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61.
Primary culture, cellular stress and differentiated function 总被引:1,自引:0,他引:1
Isolation of specialized cell types for the analysis of tissue-specific gene function often results in loss of the differentiated phenotype. Examples of this type of phenotypic change following tissue disaggregation are reviewed together with possible explanations. Close similarities between the effects of cell isolation with those of other cellular stresses such as heat or anoxia point to common biochemical mechanisms being involved. This suggests that the study of freshly isolated cells will contribute significantly to out understanding of the nature of cellular stress and its consequences for the maintenance of phenotype and induction of tissue specific gene expression. 相似文献
62.
Daniel Hoornweg Perinaz Bhada‐Tata Christopher Kennedy 《Journal of Industrial Ecology》2015,19(1):117-128
Population and per capita gross domestic product (GDP) projections are used to estimate total global municipal solid waste (MSW) generation over the twenty‐first century. Some projections for global population suggest that it will peak this century. Waste generation rates per capita generally increase with affluence, although in the most affluent countries there is also a trend toward dematerialization. The confluence of these factors means that at some point in the future total global waste generation could possibly peak. To determine when peak waste might occur, we used the shared‐socioeconomic pathway scenarios (used in Intergovernmental Panel on Climate Change [IPCC] studies) combined with estimates of municipal solid waste (MSW) generation rates, extrapolated from our work for the World Bank. Despite the expectation that total MSW generation in Organisation for Economic Co‐operation and Development (OECD) and high‐income countries will peak mid‐century, with current trajectories global peak waste is not expected before 2100. The peak could be moved forward to around 2075 and reduced in intensity by some 30% if a more aggressive sustainability growth scenario were followed, rather than the current business‐as‐usual scenario. Further, the magnitude of peak waste is sensitive to the intensity of waste generation; it could vary from 7.3 to 10.9 megatonnes per day under the sustainability scenario. The timing of peak waste will substantially depend on the development of cities in Sub‐Saharan Africa, where population growth rates are more than double the rest of the world. 相似文献
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64.
Ramesh JL Kandimalla Willayat Yousuf Wani Binukumar BK Kiran Dip Gill 《Journal of biomedical science》2012,19(1):2
Background
One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage. 相似文献65.
Hong C. Shen Fa-Xiang Ding Qiaolin Deng Suoyu Xu Xinchun Tong Xiaoping Zhang Yuli Chen Gaochao Zhou Lee-Yuh Pai Magdalena Alonso-Galicia Sophie Roy Bei Zhang James R. Tata Joel P. Berger Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2009,19(19):5716-5721
Distinct from previously reported urea and amide inhibitors of soluble epoxide hydrolase (sEH), a novel class of inhibitors were rationally designed based on the X-ray structure of this enzyme and known amide inhibitors. The structure–activity relationship (SAR) study was focused on improving the sEH inhibitory activity. Aminobenzisoxazoles emerged to be the optimal series, of which a potent human sEH inhibitor 7t was identified with a good pharmacokinetics (PK) profile. The strategy of employing aminoheterocycles as amide replacements may represent a general approach to develop mimics of known hydrolase or protease inhibitors containing an amide moiety. 相似文献
66.
Hong C. Shen Fa-Xiang Ding Qiaolin Deng Suoyu Xu Hsuan-shen Chen Xinchun Tong Vincent Tong Xiaoping Zhang Yuli Chen Gaochao Zhou Lee-Yuh Pai Magdalena Alonso-Galicia Bei Zhang Sophie Roy James R. Tata Joel P. Berger Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2009,19(18):5314-5320
3,3-Disubstituted piperidine-derived trisubstituted urea entA-2b was discovered as a highly potent and selective soluble epoxide hydrolase (sEH) inhibitor. Despite the good compound oral exposure, excellent sEH inhibition in whole blood, and remarkable selectivity, compound entA-2b failed to lower blood pressure acutely in spontaneously hypertensive rats (SHRs). This observation further challenges the premise that sEH inhibition can provide a viable approach to the treatment of hypertensive patients. 相似文献
67.
Darby Schmidt Abigail Smenton Subharekha Raghavan Ester Carballo-Jane Silvi Lubell Tanya Ciecko Tom G. Holt Michael Wolff Andrew Taggart Larissa Wilsie Mihajlo Krsmanovic Ning Ren Daniel Blom Kang Cheng Peggy E. McCann M. Gerard Waters James Tata Steven Colletti 《Bioorganic & medicinal chemistry letters》2009,19(16):4768-4772
Niacin is an effective drug for raising HDL cholesterol and reducing coronary risks, but patients show low compliance with treatment due to severe facial flushing upon taking the drug. A series of bicyclic pyrazole carboxylic acids were synthesized and tested for their ability to activate the niacin receptor. One analog, 23, showed improved potency and lacked flushing at doses that effectively altered the lipid profile of rats. 相似文献
68.
Kevin NJ Duffy JL Kirk BA Chapman KT Schleif WA Olsen DB Stahlhut M Rutkowski CA Kuo LC Jin L Lin JH Emini EA Tata JR 《Bioorganic & medicinal chemistry letters》2003,13(22):4027-4030
HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P(3) position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment. 相似文献
69.
Tata JR 《Nature reviews. Molecular cell biology》2002,3(9):702-710
A century ago, secretions from the pancreas were described as 'hormones', which we now know are secreted from all ductless glands. The development of various technologies has already contributed a great deal -- and will undoubtedly offer more -- to our understanding of their mode of action. 相似文献
70.