Molecular mechanism of regulation of OGG1: tuberin deficiency results in cytoplasmic redistribution of transcriptional factor NF-YA

The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. On the other hand, mice-deficient in the DNA repair enzyme OGG1 spontaneously develop adenoma and carcinoma. Downregulation of tuberin results in a marked decrease of OGG1 and accumulation of oxidative DNA damage, (8-oxodG) in cultured cells. In addition, tuberin haploinsufficiency is associated with the loss of OGG1 and accumulation of 8-oxodG in rat kidney tumor. Deficiency in tuberin results in decreased OGG1 and NF-YA protein expression and increased 8-oxodG in kidney tumor from TSC patients. In the current study, molecular mechanisms by which tuberin regulates OGG1 were explored. The deficiency of tuberin was associated with a significant decrease in NF-YA and loss of OGG1 in kidney tumors of Eker rat. Downregulation of tuberin by siRNA resulted in a marked decrease in NF-YA and OGG1 protein expression in human renal epithelial cells. Localization of NF-YA in wild type and tuberin-deficient cells was examined by western blot and immunostaining assays. In wild type cells, NF-YA was detected in the nucleus while in tuberin deficient cells in the cyotoplasm. Introducing adenovirus-expressing tuberin (Ad-TSC2) into tuberin-deficient cells restored the nuclear localization of NF-YA. These data define a novel mechanism of regulation of OGG1 through tuberin. This mechanism may be important in the pathogenesis of kidney tumors in patients with TSC disease

Investigating whether UK business schools need to be more business-like in order to survive in today’s dynamic environment

© Emerald Group Publishing Limited. Purpose-The purpose of this paper is to clarify whether UK business schools need to change their strategy, to adopt a more business-like approach, without compromising their role as providers of “quality education”. Business-like activities, as explained by Dart (2004, p. 294) are generally understood to be those characterised by some blend of profit motivation, the use of managerial and organisation design tools developed in for-profit business settings, and broadly framed business thinking to structure and organise activity. Design/methodology/approach-Adopting a mixed methods research design, this study involved the review of quantitative data from questionnaires sent to senior managers within UK business schools, followed by the case-study analysis of five UK-based business schools. Findings-Contemporary evidence suggests business schools have reacted to the current dynamic environment by adapting a more business-like approach, scanning the horizon and identifying new markets and opportunities for growth. However, some business schools remain ardently against a more business-like approach, considering it to work against academic clarity and research excellence, expected of universities. Originality/value-This paper illustrates the current challenges influencing strategy within five diverse UK business schools. Therefore, the original contribution of the paper lies in the authors’ empirical investigations into the current thinking and practice of existing business school leaders, in light of the changing HE policies and reduced funding arrangements

Status of marine protected areas in Egypt

Egypt has sought to protect its natural resources and marine biodiversity by establishing a network of six MPAs that are generally located in the Gulf of Aqaba and the Red Sea; most of them include interconnected marine and terrestrial sectors based on conserving coral reefs and accompanying systems. We assessed the present status of MPA networks that showed a set of important results manifested in some strengths (i.e. proper selection according to specific criteria, management plans, etc.), and also some weaknesses (i.e. a relatively small protected proportion of the Egyptian marine territorial waters, significant pressures mainly by tourism activities, etc.). Finally, some recommendations are proposed from this work (i.e. incorporate more habitats that are not well represented in the network, especially on the Mediterranean Sea; establishing a touristic carrying capacity of each area; etc.) to improve the current situation. Key words: Marine reserves, Fishing, Tourism, Conservation, Sustainable development, Egypt.Egipto ha establecido una red de seis áreas marinas protegidas (AMPs), situadas principalmente en el Golfo de Aqaba y el mar Rojo para proteger sus recursos naturales y su biodiversidad marina. La mayoría incluyen sectores terrestres y marinos interconectados con el fin de conservar los arrecifes de coral y otros sistemas acompañantes. El estado actual de la red de AMPs se manifiesta mediante algunos puntos fuertes (selección basada en criterios apropiados, existencia de planes de gestión, etc.) y también algunos puntos débiles (protección de una proporción relativamente pequeña de las aguas territoriales egipcias; presiones significativas de algunas actividades, principalmente el turismo, etc.). Finalmente, se proponen algunas recomendaciones (incorporación de más hábitats que no están bien representados en la red actual, particularmente en el Mediterráneo; establecimiento de una capacidad de carga turística para cada área; etc.) para mejorar la situación actual. Palabras clave: Reservas marinas, Pesca, Turismo, Conservación, Desarrollo sostenible, Egipto.Egypt has sought to protect its natural resources and marine biodiversity by establishing a network of six MPAs that are generally located in the Gulf of Aqaba and the Red Sea; most of them include interconnected marine and terrestrial sectors based on conserving coral reefs and accompanying systems. We assessed the present status of MPA networks that showed a set of important results manifested in some strengths (i.e. proper selection according to specific criteria, management plans, etc.), and also some weaknesses (i.e. a relatively small protected proportion of the Egyptian marine territorial waters, significant pressures mainly by tourism activities, etc.). Finally, some recommendations are proposed from this work (i.e. incorporate more habitats that are not well represented in the network, especially on the Mediterranean Sea; establishing a touristic carrying capacity of each area; etc.) to improve the current situation. Key words: Marine reserves, Fishing, Tourism, Conservation, Sustainable development, Egypt

Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients

BACKGROUND: The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. RESULTS: Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. CONCLUSION: These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients

Arsenic in the sea

Although the microdetermination of arsenic in biological materials is of interest because of its toxicity, still the determination of arsenic in sea water has received but little attention, despite the fact that most of the marine animals and plants concentrate this element in their tissues. We are in some doubt about the physiological Rignificance of arsenic, as well Bs about the forms in which it occurs in the sea

Tuberin haploinsufficiency is associated with the loss of OGG1 in rat kidney tumors

<p>Abstract</p> <p>Background</p> <p>Tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, <it>TSC-1 </it>or <it>TSC-2</it>. <it>TSC-2 </it>gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors. Loss of heterozygosity (LOH) at the <it>TSC2 </it>locus has been detected in <it>TSC</it>-associated renal cell carcinoma (RCC) and in RCC in the Eker rat. Tuberin downregulates the DNA repair enzyme 8-oxoguanine DNA-glycosylase (OGG1) with important functional consequences, compromising the ability of cells to repair damaged DNA resulting in the accumulation of the mutagenic oxidized DNA, 8-oxo-dG. Loss of function mutations of OGG1 also occurs in human kidney clear cell carcinoma and may contribute to tumorgenesis. We investigated the distribution of protein expression and the activity of OGG1 and 8-oxo-dG and correlated it with the expression of tuberin in kidneys of wild type and Eker rats and tumor from Eker rat.</p> <p>Results</p> <p>Tuberin expression, OGG1 protein expression and activity were higher in kidney cortex than in medulla or papilla in both wild type and Eker rats. On the other hand, 8-oxo-dG levels were highest in the medulla, which expressed the lowest levels of OGG1. The basal levels of 8-oxo-dG were also higher in both cortex and medulla of Eker rats compared to wild type rats.</p> <p>In kidney tumors from Eker rats, the loss of the second <it>TSC2 </it>allele is associated with loss of OGG1 expression. Immunostaining of kidney tissue shows localization of tuberin and OGG1 mainly in the cortex.</p> <p>Conclusion</p> <p>These results demonstrate that OGG1 localizes with tuberin preferentially in kidney cortex. Loss of tuberin is accompanied by the loss of OGG1 contributing to tumorgenesis. In addition, the predominant expression of OGG1 in the cortex and its decreased expression and activity in the Eker rat may account for the predominant cortical localization of renal cell carcinoma.</p

Characterizing Feeds and Feed Availability in Sud-Kivu Province, DR Congo

Animal husbandry in the Sud-Kivu province of the Democratic Republic of the Congo (DRC) is gradually moving towards stall feeding, due to demographic pressure (Battistin et al. 2009) and scarcity of collectable forages (DSRP-RDC 2005). Therefore, feed is considered one of the main constraints faced by livestock production, especially in the dry season (Katunga et al. 2009; Maass et al. 2012). Unaffordable, fluctuating prices and inaccessibility of feed concentrates and the lack of improved forages adapted to marginal conditions, making them non-competitive with food crops, further exacerbate the livestock feeding situation. This study within the African Food Security Initiative, with funding from AusAID, aimed to assess specific constraints and opportunities in the current feeding systems, as well as feed availability in this area

Orbital Aspergillosis: Voriconazole – The New Standard Treatment?

Background/Aim: To describe a case of invasive orbital aspergillosis and evaluate treatments and outcomes. Methods: A case report and review of orbital aspergillosis treatment with voriconazole in the English language literature. Conclusion: Amphotericin B with debridement is the current standard of care for orbital aspergillosis; however, its prognosis is unfavorable. When compared to amphotericin B, voriconazole demonstrates a survival benefit, has less systemic toxicity, and is better tolerated by patients. While a prospective trial comparing amphotericin B to voriconazole in orbital aspergillosis is not feasible, there is evidence to support the use of voriconazole as primary therapy

Allogeneic Guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis

No grant i

Determinants of participation in cavy marketing: Evidence from the Democratic Republic of Congo

Smallholder supply chain participation remains low despite the potential welfare gains that would result from choosing a market-oriented production. Yet, studies on determinants of market participation for commodities with underdeveloped value chains are scanty. Employing a double-hurdle model, this paper examines factors determining households’ participation in cavy marketing among cavy farmers from Sud-Kivu province in the Democratic Republic of Congo. We find that wealthier households participated less in cavy marketing while those producing more cavies were more likely to participate in their marketing. Moreover, smaller households tended to sell more cavies, while households with other livestock sold fewer cavies. The findings underscore the significance of increasing the participation in the cavy supply chains by farmers through the promotion of appropriate husbandry practices that enhance cavy productivity and production and that enable farmers to participate in markets as sellers