Differential, Tissue-specific, Transcriptional Regulation of Apolipoprotein B Secretion by Transforming Growth Factor β

n/

Sense of place in the changing process of house form: Case studies from Ankara, Turkey

This paper aims to investigate the impact of typomorphological changes of residential environments on residents’ sense of place’. Seven housing developments representing different types introduced in Ankara, Turkey since the late 19th-century are selected as case studies. Their morphological characters at the building, street and neighbourhood scales are examined, and typological transformations among the cases in terms of the degrees of continuity are identified. The paper proposes a conceptual model consisting of ten indicators to assess sense of place at the building, street and neighbourhood scales of the residents of the seven cases. The scores of sense of place are generated through structured interviews with the residents and analysed in SPSS. The results show that sense of place is negatively affected by typomorphological changes over time, particularly when mutational changes occur. Continuity in typomorphological transformation helps to maintain sense of place at a desirable level. Furthermore, physical changes at the street and neighbourhood scales have larger impact on sense of place than that at the building scale. The research thus suggests that planning and design should be responsive to traditional types in residential development, particularly at the street and neighbourhood scales to maintain residents’ sense of place

Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory disease.</p> <p>Methods</p> <p>We examined a marker of inflammation, C-reactive protein (CRP), in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models.</p> <p>Results</p> <p>Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only), serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function.</p> <p>Conclusion</p> <p>Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.</p

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

Urban Neighbourhood Forums in Ankara as a Commoning Practice

The neighbourhood forums in Ankara began to convene during the Gezi protests in 2013 and lasted about three years. The activities of Ankara Gezi forums are urban commoning practices in terms of a new set of demands and methods. This paper conceptualises urban commoning practices as method, content, and demand. This framework offers an understanding of urban commoning that is not based on monetary transaction, but focuses on seeing commoning as a social process. Commoning is not ahistorical, rather it is engaged with the historical political potential of urban spaces. Commoning as method discusses organising in commons, commoning as content focuses on the form and meaning of political action, and commoning as demand emphasises the discursive use of right to the city. The case selection of this research enables us to reflect on how urban commoning is experienced in a city under less financial investment pressure, but at the centre of national-level politics.Peer reviewe

Response to hypoxia involves smad proteins in human endothelial cells

Smad proteins are the downstream substrates of membrane ser/thr kinase TGF-β receptors, and mediate responses of endothelial cells (EC) to mechanical and metabolic stress. Oxygen deprivation (Hypoxia: Hx) is a consistent component of ischémie vascular disorders and induces an inflammatory response in vascular endothelium. This study, performed in human umbilical vein endothelial cells (HUVEC), examined the effect of Hx on activity of Smads and their target gene TGF-β2, a cytokine regulator of inflammation in EC. RNase protection studies showed that exposure to Hx (1% O2) increased mRNA levels of TGF-β2 by 10-fold in a time-dependent fashion (P \u3c .01). Parallel increases in active and latent TGF-β2 protein were found by measuring the response of a TGF-βresponsive luciferase construct in a bioassay. Hx stimulated TGF-β2 transcription in HUVEC, determined by activity of a TGF-β2 CAT promoter construct, by 3-fold; Hxinduced transcription was increased by a further 4-fold (P \u3c .01) after cotransfection of HUVEC with Smad 3/4 expression vectors. Hx also increased transcription from a known TGF-β-responsive promoter, 3TP-lux, by 10-fold (P \u3c .01); cotransfection of Smad 3/4 vectors increased the activity of 3TP-lux by a further 3-fold ( P \u3c .01). Smad association with DNA was shown with EMSA using a Smad-binding oligonucleotide, SEE, as probe. Binding to SBE occurred only with nuclear extracts from hypoxic but not normoxic HUVEC, was not competed by oligonucleotides corresponding to DNA-binding sites of SP1 or HIF-1, and was supershifted with antibody to Smad 3 and 4 but not to HIF-1 or preimmune sera. To further examine the effects of Hx on EC signal transduction and function, total RNA obtained from HUVEC exposed to Hx for increasing time periods was used for mRNA transcript profiling by cDNA arrays (Clonetech, Atlas 1.2). Results were normalized to β-actin and show that mRNA of TGF-β l, -β2, and their upstream regulators such as TGF-β RI and Ang II Rl were induced at 18h after Hx compared to normoxia. Furthermore, Hx induced mRNAs of Smad co-factors SP1 and -2, which cooperate to inhibit Gl cell cycle progression. mRNA levels of Smads, Jak-Stat proteins, or NF-KB were unchanged, but HIF-1 mRNA was increased. In sum, Hx-induced increases in TGF-β2, TGF-β RI, and Smad 3/4 function in EC suggest that this pathway plays an important role in endothelial response to hypoxic stress