Cadherin-9 Is a Novel Cell Surface Marker for the Heterogeneous Pool of Renal Fibroblasts

BACKGROUND: Interstitial fibroblasts are a minor, but nevertheless very important, component of the kidney. They secrete and remodel extracellular matrix and they produce active compounds such as erythropoietin. However, studying human renal fibroblasts has been hampered by the lack of appropriate surface markers. METHODS AND FINDINGS: The expression of cadherin-9 in various human renal cell lines and tissues was studied on the mRNA level by RT-PCR and on the protein level with the help of newly generated cadherin-9 antibodies. The classical type II cadherin-9, so far only described in the neural system, was identified as a reliable surface marker for renal fibroblasts. Compared to FSP1, a widely-used cytosolic renal fibroblast marker, cadherin-9 showed a more restricted expression pattern in human kidney. Under pathological conditions, cadherin-9 was expressed in the stroma of renal cell carcinoma, but not in the tumor cells themselves, and in renal fibrosis the percentage of cadherin-9-positive cells was clearly elevated 3 to 5 times compared to healthy kidney tissue. Induction of epithelial mesenchymal transition in renal epithelial cells with cyclosporin-A, which causes renal fibrosis as a side effect, induced cadherin-9 expression. Functional studies following siRNA-mediated knockdown of cadherin-9 revealed that it acts in the kidney like a typical classical cadherin. It was found to be associated with catenins and to mediate homophilic but not heterophilic cell interactions. CONCLUSIONS: Cadherin-9 represents a novel and reliable cell surface marker for fibroblasts in healthy and diseased kidneys. Together with the established marker molecules FSP1, CD45 and alpha smooth muscle actin, cadherin-9 can now be used to differentiate the heterogenic pool of renal fibroblasts into resident and activated fibroblasts, immigrated bone marrow derived fibroblast precursors and cells in different stages of epithelial mesenchymal transition

Obelix vs. Asterix : size of US commercial banks and its regulatory challenge

Big banks pose substantial costs to society in the form of increased systemic risk and government bailouts during crises. So the question is: Should regulators limit the size of banks? To answer this question, regulators need to assess the potential costs of such regulations. If big banks enjoy substantial scale economies (i.e., average costs get lower as bank size increases), limiting the size of banks through regulations may be inefficient and likely to reduce social welfare. However, the literature offers conflicting results regarding the existence of economies of scale for the biggest US banks. We contribute to this literature using a novel approach to estimating nonparametric measures of scale economies and total factor productivity (TFP) growth. For US commercial banks, we find that around 73 % of the top one hundred banks, 98 % of medium and small banks, and seven of the top ten biggest banks by asset size exhibit substantial economies of scale. Likewise, we find that scale economies contribute positively and significantly to their TFP growth. The existence of substantial scale economies raises an important challenge for regulators to pursue size limit regulations

Huntington's disease: a clinical review

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring full-time care, and finally death. The most common cause of death is pneumonia, followed by suicide

The financialization of mass wealth, banking crises and politics over the long run

The co-evolution of democratic politics and mass, financialized wealth has destabilized highly integrated financial systems and the socio-political underpinnings of neoliberal policy norms at domestic and global levels. Over the long run, it has increased the political pressure on governments to undertake bailouts during major banking crises and, by raising voters’ attentiveness to wealth losses and distributional inequities, has sharply raised the bar for government performance. The result has been more costly bailouts, greater political instability and the sustained politicization of wealth cleavages in crisis aftermaths. We underline the crucial importance and modernity of this phenomenon by showing how the high concentration of wealth in pre-1914 Britain and America among elites was associated with limited crisis interventions and surprisingly tranquil political aftermaths. By contrast, the 2007–2009 crises in both countries epitomise the political dilemmas facing elected governments in a new world of mass financialized wealth and the impact on political polarization and democratic politics. We show that these dilemmas were embryonic in the interwar period and highlight how the evolutionary forces shaping policy and political outcomes reveal the importance of time, context and the effects of long cycles in the world economy and global politics