A novel approach to identify driver genes involved in androgen-independent prostate cancer

Abstract Background Insertional mutagenesis screens have been used with great success to identify oncogenes and tumor suppressor genes. Typically, these screens use gammaretroviruses (γRV) or transposons as insertional mutagens. However, insertional mutations from replication-competent γRVs or transposons that occur later during oncogenesis can produce passenger mutations that do not drive cancer progression. Here, we utilized a replication-incompetent lentiviral vector (LV) to perform an insertional mutagenesis screen to identify genes in the progression to androgen-independent prostate cancer (AIPC). Methods Prostate cancer cells were mutagenized with a LV to enrich for clones with a selective advantage in an androgen-deficient environment provided by a dysregulated gene(s) near the vector integration site. We performed our screen using an in vitro AIPC model and also an in vivo xenotransplant model for AIPC. Our approach identified proviral integration sites utilizing a shuttle vector that allows for rapid rescue of plasmids in E. coli that contain LV long terminal repeat (LTR)-chromosome junctions. This shuttle vector approach does not require PCR amplification and has several advantages over PCR-based techniques. Results Proviral integrations were enriched near prostate cancer susceptibility loci in cells grown in androgen-deficient medium (p < 0.001), and five candidate genes that influence AIPC were identified; ATPAF1, GCOM1, MEX3D, PTRF, and TRPM4. Additionally, we showed that RNAi knockdown of ATPAF1 significantly reduces growth (p < 0.05) in androgen-deficient conditions. Conclusions Our approach has proven effective for use in PCa, identifying a known prostate cancer gene, PTRF, and also several genes not previously associated with prostate cancer. The replication-incompetent shuttle vector approach has broad potential applications for cancer gene discovery, and for interrogating diverse biological and disease processes.http://deepblue.lib.umich.edu/bitstream/2027.42/109477/1/12943_2014_Article_1323.pd

Developing Dementia-Friendly Tourism Destinations: An Exploratory Analysis

Dementia is emerging as a global issue. Increases in life expectancy create an older population structure with accompanying health needs but also high lifestyle expectations. For example existing generations have come to expect to be able to participate in leisure and tourism activities in later life, which can be constrained by the onset of dementia. Leading healthy lifestyles and engaging in tourism activities are viewed as fundamental to remaining active and contributing to slowing the progress of dementia. This study is the first to examine the challenges and implications of the growing scale of dementia and the business opportunities this may create for destinations wishing to achieve dementia-friendly status. The paper reports results from an initial scoping study with tourism businesses in a coastal resort in the United Kingdom with such ambitions to assess the nature of the issues that arose from a series of face-to-face interviews

Barriers to leisure participation for people with dementia and their carers: An exploratory analysis of carer and people with dementia's experiences.

Leisure has emerged as a prominent research theme within the growing body of knowledge on dementia, with a focus on physical activity. Yet participation in any form of leisure presupposes an ability to freely choose to partake in activities and to negotiate one's way around key barriers. In the case of dementia, the ability to undertake leisure activities is subject to a greater range of barriers, structured in a hierarchical manner that contributes to social exclusion if not addressed. This study based on focus groups with people with dementia and their family members conducted in Dorset, UK illustrates a range of barriers to leisure participation. How to create or maintain leisure opportunities for those living with dementia where households affected by dementia do not adopt avoidance behaviour, compounding a sense of isolation and exclusion is a challenge. Leisure can be an important strategy framed as a form of resistance to the social disabilities experienced by those living with dementia and it is potentially isolating impact

A TSC22-like motif defines a novel antiapoptotic protein family

The apoptotic programme is evolutionarily conserved between yeast and metazoan organisms. We have previously identified a number of mammalian cDNAs capable of suppressing the deleterious effects of Bax expression in yeast. We herein report that one such suppressor, named Tsc22(86), represents the C-terminal 86 amino acids of the previously characterized leucine zipper (LZ) motif-containing transcriptional regulator Tsc22. Employing a genome-wide two-hybrid screen, functional genomics, and deletion mutagenesis approaches, we conclude that Tsc22(86)-mediated antiapoptosis is independent of the LZ motif and is likely independent of effects on gene transcription. Rather, a 16-residue sequence within the conserved 56-residue TSC22 domain is necessary for antiapoptosis. The presence of a similar sequence was used to predict an antiapoptotic role for two yeast proteins, Sno1p and Fyv10p. Overexpression and knock-out experiments were used to validate this prediction. These findings demonstrate the potential of studying heterologous proteins in yeast to uncover novel biological insights into the regulation of apoptosis

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Novel materials for urban farming

Scarcity of natural resources, shifting demographics, climate change, and increasing waste are four major challenges in the quest to feed the exploding world population. These challenges serve as the impetus to harness novel technologies to improve agriculture, productivity, and sustainability. Urban farming has several advantages over conventional farming: higher productivity, improved sustainability, and the ability to provide fresh food all year round. Novel materials are key to accelerating the evolution of urban farming – with their ability to facilitate controlled release of nutrients and pesticides, improved seed health, substrates with better water retention capability, more efficient recycling of agricultural waste, and precise plant health monitoring. Materials science enables environmental sustainability and higher harvest yields in urban farms. Here, Singapore is used as an example of a land-scarce city where urban farming may be the solution for future food production. Potential research directions and challenges in urban farming are highlighted, and how material optimization and innovation drive the development of urban farming to meet national and global food demands is briefly discussed. This review serves as a guide for researchers and a reference for stakeholders of urban farms, policy makers, and other interested parties.Ministry of Education (MOE)Singapore Food AgencySubmitted/Accepted versionY.M.L. is grateful for funding support from the Ministry of Education under an AcRF Tier 1 thematic grant (No. RT09/20) and from the Panasonic Factory Solutions Asia Pacific Singapore (supported under the Singapore Food Agency Agriculture Productivity Fund)

A marketing plan for Levi\u27s Tailored Jeans

Levi Strauss Co® started in 1873. In 1972, Levi Strauss Philippines Inc® was created as the local subsidiary for the global firm. Levi\u27s®, being the pioneer in jeans has become the brand of choice for men aged 35 to 45. The brands period of existence may have contributed to the image that the brand projects, which is in contrast to the younger target market that Levi\u27s® is trying to capture. As what is evident around us, jeans has become a staple in everybodys wardrobe while Levi\u27s® has created a wide range of product lines in their efforts to penetrate the market aged 18 to 24 years old. To achieve the company\u27s objective, the group decided to create a sub-line of the Tailored Jeans® line to be known as Black Tab, the jeans specifically for the young market. The line caters to ages 18-24 from the socio-economic classes A, B and C. We aim to accomplish the following: (a) create awareness of the line among the target market and get their interest so that they would be familiar with the line and make it known to them that the Tailored Jeans® line is a product line that is created especially for them, (b) establish brand loyalty to further capture the target market an allow for a higher profitability of the brand in the market. We aim to achieve these objectives through the strategic implementation of selling strategies, advertising, public relation programs and sales promotions. A net income of Php3,033,543 is expected after the first year implementation of this marketing plan

Direct Amidation of <i>N</i>‑Boc- and <i>N</i>‑Cbz-Protected Amines via Rhodium-Catalyzed Coupling of Arylboroxines and Carbamates

<i>N</i>-Boc- and <i>N</i>-Cbz-protected amines are directly converted into amides by a novel rhodium-catalyzed coupling of arylboroxines and carbamates, replacing the traditional two-step deprotection–condensation sequence. Both protected anilines and aliphatic amines are efficiently transformed into a wide variety of secondary benzamides, including sterically hindered and electron-deficient amides, as well as in the presence of acid-labile and reducible functional groups