Antonakis, 2009), and may fail to provide insights and understanding of novel contexts or to reveal indigenous aspects of management and leadership (Tsui, 2007). Consequently, there have been increasing calls for indigenous management and leadership research within Asian countries (see Li et al., 2014; Lyles, 2009; Tsui, 2004; Wolfgramm, Spiller, & Voyageur, 2014). Over the past 30 years, managerial effectiveness and leadership effectiveness have been substantially neglected areas of management research (Noordegraaf & Stewart, 2000; Yukl, Gordon, & Taber, 2002). In addition, there has been little agreement on what specific behaviors distinguish effective managers from ineffective ones. Furthermore, more research is needed to examine the managerial and leadership behaviors that are critical for shaping the performance of individuals, groups and organizations (see Borman & Brush, 1993; Cammock, Nilakant & Dakin, 1995; Mumford, 2011; Noordegraaf & Stewart, 2000; Yukl et al., 2002). While most of the research related to managerial and leadership effectiveness has been conducted in the U.S., the few notable non-U.S. studies include that of Cammock et al. (1995) in New Zealand who developed a behavioral lay model of managerial effectiveness using the repertory grid technique. Another notable exception is the cumulative series of perceived managerial and leadership effectiveness studies conducted by Hamlin with various indigenous co-researchers in Western and non-Western countries (see Hamlin & Patel, 2012; Ruiz, Wang, & Hamlin, 2013) using Flanagan’s (1954) critical incident technique (CIT)

Characterization of poly(ethylene oxide)-b-poly(L-laciide) block copolymer by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

A poly(ethylene oxide)-b-poly(L-lactide) diblock copolymer (PEO-b-PLLA) is characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and a block length distribution map is constructed. Although the MALDI-TOF mass spectrum of PEO-b-PLLA is very complicated, most of the polymer species were identified by isolating the overlapped isotope patterns and by fitting the overlapped peaks to the Schulz-Zimm distribution function. Reconstructed MALDI-TOF MS spectrum was nearly identical to the measured spectrum and this method shows its potential to be developed as an easy and fast analysis method of low molecular weight block copolymers.X1110sciescopuskc