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Vectorial secretion of CTGF as a cell-type specific response to LPA and TGF-β in human tubular epithelial cells
Jonathan Zuehlke, Astrid Ebenau, Bettina Krueger, Margarete Goppelt-Struebe
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-25
Abstract: Tubular epithelial cells of proximal and distal origin were isolated from human kidneys and cultured as polarized cells in insert wells. The pro-fibrotic stimuli lysophosphatidic acid (LPA) and transforming growth factor β (TGF-β) were used to induce CTGF secretion.LPA activated CTGF secretion in proximal tubular cells when applied from either the apical or the basolateral side as shown by immunocytochemistry. CTGF was secreted exclusively to the apical side. Signaling pathways activated by LPA included MAP kinase and Rho kinase signaling. TGF-β applied from either side also stimulated CTGF secretion primarily to the apical side with little basolateral release.Interestingly, TGF-β activation induced different signaling pathways depending on the side of TGF-β application. Smad signaling was almost exclusively activated from the basolateral side most prominently in cells of distal origin. Only part of these cells also synthesized CTGF indicating that Smad activation alone was not sufficient for CTGF induction. MAP kinases were involved in apical TGF-β-mediated activation of CTGF synthesis in proximal cells and a subset of epithelial cells of distal origin. This subpopulation of distal tubular cells was also able to internalize recombinant apical CTGF, in addition to proximal cells which were the main cells to take up exogenous CTGF.Analysis of polarized human primary renal epithelial cells in a transwell system shows that vectorial secretion of the pro-fibrotic protein CTGF depends on the cell type, the stimulus and the signaling pathway activated. In all conditions, CTGF was secreted mainly to the apical side upon TGF-β and LPA treatment and therefore, likely contributes to increased urinary CTGF levels in vivo. Moreover, CTGF secreted basolaterally may be active as paracrine pro-fibrotic mediator.Connective tissue growth factor (CTGF, CCN2) is a secreted matricellular protein which has been associated with fibrotic diseases, often mediating the pro-fibrotic effects
Distinct Mesenchymal Alterations in N-Cadherin and E-Cadherin Positive Primary Renal Epithelial Cells
Christof Keller, Sven Kroening, Jonathan Zuehlke, Frank Kunath, Bettina Krueger, Margarete Goppelt-Struebe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043584
Abstract: Background Renal tubular epithelial cells of proximal and distal origin differ markedly in their physiological functions. Therefore, we hypothesized that they also differ in their capacity to undergo epithelial to mesenchymal alterations. Results We used cultures of freshly isolated primary human tubular cells. To distinguish cells of different tubular origin we took advantage of the fact that human proximal epithelial cells uniquely express N-cadherin instead of E-cadherin as major cell-cell adhesion molecule. To provoke mesenchymal alteration we treated these cocultures with TGF-β for up to 6 days. Within this time period, the morphology of distal tubular cells was barely altered. In contrast to tubular cell lines, E-cadherin was not down-regulated by TGF-β, even though TGF-β signal transduction was initiated as demonstrated by nuclear localization of Smad2/3. Analysis of transcription factors and miRNAs possibly involved in E-cadherin regulation revealed high levels of miRNAs of the miR200-family, which may contribute to the stability of E-cadherin expression in human distal tubular epithelial cells. By contrast, proximal tubular epithelial cells altered their phenotype when treated with TGF-β. They became elongated and formed three-dimensional structures. Rho-kinases were identified as modulators of TGF-β-induced morphological alterations. Non-specific inhibition of Rho-kinases resulted in stabilization of the epithelial phenotype, while partial effects were observed upon downregulation of Rho-kinase isoforms ROCK1 and ROCK2. The distinct reactivity of proximal and distal cells was retained when the cells were cultured as polarized cells. Conclusions Interference with Rho-kinase signaling provides a target to counteract TGF-β-mediated mesenchymal alterations of epithelial cells, particularly in proximal tubular epithelial cells. Furthermore, primary distal tubular cells differed from cell lines by their high phenotypic stability which included constant expression of E-cadherin. Our cell culture system of primary epithelial cells is thus suitable to understand and modulate cellular remodeling processes of distinct tubular cells relevant for human renal disease.
CAG Repeats Determine Brain Atrophy in Spinocerebellar Ataxia 17: A VBM Study
Kathrin Reetz,Alexandra Kleiman,Christine Klein,Rebekka Lencer,Christine Zuehlke,Kathrin Brockmann,Arndt Rolfs,Ferdinand Binkofski
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015125
Abstract: Abnormal repeat length has been associated with an earlier age of onset and more severe disease progression in the rare neurodegenerative disorder spinocerebellar ataxia 17 (SCA17).
Under the Flag of Blue and White: Mary as an A-NationalSymbol in the Greek-Orthodox Community in Israel  [PDF]
Jonathan Ventura
Sociology Mind (SM) , 2011, DOI: 10.4236/sm.2011.14029
Abstract: Marian devotion and rituals have been the apex of Christian believers’ journey for centuries. In spite of its importance in many disciplines, Marian devotion and rituals in Israel have been neglected. In this article I will outline several social and religious aspects of Marian devotion in the Greek-Orthodox community in Israel. Using several case-studies of Marian devotion around the world I will address the question is Mary a national symbol in Israel? Since one of the most important Marian devotion sites is located in Israel and centered in Mary’s place of ascension in Gethsemane, addressing this site directly is crucial. I will express a new concept more fitting to the Israeli case—Mary as an a-national symbol. This research is based upon a combination of two main methodologies: participant observations and in-depth interviews with believers (local Greek and Palestinian residents as well as pilgrims) and clergymen. The research focuses on a procession taking place in the Old City of Jerusalem in the end of August, celebrating Mary’s legacy and resurrection.
On the Robustness of Strategic Experimentation to Persuasive Cheap Talk  [PDF]
Jonathan Rosborough
Theoretical Economics Letters (TEL) , 2012, DOI: 10.4236/tel.2012.25097
Abstract: This paper develops a model in which a privately informed seller attempts to indirectly influence the experimentation strategy of a buyer by sending costless signals. The question under consideration is whether there is any credible way in which this single rational seller could influence the buyer’s decisions. We provide bounds on information transmission in equilibrium, and show that there exists no reporting strategy for the seller which changes the experimentation strategy of the buyer. These results demonstrate the robustness of a class of learning models to coercion.
Investor Na？veté and Asset Prices  [PDF]
Jonathan Cook
Journal of Mathematical Finance (JMF) , 2013, DOI: 10.4236/jmf.2013.34047
Abstract:

This paper describes strategic behavior in a nonequilibrium model of asset pricing with heterogeneous sophistication. Both risk and return are increasing in the na?veté of investors in the market. Optimal investment involves in considering the effect that na?e investors have on the market. Further, we derive a simple characterization of the asset price dynamics that results from an arbitrary combination of a countably infinite set of investor types.

Surgery for Acute Stanford Type A Aortic Dissection in an Inner City Community Hospital: Single Surgeon’s Experience  [PDF]
Jonathan Nwiloh
World Journal of Cardiovascular Surgery (WJCS) , 2016, DOI: 10.4236/wjcs.2016.62005
Abstract: Objective: An inverse relationship between volume and mortality in some cardiothoracic surgical procedures has been previously established, leading to suggestions that acute aortic dissection should not be operated in community or low volume heart centers. We therefore reviewed our experience to compare with published data. Methods: Retrospective review of 27 patients who underwent proximal aortic surgery by a single surgeon at an inner city community hospital between May 2004 and April 2015. 16 patients, mean age 51.7 ± 13.6 years old, 75.0% males underwent emergency surgery for acute Stanford type A aortic dissection, while 9 with root or ascending aortic aneurysm, mean age 50.3 ± 15.0 years old, 88.9% males had elective proximal aortic surgery. 2 patients with arch aneurysm were excluded. Results: Four (25.0%) patients with acute dissection were in Penn class A, 3 (18.7%) Penn B, 3 (18.7%) Penn C and 6 (37.5%) Penn B+C. 10 (62.5%) patients underwent emergency root replacement with 60.0% (6/10) mortality all related to malperfusion including 2 patients with bloody stools, while 6 (37.5%) underwent supracoronary graft replacement with 16.6% (1/6) mortality from cardiac tamponade. The 5-year survival was 89.0%. In patients with aortic aneurysm, 8 (88.9%) underwent elective root replacement and 1 (11.1%) supracoronary graft replacement with zero mortality. Conclusion: Supracoronary graft replacement is performed for the majority of uncomplicated acute type A dissections and can be undertaken by the average general cardiac surgeon with acceptable results. Visceral malperfusion especially when associated with bloody stools portends a poor prognosis, and aortic dissection should be excluded in any Marfan patient presenting with acute abdomen. Delaying intervention in attempting transfer to a tertiary hospital can potentially increase preoperative mortality, known to rise with each passing hour from onset of acute dissection. Patients presenting therefore to community hospitals should probably undergo surgery there to avoid complications associated with delay.
Further Properties of Reproducing Graphs  [PDF]
Jonathan Jordan, Richard Southwell
Applied Mathematics (AM) , 2010, DOI: 10.4236/am.2010.15045
Abstract: Many real world networks grow because their elements get replicated. Previously Southwell and Cannings introduced a class of models within which networks change because the vertices within them reproduce. This happens deterministically so each vertex simultaneously produces an offspring every update. These offspring could represent individuals, companies, proteins or websites. The connections given to these offspring depend upon their parent’s connectivity much as a child is likely to interact with their parent’s friends or a new website may copy the links of pre-existing one. In this paper we further investigate one particular model, ‘model 3’, where offspring connect to their parent and parent’s neighbours. This model has some particularly interesting features, including a degree distribution with an interesting fractal-like form, and was introduced independently under the name Iterated Local Transitivity by Bonato et al. In particular we show connections between this degree distribution and the theory of integer partitions and show that this can be used to explain some of the features of the degree distribution; we give exact formulae for the number of complete subgraphs and the global clustering coefficient and we show how to calculate the minimal cycle basis.
Assessing outcomes after fast track surgical management of corpus cancer  [PDF]
Jonathan Carter, Shannon Philp
Open Journal of Obstetrics and Gynecology (OJOG) , 2011, DOI: 10.4236/ojog.2011.13026
Abstract: Objective: The aim of the study was to audit the outcomes of patients with corpus cancer managed with a fast track surgery (FTS) program. Design: Clinical audit of outcomes after laparotomy for corpus cancer and managed by FTS principles. Setting: Tertiary hospital, University based subspecialty gynaecological oncology practice. Population or Sample: Consecutive patients with uterine corpus cancer. There were no exclusions. Methods: Three year audit of FTS Database. Main Outcome Measures: Ability to tolerate early oral feeding (EOF), length of stay (LOS), perioperative complication rate and readmission rate. Results: Sixty six patients were operated upon whose median age was 59.5 years. Forty six (70%) had stage I disease, 7 (11%) stage II, 9 (14%) stage III and 4 (6%) had stage IV disease. Twenty seven (41%) had lymph node sampling performed. Median operating time was 2.5 hours. Mean BMI was 30 kg/m2 (Range: 18 - 47). Fifty patients (76%) were classified as over-weight or obese. Twenty four patients (36%) had a “non-zero” performance status. Mean intraoperative EBL was 227 ml. Median LOS was 3.0 days. There were 3 (5%) intraoperative complications. There were no intraoperative ureteric, bowel or vascular injuries. Postoperatively, 13 (20%) patients experienced a total of 24 adverse events. Only 2 (3%) patients experienced complications greater than grade 2. Conclusion: This audit shows that in an unselected group of patients undergoing laparotomy as management for their uterine malignancy and managed by a FTS protocol, overall excellent results can be achieved.
Using Nursery Rhymes to Foster Phonological and Musical Processing Skills in Kindergarteners  [PDF]
Jonathan Bolduc, Pascal Lefebvre
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.34075
Abstract: The aim of this study was to assess the efficiency of four learning conditions to develop phonological and musical processing skills through a set of 10 nursery rhymes. According to the analysis of the teachers’ practices, eight kindergarten classes (n = 100 kindergarteners) were paired and assigned to one of the following conditions: 1) music, 2) language, 3) combined [music and language], and 4) passive listening (control classes). Participants in conditions 1, 2, and 3 were met for 40 minutes per week over a ten-week period. In condition 1, the nursery rhymes were supplemented by musical activities and in condition 2 by language activities. Condition 3 was a combination of activities from conditions 1 and 2. In condition 4, children listened to a recording of the same nursery rhymes for 15 minutes daily during free exploration periods. No intervention was proposed for this control condition. All participants were evaluated using the same phonological and musical processing measures prior to and after the implementation of the program. Results indicated that children in conditions 1, 2 and 3 significantly improved their phonological awareness and their invented spelling skills at post-test. However, only the two conditions in which the music component was integrated enhanced significantly their results at the verbal memory task. Children in conditions 1, 3 and 4 enhanced tonal and rhythm perception skills. This study demonstrated that supplementing nursery rhymes with language activities is an efficient manner to develop emergent literacy skills, but the addition of musical activities could also boost phonological processing skills.
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