Dual role of Sirtuin 3 in carcinogenesis

Različiti oblici raka jedan od najčešćih uzroka smrtnosti širom svijeta, a s obzirom da mnogi terapeutici vremenom gube djelotvornost, potrebno je razviti nove strategije liječenja. Mnoga istraživanja pokazala da se potencijalne terapije raka mogu bazirati na manipulacijama nad Sirt3, NAD+ ovisne deacetilaze dominantno smještene u mitohondrijima. Sirt3 kontrolira acetilacijski status proteina i tako regulira obranu stanice od stresa, produkciju reaktivnih kisikovih vrsta, metabolizam, ATP sintezu, stanični ciklus, apoptozu i proliferaciju zbog čega se naglašava njegova važna uloga u karcinogenezi. No, ovisno o specifičnom staničnom kontekstu, tj. vrsti raka kao i eksperimentalnim uvjetima, Sirt3 pokazuje ili onkogena ili tumor-supresorska svojstva iz čega proizlazi njegova dualnost. Stoga je cilj ovog rada razjasniti uloge Sirt3 u biologiji raka te objediniti poznate podatke i mehanizme kojima Sirt3 svojim proonkogenim i/ili tumor-supresorskim svojstvima utječe na proliferaciju, metabolizam, metastaziranje, upalu i angiogenezu raka. Na temelju obrađenih podataka za desetak vrsta tumora, može se zaključiti kako su različiti tumor-supresorski ili proonkogeni Sirt3-ovisni mehanizmi prisutni u različitim, ali i unutar istih tipova tumora što dodatno naglašava dualnost. Odnosno kroz aktivaciju i inhibiciju različitih signalnih puteva i/ili transkripcijskih faktora kao i kroz regulaciju razine oksidativnog oštećenja Sirt3 može kontrolirati ishod karcinogeneze pa tako kod raka pluća ne-malih stanica i oralnog raka djeluje kao onkogen, a kod raka pluća malih stanica, raka jetre, žučnih vodova i prostate pokazana je tumor-supresorska uloga. Posebno se zanimljivi rezultati za rak debelog crijeva, jajnika i dojke kod kojih je u različitim ekspreimentima potvrđena i proonkogena i tumor-supresorska uloga unutar istog tipa raka.Cancer is one of the most frequent causes of mortality worldwide, and because of many cancer therapeutics lose their efficiency with time, it is urgent to develop novel curing strategies. Many researches have shown that potential therapies could be based on Sirtuin 3 (Sirt3) manipulation. Sirt3 is NAD+ dependent deacetylase dominantly located in mitochondria that controls protein-acetylation status in cells, regulates cellular stress response, reactive oxygen species (ROS) production, cell metabolism, ATP synthesis, cell cycle, apoptosis and proliferation, thus having a very important role in tumorigenesis. However, depending on the cellular context, type of cancer and experimental conditions Sirt3 can have a dual role – it can act as oncogene and/or tumor supressor. Therefore, aim of this paper is to elucidate roles of Sirt3 in cancer biology and to assemble known information and mechanisms on how Sirt3, with its oncogene or tumor supressor properties, affects cancer proliferation, metabolism, metastasis, inflamation and angiogenesis. Based on processed data for several cancer types, it could be concluded that different oncogene or tumor supressor Sirt3-depended mechanisms are present in the different, but also within the same types of cancer, which further emphasizes duality of Sirt3. Thus, through activation or inhibiton of various signling pathways and/or transcriptional factors along with oxidative damage regulation, Sirt3 controls outcome of carcinogenesis. For inastance, Sirt3 acts as oncogen in non-small cell lung cancer and oral cancer, whereas in small-cell lung cancer, hepatocelullar carcinoma, cholangiocarcinoma and prostate cancer as tumor suppressor. Results for colorectal, ovarian and breast cancer are especially interesting because researches have sh

Addressing Enrollment Declines Through International Partnerhips

The enrollment declines in information systems (IS) related fields over the past several years has led to research that has examined the causes of it and a variety of possible approaches to reverse this trend. With the recent economic downturn resulting in cuts in education budgets, the need to increase enrollments in IS has become critical for many departments in this field. The objective of this research is to discuss how international partnerships can be utilized as an additional means to improve enrollments, which is an approach that has not been addressed before in the literature. The author illustrates the opportunities possible with international partnerships through a case involving an IS department located in the Southeastern United States and multiple universities in Asia. This research then highlights strategies to establish a successful international partnership followed by some concluding remarks

NOVICE TEACHERS’ PERCEPTIONS OF THEIR PREPAREDNESS TO TEACH STUDENTS EXPERIENCING TRAUMA: A MIXED METHODS STUDY

The purpose of this mixed-methods study was to explore how graduates of traditional teacher preparation programs perceived their preparedness to teach students experiencing trauma stemming from adverse childhood experiences (ACEs). The study focused on the perceptions of novice teachers working in Title 1 schools across two school districts in Central Florida. The quantitative research portion of the study involved an online survey addressing the impact of teacher preparation program coursework and clinical experiences on the teachers’ perceptions of preparedness. Qualitative data was gathered from semi-structured interviews after the survey to give voice to the novice teachers’ perceptions of preparedness. Study findings yielded implications relevant to the critical need for the inclusion of SEL competencies and trauma-informed teaching practices in teacher preparation programs. A clear need exists for leadership and faculty in traditional teacher preparation programs to purposefully transform university coursework and clinical experiences and ensure program outcomes include aspects of trauma-informed care

MINDFUL SOFTWARE IMPLEMENTATIONS: A CASE STUDY OF A UNIVERSITY PORTAL SYSTEM

Despite several high-profile examples of software implementation failures, it is common today for organizations to fall into the same mindless traps that have plagued those prominent failures. The goal of this research is to examine how organizations avoid these traps and what efforts, if any, are made to ensure that they do not fall victim to them again in the future. A case study approach involving a series of in-depth interviews was conducted to explore this phenomenon. The findings of this study reveal several rich insights that may be useful to both practitioners and researchers

Time-Domain Finite Elements for Virtual Testing of Electromagnetic Compatibility

The paper presents a time-domain finite-element solver developed for simulations related to solving electromagnetic compatibility issues. The software is applied as a module integrated into a computational framework developed within a FP7 European project High Intensity Radiated Field – Synthetic Environment (HIRF SE) able to simulate a large class of problems. In the paper, the mathematical formulation is briefly presented, and special emphasis is put on the user point of view on the simulation tool-chain. The functionality is demonstrated on the computation of shielding effectiveness of two composite materials. Results are validated through experimental measurements and agreement is confirmed by automatic feature selective algorithms

Implementing a SOA Using Scrum: Achieving Improved Productivity using Service Trees

Service Oriented Architecture (SOA) is spreading widely today in a variety of development environments. Many organizations pursing a SOA, however, are unaware of the impact that this approach has on their development methodology and implementation strategies, which may be inappropriate and inefficient. Some issues caused by an inappropriately managed SOA implementation include dependency conflicts, inefficient time utilization, and ineffective utilization of resources resulting in a backlog of tasks. The individuality of services creates a gap that makes service implementation a relevant topic to pursue which can be addressed through the granular development of these services. Consequently, this research-in-progress examines SOA-based services development by focusing on service generation and proposing the concept of service trees whose branches serve as nodes of SOA-based services. Further, implementing the tree’s branches utilizing the scrum development methodology produces an approach where multiple services can be developed in parallel, offering a means to improve the productivity of a SOA implementation

LEAPing forward: A Case Study Employing High Impact Practices in Undergraduate Education

In support of a major curriculum association initiative adopted by a large Midwestern business college, faculty adopted a hands-on community service-based project in an undergraduate business project management course. The project was developed in order to incorporate the specific High-Impact Educational Practice (HIP) of service or community-based learning, as defined by the Liberal Education and America’s Promise (LEAP) initiative. This research describes (1) how the project management faculty revised the course to incorporate service and community-based learning, (2) related student activities, (3) preliminary results, and (4) next steps