The functional role of ADAMTS-1 and -15 in prostate cancer progression

Introduction: Prostate cancer is a leading cause of cancer death in men. Death is usually a consequence of castration resistant tumour progression. Some metalloproteinases are implicated in the process of cancer progression. ADAMTS proteinases (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) are metalloproteinases that play diverse roles in tissues. Prostate cancer cells express ADAMTS-1 and -15 but the role played by these proteinases in prostate cancer progression is unknown. This study was designed to determine the role of ADAMTS-1 and 15 in prostate cancer progression. Materials & Methods: Prostate cancer and stromal cell tumour spheroids were grown in 3-dimensional culture in ECM gel containing a quenched-fluorescent substrate. The tumour spheroids were observed for evidence of proteolytic activity. Prostate cancer cells were treated with DHT and TNF. Changes in expression of ADAMTS-1 and -15 were analysed. ADAMTS-1 and -15 expression was knocked-down in PC3 prostate cancer cells and the effect of knock-down on proliferation, migration and invasion was analysed. Results: Tumour spheroids emitted fluorescence after approximately 24 hours in culture, indicating proteolytic activity. DHT and TNF down-regulated ADAMTS-15 expression in LNCaP cells and stromal cells respectively. The validated anti-ADAMTS- 15 antibody detected 50kDa bands, suggesting a novel cleavage site within the disintegrin-like domain of ADAMTS-15. ADAMTS-1 and 15 knock-down had no effect on proliferation, migration or invasion of PC3 prostate cancer cells. Conclusions: Prostate cancer and stromal cells degrade components of the surrounding ECM. ADAMTS-15 but not ADAMTS-1 expression is androgen and TNF-regulated. ADAMTS-1 and 15 expression do not affect the proliferation, migration or invasive potential of PC3 cells in vitro. Cleavage of ADAMTS-15 in the disintegrin-like domain results in the release of a C-terminal fragment with potential anti-angiogenic properties. Down-regulation by DHT in prostate cancer cells suggests that ADAMTS-15 could be playing an anti-tumour role in prostate cancer progression

Effects of Library Infrastructure on Turnover Intentions of Librarians: A Study of University Libraries in South-South and South-East of Nigeria

Research into the phenomenon of turnover intentions of employees and its effects on organizational development is crucial; hence this study investigated the effects of library infrastructure on turnover intentions of librarians in university libraries in South-South and South-East of Nigeria. The study adopted a descriptive survey using total enumeration method with 400 academic librarians from the two zones in participation. The instrument for data collection was questionnaire which was subjected to a reliability test using Cronbach’s alpha reliability coefficient with a result of 0.72, which means that the instrument was good and reliable since the test result is above the acceptance point of 0.50. All the questionnaires administered on the respondents were retrieved with 334 of the questionnaires found usable for the analysis. Findings revealed that inadequate infrastructure have the tendency of increasing the turnover intentions of librarians in the university libraries in South-South and South East of Nigeria (X = 3.03); while advancement in library infrastructure enhances professional development and increase the chance of retaining librarians in the library (X = 3.05). Evidence from the study indicated that a higher deficiency in library infrastructure will increase the level of turnover intentions of librarians in the university libraries in South-South and South-East of Nigeria. The study recommended that the university librarians and university managements in South-south and South-east of Nigeria should holistically assess their library infrastructure with a view of ascertaining their state and make available budgetary allocation that will take care of dilapidated library infrastructure to mitigate the effects of turnover intentions of librarians in university libraries in South-South and South-East of Nigeria

Effects of Library Infrastructure on Turnover Intentions of Librarians: A Study of University Libraries in South-South and South-East of Nigeria

Research into the phenomenon of turnover intentions of employees and its effects on organizational development is crucial; hence this study investigated the effects of library infrastructure on turnover intentions of librarians in university libraries in South-South and South-East of Nigeria. The study adopted a descriptive survey using total enumeration method with 400 academic librarians from the two zones in participation. The instrument for data collection was questionnaire which was subjected to a reliability test using Cronbach’s alpha reliability coefficient with a result of 0.72, which means that the instrument was good and reliable since the test result is above the acceptance point of 0.50. All the questionnaires administered on the respondents were retrieved with 334 of the questionnaires found usable for the analysis. Findings revealed that inadequate infrastructure have the tendency of increasing the turnover intentions of librarians in the university libraries in South-South and South East of Nigeria (X = 3.03); while advancement in library infrastructure enhances professional development and increase the chance of retaining librarians in the library (X = 3.05). Evidence from the study indicated that a higher deficiency in library infrastructure will increase the level of turnover intentions of librarians in the university libraries in South-South and South-East of Nigeria. The study recommended that the university librarians and university managements in South-south and South-east of Nigeria should holistically assess their library infrastructure with a view of ascertaining their state and make available budgetary allocation that will take care of dilapidated library infrastructure to mitigate the effects of turnover intentions of librarians in university libraries in South-South and South-East of Nigeria

Androgen receptor (AR) antagonism triggers acute succinate‐mediated adaptive responses to reactivate AR signaling

Abstract Treatment‐induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration‐resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate dehydrogenase (SDH), a TCA cycle enzyme with well‐known tumor suppressor activity. We show that AR directly regulates transcription of its catalytic subunits (SDHA, SDHB) via androgen response elements (AREs). ARPI acutely suppresses SDH activity, leading to accumulation of the oncometabolite, succinate. Succinate triggers calcium ions release from intracellular stores, which in turn phospho‐activates the AR‐cochaperone, Hsp27 via p‐CaMKK2/p‐AMPK/p‐p38 axis to enhance AR protein stabilization and activity. Activation of this pathway was seen in tissue microarray analysis on prostatectomy tissues and patient‐derived xenografts. This adaptive response is blocked by co‐targeting AR with Hsp27 under both in vitro and in vivo studies, sensitizing PCa cells to ARPI treatments

Colonialism, migration and intergroup relations in Africa: The Igbo and their Southern Cameroon neighbours, 1916-2014

Migration has been an inseparable and indispensable part of the history of the Igbo nation. However, the nature, dynamics, and drivers of migration among the Igbo significantly altered since colonial era. Scholars have interrogated aspects of migration and its impact on the Igbo nation. Not many studies; however, have interrogated Igbo migration into Cameroon as well as the Igbo-Cameroon Intergroup relations during the period under review. This paper, therefore, examines the drivers of migration, the nature, dynamics, and impact of Igbo-Cameroon intergroup relations on both groups during the period under review. The study utilized primary and secondary sources while thematic, historical descriptive and analytical approaches were employed in the analysis of its data. The study reveals that colonialism impacts the nature of migration among the Igbo, particularly, from the 20th century up to the mid-20th century.</p