Downregulation of BORIS/CTCFL leads to ROS-dependent cellular senescence and drug sensitivity in MYCN-amplified neuroblastoma.

Brother of Regulator of Imprinted Sites (BORIS) or CCCTC-binding factor like (CTCFL) is a nucleotide-binding protein, aberrantly expressed in various malignancies. Expression of BORIS has been found to be associated with the expression of oncogenes which regulate the reactive oxygen species (ROS) biogenesis, DNA double-strand break repair, regulation of stemness, and induction of cellular senescence. In the present study, we have analyzed the effects of knockdown of BORIS, a potential oncogene, on the induction of senescence and tumor suppression. Loss of BORIS downregulated the expression of critical oncogenes such as BMI1, Akt, MYCN, and STAT3, whereas overexpression increased their respective expression levels in MYCN-amplified neuroblastoma cells. BORIS knockdown exhibited high levels of ROS biogenesis, indicating an upregulated mitochondrial superoxide production and thereby induction of senescence. Our study also showed that the loss of BORIS facilitated cellular senescence through the disruption of telomere integrity via altering the expression of various proteins required for telomere capping (POT1, TRF2, and TIN1). In addition to affecting ROS production and DNA damage, BORIS knockdown sensitized the cells toward chemotherapeutic drugs and induced apoptosis. Tumor induction studies on in vivo xenograft mouse models showed that cells with loss of BORIS/CTCFL failed to induce tumors. From our study, we conclude that silencing BORIS/CTCFL influences tumor growth and proliferation by regulating key oncogenes. The results also indicated that the BORIS knockdown can cause cellular senescence and upon a combinatorial treatment with chemotherapeutic drugs can induce enhanced drug sensitivity in MYCN-amplified neuroblastoma cells.

Identification of suitable housing system for dairy cattle in North East Zone of Tamil Nadu, India, with respect to microclimate.

AIM: To identify the suitable roofing pattern for dairy cattle in North East Zone of Tamil Nadu, India, based on micro climatic conditions. MATERIALS AND METHODS: Initially, survey was conducted to identify and categorize the major housing patterns existing in the region for further detailed investigation. In total, 30 farmers/farms consisting of five housing types with six replicates were selected. Temperature and temperature humidity index (THI) were recorded using the maximum-minimum thermometer and digital thermo-hygrometers. The study was conducted for 1 year covering four seasons namely South West monsoon (June-August), North East monsoon (September-November), cold season (December-February), and summer season (April-May). The data were statistically analyzed using statistical package SPSS 17. RESULTS: Animal shelters with cement sheets recorded the highest temperature (26.71±1.13°C) and THI (77.23±1.76) at 8.00 am, whereas the lowest temperature (24.83±1.17°C) and THI (74.54±1.72) were recorded in the thatched shed. There was significant difference (p<0.01) in temperature and THI at 8.00 am during South West monsoon and North East monsoon seasons between the housing types. During cold and summer seasons, there was no significant difference (p≥0.05) in the environmental variables among various shelter systems. CONCLUSION: Thatched housing is found to be the suitable one with respect to the climatic variables, followed by tile roof and metal roof. The cement sheet roofed housing is found to be the most unsuitable one in the region for dairy cattle.