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A Transgenic Model for Conditional Induction and Rescue of Portal Hypertension Reveals a Role of VEGF-Mediated Regulation of Sinusoidal Fenestrations
Dalit May, Valentin Djonov, Gideon Zamir, Miklosh Bala, Rifaat Safadi, Miriam Sklair-Levy, Eli Keshet
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021478
Abstract: Portal hypertension (PH) is a common complication and a leading cause of death in patients with chronic liver diseases. PH is underlined by structural and functional derangement of liver sinusoid vessels and its fenestrated endothelium. Because in most clinical settings PH is accompanied by parenchymal injury, it has been difficult to determine the precise role of microvascular perturbations in causing PH. Reasoning that Vascular Endothelial Growth Factor (VEGF) is required to maintain functional integrity of the hepatic microcirculation, we developed a transgenic mouse system for a liver-specific-, reversible VEGF inhibition. The system is based on conditional induction and de-induction of a VEGF decoy receptor that sequesters VEGF and preclude signaling. VEGF blockade results in sinusoidal endothelial cells (SECs) fenestrations closure and in accumulation and transformation of the normally quiescent hepatic stellate cells, i.e. provoking the two processes underlying sinusoidal capillarization. Importantly, sinusoidal capillarization was sufficient to cause PH and its typical sequela, ascites, splenomegaly and venous collateralization without inflicting parenchymal damage or fibrosis. Remarkably, these dramatic phenotypes were fully reversed within few days from lifting-off VEGF blockade and resultant re-opening of SECs' fenestrations. This study not only uncovered an indispensible role for VEGF in maintaining structure and function of mature SECs, but also highlights the vasculo-centric nature of PH pathogenesis. Unprecedented ability to rescue PH and its secondary manifestations via manipulating a single vascular factor may also be harnessed for examining the potential utility of de-capillarization treatment modalities.
Complications of high grade liver injuries: management and outcomewith focus on bile leaks
Miklosh Bala, Samir Gazalla, Mohammad Faroja, Allan I Bloom, Gideon Zamir, Avraham I Rivkind, Gidon Almogy
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2012, DOI: 10.1186/1757-7241-20-20
Abstract: This is a retrospective study of patients with liver injury admitted to Hadassah-Hebrew University Medical Centre over a 10-year period. Grade 3-5 injuries were considered to be high grade. Collected data included the number and types of liver-related complications. Interventions which were required for these complications in patients who survived longer than 24 hours were analysed.Of 398 patients with liver trauma, 64 (16%) were found to have high-grade liver injuries. Mechanism of injury was blunt trauma in 43 cases, and penetrating in 21. Forty patients (62%) required operative treatment. Among survivors 22 patients (47.8%) developed liver-related complications which required additional interventional treatment. Bilomas and bile leaks were diagnosed in 16 cases post-injury. The diagnosis of bile leaks was suspected with abdominal CT scan, which revealed intraabdominal collections (n = 6), and ascites (n = 2). Three patients had continuous biliary leak from intraabdominal drains left after laparotomy. Nine patients required ERCP with biliary stent placement, and 2 required percutaneous transhepatic biliary drainage. ERCP failed in one case. Four angioembolizations (AE) were performed in 3 patients for rebleeding. Surgical treatment was found to be associated with higher complication rate. AE at admission was associated with a significantly higher rate of biliary complications. There were 24 deaths (37%), the majority from uncontrolled haemorrhage (18 patients). There were only 2 hepatic-related mortalities due to liver failure.A high complication rate following high-grade liver injuries should be anticipated. In patients with clinical evidence of biliary complications, CT scan is a useful diagnostic and therapeutic tool. AE, ERCP and temporary internal stenting, together with percutaneous drainage of intra-abdominal or intrahepatic bile collections, represents a safe and effective strategy for the management of complications following both blunt and penetrating he
Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression
Sophie Kirshberg, Uzi Izhar, Gail Amir, Jonathan Demma, Fiona Vernea, Katia Beider, Zippora Shlomai, Hanna Wald, Gideon Zamir, Oz M. Shapira, Amnon Peled, Ori Wald
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024856
Abstract: Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations.
Morphological and Biochemical Changes in Ginseng Seedling Roots Affected with Stripe Symptoms  [PDF]
Zamir K. Punja, Mahfuzur Rahman
American Journal of Plant Sciences (AJPS) , 2015, DOI: 10.4236/ajps.2015.616257
Abstract: A unique symptom of longitudinal red stripes on the surface of one-year-old ginseng roots was studied to determine the morphological and biochemical changes taking place. Light and scanning electron microscopy, measurements of phenolic and mineral element content, and enzyme activity, were compared between healthy and stripe-affected root tissues. Light microscopy revealed that the root epidermis had ruptured and fissures extended for 3 - 4 cell layers into the cortex. Phenolic compounds accumulated in the epidermal cells which stained with Toluidine blue 0. Total phenolic content was higher in tissues from striped roots compared to healthy roots and HPLC profiles showed increases in a number of specific phenolic compounds. Analysis of epidermal tissues by SEM-EDX for mineral element content showed a marked increase in levels of iron, silicon and aluminum and a decline in potassium in striped root tissues. The activity of the enzymes phenylalanine ammonia lyase and peroxidase were also found to be higher in striped root tissues. Striping of ginseng roots is a physiological condition caused by a rupture of the epidermis due to rapid growth of underlying cells, which results in phenolic accumulation and sequestration of several minerals. Further oxidation causes a visible red striping on the root surface.
The Principle of the Eternal-Feminine in Rossini’s L’Italiana in Algeri: Isabella as the Italian Super-Woman
Zamir, Sara
Anuario Musical , 2011,
Abstract: The term Eternal-Feminine, or Das Ewig-Weibliche, first appeared in the last verses of the second part of Goethe’s Faust (completed 1832). It, subsequently, became the subject of speculation and a riddle which scholars have been trying to solve ever since. The term gradually came to represent a cultural principle regarding the image of femininity and it reached its Romantic apex, in the 19th Century, when various female archetypes were fused into a singe heroine. The present article aims to explore Isabella’s character in Rossini’s L’Italiana in Algeri in the light of the principle of the Eternal-Feminine. Although Goethe was still in the process of writing the second part of Faust when L’Italiana premiered (1813) in Italy, the cultural principle of the Eternal- Feminine can be used retrospectively in the analysis of Isabella as the central female protagonist of the opera. A thorough reading of her character suggests an aesthetic approach that makes use of certain Romantic aspects of the Eternal-Feminine principle. The present article focuses specifi cally on the Cruda sorte! Amor tiranno! scene and briefl y refers to other scenes as well. La expresión Eterno Femenino (Eternal-Feminine, o Das Ewig-Weibliche), apareció por primera vez en los últimos versos de la segunda parte del Fausto de Goethe (acabado en 1832). Posteriormente, se convirtió en tema de especulación, y en un enigma que los estudiosos han estado intentando resolver desde entonces. La expresión vino a identificar, con el paso del tiempo, un principio cultural relacionado con la imagen de la feminidad y alcanzó su extremo romántico, en el siglo XIX, cuando diversos arquetipos femeninos se fundieron en una sola heroína. El presente artículo pretende explorar el personaje de Isabella en La italianaen Argel de Rossini, a la luz del principio del Eterno Femenino. Aunque Goethe se encontraba todavía escribiendo la segunda parte de su Fausto cuando se estrenó La italiana (1813) en Italia, el principio cultural del Eterno Femenino puede utilizarse retrospectivamente en el análisis de Isabella como protagonista femenino central de la ópera. La lectura minuciosa de su personaje sugiere una aproximación estética que hace uso de ciertos aspectos románticos del principio del Eterno Femenino. El presente artículo se centra específicamente en la escena del Cruda sorte! Amor tiranno! y se refiere brevemente, también, a otras escenas.
A PORTRAITURE OF HELEN, QUEEN OF TROY IN BOITO'S Mefistofele: Coincidentia Oppositorum
European Review of Artistic Studies , 2010,
Abstract: In this study we attempt to understand some of the aesthetical features implementedby Arrigo Boito (1842-1918) for the dramaturgic formation of the final act of theopera Mefistofele. Doing that, we will focus on the bifocal character of Helen, both asflash-and-blood woman and as the divine Queen of Troy. Disregarding thecontroversial criticism of the value of the music, the analysis below reveals deepconcern for the dramatic coherence practiced by musical associations and culturalsignals. It shows that the composer has sincerely made an effort to characterize bothfacets of Helen-i.e. femininity and Royalty in the manner of collision of contrasts-Coincidentia Oppositorum. That special polar aesthetic approach constitutes aconvincing musico-dramatic whole made out of extremes.
Anti-Structure Problems
Ram Zamir
Mathematics , 2011,
Abstract: The recent success of structured solutions for a class of information-theoretic network problems, calls for exploring their limits. We show that sum-product channels resist a solution by structured (as well as random) codes. We conclude that the structured approach fails whenever the channel operations do not commute (or for general functional channels, when the channel function is non decomposable).
Where Have All the Crop Phenotypes Gone?
Dani Zamir
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001595
Abstract: Summary In crop genetics and breeding research, phenotypic data are collected for each plant genotype, often in multiple locations and field conditions, in search of the genomic regions that confer improved traits. But what is happening to all of these phenotypic data? Currently, virtually none of the data generated from the hundreds of phenotypic studies conducted each year are being made publically available as raw data; thus there is little we can learn from past experience when making decisions about how to breed better crops for the future. This ongoing loss of phenotypic information, particularly about crop productivity, must be stopped if we are to meet the considerable challenge of increasing food production sufficiently to meet the needs of a growing world population. Here I present a road map for developing and implementing an information network to share data on crop plant phenotypes.
Indoor Tanning, Sunbathing, and the Hazard of Skin Cancer: The Effect of the Tan Tax  [PDF]
Gideon Yaniv, Erez Siniver
Theoretical Economics Letters (TEL) , 2015, DOI: 10.4236/tel.2015.51007
Abstract: In July2010, a10 percent federal sales tax on indoor tanning, known as the tan tax, went into effect. Applauding the imposition of the new tax, the American Academy of Dermatology (AAD) foresees that by discouraging indoor tanning, the tan tax will significantly reduce the risk of skin cancer and consequently the future costs of its treatment, currently amounting to $1.8 billion each year. Recognizing, however, that an alternative to indoor tanning may be the riskier practice of sunbathing, the present paper offers a rational-choice model for addressing the individual’s indoor and outdoor tanning decisions, which is applied to examining his or her response to the imposition of a tan tax and the consequent effect on the hazard of developing skin cancer. The paper challenges the AAD’s forecast, identifying conditions under which a tan tax will rather exacerbate the hazard of skin cancer.
The Game of Monetary Policy, Inflation and Economic Growth  [PDF]
Gladys Wauk, Gideon Adjorlolo
Open Journal of Social Sciences (JSS) , 2019, DOI: 10.4236/jss.2019.73022
Abstract: Ghana has been confronted with series of economic problems to the extent of calling on the IMF for a bailout after every eight years. This situation has persisted in spite of various monetary authority stabilization policies. This paper therefore focuses on investigating the games of monetary policy, inflation and economic growth of the Ghanaian economy for the period of 1982-2017. Using Autoregressive Distributed Lag (ARDL) to cointegration model, it was revealed from the study that in the long run interest rate significantly influences economic growth but in a negative direction, implies that a higher interest rate has the tendency to restrained economic growth and inflationary pressures. In relation to exchange rate, the long run result indicates an insignificant negative effect on economic growth. The general results suggest that macroeconomic variable which influences economic growth is interest rate and exchange rate. This is evidence that macroeconomic instabilities have significant effect on economic growth. This therefore calls for fiscal discipline and autonomy power to the Bank of Ghana with less interreference from the government to enable the smooth implementation of monetary policies without any string of politics attached.
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