Activin A and Cell-Surface GRP78 Are Novel Targetable RhoA Activators for Diabetic Kidney Disease

Diabetic kidney disease (DKD) is the leading cause of kidney failure. RhoA/Rho-associated protein kinase (ROCK) signaling is a recognized mediator of its pathogenesis, largely through mediating the profibrotic response. While RhoA activation is not feasible due to the central role it plays in normal physiology, ROCK inhibition has been found to be effective in attenuating DKD in preclinical models. However, this has not been evaluated in clinical studies as of yet. Alternate means of inhibiting RhoA/ROCK signaling involve the identification of disease-specific activators. This report presents evidence showing the activation of RhoA/ROCK signaling both in vitro in glomerular mesangial cells and in vivo in diabetic kidneys by two recently described novel pathogenic mediators of fibrosis in DKD, activins and cell-surface GRP78. Neither are present in normal kidneys. Activin inhibition with follistatin and neutralization of cell-surface GRP78 using a specific antibody blocked RhoA activation in mesangial cells and in diabetic kidneys. These data identify two novel RhoA/ROCK activators in diabetic kidneys that can be evaluated for their efficacy in inhibiting the progression of DKD.     

Miscible-Solvent-Assisted Two-Phase Synthesis of Monolayer-Ligand-Protected Metal Nanoclusters with Various Sizes

Effective yet versatile synthetic strategies for size-tunable metal nanoclusters (NCs) are scarce. This has hampered the development of this unique class of nanomaterials. Here, a general protocol is reported for the synthesis of high-quality metal NCs protected by a variety of organic ligands (e.g., selenolate, thiolate, and phosphine) based on a miscible-solvent-assisted phase transfer between water and organic solution. This method is demonstrated to be facile, rapid (≤3 h), scalable (gram-scale), and versatile. The size of the selenolated and thiolated Au NCs can be tuned from Au₁₀ to Au₆₁ by simply varying the miscible solvent in proportions and types. The advantages of this method, such as quick phase separation and no need for purification treatment, enable real-time monitoring of metal NC growth within the NaBH₄ reduction system. The results show that the size of Au NCs gradually increases with increasing valence electron count by a stepwise 2x e^- hopping mechanism (x = 0–5), i.e., 0 e^- → 2 e^- → 4 e^- → 8 e^- → 18 e^- → 22 e^- → 32 e^-.     

An improved method for preparing monolithic aerogels based on methyltrimethoxysilane at ambient pressure Part II: Microstructure and performance of the aerogels

The microstructures, physical properties and mechanical properties of the methyltrimethoxysilane (MTMS) derived aerogels, prepared at ambient pressure using an improved method reported in Part I, have been comprehensively characterised in this paper, as Part II. The study has revealed sophisticated pore structures and morphologies of the aerogels produced, and demonstrated the relationships between the key processing conditions and microstructures of the resultant aerogels. The results of the study also help to further understand the effect of microstructure changes on the macrostructure, volume shrinkage and performances of the aerogels, and provide a general guide on how to manipulate the processing conditions to produce monolithic MTMS based aerogels with desirable structure and properties by ambient pressure drying.     

Investigation of Eccentric Open Eye Formation in a Slab Caster Tundish

Metallurgical and Materials Transactions B - Inert gas shrouding in tundish can result in the formation of a tundish open eye (TOE) due to the presence of reversed flows on the upper surface of the...     

Current status and future trends for disposable technology in the biopharmaceutical industry

Single use technology (SUT) is in widespread use throughout the biopharmaceutical industry where it is replacing traditional stainless steel plant particularly for the manufacture of small volume, high value products. The key drivers for SUT uptake include reduction of regulatory risk, lower capital and energy costs and increased facility flexibility. Disposable technology is now well established for cell culture, liquid handling and storage but its application to some downstream operations is proving more intractable. Single‐use chromatography resins are generally uneconomic at process scale and there are limitations on large‐scale tangential flow filtration capacities. The development of disposable sensor technology is lagging behind that of bioreactors and capacities for microbial culture are presently limited to 2000 litres. Concerns regarding compatibility of equipment from different suppliers and extractable and leachable testing are being addressed but continue to influence uptake of SUT by traditional manufacturers. Complete ‘plug and play’ disposable process trains, however, are becoming increasingly available and are being embraced by Contract Manufacturing Organisations (CMOs) with multiproduct facilities. © 2013 Society of Chemical Industry     

20号花园 可带走的花园

是否我们可以自己设计一下明日的花园,设计一下使生物多样性更加丰富的环境呢？请想象一下在一个世界里每个公民都有机会关注自己的微生境。从屋顶露台到停车场、从郊外花园到工业垃圾场——对于一只袋子来说,每一个空间都是不小的,即使只有一棵树及其相关的生态系统。与其面对日渐消减的生物多样性而感到困顿,     

Ethical and professional considerations in divorce and child custody cases.

The provision of psychological (e.g., psychotherapy, coparenting, mediation, collaborative divorce, child custody evaluation) services for families of divorce are growing specialties for many clinical and forensic psychologists. However, practice in domestic relations psychology, such as divorce and custody assessment and testimony, is a high-risk venture for incurring ethics complaints and law suits. The lead article and the three commentaries that follow enumerate the various roles practitioners might play, clarify how each role requires specific skill sets that may be outside one’s particular competence and necessitate additional training, describe how countertransferential issues arise, urge meticulous record keeping, discuss some of the subtleties of confidentiality and the releasing of information, describe how transparency in clarifying expectations leads to a lowering of contentiousness, and provide tips for divorce and forensic practice. The special challenges associated with psychologists being tempted to move beyond their role on a case and those of particularly high-risk situations (e.g., complaints of child abuse or domestic violence) are also discussed. Suggestions are offered to help psychologists better serve the public while taking steps to better inoculate themselves from complaints. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Backyard shacks,informality and the urban housing crisis in South Africa: stopgap or prototype solution?

Rapid urbanisation in the South has contributed to the growth of informal housing on a large scale. South Africa’s experience is somewhat unusual in that the growth of informality appears to have taken the form of backyard shacks in established townships rather than free-standing shacks in squatter settlements. This is potentially important for household well-being (e.g. better access to services) and for the efficient functioning of urban areas. The paper develops a framework for assessing the impacts and applies it to the country’s leading metropolitan region, Gauteng. It finds that people are slightly better-off in backyards than in shacks elsewhere, although the wider benefits for urban areas are equivocal. In some respects backyard shacks are a stopgap for poor households desperate for somewhere to live. In other respects they represent a kind of prototype solution to the urban housing crisis. The government could do more to improve basic dwelling conditions and to relieve the extra pressure on local services.