Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise

The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft, and in vitro models to investigate the impact of chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double-strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose dependent fashion as revealed by accumulating γH2AX foci. This damage was associated with apoptotic oocyte death and resulted in the activation of ATM. It appeared that the repair response enabled a minor proportion of oocytes (34.7%) and granulosa cells (12.1%) to survive while the majority succumbed to apoptotic death. Paradoxically, inhibition of ATM by KU-55933 resulted in improved survival, probably via prevention of downstream activation of TAp63α. Furthermore, doxorubicin caused vascular and stromal damage in the human ovary, which might impair ovarian function both pre- and post-menopausally. Chemotherapy-induced premature ovarian aging appears to result from a complex process involving both the germ- and non-germ cell components of the ovary. These effects may have clinical implications in aging both for premenopausal and postmenopausal cancer survivors

Behavioral Accounting and its Interactions

Behavioral accounting is a branch of accounting that is related to behavior besides the accounting knowledge. It deals with the attitude and behavior of people when they are encountered with an accounting phenomenon which determines the behavior that they will show in decision‐making. This special area of accounting addresses such aspects as human information‐processing behavior, judgment quality, accounting problems that are created by users and providers of accounting information, and accounting information users’ and producers’ decision‐making skills. Behavioral research tries to find out how individuals make decisions and interact and influence other individuals, organizations, markets, and society. Behavioral accounting concept is examined under the topics of the influence of accounting information on behavior, managerial control (budget participation, nonfinancial measures, leadership, and balanced scorecard), auditing (auditor‐client negotiations, auditor’s judgment, and decision‐making), and ethics (ethical decision‐making, ethical orientation, and rationalizations on unethical behavior) in this chapter

The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse

BACKGROUND: Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). METHOD: In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16). RESULTS: Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. However, p16 staining was stronger (++) in the oocytes of all primordial, and 57.4 ± 3.1% of primary follicles compared to the remaining primary and more advanced follicles (+). Interestingly, primary follicles with weaker (+) oocyte staining for p16 had significantly larger mean follicle diameter compared to the primary and primordial follicles with stronger (++) oocyte staining (55.6 ± 2.1 vs. 32.0 ± 1.0 and 26.5 ± 0.7 μm, respectively, p < 0.0001). This difference in follicle diameter was mainly due to a larger mean oocyte diameter (primary follicles, stronger vs. weaker, 19.6 ± 0.6 vs. 31.5 ± 1.4 μm, p < 0.0001). Oocytes of atretic follicles showed stronger staining with all four CDKIs. CONCLUSIONS: These preliminary findings suggest that the initiation of oocyte growth, which seems to lead follicle growth, is associated with diminished p16 expression in the mouse ovary. Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth

Muhasebe dersi alan ogrencilerin etik karar alma surecini etkileyen faktorler uzerine bir arastirma

In our study, we investigated whether the department, grade and having taken accounting ethics courses affect the ethical decison-making of first grade and fourth grade students attending Business Administration and Public Finance departments of Akdeniz University. According to our findings, which are in conformity with other studies, women have a stronger ethical judgement, business administration students have more flexible ethical values and the students that have already taken accounting ethics courses have stronger ethical values. Considering the findings of this work and other studies, we conclude that it may be helpful if the students were given accounting ethics courses.peer-reviewe

White'in Heteroskedisite Tutarli Kovaryans Matrisi Tahmini Yoluyla Heteroskedisite Altinda Model Tahmini

This paper presents estimation of the White’s Heteroskedasticity Consistent Covariances and simple a solutions suggestion for Heteroskedasticity problem. According to White “when heteroskedasticity can not be completely eliminated, the heteroskedasticity consistent covariance matrix allows correct inferences and coefidence intervals to be obtained.”White, Heteroskedasticity, Robus Estimation; Heteroskedasticity Consistent Covariance, Eviews

Enhancement of Neoangiogenesis and Follicle Survival by Sphingosine-1-Phosphate in Human Ovarian Tissue Xenotransplants

Ovarian transplantation is one of the key approaches to restoring fertility in women who became menopausal as a result of cancer treatments. A major limitation of human ovarian transplants is massive follicular loss during revascularization. Here we investigated whether sphingosine-1-phosphate or its receptor agonists could enhance neoangiogenesis and follicle survival in ovarian transplants in a xenograft model. Human ovarian tissue xenografts in severe-combined-immunodeficient mice were treated with sphingosine-1-phosphate, its analogs, or vehicle for 1–10 days. We found that sphingosine-1-phosphate treatment increased vascular density in ovarian transplants significantly whereas FTY720 and SEW2871 had the opposite effect. In addition, sphingosine-1-phosphate accelerated the angiogenic process compared to vehicle-treated controls. Furthermore, sphingosine-1-phosphate treatment was associated with a significant proliferation of ovarian stromal cell as well as reduced necrosis and tissue hypoxia compared to the vehicle-treated controls. This resulted in a significantly lower percentage of apoptotic follicles in sphingosine-1-phosphate-treated transplants. We conclude that while sphingosine-1-phosphate promotes neoangiogenesis in ovarian transplants and reduces ischemic reperfusion injury, sphingosine-1-phosphate receptor agonists appear to functionally antagonize this process. Sphingosine-1-phosphate holds great promise to clinically enhance the survival and longevity of human autologous ovarian transplants

An Empirical Approach to Determine the Relationship Strength between Internet Media and Online Readership

İnternet gazeteciliğinin gelişimiyle birlikte Web üzerindeki içerik sürekli artmakta, medya hizmetlerinin odağı medyatör ile hızlı biçimde kendisini ilgilendiren haberlere erişmek isteyen okur arasındaki ilişkiye kaymaktadır. Bu isteğin gerçekleştirilmesi, daha önce okurun düzensiz davranışlarına göre kişiselleştirilmiş Web içeriğinin oluşturulmasına dayalıdır. Bu çalışmada İnternet gazetesi okurlarının kendi istedikleri tür haber yazılarına hızlı ulaşımında elverişli sonuçlar elde edebilmek amacıyla kişiselleştirmede daha ileri gidebilmek için okurların tercihleri incelenmektedir. Tercih davranışlarını saptayabilmek amacıyla ilişki yönetimi ölçüm teknikleri, özellikle de RFM yaklaşımı, CRM çalışmalarından ödünç alınmış ve okur ile içerik türleri arasındaki ilişkiye uyarlanmıştır.Web content in the context of online news is growing at a rapid speed where traditional news reading habits shift in favour of the Internet version. At the same time readership behaviour also changes from print paper readers to more selective online users, who expect news services follow general trends of the online media such as dynamic customised content and personalisation. In an environment where users are often reluctant to fill forms or reveal their preferences in news content, this entails that the online news Web site has to track the behaviour of the reader and serve the reader the content that fits his or her requirements. In this study online readership preferences are observed to produce personalised content, types of news articles that are more relevant to the reader’s preferred categories. The problem is then reduced to determining the strength of the relationship between the reader node and the news category nodes, at which a relationship metric is borrowed from Customer Relationship Management studies