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Oseifuah, Emmanuel K., George NovisiKwadzo ., and Vukor-Quarshie . "Bachelor of Commerce Programme and employability of University of Venda graduates, South Africa." Journal of Economics and Behavioral Studies 6, no. 4 (April 30, 2014): 291–301. http://dx.doi.org/10.22610/jebs.v6i4.492.
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Since its establishment two and half decades ago, the School of Management Sciences at the University of Venda (UNIVEN) has produced hundreds of Bachelor of Commerce (BCOM) graduates for the South African work force. Yet the School has had no formal feedback from its graduates regarding the relevance, usefulness, strengths and weakness of its BCOM programmes. The purpose of this study was to assess the impact of the BCOM (Accounting) programme on job prospects of UNIVEN graduates. A structured questionnaire was sent to a sample of 61 graduates of UNIVEN’s BCOMA programme through the Snowball technique of tracing survey respondents. The questionnaire sought the participating graduates’ opinions on several aspects of their educational experience at Univen including adequacy of the training and employability, among others. The study used the IBM SPSS version 21 to analyse the study data. The key findings of the study suggest that the components of the BCOMA programme that need major improvement to increase the employability of graduates are training in practical skills, using computers in Accounting training, as well as improvement in teaching and delivery methods. The study also found that modules offered in the BCOM programme were relevant to the graduate’s job needs.
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Smallwood, Margaret Garnett. "The Need for Cross-Cultural Communication Instruction in U.S. Business Communication Courses." Business and Professional Communication Quarterly 83, no. 2 (February 19, 2020): 133–52. http://dx.doi.org/10.1177/2329490620903730.
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U.S. undergraduate business communication (BCOM) classes teach students workplace communication fundamentals, but may not build the cross-cultural communication (CCC) skills that learners will need in today’s global workplace. This project surveyed BCOM instructors and students about the importance of including cross-cultural material in BCOM classes. While all instructors considered it at least moderately important to include CCC material, most covered the subject briefly. Students showed interest in receiving CCC training in their BCOM courses but received limited information about it in their classes. Incorporating CCC comprehensively and systematically into BCOM classrooms may help students become competent intercultural communicators.
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McGann, Susie, Norman W. Evans, Benjamin L. McMurry, and Kurt Sandholtz. "Challenges in BCOM: Student and Faculty Perceptions on English as an Additional Language." Business and Professional Communication Quarterly 83, no. 3 (August 4, 2020): 309–35. http://dx.doi.org/10.1177/2329490620944880.
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Business remains a popular major for international students in the United States. Little is known, however, about how these students fare in business communication (BCOM) classes. This qualitative study evaluates the challenges and needs of English as an additional language (EAL) students in BCOM courses at a private university in the United States. We surveyed and interviewed 15 BCOM instructors and 30 students previously enrolled in BCOM. Results reveal faculty are aware of some, but not all, of the linguistic, cultural, emotional, time, and accommodation challenges EAL students face. We discuss suggestions for accommodating EAL students’ unique needs in BCOM courses.
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Cheung, Derek, Jeff Cheung, Vicky Cheung, and Li Jin. "A New Quantitative Gait Analysis Method Based on Oscillatory Mechanical Energies Measured near Body Center of Mass." Sensors 22, no. 22 (November 9, 2022): 8656. http://dx.doi.org/10.3390/s22228656.
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Human locomotion involves the modulation of whole-body mechanical energy, which can be approximated by the motion dynamics at the body’s center of mass (BCOM). This study introduces a new method to measure gait efficiency based on BCOM oscillatory kinetic energy patterns using a single inertia measurement unit (IMU). Forty-seven participants completed an overground walk test at a self-selected speed. The average oscillatory energy (OE) at BCOM during walking was derived from measured acceleration data. The total OE showed a positive correlation with forward-walking velocity. The ratio of total OE to constant forward kinetic energy for healthy adults varied from ~1–5%, which can be considered the percent of oscillatory energy required to maintain gait posture for a given forward-walking velocity. Mathematically, this ratio is proportional to the square of the periodic peak-to-peak displacement of BCOM. Individuals with gait impairments exhibited a higher percentage of oscillatory energy, typically >6%. This wearable IMU-based method has the potential to be an effective tool for the rapid, quantitative assessment of gait efficiency in clinical and rehabilitation settings.
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Hati, A. K., B. Paital, K. N. Naik, A. K. Mishra, G. B. N. Chainy, and L. K. Nanda. "Constitutional, organopathic and combined homeopathic treatment of benign prostatic hypertrophy: a clinical trial." Homeopathy 101, no. 04 (October 2012): 217–23. http://dx.doi.org/10.1016/j.homp.2012.08.005.
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Background: Benign Prostatic Hypertrophy (BPH) is common in older men. This study compared homeopathic treatment strategies using constitutional medicines (CM) or organopathic medicines (OM) alone or in combination (BCOM) in patients suffering from BPH.Methods: 220 men aged 30–90 years were recruited in Odisha, India. Patients presenting symptoms of prostatism, with or without evidence of bladder outflow obstruction were included in the study. Patients with serum prostate specific antigen (PSA)> 4 nmol/mL, malignancy, complete urine retention, stone formation and gross bilateral hydronephrosis were excluded. Patients were sequentially allocated to OM, CM or BCOM. The main outcome measure was the International Prostate Symptom Score (IPSS).Results: 73, 70 and 77 patients respectively were sequentially allocated to OM, CM or BCOM. 180 patients (60 per group) completed treatment and were included in the final analysis. Overall 85% of patients showed improvement of subjective symptoms such as frequency, urgency, hesitancy, intermittent flow, unsatisfactory urination, feeble stream, diminution of residual urine volume but there was no reduction in prostate size. Treatment response was highest with BCOM (38.24%) compared to OM (31.62%) and CM (30.15%). Effect sizes were highest for the decrease in IPSS, residual urine volume and urinary flow rate.
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Simonetti, Emeline, Elena Bergamini, Giuseppe Vannozzi, Joseph Bascou, and Hélène Pillet. "Estimation of 3D Body Center of Mass Acceleration and Instantaneous Velocity from a Wearable Inertial Sensor Network in Transfemoral Amputee Gait: A Case Study." Sensors 21, no. 9 (April 30, 2021): 3129. http://dx.doi.org/10.3390/s21093129.
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The analysis of the body center of mass (BCoM) 3D kinematics provides insights on crucial aspects of locomotion, especially in populations with gait impairment such as people with amputation. In this paper, a wearable framework based on the use of different magneto-inertial measurement unit (MIMU) networks is proposed to obtain both BCoM acceleration and velocity. The proposed framework was validated as a proof of concept in one transfemoral amputee against data from force plates (acceleration) and an optoelectronic system (acceleration and velocity). The impact in terms of estimation accuracy when using a sensor network rather than a single MIMU at trunk level was also investigated. The estimated velocity and acceleration reached a strong agreement (ρ > 0.89) and good accuracy compared to reference data (normalized root mean square error (NRMSE) < 13.7%) in the anteroposterior and vertical directions when using three MIMUs on the trunk and both shanks and in all three directions when adding MIMUs on both thighs (ρ > 0.89, NRMSE ≤ 14.0% in the mediolateral direction). Conversely, only the vertical component of the BCoM kinematics was accurately captured when considering a single MIMU. These results suggest that inertial sensor networks may represent a valid alternative to laboratory-based instruments for 3D BCoM kinematics quantification in lower-limb amputees.
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VenkataRathnam, T. "BCOM: Best Constraints for Overlay network Maintainance." IOSR Journal of Engineering 02, no. 09 (September 2012): 01–05. http://dx.doi.org/10.9790/3021-02950105.
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Layton, Paul. "Leonard le Marchant Minty, BSc, BCom, LLB, PhD." Medico-Legal Journal 53, no. 4 (December 1985): 227. http://dx.doi.org/10.1177/002581728505300409.
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Choi, Kyeongjin. "bCom ldan rig ral on the Methods for Proving Momentariness." Journal of Indian and Buddhist Studies (Indogaku Bukkyogaku Kenkyu) 65, no. 3 (2017): 1289–94. http://dx.doi.org/10.4259/ibk.65.3_1289.
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Jurado, CA, A. Tsujimoto, H. Watanabe, NG Fischer, JA Hasslen, H. Tomeh, AG Baruth, WW Barkmeier, and F. Garcia-Godoy. "Evaluation of Polishing Systems for CAD/CAM Polymer-Infiltrated Ceramic-Network Restorations." Operative Dentistry 46, no. 2 (March 1, 2021): 219–25. http://dx.doi.org/10.2341/20-006-l.
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SUMMARY Objective: The purpose of this study was to evaluate the effectiveness of five different polishing systems on a computer-aided design and computer-aided manufacturing (CAD/CAM) polymer-infiltrated ceramic-network restoration with nanoscale assessment using atomic force microscopy (AFM) and visual assessment performed by dental school senior students and faculty members. Method: Forty-eight full coverage crowns were milled out of polymer-infiltrated ceramic-network CAD/CAM blocks (Vita Enamic) for polishing with one company proprietary, two ceramic and two composite polishing systems. The prepared crowns were divided into six groups: (1) no polishing (control); (2) polishing with Vita Enamic Polishing Kit (VEna); (3) polishing with Shofu Porcelain Laminate Polishing Kit (SCer); (4) polishing with Brasseler Dialite Feather lite All-Ceramic Adjusting & Polishing System (BCer); (5) polishing with Shofu Composite Polishing Kit (SCom); and (6) polishing with Brasseler Composite Polishing Kit (BCom). The polished crown surface topography was observed, and surface roughness and area were measured with AFM. In addition, polished crowns were visually assessed by 15 senior dental students and 15 dental school faculty members. Results: All polishing treatments significantly reduced the surface roughness and area of the crown compared with the control. SCom and BCom showed significantly higher surface area than VEna, and the SCer and BCer groups were intermediate, showing no significant difference from either VEna or SCom and BCom. There were no significant differences in surface roughness between any of the systems. Dental students and faculty members classified the groups polished with VEna, SCer, and BCer groups as clinically acceptable, and they selected BCer group as the best polished restorations and the control group as the least polished restorations. Conclusions: Ceramic and composite polishing systems produced similar polishing results as that observed using a company proprietary polishing system. However, effectiveness for polishing using a company proprietary and ceramic polishing system tends to be higher than composite polishing systems.
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Germanotta, Marco, Chiara Iacovelli, and Irene Aprile. "Evaluation of Gait Smoothness in Patients with Stroke Undergoing Rehabilitation: Comparison between Two Metrics." International Journal of Environmental Research and Public Health 19, no. 20 (October 18, 2022): 13440. http://dx.doi.org/10.3390/ijerph192013440.
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The use of quantitative methods to analyze the loss in gait smoothness, an increase in movement intermittency which is a distinguishing hallmark of motor deficits in stroke patients, has gained considerable attention in recent years. In the literature, the spectral arc length (SPARC), as well as metrics based on the measurement of the jerk, such as the log dimensionless jerk (LDLJ), are currently employed to assess smoothness. However, the optimal measure for evaluating the smoothness of walking in stroke patients remains unknown. Here, we investigated the smoothness of the body’s center of mass (BCoM) trajectory during gait, using an optoelectronic system, in twenty-two subacute and eight chronic patients before and after a two-month rehabilitation program. The two measures were evaluated for their discriminant validity (ability to differentiate the smoothness of the BCoM trajectory calculated on the cycle of the affected and unaffected limb, and between subacute and chronic patients), validity (correlation with clinical scales), and responsiveness to the intervention. According to our findings, the LDLJ outperformed the SPARC in terms of the examined qualities. Based on data gathered using an optoelectronic system, we recommend using the LDLJ rather than the SPARC to investigate the gait smoothness of stroke patients.
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Parr, James A. "Reminiscing: Comedia, BCom, Everett, Other Players, and a Strong Supporting Cast." Bulletin of the Comediantes 68, no. 2 (2016): 236–42. http://dx.doi.org/10.1353/boc.2016.0036.
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Li, T. S. "Tertiary Communities of Practice: Rationale, Desirability, and A BCOM Foundational Conceptual Design." Information Technology, Education and Society 13, no. 2 (January 1, 2012): 29–52. http://dx.doi.org/10.7459/ites/13.2.04.
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Shahzad, Umer, Sangram Keshari Jena, Aviral Kumar Tiwari, Buhari Doğan, and Cosimo Magazzino. "Time-frequency analysis between Bloomberg Commodity Index (BCOM) and WTI crude oil prices." Resources Policy 78 (September 2022): 102823. http://dx.doi.org/10.1016/j.resourpol.2022.102823.
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Shin, Kyung-Chul, Min-Ju Seo, Yeong-Su Kim, and Soo-Jin Yeom. "Molecular Properties of β-Carotene Oxygenases and Their Potential in Industrial Production of Vitamin A and Its Derivatives." Antioxidants 11, no. 6 (June 16, 2022): 1180. http://dx.doi.org/10.3390/antiox11061180.
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β-Carotene 15,15′-oxygenase (BCO1) and β-carotene 9′,10′-oxygenase (BCO2) are potential producers of vitamin A derivatives, since they can catalyze the oxidative cleavage of dietary provitamin A carotenoids to retinoids and derivative such as apocarotenal. Retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it, and are essential nutrients for humans and highly valuable in the food and cosmetics industries. β-carotene oxygenases (BCOs) from various organisms have been overexpressed in heterogeneous bacteria, such as Escherichia coli, and their biochemical properties have been studied. For the industrial production of retinal, there is a need for increased production of a retinal producer and biosynthesis of retinal using biocatalyst systems improved by enzyme engineering. The current review aims to discuss BCOs from animal, plants, and bacteria, and to elaborate on the recent progress in our understanding of their functions, biochemical properties, substrate specificity, and enzyme activities with respect to the production of retinoids in whole-cell conditions. Moreover, we specifically propose ways to integrate BCOs into retinal biosynthetic bacterial systems to improve the performance of retinal production.
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NDIDI, OSEGI EMMANUEL, WOKOMA BIOBELE ALEXANDER, OJUKA OTONYE, BRUCE-ALLISON SA, and CHUJOR CORNELIUS CHICHI. "SWAMI: A SWARM-INTELLIGENT OPTIMIZATION TECHNIQUE FOR VOLTAGE COLLAPSE MITIGATION." Journal of Engineering Studies and Research 28, no. 2 (September 1, 2022): 33–47. http://dx.doi.org/10.29081/jesr.v28i2.004.
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In this paper, a voltage collapse optimization system based on comparative studies of swarm-intelligent techniques is proposed for voltage collapse mitigation in power system network. The approach draws inspiration from the idea of utilizing the intelligent behavior of swarm-based artificial machine intelligence technique coined SWAMI for voltage collapse minimization or prevention through dynamic shunt compensation of overloaded power network buses. Several simulation studies have been conducted considering three very popular and successful SWAMI agents – the PSOM, BCOM and ACOM on an IEEE benchmark power network with promising results. Simulation studies showed that the PSOM SWAMI exhibited the most stable response in terms of voltage profile collapse and recovery from voltage collapse state after voltage sensitivity studies. Safe margins of loading and optimal shunt compensations are determined based on the SWAMI techniques.
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Martínez, Anabela, Jorge Cantero, Antonio J. Meléndez-Martínez, and Margot Paulino. "A Computer Simulation Insight into the Formation of Apocarotenoids: Study of the Carotenoid Oxygenases BCO1 and BCO2 and Their Interaction with Putative Substrates." Molecules 27, no. 22 (November 13, 2022): 7813. http://dx.doi.org/10.3390/molecules27227813.
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Carotenoids are isoprenoid pigments, and sources of vitamin A in humans. The first metabolic pathway for their synthesis is mediated by the enzymes β,β-carotene-15,15′-dioxygenase (BCO1) and β,β-carotene-9′,10′-dioxygenase (BCO2), which cleave carotenoids into smaller compounds, called apocarotenoids. The objective of this study is to gain insight into the interaction of BCO1 and BCO2 with carotenoids, adding structural diversity and importance in the agro-food and/or health sectors. Homology modeling of BCO1 and BCO2, and the molecular dynamics of complexes with all carotenoids were performed. Interaction energy and structures were analyzed. For both enzymes, the general structure is conserved with a seven beta-sheet structure, and the β-carotene is positioned at an optimal distance from the catalytic center. Fe2+ forms in an octahedral coordination sphere with four perfectly conserved histidine residues. BCO1 finds stability in a structure in which the β-carotene is positioned ready for enzymatic catalysis at the 15–15′ bond, and BCO2 in positioning the bond to be cleaved (C9–C10) close to the active site. In BCO1 the carotenoids interact with only seven residues with aromatic rings, while the interaction of BCO2 is much more varied in terms of the type of interaction, with more residues of different chemical natures.
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Bradley, Madelyn, Joseph Arballo, Molly Black, John Erdman, and Jaume Amengual. "Tissue Lycopene Accumulation in Transgenic Mice Lacking One or Both Carotenoid Cleaving Enzymes." Current Developments in Nutrition 6, Supplement_1 (June 2022): 55. http://dx.doi.org/10.1093/cdn/nzac049.001.
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Abstract Objectives To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-carotene oxygenase 2(BCO2) or both on tissue accumulation of lycopene dosed transgenic mice. Previous work from our laboratories suggests that BCO2 appears to be the primary carotenoid cleavage enzyme for lycopene in vivo. Methods Three-week old C57BL/6 male and female mice (wild type [WT], Bco1-/-, Bco2-/-, Bco1-/- X Bco2-/- double knock out [DKO]) were divided into groups based on genotype (n = 8 per group/per gender) and fed a powdered AIN 93G diet for 2 weeks. The mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil after which they were fasted and sacrificed. Liver, serum, and extra-hepatic tissues were harvested. Lycopene concentration was measured with high-performance liquid chromatography. Data analyses were performed using one-way ANOVA. Results On a concentration basis, liver, duodenum and adrenal lycopene were higher than other tissues. Serum and tissues of DKO mice accumulated the highest lycopene. DKO mice had significantly higher lycopene than Bco1-/- mice in the liver (P < .002), heart (P < .004), adipose (P < .03), and the testes (P < .004). Compared to Bco2-/- mice, DKO mice had greater accumulation in the serum (P < .001), intestine (P < .04), heart (P < .0001), kidneys (P < .0001), adipose (P < .04), and testes (P < .0001). Liver (P < .007) and adrenal (ns) tissues in Bco2-/- mice had higher levels of lycopene than Bco1-/- mice whereas Bco1-/- mice had significantly higher levels in the kidneys (P < .001) and tended to have greater accumulation in other tissues. Conclusions Accumulation of lycopene in tissues depended upon gender, genotype and tissue type. The abolition of both enzymes and mice of a female sex generated a higher accumulation. We are probing whether tissue-specific expression levels of BCO1, BCO2 or carotenoid transport proteins explain differential tissue accumulation across genotypes. Funding Sources N/A.
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Strychalski, Janusz, Andrzej Gugołek, Edyta Kaczorek-Łukowska, Zofia Antoszkiewicz, and Paulius Matusevičius. "The BCO2 Genotype and the Expression of BCO1, BCO2, LRAT, and TTPA Genes in the Adipose Tissue and Brain of Rabbits Fed a Diet with Marigold Flower Extract." International Journal of Molecular Sciences 24, no. 3 (January 24, 2023): 2304. http://dx.doi.org/10.3390/ijms24032304.
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This study was undertaken to evaluate the effect of the BCO2 genotype and dietary supplementation with marigold flower extract on the expression of BCO1, BCO2, LRAT, and TTPA genes in the adipose tissue and brain of rabbits. The concentrations of lutein, zeaxanthin, β-carotene, retinol, and α-tocopherol were determined in samples collected from rabbits. Sixty young male Termond White rabbits were allocated to three groups based on their genotype at codon 248 of the BCO2 gene (ins/ins, ins/del, and del/del). Each group comprised two subgroups; one subgroup was administered a standard diet, whereas the diet offered to the other subgroup was supplemented with 6 g/kg of marigold flower extract. The study demonstrated that the BCO2 genotype may influence the expression levels of the BCO2, LRAT, and TTPA genes in adipose tissue, and TTPA and BCO1 genes in the brain. Moreover, an increase in the amount of lutein in the diet of BCO2 del/del rabbits may increase the expression of BCO1, LRAT, and TTPA genes in adipose tissue, and the expression of the BCO2 gene in the brain. Another finding of the study is that the content of carotenoids and α-tocopherol increases in both the adipose tissue and brain of BCO2 del/del rabbits.
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Lindqvist, Annika, Yu-Guang He, and Stefan Andersson. "Cell Type-specific Expression of β-Carotene 9', 10'-Monooxygenase in Human Tissues." Journal of Histochemistry & Cytochemistry 53, no. 11 (June 13, 2005): 1403–12. http://dx.doi.org/10.1369/jhc.5a6705.2005.
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The symmetrically cleaving β-carotene 15, 15'-monooxygenase (BCO1) catalyzes the first step in the conversion of provitamin A carotenoids to vitamin A in the mucosa of the small intestine. This enzyme is also expressed in epithelia in a variety of extraintestinal tissues. The newly discovered β-carotene 9', 10'-monooxygenase (BCO2) catalyzes asymmetric cleavage of carotenoids. To gain some insight into the physiological role of BCO2, we determined the expression pattern of BCO2 mRNA and protein in human tissues. By immunohistochemical analysis it was revealed that BCO2 was detected in cell types that are known to express BCO1, such as epithelial cells in the mucosa of small intestine and stomach, parenchymal cells in liver, Leydig and Sertoli cells in testis, kidney tubules, adrenal gland, exocrine pancreas, and retinal pigment epithelium and ciliary body pigment epithelia in the eye. BCO2 was uniquely detected in cardiac and skeletal muscle cells, prostate and endometrial connective tissue, and endocrine pancreas. The finding that the BCO2 enzyme was expressed in some tissues and cell types that are not sensitive to vitamin A deficiency and where no BCO1 has been detected suggests that BCO2 may also be involved in biological processes other than vitamin A synthesis.
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De Jager, Eloise. "Thuthuka students' perceptions of factors influencing success." Journal of Economic and Financial Sciences 7, no. 1 (April 30, 2014): 53–72. http://dx.doi.org/10.4102/jef.v7i1.130.
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South Africa has a shortage of black (African and coloured) chartered accountants. The Thuthuka Project, initiated by the South African Institute for Chartered Accountants (SAICA), aims to increase the number of black accounting students. The Thuthuka Project includes funding, as well as a comprehensive support programme, for black students to study BCom Accounting (or equivalent) at a SAICA-accredited university. This article reports on research into the factors that promote and hinder the academic success of Thuthuka students. The findings of this study might help other students to achieve success and may assist in the transformation of the chartered accountancy profession. A questionnaire was used to gather data on the perceived success factors of Thuthuka students (from all the SAICA-accredited universities in South Africa). It was found that Thuthuka students believed that support was the main factor contributing to their success, followed by individual commitment.
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Arballo, Joseph, Jaime Amengual, Molly Black, and John Erdman. "Impact of Carotenoid Cleaving Enzymes on Lycopene Accumulation in Transgenic Mice." Current Developments in Nutrition 5, Supplement_2 (June 2021): 69. http://dx.doi.org/10.1093/cdn/nzab034_003.
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Abstract Objectives To evaluate the role of β-carotene oxygenase 1 (BCO1) and BCO2 on lycopene tissue distribution. Methods Three-week old C57BL/6 male and female mice (wild type [WT], Bco1−/−, Bco2−/−, Bco1−/− × Bco2−/− double knock out [DKO]) were divided into groups based on genotype (n = 16 per group split evenly by sex) and fed a powdered AIN 93G control diet for 2 weeks. After this period, mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil. 12 h-fasted mice were then sacrificed, and liver, serum, heart, kidney, intestine, gonadal adipose, prostate, spleen, and testes were harvested. Tissues were preserved in liquid nitrogen and stored at −80 until analyses. We measured lycopene levels in all samples by using high-performance liquid chromatography. Data analyses were performed using two-way ANOVA, followed by the Sidaks test with a statistical significance threshold of P < 0.05. Results Female mice showed higher lycopene levels in the intestine (P < 0.045) and liver (P < 0.007) irrespective of genotype, while male mice had higher lycopene levels in serum (P < 0.004). Intestine, serum, and kidneys exhibited higher lycopene levels in DKO mice compared to all other genotypes (P < .0001), while having higher lycopene levels in testes (P < 0.0001) compared to Bco2−/− and WT mice and adipose (P < 0.005) only in comparison to Bco2−/− mice. DKO exhibited higher lycopene levels in the spleen compared to Bco1−/− mice (P < 0.02). Lycopene levels in the liver (P < 0.0001) were higher in Bco2−/− mice compared to Bco1 −/− and DKO mice, while Bco1−/− mice had lower hepatic lycopene levels compared to all other genotypes. Conclusions Female mice accumulated higher lycopene levels in most tissues compared to males. These results were consistent when data were corrected by total tissue weight. The data suggest the absence of BCO2 favors carotenoid accumulation in many extrahepatic tissues, an effect that is enhanced in the absence of both carotenoid cleaving enzymes. Funding Sources Internal funding, University of Illinois Urbana Champaign.
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Strychalski, Janusz, Andrzej Gugołek, Zofia Antoszkiewicz, Dorota Fopp-Bayat, Edyta Kaczorek-Łukowska, Anna Snarska, Grzegorz Zwierzchowski, Angelika Król-Grzymała, and Paulius Matusevičius. "The Effect of the BCO2 Genotype on the Expression of Genes Related to Carotenoid, Retinol, and α-Tocopherol Metabolism in Rabbits Fed a Diet with Aztec Marigold Flower Extract." International Journal of Molecular Sciences 23, no. 18 (September 11, 2022): 10552. http://dx.doi.org/10.3390/ijms231810552.
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This study investigated the effect of the BCO2 genotype and the addition of Aztec marigold flower extract to rabbit diets on the expression of BCO1, BCO2, LRAT, and TTPA genes in the liver. The levels of lutein, zeaxanthin, β-carotene, retinol, and α-tocopherol in the liver and blood serum of rabbits, as well as plasma biochemical parameters and serum antioxidant enzyme activities were also determined. Sixty male Termond White growing rabbits were divided into three groups based on their genotype at codon 248 of the BCO2 gene (ins/ins, ins/del and del/del); each group was divided into two subgroups: one subgroup received a standard diet, and the other subgroup was fed a diet supplemented with 6 g/kg of marigold flower extract. The obtained results indicate that the BCO2 genotype may affect the expression levels of BCO1 and BCO2 genes in rabbits. Moreover, the addition of marigold extract to the diet of BCO2 del/del rabbits may increase the expression level of the BCO2 gene. Finally, an increase in the amount of lutein in the diet of rabbits with the BCO2 del/del genotype contributes to its increased accumulation in the liver and blood of animals without compromising their health status or liver function.
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van Antwerpen, Sumei. "The quality of teaching and learning of BCom honours degree students at an open distance learning university in South Africa." Africa Education Review 12, no. 4 (October 2, 2015): 680–95. http://dx.doi.org/10.1080/18146627.2015.1112159.
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Fourie, S., and E. Contogiannis. "The Impact of Business Ethics Education on Attitudes Toward Corporate Ethics of BCom. Accounting Students at the University of Zululand." South African Journal of Accounting Research 28, no. 1 (January 2014): 1–23. http://dx.doi.org/10.1080/10291954.2014.11463124.
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Lim, Ji Ye, Chun Liu, Kang-Quan Hu, Donald E. Smith, Dayong Wu, Stefania Lamon-Fava, Lynne M. Ausman, and Xiang-Dong Wang. "Dietary β-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet–Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice." Journal of Nutrition 149, no. 9 (June 18, 2019): 1553–64. http://dx.doi.org/10.1093/jn/nxz106.
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ABSTRACT Background β-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by β-carotene-15,15′-oxygenase (BCO1) to generate vitamin A, and by β-carotene-9′,10′-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. Objectives We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. Methods Six-week-old male wild-type (WT) and BCO1−/−/BCO2−/− double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. Results Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P < 0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice (P < 0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 (Acc1) in the MAT of WT mice but not DKO mice (P < 0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice (P < 0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice (P < 0.05). Conclusion BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.
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Daniels, Michael, Neil Huang, Gregory Dolnikowski, Gregory Matuszek, Ji Ye Lim, Nirupa Matthan, and Xiang-Dong Wang. "Ablation of Carotenoid Cleavage Enzymes BCO1 & BCO2 Alters Gut Microbial and Plasma Metabolomic Profiles in High Refined Carbohydrate Diet-Fed Mice." Current Developments in Nutrition 6, Supplement_1 (June 2022): 56. http://dx.doi.org/10.1093/cdn/nzac049.002.
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Abstract Objectives β-Carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) cleave carotenoids to form vitamin A or apo-carotenoid species. Beyond these roles, BCO1 and BCO2 have been implicated in modulating lipid, cholesterol, and oxidative stress-related processes, yet less is known about their combined influence on shaping gut microbial and plasma metabolic profiles. Current intake of refined carbohydrates and added sugars exceeds the recommendations within the Dietary Guidelines for Americans, which may contribute to the development of nonalcoholic fatty liver disease (NAFLD). In the present study, we aimed to uncover whether mice with systemic ablation of BCO1-/-/BCO2-/- (DKO) display distinctive phenotypes in response to a high refined carbohydrate diet (HRCD) model of NAFLD. Methods Male, six-week-old C57BL/6J wild type mice (WT) and DKO mice were fed a chow diet or a HRCD (66.5% carbs including sucrose) for 24 weeks. We used fecal and plasma samples to respectively perform 16S rDNA sequencing, and both targeted and untargeted metabolomics using our UHPLC-QTOF-MS platform, a targeted Biocrates MxP Quant 500 kit, and a complimentary untargeted analysis of phospholipids from the METLIN database. Data were analyzed using QIIME2-DEseq2, MetaboAnalyst 5.0, MassHunter Qualitative Analysis, and MicrobiomeAnalyst. Results HRCD-fed WT and DKO mice developed similar levels of hepatic steatosis although DKO mice had significantly higher hepatic levels of malondialdehyde (MDA). Interestingly, in both chow-fed and HRCD-fed DKO mice, plasma adiponectin and hepatic bile acids were significantly lower compared to respective WT groups. Our metabolomics data revealed that DKO mice displayed significant alterations in ceramide, cholesterol ester, triglyceride, and phospholipid classes under both chow and HRCD conditions. Additionally, when compared to HRCD-fed WT mice, HRCD-fed DKO mice displayed significantly reduced alpha diversity and possessed significant compositional differences based on Bray Curtis dissimilarity measures. Conclusions BCO1/BCO2 DKO mice display altered metabolomic and gut microbial profiles. Carotenoid cleavage enzymes affect diverse physiological processes, which involve lipid metabolism and the gut microbiome. Funding Sources USDA/ARS and NIFA/AFRI.
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Zandria, Saayman, Zogli Luther-King Junior, and Pelser Hennie. "Queen Bee Syndrome at the Workplace; Perspectives of Female Business Students at a South African Private University." Journal of Social Sciences Research, no. 64 (April 5, 2020): 406–12. http://dx.doi.org/10.32861/jssr.64.406.412.
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It has been found out that some female leaders exercise certain behavioural traits in the workplace that are discriminatory towards other females. This behaviour is referred to as the Queen Bee Syndrome. To shed light on the syndrome, this paper aims to discover the perceptions of final year female Bachelor of Commerce (BCom) students in a South African private university about their opinions on female leadership and to discover the prevalence of the Queen Bee Syndrome. Qualitative interviews were conducted on final year female students in a South African private university in Pietermaritzburg. The sample was obtained using snowball sampling method. The information gathered was analysed using content analysis. The key discoveries made were that the female students generally would prefer to work with a male manger due to the negative characteristics of competitiveness, emotionality and jealousy that was associated with the female leaders they have worked with. Respondents were also of the opinion that the Queen Bee Syndrome exists and that it is a resultant of society norms spilling over into the workplace. It is believed that social norms contribute to this problem, hence it is crucial that discriminatory behaviour in society be alleviated to strengthen and support the current women movement fighting for equality.
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Chiaverelli, Rachel A., Kang-Quan Hu, Chun Liu, Ji Ye Lim, Michael S. Daniels, Hui Xia, Jonathan Mein, Johannes von Lintig, and Xiang-Dong Wang. "β-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice." Molecules 28, no. 3 (February 1, 2023): 1383. http://dx.doi.org/10.3390/molecules28031383.
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High dietary intake of β-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by β-carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) to produce retinol and apo-10′-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1−/−/BCO2−/− double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10′-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-β-apo-10′-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.
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Музраева, Деляш Николаевна, Антонина Саар-ооловна Донгак, and Ольга Александровна Максимова. "Тексты Праджняпарамиты в коллекции тувинского института." New Research of Tuva, no. 4 (November 30, 2022): 127–36. http://dx.doi.org/10.25178/nit.2022.4.10.
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В статье дается описание буддийских текстов из разряда литературы Праджняпарамиты, которые хранятся в Научном архиве Тувинского института гуманитарных и прикладных социально-экономических исследований при Правительстве Республики Тыва.
Вводятся в научный оборот описания рукописей и ксилографических изданий таких сочинений, как «Алмазная сутра» или «Ваджраччхедика» (тиб. ’phags pa shes rab kyi pha rol tu phyin pa rdo rje gcod pa zhes bya ba theg pa chen po’i mdo), «Сутра сердца бхагавати праджняпарамита хридая» (тиб. bcom ldan ’das ma shes rab kyi pha rol tu phyin pa’i snying po bzhugs so), «Праджняпарамита в 8000 строф (шлок)» (тиб. ’phags pa shes rab kyi pha rol tu phyin pa brgyad stong pa bzhugs so) и др. Важность данных сутр в традиции махаяны неизменна и на сегодняшний день. Об этом свидетельствуют комментарии как высоких традиционных учителей буддизма, так и ученых-буддологов нашего времени.
Среди текстов описываемой коллекции встретились также сокращенные версии, относящиеся к т. н. «сакральным формулам», краткие извлечения из текстов в составе сборников и подборок. Суть учения о запредельной мудрости праджняпарамиты (тиб. shes rab kyi pha rol tu phyin pa) — познание пустотности явлений — представляет интерес как для практиков традиции, так и для ученых-философов, антропологов, культурологов и специалистов др. дисциплин.
Рассмотренные источники занимают важное место в истории распространения буддизма в регионах России (Тува, Бурятия, Калмыкия) и Монголии. Тексты праджняпарамиты являлись обязательным атрибутом буддийских храмов.
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Kampamba, Johnson, Emmanuel Tembo, and Boipuso Nkwae. "An evaluation of the relevance of real estate curricula in Botswana." Property Management 35, no. 3 (June 19, 2017): 275–305. http://dx.doi.org/10.1108/pm-12-2015-0065.
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Purpose The purpose of this paper is to establish the relevance of the real estate curricula being offered by the two universities in Botswana to industry. Design/methodology/approach This is a cross-sectional study in which a designed questionnaire was administered to the practitioners in real estate obtained from the membership list of the Real Estate Institute of Botswana (REIB), final-year students and former graduates of the Bachelor of Land Management programme using proportionate stratified random sampling technique. This resulted into the total population of 150 elements. Students for the Bachelor of Commerce in Real Estate (BCom RE) at Ba Isago and BSc Real Estate programme at the University of Botswana were excluded from the population because they did not have graduate degrees yet; therefore the study sample was drawn from the identified population at 90 per cent confidence level with a 10 per cent margin of error. The sampling frame composed of 122 registered property valuers and managers, 14 alumni and 14 final-year students of Land Management (150). The sample size of 60 was determined at 90 per cent level of confidence with a 10 per cent margin of error. The questionnaire was administered through e-mail using a contact list from the REIB to their members. It was also e-mailed to the alumni and physically administered to the final-year students as well. A 60 per cent response rate was achieved. Findings It was established that the three programmes offered at the two universities in their current form are relevant to the industry. The overall average scores out of 5 for these programmes were 4.14 for BSc Real Estate – UB, 4.10 for Bachelor Land Management – UB and 3.97 for BCom RE – Ba Isago University College. By using analysis of variance, the study further established that there were no significant differences between the two programmes that are offered at UB and the one at Ba Isago University College. This was established by looking at the computed F-test (0.89) and the critical F-test (2.36). Since the computed F-test was less than the critical F-test value, it was concluded that there is no significant statistical differences among the three programmes being offered in the two universities. Research limitations/implications The major limitation in this study was the use of an e-mailed questionnaire to the property practitioners and alumni of the Land Management programme which is characterised by a low response rate. Practical implications Since the three overall mean scores are close to and above 4.00, it means the current programmes offered at the two universities are relevant to the industry. Social implications The research results might be useful to the society and should be used to enhance the social uplifting of society by contributing to the decisions that are made which might affect the society as a whole. Originality/value This is the first study to be conducted in Botswana which was meant to establish if the real estate programmes offered in the two universities were relevant. It is the first study to compare and evaluate the relevance of the contents of three real estate programmes locally.
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Aloum, Lujain, Eman Alefishat, Abdu Adem, and Georg Petroianu. "Ionone Is More than a Violet’s Fragrance: A Review." Molecules 25, no. 24 (December 10, 2020): 5822. http://dx.doi.org/10.3390/molecules25245822.
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The term ionone is derived from “iona” (Greek for violet) which refers to the violet scent and “ketone” due to its structure. Ionones can either be chemically synthesized or endogenously produced via asymmetric cleavage of β-carotene by β-carotene oxygenase 2 (BCO2). We recently proposed a possible metabolic pathway for the conversion of α-and β-pinene into α-and β-ionone. The differences between BCO1 and BCO2 suggest a unique physiological role of BCO2; implying that β-ionone (one of BCO2 products) is involved in a prospective biological function. This review focuses on the effects of ionones and the postulated mechanisms or signaling cascades involved mediating these effects. β-Ionone, whether of an endogenous or exogenous origin possesses a range of pharmacological effects including anticancer, chemopreventive, cancer promoting, melanogenesis, anti-inflammatory and antimicrobial actions. β-Ionone mediates these effects via activation of olfactory receptor (OR51E2) and regulation of the activity or expression of cell cycle regulatory proteins, pro-apoptotic and anti-apoptotic proteins, HMG-CoA reductase and pro-inflammatory mediators. α-Ionone and β-ionone derivatives exhibit anti-inflammatory, antimicrobial and anticancer effects, however the corresponding structure activity relationships are still inconclusive. Overall, data demonstrates that ionone is a promising scaffold for cancer, inflammation and infectious disease research and thus is more than simply a violet’s fragrance.
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Dunga, Steven Henry. "An Exploratory Study Of The Variation In Unemployment Length Of Graduates Of Different Degree Programs." International Business & Economics Research Journal (IBER) 15, no. 2 (March 3, 2016): 69. http://dx.doi.org/10.19030/iber.v15i2.9636.
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The drive to reduce poverty and unemployment in most developing or newly industrialized countries has many forms, the most common avenue, however, is the provision of education and a resultant expectation of employment. South Africa has in the past decade struggled with the issue of unemployment. Even in the face of very high graduate rates compared to other countries in the region, there is still high unemployment. The most common in South Africa is frictional as opposed to structural. An obvious expectation is that once people have attended tertiary education, getting a job should be easier than those without any education. However, there seems to be a mismatch between the skills required in the workplace and the skills the graduates looking for jobs have. Using data from graduates of one of the big universities in South Africa, the study investigated on the time, graduates take to get a job focusing on graduates from different degree programs. The results show that graduates eventually get employed but differences exist in the waiting period. The results show that of the six degree programs namely Bachelor of Commerce in Economics, BCom Human Resources, Bachelor of Arts Psychology, Bachelor of Education (BEd), Bachelor of Science and Bachelor of Arts in Law, the law degree graduates have the longest waiting period and the BEd has the shortest waiting period before getting employed. The study, however, showed that all the graduates in the sample were employed. The results also indicated that 58percent of the graduates in the sample were not employed in the field they studied in. The study therefore recommended that to deal with unemployment in general, people should be afforded the opportunity to study for a degree, and that although low paying, BEd provides higher prospects of employment than most other degrees.
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Noufou, Ouedraogo, Davar Rezania, and Muhammad Hossain. "Measuring and exploring factors affecting students’ willingness to engage in peer mentoring." International Journal of Mentoring and Coaching in Education 3, no. 2 (June 6, 2014): 141–57. http://dx.doi.org/10.1108/ijmce-11-2012-0071.
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Purpose – The purpose of this paper is to measure students’ willingness to mentor their peers and explores key factors to student peer mentoring effectiveness. Design/methodology/approach – The paper uses a hybrid research methodology consisting of a survey and a focus group discussion. The survey was conducted with students of a bachelor of commerce (BCom) program of a North American university to analyze the impact of organizational culture and altruism on their willingness to mentor their peers. The focus group discussion was carried out with students of the same program to explore the objectives, focus, and factors contributing to their willingness to mentor and to peer mentoring effectiveness. Findings – Organizational culture and altruism significantly affect students’ emotional and intentional willingness to mentor their peers. Peer mentoring can help students prepare their transition from high school to university, guide them through university programs, and help them prepare their transition from university to workplace. Critical factors to peer mentoring effectiveness include a good fit between mentors and mentees, a reasonable ratio of mentor to protégés, and an understanding of and a willingness to address each student's specific needs. Practical implications – Business schools should embrace and promote a culture of mutual help, look for altruistic students as prospective peer mentors, and promote voluntary student peer mentoring. A mentoring program should be flexible enough to meet each student's needs. Attention should be paid to finding a good fit between mentors and protégés. Communication should focus on the benefits of student peer mentoring for mentors and protégés. Originality/value – This research brings empirical evidence on peer mentoring by testing and confirming the impact of altruism and organizational culture on students’ willingness to mentor their peers. It also provides practical insight to business schools for implementing student peer mentoring programs.
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Uppal, Sheetal, Igor B. Rogozin, T. Michael Redmond, and Eugenia Poliakov. "Palmitoylation of Metazoan Carotenoid Oxygenases." Molecules 25, no. 8 (April 22, 2020): 1942. http://dx.doi.org/10.3390/molecules25081942.
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Abundant in nature, carotenoids are a class of fat-soluble pigments with a polyene tetraterpenoid structure. They possess antioxidant properties and their consumption leads to certain health benefits in humans. Carotenoid cleavage oxygenases (CCOs) are a superfamily of enzymes which oxidatively cleave carotenoids and they are present in all kingdoms of life. Complexity of CCO evolution is high. For example, in this study we serendipitously found a new family of eukaryotic CCOs, the apocarotenoid oxygenase-like (ACOL) family. This family has several members in animal genomes and lacks the animal-specific amino acid motif PDPCK. This motif is likely to be associated with palmitoylation of some animal CCOs. We recently demonstrated that two mammalian members of the carotenoid oxygenase family retinal pigment epithelial-specific 65 kDa protein (RPE65) and beta-carotene oxygenase 2 (BCO2) are palmitoylated proteins. Here we used the acyl-resin-assisted capture (acyl-RAC) method to demonstrate protein palmitoylation and immunochemistry to localize mouse BCO2 (mBCO2) in COS7 cell line in the absence and presence of its substrate β-carotene. We demonstrate that mBCO2 palmitoylation depends on the evolutionarily conserved motif PDPCK and that metazoan family members lacking the motif (Lancelet beta-carotene oxygenase-like protein (BCOL) and Acropora ACOL) are not palmitoylated. Additionally, we observed that the palmitoylation status of mBCO2 and its membrane association depend on the presence of its substrate β-carotene. Based on our results we conclude that most metazoan carotenoid oxygenases retain the evolutionarily conserved palmitoylation PDPCK motif to target proteins to internal membranes depending on substrate status. Exceptions are in the secreted BCOL subfamily and the strictly cytosolic ancient ACOL subfamily of carotenoid oxygenases.
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Eimer, Helmut. "Schaeffer, Kurtis R. and van der Kuijp, Leonard W.J., An Early Tibetan Survey of Buddhist Literature: The Bstan pa rgyas pa rgyan gyi nyi 'od of Bcom ldan ral gri." Indo-Iranian Journal 53, no. 4 (2010): 367–72. http://dx.doi.org/10.1163/001972410x517300.
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Wedemeyer, Christian K. "An Early Tibetan Survey of Buddhist Literature: The Bstan Pa Rgyas Pa Rgyan Gyi Nyi 'Od of Bcom Ldan Ral Gri - By Kurtis Schaeffer and Leonard W. J. van der Kuijp." Religious Studies Review 37, no. 2 (June 2011): 153. http://dx.doi.org/10.1111/j.1748-0922.2011.01521_4.x.
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Marx, Johan, and Cecilia Jacoba de Swardt. "Towards a competency-based undergraduate qualification in risk management." Qualitative Research in Financial Markets 12, no. 1 (November 1, 2019): 96–117. http://dx.doi.org/10.1108/qrfm-10-2018-0110.
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Purpose The purpose of this paper is first to determine the competencies required of risk managers and second to consider the implications of such competencies in determining modules for inclusion in the curriculum framework of an undergraduate qualification in risk management. Design/methodology/approach A qualitative research approach was followed, involving risk management professionals in a focus group and making use of interactive qualitative analysis (IQA). Findings The competencies identified are managerial and risk management knowledge, attributes such as assertiveness and steadfastness and ethical values, as well as people and technical skills. These are explained in greater detail in this paper. Research limitations/implications The unique contribution of the current research was the innovative use of IQA for data collection, the removal of subjectivity and the rigour in analysing and presenting the results. The results provide a starting point for designing a curriculum that will both meet the requirements of the professional body and will equip graduates with the best possible combination of knowledge, attributes, values and skills needed by the risk management profession. The implications for further research include that a comparative IQA study of the competencies of risk managers using academics from the field could be undertaken, as well as a study of the design, benchmarking and validation of a proposed curriculum for an undergraduate degree in risk management. The purpose of this study was not to compile a curriculum for a new BCom (risk management). However, this was beyond the scope of the current study. IQA uses rigour and eliminates the bias of the researcher, and the one limitation of this research lies in the use of a focus group, which resulted in the findings not being generalizable as the case would have been with a representative sample used in the positivist paradigm and using appropriate statistical analysis. However, this study was exploratory and could serve as a valuable starting point for further research in this area to perform a comprehensive curriculum development. Practical implications This study found that constituents of the focus group perceived that the following competencies are required of risk managers, namely, knowledge, skills, attributes and values. These competencies correspond closely with the competencies indicated in the Risk and Insurance Management Society (RIMS) Professional Core Competency Model, except that RIMS subdivides knowledge into three categories, namely, business, organisational and risk management knowledge. Similarly, RIMS distinguishes between management skills and technical skills. The attributes identified by the focus group of this study were similar to those identified by RIMS. However, the focus group emphasised values such as integrity, ethical conduct, respect and accountability. However, unlike RIMS, these were not perceived as one of the five core competencies, but rather as a stand-alone competency in its own right, which risk managers need to be successful. RIMS could consider reviewing its core competencies by allocating three closely related aspects, namely communication, collaboration and consultation to technical skills. Core competencies may be replaced by core values, which are literally at the centre of all the competencies required. Such core values are enhanced by the RIMS Code of Ethics (2019) and significantly contribute to the professionalization of risk management. RIMS could also consider providing guidelines to universities for those competencies that could be taught or learnt, to be included in their curricula and to accredit universities who meet such requirements. Social implications The findings of this study also serve as a starting point for the reintroduction of a BCom (risk management) degree by Unisa. Despite the requirements of the South African Qualifications Authority (SAQA) and the Council for Higher Education (CHE), this study demonstrated that a specialised degree in risk management needs to be offered to meet the need expressed by IRMSA for professional risk managers in Southern Africa, and such a degree should ideally be curriculated based on the competencies identified in this article. The implication for public policy is that SAQA and the CHE need to reconsider their rigid stance about the composition of specialised qualifications, and rather set a range of 33-50% for subjects from the field of specialisation that must be included in the curricula of specialised degrees. As indicated by this research, a combination of subjects from different disciplines is required to enhance the competencies and employability of risk management graduates. Originality/value The use of IQA is a novel way of ensuring rigour and objectivity in arriving at the required knowledge, attributes, values and skills of risk managers, and aids in the compilation of a new curriculum for an undergraduate qualification in risk management, thus ensuring the qualification will provide a competency-based qualification that will meet the needs of the profession.
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Arballo, Joseph, Jaume Amengual, and John W. Erdman. "Lycopene: A Critical Review of Digestion, Absorption, Metabolism, and Excretion." Antioxidants 10, no. 3 (February 25, 2021): 342. http://dx.doi.org/10.3390/antiox10030342.
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Lycopene is a non-provitamin A carotenoid that exhibits several health benefits. Epidemiological data support a correlation between lycopene intake and the attenuation of several chronic diseases, including certain types of cancers and cardiovascular diseases. It is currently unknown whether the beneficial effects are from the native structure of lycopene or its metabolic derivatives: lycopenals, lycopenols, and lycopenoic acids. This literature review focuses on the current research on lycopene digestion, absorption, metabolism, and excretion. This review primarily focuses on in vivo studies because of the labile nature and difficulty of studying carotenoids within in vitro experimental models. The studies presented address tissue accumulation of lycopene, the modification of bioavailability due to genetic and dietary factors, and lycopene cleavage by the enzymes ß-carotene oxygenase 1 (BCO1) and ß-carotene oxygenase 2 (BCO2). The current literature suggests that the majority of lycopene is cleaved eccentrically by BCO2, yet further research is needed to probe the enzymatic cleavage activity at the tissue level. Additionally, results indicate that single nucleotide polymorphisms and dietary fat influence lycopene absorption and thus modify its health effects. Further research exploring the metabolism of lycopene, the mechanisms related to its health benefits, and optimal diet composition to increase the bioavailability is required.
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Mungai, Joseph, and Wanjiku Nganga. "Benchmarking of Undergraduate Computing Curricula in Kenya." INTERNATIONAL JOURNAL OF MANAGEMENT & INFORMATION TECHNOLOGY 6, no. 1 (September 30, 2013): 727–37. http://dx.doi.org/10.24297/ijmit.v6i1.754.
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This study investigated the quality of undergraduate computing curricula at Kenyan universities, how they compare locally and regionally with equivalent programs and how closely they meet the ICT sector needs. It was guided by four objectives i.e. to undertake an ontological mapping of computing curricula, to identify appropriate benchmarking criteria, to develop and test a benchmarking tool, and to investigate the alignment of these curricula to computing skills requirement. The study was deemed important by the plethora of academic computing programs of varying degrees of utility and credibility, which are a product of the escalating demand for computing education in Kenya given the development of Vision 2030 and the rapid growth of the ICT industry. To achieve its objectives, the study adopted a quantitative and qualitative cross-sectional descriptive survey of computing curricula offered locally (in Kenya) and regionally (from best practicing countries, USA and India). A sample of 70.3% was drawn from the target population for ontological mapping. Two research instruments, i.e. a questionnaire and a document analysis framework that were administered to a cross-section of 11 public/private universities. The study established that there are 24 undergraduate computing programs under 6 titles, viz. BSc., BCom., BTech., BB., BEd. and BEng. The two most populous programs are BSc. Computer Science (CS) and BSc. Information Technology (IT), which were selected to help identify two benchmarking criteria: Percent weight allocation of core hours within ACM knowledge areas and Relative performance capabilities of computing graduates. Using these criteria a benchmarking tool was developed and tested, which depicted disparities among the respondents in the percent weight allocation of core hours in CS programs. Similarly, it portrayed overlaps in the relative performance capabilities of CS and IT graduates, an outcome that queried the uniqueness of these programs. As such, its results indicate that the quality of the two computing programs is relatively insufficient. However, it further establishes that the computing curricula are aligned to meet the top 3 highly demanded computing skills i.e. Networking, Software development and Internet skills albeit insufficient percent weight allocation of core hours in Software development. It therefore recommends further testing and refining of the established benchmarking tool, the need to re-focus the computing programs and supports the call to institute a regulatory body and qualifications framework for computing education and skills.Â
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Gojo, Johannes, Felix Schmitt-Hoffner, Monika Mauermann, Katja von Hoff, Martin Sill, Andrey Korshunov, Damian Stichel, et al. "ETMR-06. Molecular and clinical characteristics of CNS tumors withBCOR(L1) fusion/internal tandem duplication." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i50. http://dx.doi.org/10.1093/neuonc/noac079.184.
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Abstract Central nervous system (CNS) tumor with BCOR internal tandem duplication (BCOR-ITD) have recently been introduced in the 5th edition of the WHO classification of CNS tumors, however, their molecular makeup and clinical characteristics remain widely enigmatic. This is further complicated by the recent discovery of tumors characterized by gene fusions involving BCOR or its homologue BCORL1. We identified a cohort of 206 BCOR altered CNS tumors via DNA methylation profiling and conducted in-depth molecular and clinical characterization in an international effort. By performing t-SNE clustering analysis we found that BCOR-fusion tumors form a distinct cluster (n=61), adjacent to BCOR-ITD cases (n=145). The identified fusion partners of BCOR(L1) included EP300 (n=20), CREBBP (n=5), and NUTM2HP (n=1). Notably, three cases within the BCOR-ITD cluster harbored a c-terminal intragenic deletion within BCOR. With respect to clinical characteristics gender ratio was balanced in BCOR-fusion cases (m/f, 1.1), whereas predominance of male patients was observed in the BCOR-ITD group (m/f, 1.5). Moreover, age at diagnosis of BCOR-fusion patients was higher as compared to BCOR-ITD cases (15 vs 4.5 years). Interestingly, BCOR-fusion tumors were exclusively found in the supratentorial region being originally diagnosed as ependymomas or gliomas whereas BCOR-ITD emerged across the entire CNS with diverse original diagnoses. 8% of BCOR-ITD and none of BCOR-fusion cases were disseminated at diagnosis. In line with this observation, 40% of first relapses within the BCOR-ITD group were metastatic which was less frequent in BCOR-fusion tumors. Survival estimates demonstrated no differences, generally showing short median PFS (BCOR-fusion, 2 years, n=15; BCOR-ITD, 1.8 years, n=55) and intermediate OS rates (BCOR-fusion, 6.8 years, n=18; BCOR-ITD 6.3 years, n=60). Further molecular and clinical characterization is ongoing potentially revealing first therapeutic leads for these highly aggressive CNS tumor types.
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Cao, Qi, Sigal Gery, Seyedmehdi Shojaee, Micah Gearhart, Vivian Bardwell, Markus Muschen, and H. Phillip Koeffler. "BCOR Is Involved in Myeloid Cell Growth Control by Regulating Hox Genes." Blood 120, no. 21 (November 16, 2012): 3445. http://dx.doi.org/10.1182/blood.v120.21.3445.3445.
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Abstract Abstract 3445 BCOR interacts with Polycomb group (PcG) proteins to form a PRC1-like transcriptional repressive complex. BCOR is an essential developmental regulator: hemizygous mutation of BCOR in males causes gestational lethality, and heterozygous mutation in females causes the X-linked developmental disorder Oculofaciocardiodental syndrome (OFCD). Studies in humans, cell lines and mice indicate that BCOR plays key roles in the regulation of early embryonic development, mesenchymal stem cell function and hematopoiesis. Recently, recurrent somatic BCOR mutations have been reported in retinoblastoma, medulloblastoma and acute myelogenous leukaemia (AML) suggesting BCOR functions as a tumor suppressor protein. The goal of the current study was to begin elucidating the function of BCOR in normal hematopoiesis and in hematopoietic transformation. To examine this in the mouse we transduced bone marrow (BM) from mice harboring a conditional Bcor deletion allele (BcorFl/Y) with lentivirus expressing CRE. FACS analysis showed that with CRE, 83% of Bcor-/Y (Bcor KO) BM cells kept in IL3, IL6 and stem cell factor (SCF) were CD34+ compared to 95% of non-induced BcorFl/Y (Bcor WT) BM cells. Moreover, following G-CSF treatment, Bcor KO BM cells showed a much higher incidence of cell differentiation (40.5%) compared to Bcor WT cells (5.4%) as shown by CD11b/Gr-1 FACS analysis. Surprisingly, Bcor KO BM cells also showed significantly higher proliferation rates in liquid culture and methycellulose colony assays. To identify BCOR downstream target genes, we compared the gene expression profiles between Bcor KO and WT BM cells. Real-time-PCR of individual Hox genes confirmed the upregulation of HoxA5, HoxA7 and HoxA9 in Bcor KO BM cells, which are known to increase self-renewal of immature hematopoietic cells. In addition, ChIP analysis showed specific binding of BCOR to HoxA7 promoter. In conclusion, our results from mouse experiments suggest that BCOR is involved in maintaining the CD34+ stem cell state and loss of BCOR leads to enhanced myeloid cell differentiation and proliferation possibly by regulating Hox genes. In addition, we examined BCOR expression levels in a large panel of human leukemic cell lines; high level BCOR mRNA and protein were detected in most cell lines. Notably, 2 cell lines, U937 and HL60, had low levels of BCOR mRNA and no detectable BCOR protein. Treatment of both cell lines with the differentiation inducers ATRA, Vitamin D3 or DMSO lead to a mark induction in BCOR expression both at the mRNA and protein level, suggesting that BCOR may be involved in myeloid cell differentiation. Further investigation should shed more light on the roles BCOR that plays in normal hematopoiesis and whether BCOR loss later in hematopoiesis could result in a differentiation block. Disclosures: No relevant conflicts of interest to declare.
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Raghuvanshi, Shiva, Vanessa Reed, William S. Blaner, and Earl H. Harrison. "Cellular localization of β-carotene 15,15′ oxygenase-1 (BCO1) and β-carotene 9′,10′ oxygenase-2 (BCO2) in rat liver and intestine." Archives of Biochemistry and Biophysics 572 (April 2015): 19–27. http://dx.doi.org/10.1016/j.abb.2014.12.024.
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Lim, Ji Ye, Chun Liu, Kang-Quan Hu, Donald E. Smith, and Xiang-Dong Wang. "Ablation of carotenoid cleavage enzymes (BCO1 and BCO2) induced hepatic steatosis by altering the farnesoid X receptor/miR-34a/sirtuin 1 pathway." Archives of Biochemistry and Biophysics 654 (September 2018): 1–9. http://dx.doi.org/10.1016/j.abb.2018.07.007.
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El Ayachi, I., X. Y. Zou, X. Yan, Y. Lou, and G. T. J. Huang. "Expression of Normal or Mutated X-Linked BCOR Transcripts in OFCD iPSCs." Journal of Dental Research 99, no. 2 (November 27, 2019): 196–203. http://dx.doi.org/10.1177/0022034519890323.
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Reprogramming diseased cells with mutated genes into induced pluripotent stem cells (iPSCs) can allow studies of disease mechanism and correct the mutation. Oculofaciocardiodental (OFCD) syndrome is a developmental disorder caused by heterozygous mutations in the X-linked BCL-6 corepressor ( BCOR) gene. In this present study, we aimed to reprogram stem cells from a tooth apical papilla (SCAP) of a patient with OFCD, termed SCAP-O, into iPSCs. The SCAP-O carry a copy of the BCOR gene having 1 nucleotide deletion in 1 of the alleles, therefore harboring a mixture of cells expressing either normal (SCAP-O BCOR-WT) or mutated (SCAP-O BCOR-mut) BCOR transcripts. We subcloned SCAP-O and separated SCAP-O BCOR-WT and SCAP-O BCOR-mut as verified by sequencing. The selected subclone SCAP-O BCOR-mut expressed only the mutated BCOR transcripts and remained in such condition after multiple passages. We reprogrammed SCAP-O and subclone SCAP-O BCOR-mut into transgene-free iPSCs using an excisable lentiviral vector system (hSTEMCCA-loxP) carrying 4 reprogramming factors in a single cassette, followed by removal of transgenes via Cre-mediated excision. We found that after reprogramming SCAP-O or subclone SCAP-OBCOR-mut into iPSCs, some of the iPSC clones expressed either solely the normal BCOR-WT or BCOR-mut transcripts, while other clones expressed both BCOR-WT and BCOR-mut transcripts. This is our first step toward establishing OFCD study models by generating isogenic control BCOR-WT iPSCs versus BCOR-mut iPSCs.
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Nakata, Satoshi, Ming Yuan, Jeffrey A. Rubens, Ulf D. Kahlert, Jarek Maciaczyk, Eric H. Raabe, and Charles G. Eberhart. "BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets." International Journal of Molecular Sciences 22, no. 8 (April 10, 2021): 3913. http://dx.doi.org/10.3390/ijms22083913.
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Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.
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Piontek, Martin, Dominik Kirchhofer, Lisa Gabler, Daniela Lötsch-Gojo, Christine Pirker, Felix Schmitt-Hoffner, Carola N. Jaunecker, Marcel Kool, Walter Berger, and Johannes Gojo. "ETMR-11. Transcriptional changes upon knockdown of alteredBCOR/BCORL1 transcripts in preclinical models of CNS embryonal tumors with BCOR-related alterations." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i51—i52. http://dx.doi.org/10.1093/neuonc/noac079.189.
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Abstract BCL-6 transcriptional corepressor (BCOR) is an epigenetic regulator that silences gene expression mainly via the polycomb repressive complex 1.1 (PRC1.1). BCOR genomic alterations are found in a variety of different tumors and recently central nervous system (CNS) tumors with BCOR internal tandem duplication (ITD) were classified as a distinct molecular subgroup. We established and characterized two cell models derived from BCOR altered CNS tumor patients. One model is characterized by a frameshift mutation in the BCOR gene resulting in the expression of a truncated protein lacking the C-terminal PUFD domain required for correct assembly of the PRC1.1. Additionally, this model harbors a translocation of the BCOR homologue BCORL1. The second model has a characteristic internal tandem duplication (ITD) within the BCOR gene. To study the effects of mutated BCOR/BCORL1 on gene expression, we performed siRNA mediated knockdown of altered BCOR/BCORL1 transcripts in both models and analyzed transcriptional changes by mRNA expression array. Differentially expressed genes in BCOR/BCORL1 knockdown versus wild type conditions were enriched for signaling pathways involved in cell cycle progression, cell growth, DNA replication and cancer. This suggests that the alterations in BCOR/BCORL1 might have pro-oncogenic effects and thereby contribute to the aggressive phenotype of this disease. Especially in the BCOR ITD model knockdown of BCOR led to transcriptional downregulation of genes associated with the development of brain tumors such as FGF18, PDGFA and PDGFRA. Our results indicate that specific BCOR/BCORL1 alterations might impair its endogenous function as transcriptional repressor and deregulate the expression of multiple PRC1.1 target genes. An in depth characterization of epigenetic and transcriptional changes in BCOR/BCORL1 altered CNS tumors could lead to the identification of critical downstream effectors and ultimately reveal new therapeutic vulnerabilities.
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Schaefer, Eva Johanna, Iman Fares, Clifford Meyer, Paloma Cejas, Annie Apffel, Monica Schenone, Henry W. Long, and R. Coleman Lindsley. "Dual Effects of BCOR-PRC1.1 Dependent Gene Regulation Mediate Cooperation of BCOR and TET2 Mutations in Myeloid Transformation." Blood 132, Supplement 1 (November 29, 2018): 651. http://dx.doi.org/10.1182/blood-2018-99-119519.
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Abstract Myeloid transformation occurs via stepwise acquisition of driver mutations that have distinct positions in the clonal hierarchy. BCOR mutations are common in myelodysplastic syndromes (MDS), but rarely occur as initiating events, instead typically arising in the context of other pre-existing mutations, such as TET2. BCOR encodes a subunit of the Polycomb Repressive Complex 1.1 (PRC1.1) which mediates gene repression by regulating H2AK119 via RING1 ubiquitin ligase activity. We hypothesized that BCOR mutations exert context dependent effects on chromatin regulation, thereby mediating conditional clonal selection during disease progression. We used CRISPR/Cas9 genome editing to establish an isogenic human leukemia cell line model harboring BCOR, TET2, or concurrent BCOR and TET2 mutations. Whereas TET2 deficiency alone caused no effect on cell growth properties, isolated loss of BCOR caused a significant decrease in cell proliferation. Concomitant inactivation of TET2 and BCOR reversed the negative impact of BCOR mutations and resulted in enhanced proliferation suggesting that TET2 and BCOR deficiencies cooperate to drive a distinct cell growth phenotype that is not evident when either gene is knocked out alone. To define the impact of BCOR deficiency on PRC1.1 complex assembly we performed PCGF1 co-immunoprecipitation followed by mass spectrometry (IP/MS) in cells with and without BCOR deficiency. BCOR mutations caused a marked decrease in PRC1.1 complex abundance without disrupting complex integrity. Even in the absence of BCOR, PCGF1 interactions with other PRC1 components (RING1A/B, SKP1, KDM2B, USP7) were maintained. By contrast, reciprocal BCOR IP/MS in cells with and without PCGF1 deletion showed that PCGF1 is required for RING1A/B and RYBP binding, but does not regulate complex abundance. These data suggest that BCOR is critical for maintaining PRC1.1 stability while PCGF1 selectively recruits core enzymatic components to the complex. To evaluate the role of PRC1.1 enzymatic function in regulating target loci, we performed RNA-seq and ChIP-seq analysis in PCGF1 deficient cells that lack PRC1.1-RING1 interactions. 931 genes were significantly upregulated (FC>2, padj≤0.05) in PCGF1 deficient cells compared to control. In wild type cells, these genes were bound by PRC1 (RING1B) and PRC2 (SUZ12) and marked by high levels of repressive histone marks (H3K27me3, H2AK119ub). In PCGF1 deficient cells, RING1B binding and repressive marks were lost at these loci, while BCOR binding was maintained and the active H3K27ac mark significantly increased. These data suggest that selective loss of PRC1.1 enzymatic activity causes derepression of PRC1.1 target loci. To determine whether derepression of PRC1.1 targets underlies the cooperative phenotypic effect of TET2 and BCOR inactivation, we compared the transcriptional and epigenetic state of BCOR/TET2 deficient cells to that of control, TET2, and BCOR deficient cells. Indeed, a subset of genes that were derepressed in PCGF1 deficient cells also showed increased expression, loss of repressive and gain of activating marks in BCOR-TET2 deficient cells, but not in cells with sole BCOR or TET2 deficiency. Derepressed genes were specifically enriched for involvement in developmental processes and cell signaling, including the leukemia-associated HOXA gene cluster. In contrast to PCGF1 deficient cells, BCOR deficient cells also displayed significant transcriptional downregulation of genes involved in metabolism and cell cycle progression, consistent with the negative effect of BCOR mutations on cell growth properties. In wild type cells, these BCOR-dependent loci had high levels of PRC1.1 (BCOR) binding, active histone marks, and high chromatin accessibility. Remarkably, expression of nearly all (590/622) BCOR-dependent genes was restored after introduction of concurrent TET2 deletion. Our data suggest that the BCOR-PRC1.1 complex fulfills a dual epigenetic role via RING1-dependent regulation of gene repression at some target loci and RING1-independent maintenance of active transcription at other loci. Accordingly, inactivation of BCOR alone is sufficient to derepress key leukemia-associated targets, but incurs a metabolic liability that limits transformation potential. Concurrent inactivation of TET2 may therefore enable transformation by attenuating negative impacts of BCOR mutations on active transcription. Disclosures No relevant conflicts of interest to declare.
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Tanaka, Tomoyuki, Yaeko Nakajima-Takagi, Sha Si, Atsunori Saraya, Sone Hirohito, Haruhiko Koseki, and Atsushi Iwama. "Role of the Polycomb Gene Bcor in Hematopoiesis." Blood 124, no. 21 (December 6, 2014): 4312. http://dx.doi.org/10.1182/blood.v124.21.4312.4312.
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Abstract Polycomb group (PcG) proteins are epigenetic regulators crucial for the maintenance and differentiation of stem cells. PcG proteins form in the nucleus two kinds of complexes, PRC (polycomb repressive complex) 1 containing Pcgf family proteins and PRC2. PRC1 ubiquitylates histone H2A at lysine 119 and PRC2 trimethylates lysine 27 of histone H3. Bcor (BCL6 corepressor) together with Pcgf1 has recently been demonstrated to form a non-canonical PRC1 distinct from canonical PRC1 containing Cbx and Bmi1/Pcgf4. Of note, recurrent somatic mutations have been identified in BCOR in myeloid malignancies such as acute myeloid leukemia and myelodysplastic syndrome. However, little is known about its role in hematopoiesis and hematological malignancies. In this study, we investigated the role of Bcor in hematopoiesis using Bcor conditional knockout mice. We first examined basal levels of Bcor expression in BM hematopoietic cell populations by real-time qPCR and found that Bcor is ubiquitously expressed with the highest expression in Flk2-CD34+c-Kit+Sca-1+Lineage- ST-HSCs. We transplanted total bone marrow (BM) cells (CD45.2+) from Bcor floxed male mice (Bcorf/Y ; Bcor is located at X chromosome) crossed with Rosa::Cre-ERT mice into lethally irradiated recipient mice with the equal numbers of BM cells from CD45.1+ congenic WT mice and deleted Bcor by inducing nuclear translocation of Cre by tamoxifen injection at 4 weeks post-transplantation. Chimerism of Bcor-/Y cells in the peripheral blood gradually decreased in all lineages by 6 months after tamxifen injection. BM analysis also showed decreased chimerism of Bcor-/Y cells in Lineage-Sca-1+c-Kit+ (LSK) HSCs/MPPs and myeloid progenitors at 7 months after tamoxifen injection. In non-competitive repopulating assays, recipient mice repopulated with Bcor-/Y BM cells showed leukopenia mainly due to impaired B lymphopoiesis. BM analysis showed CD34-LSK HSC number was significantly decreased in recipients repopulated with Bcor-/Y BM cells compared to the controls. However, no mice showed any signs of myeloid malignancies. These data suggested that Bcor is essential for the maintenance of repopulating capacity of HSCs. We then examined the effects of deletion of Bcor on HSC growth in vitro. Bcor-/Y CD34-LSK cells were cultured for 14 days. Deletion of Bcor profoundly impaired the growth of CD34-LSK cells in the presence of SCF, TPO and IL3 but not significantly in the presence of SCF and TPO only. This finding suggests that Bcor is critical for IL3-responsive proliferation and differentiation. To understand molecular mechanisms underlying defective hematopoiesis in the absence of Bcor, we performed western blot analysis in LK cells and gene expression analysis in LSK cells. Western blot analysis revealed no significant difference in the levels of global H3K27me3 and H3K36me2 between Bcor-/Y LK cells and control. Unexpectedly, however, the level of global H2A119ub1 was not reduced at all in Bcor-/Y LK cells compared to control. Gene expression analysis revealed a trend of de-repression of PRC2 genes, but major target genes of canonical PRC1, such as cyclin-dependent kinase inhibitor genes were not altered in expression in Bcor-/Y LSK cells. These results indicate that Bcor regulates hematopoietic cells in a way different from canonical PRC1. Taken together, Bcor plays an important role in normal hematopoiesis, but its simple loss is not sufficient to induce myeloid malignancies within a short latency. To identify the target genes of Bcor in more detail, we are currently working on RNA sequencing and ChIP-sequencing of histone modifications in Bcor-/Y stem/progenitor cells. Disclosures No relevant conflicts of interest to declare.
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Shojaee, Seyedmehdi, Huimin Geng, Micah Gearhart, Vivian Bardwell, and Markus Muschen. "BCL6 Interacting Corepressor (BCOR) Functions As Lineage-Specific Tumor Suppressor in B Lymphoid and Myeloid Leukemia." Blood 120, no. 21 (November 16, 2012): 1301. http://dx.doi.org/10.1182/blood.v120.21.1301.1301.
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Abstract Abstract 1301 Background: BCL6-interacting corepressor (BCOR) has been first characterized as a BCL6-binding protein and co-repressor of BCL6 along with NCOR and SMRT. The main function of BCOR is to potentiate the transcriptional repression by BCL6. BCOR is also capable of binding with different histone deacetylases(HDACs), demethylase and H2A ubiquitin ligase which suggests chromatin modification as a mechanism of BCL6-independent transcriptional repression by BCOR. Using next generation sequencing, it has been shown that BCOR is recurrently mutated in myelodysplastic syndrome (MDS; Tiacci et al. Blood 2012) and acute myeloid leukemia (AML; Yoshida et al. Nature 2011). BCOR mutations in AML are typically associated with lack or low expression of a truncated BCOR protein which suggest a tumor-suppressor role for BCOR in MDS and AML. Recently we have shown that BCOR's main ligand, BCL6 promotes drug-resistance and survival in B cell lineage Ph+ALL and CML (Duy et al., Nature 2011). Considering the interactive function of BCL6 and BCOR we hypothesized that BCOR, although a tumor suppressor in MDS and AML, acts in concert with BCL6 to promote survival and drug-resistance in Ph+ ALL and CML. Results: To study the role of BCOR in a genetic experiment, we developed a CML and Ph+ ALL leukemia model based on bone marrow progenitor cells from male mice carring a loxP-flanked allele of Bcor (Bcorfl/Y) and mice in which BCOR overexpression can be induced by excision of a loxP-flanked Stop-cassette (BcorLSL). In Bcorfl/Ymice, exon 3 of Bcor is flanked by loxP sites and in BcorLSL mice an extra allele of Bcor has been inserted into Rosa26 locus with a stop codon flanked by loxP sites upstream of the start codon. On the basis of this model, bone marrow hematopoietic stem and progenitor cells from Bcorfl/Y and BcorLSL mice were transformed with BCR-ABL1 under B lymphoid (IL7; Ph+ ALL) and stem/progenitor cell (IL3, IL6, SCF; CML) conditions. Cre-mediated deletion of loxP sequences causes the deletion of Bcor in Bcorfl/Y cells and the over-expression of Bcor in BcorR26cells. Transduction of the ALL and CML cells with tamoxifen (4-OHT)-inducible Cre-ERT2 or ERT2 empty vectors were used to inducibly activate Cre in Ph+ ALL- and CML-like leukemia cells. Inducible deletion of Bcor in B cell lineage (CD19+ B220+) Ph+ ALL results in massive cell death. Surprisingly, deletion of Bcor had no significant effect on CML-like (LSK and myeloid phenotype) cells. Gain-of-function studies with the BcorLSL system revealed that inducible overexpression of BCOR significantly increases the ability of Ph+ ALL-like leukemia cells to form colonies in semi-solid methylcellulose culture, whereas inducible activation of BCOR in BcorLSL CML-like cells had the opposite effect. Comparing the basal level of Bcor between Ph+ ALL and CML shows that there is significantly higher amount of Bcor in Ph+ ALL as compared to CML. In vivo injection and Cre-mediated deletion of BCOR in Bcorfl/YPh+ ALL shows that the Bcor is required to initiate B cell lineage Ph+ ALL in vivo and cause fatal disease (p=0.001). Five out of 7 mice, injected with Bcorfl/-Ph+ ALL survive with no sign of tumor growth until the end of experiment (240 days after injection) while all mice injected with wild type cells died within the first 15 days. In addition, we tested the impact of Bcor deletion and Bcor overexpression on TKI-sensitivity of Ph+ ALL and CML-like leukemia cells. While Bcor-deletion dramatically sensitized Ph+ALL cells to TKI-treatment (e.g. Imatinib), no effects on TKI-sensitivity were observed in CML-like leukemia. Conclusion: Our genetic studies demonstrate an unexpected lineage-specific effect of BCOR function in B cell lineage Ph+ ALL and myeloid lineage CML. While both leukemia types are induced by BCR-ABL1, BCOR function was critical for the survival and leukemia-initiation of Ph+ ALL, but not CML. The findings in B cell lineage Ph+ ALL are consistent with our hypothesis that BCOR mediates TKI-resistance and survival in Ph+ ALL in concert with BCL6. Our findings in CML support a role of BCOR as tumor suppressor in myeloid leukemia as was observed for MDS and AML. In myeloid leukemias, BCOR activity may predominantly involve HDACs and, hence, BCL6-independent pathways of transcriptional repression. Disclosures: No relevant conflicts of interest to declare.