The transcription factor Nrf2 is an important modulator of antioxidant and drug metabolism, carbohydrate and lipid metabolism, as well as heme and iron metabolism. Regulation of Nrf2 expression occurs transcriptionally and post-transcriptionally. Post-transcriptional regulation entails ubiquitination followed by proteasome-dependent degradation. Additionally, Nrf2-mediated gene expression is subject to negative regulation by ATF3, Bach1 and cMyc. Nrf2-mediated gene expression is an important regulator of a cell’s response to radiation. Although a majority of studies have shown that Nrf2 deficient cells are radiosensitized and Nrf2 over expression confers radioresistance, Nrf2’s role in mediating the radiation response of crypt cells is controversial. The Nrf2 activator CDDO attenuates radiation-mediated crypt injury, whereas intestinal crypts in Nrf2 null mice are radiation resistant. Further investigation is needed in order to define the relationship between Nrf2 and radiation sensitivity in Lgr5+ and Bmi1+ cells that regulate regeneration of crypt stem cells. In hematopoietic compartments Nrf2 promotes the survival of irradiated osteoblasts that support long-term hematopoietic stem cell (LT-HSC) niches. Loss of Nrf2 in LT-HSCs increases stem cell intrinsic radiosensitivity, with the consequence of lowering the LD5030. An Nrf2 deficiency drives LT-HSCs from a quiescent to a proliferative state. This results in hematopoietic exhaustion and reduced engraftment after myoablative irradiation. The question of whether induction of Nrf2 in LT-HSC enhances hematopoietic reconstitution after bone marrow transplantation is not yet resolved. Irradiation of the lung induces pulmonary pneumonitis and fibrosis. Loss of Nrf2 promotes TGF-β/Smad signaling that induces ATF3 suppression of Nrf2-mediated target gene expression. This, in turn, results in elevated reactive oxygen species (ROS) and isolevuglandin adduction of protein that impairs collagen degradation, and may contribute to radiation-induced chronic cell injury. Loss of Nrf2 impairs ΔNp63 stem/progenitor cell mobilization after irradiation, while promoting alveolar type 2 cell epithelial-mesenchymal transitions into myofibroblasts. These studies identify Nrf2 as an important factor in the radiation response of normal tissue.

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Ewing sarcoma is a rare cancer found in children and young adults. Long term survival rates are approximately 70% for patients who present without clinically overt metastases. However, 5 year survival is less than 20% for patients with recurrent tumors or metastasis. Thus, there is a need to improve local tumor control and to treat metastatic disease. Eighty five percent of these cancers are driven by the reciprocal chromosomal translocation t (11;22) (q24;q12), a consequence of a fusion between the 5' portion of Ewing sarcoma breakpoint region 1 on EWSR1 (chromosome 22) and the 3' portion of Friend leukemia virus integration site 1 on FLI1 (chromosome 11). Nucleophosmin1 (NPM1) is a chaperone protein involved in many cellular functions, including DNA repair. NPM1 has been shown to be a novel prognostic biomarker for patients with localized Ewing's sarcoma. Overall survival is significantly lower for patients whose tumors express high levels of NPM1. Besides promoting repair of DNA double strand breaks NPM1 directly interacts with and induces c-Myc-induced hyperproliferation and transformation. Consistent with this knowledge is the observation that relapsed Ewing's patients exhibit high levels of c-Myc expression compared to disease-free patients. Therefore, we wanted to ascertain whether NPM1 represented a molecular target for controlling growth of Ewing's sarcoma. CRISPR/Cas9-mediated targeting of NPM1 exons 3 and 4, as well as lentivirus-mediated shRNA targeting of NPM1 mRNA revealed that targeting of NPM1 expression reduced survival (colony formation) of TC32 and A673 cells (P<0.05). NPM shRNA also reduced TC32 sphere formation under non-adherent conditions. YTR107 and NSC348884 are small molecule inhibitors of NPM1 oligomerization, which is required for NPM1 activity. Both drugs reduced survival of TC32 and A673 Ewing's sarcoma cells in a dose-dependent fashion (P<0.05). We interpret these data to indicate that NPM1 represents a potential molecular target for controlling growth of Ewing's sarcoma. Supported in part by RO1CA140409. Citation Format: Geri Traver, Konjeti R. Sekhar, Narsimha R. Renthala, Peter A. Crooks, Maxwell Ofori, Michael L. Freeman. Targeting NPM1 for controlling growth of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3189.

Undoubtedly, HIV/AIDS menace has been a major source of concern to everyone, particularly, the people of Lower Manya Krobo Municipality (LMKM) as the area has always recorded a higher rate of infections compared with other districts in Ghana. Against this backdrop, the study sought to assess the HIV/AIDS knowledge of Senior High School students in the Lower Manya Krobo Municipality of the Eastern Region of Ghana. To obtain the respondents, a simple random sampling technique was adopted to select 300 students, comprising 120 boys and 180 girls proportionately selected from the four public Senior High Schools in the Municipality. A-37 item questionnaire adapted from Wanjiru Helen Wairimu was used for the data collection. The obtained data were analysed using descriptive statistics (means, standard deviations, frequencies, and percentages). The study found that the majority of the senior high school students in the LMKM of Ghana have high knowledge about HIV/AIDS through several available sources within their domain. However, it was again found out that HIV/AIDS knowledge they have does not have much impact and influence on their sexual behaviour. Several recommendations were suggested which include; the fact that the Ministry of Health in collaboration with other important educational agencies should intensify sex education to students and the community members in order to strengthen their awareness of HIV/AIDS.

The study objective was to assess the perceptions of Junior High School (JHS) Social Studies teachers in the Yilo Krobo Municipality of the Eastern Region of Ghana on teachers' Pedagogical Content Knowledge (PCK). The study adopted Shulman's theory of Pedagogical Content Knowledge (PCK) as its theoretical framework. The philosophical approach upon which the study is hinged on is the ideology of interpretivism and positivism, in other words, pragmatism. The study used a mixed methodological approach as well as a descriptive survey design. A random sampling technique was used for the study. The study participants were JHS social studies teachers in Yilo-Krobo Municipality, Ghana. Eighty (80) out of the one hundred and two (102) representing 78.43% JHS Social Studies teachers were selected from the fifty-four JHSs in the Municipality. Both Questionnaire and interview guide were used for data collection. The survey data was analyzed using descriptive statistics and the interview data was analyzed using content analysis. The study indicated that at the heart of the PCK concept is the idea that 'deep knowledge' of content is essential for effective teaching and cannot be taken for granted; that it has a significant bearing on teaching and student learning, and that it is used as a cadre to define professional teaching knowledge. PCK also provides the uniquely necessary knowledge for the transformation of the different types of knowledge required for Social Studies teaching and evolves over time due to the progressive awareness of students' needs, while a wealth of content knowledge is imperative for the development of a comprehensive pedagogical content knowledge. The paper recommends that the Ghana Education Service (GES) should conduct regular in-service training for teachers on the enhancement of their PCK, to enable them select appropriate TLMs and pedagogical approaches that foster meaningful learning for students.

Some practices are barbaric, atrocious, backward, immoral, commoditization and an abusive violation of the sexual and human rights of the powerless. Widowhood rites are performed at the fresh funeral and during the final funeral rites. Widows prefer to be inherited by their grandsons so that they are free to choose a man of their choice and still hold on to their deceased husband assets. The Talensi widow would strangle a goat and part of the skin is used to cover the private of the dead for burial. The Nabdams would slaughter a sheep and an elder will slaughter it. In both cases older women served as the enforcers and custodians of such practices. The purpose of this study was to examine widowhood rites practices among the people of Talensi and Nabdam in the Upper East Region of Ghana. The study employed ethnography research method. Purposive sampling technique was used to sample twenty (20) widows from Talensi and Nabdam. The study recommended that Ghana's widows need to lead in the reporting of violations of their rights to the appropriate state institutions responsible and follow up to ensure justice is delivered. Non-governmental Organizations and Community-based organizations which are advocating for the abolition of widowhood rites should collaborate with traditional authorities to modify the practices.