Meiosis-Specific Loading of the Centromere-Specific Histone CENH3 in Arabidopsis thaliana

Centromere behavior is specialized in meiosis I, so that sister chromatids of homologous chromosomes are pulled toward the same side of the spindle (through kinetochore mono-orientation) and chromosome number is reduced. Factors required for mono-orientation have been identified in yeast. However, comparatively little is known about how meiotic centromere behavior is specialized in animals and plants that typically have large tandem repeat centromeres. Kinetochores are nucleated by the centromere-specific histone CENH3. Unlike conventional histone H3s, CENH3 is rapidly evolving, particularly in its N-terminal tail domain. Here we describe chimeric variants of CENH3 with alterations in the N-terminal tail that are specifically defective in meiosis. Arabidopsis thaliana cenh3 mutants expressing a GFP-tagged chimeric protein containing the H3 N-terminal tail and the CENH3 C-terminus (termed GFP-tailswap) are sterile because of random meiotic chromosome segregation. These defects result from the specific depletion of GFP-tailswap protein from meiotic kinetochores, which contrasts with its normal localization in mitotic cells. Loss of the GFP-tailswap CENH3 variant in meiosis affects recruitment of the essential kinetochore protein MIS12. Our findings suggest that CENH3 loading dynamics might be regulated differently in mitosis and meiosis. As further support for our hypothesis, we show that GFP-tailswap protein is recruited back to centromeres in a subset of pollen grains in GFP-tailswap once they resume haploid mitosis. Meiotic recruitment of the GFP-tailswap CENH3 variant is not restored by removal of the meiosis-specific cohesin subunit REC8. Our results reveal the existence of a specialized loading pathway for CENH3 during meiosis that is likely to involve the hypervariable N-terminal tail. Meiosis-specific CENH3 dynamics may play a role in modulating meiotic centromere behavior

The PPAR α/γ Agonist Saroglitazar Improves Insulin Resistance and Steatohepatitis in a Diet Induced Animal Model of Nonalcoholic Fatty Liver Disease

Abstract Insulin resistance and hepatic lipid accumulation constitute the metabolic underpinning of nonalcoholic steatohepatitis (NASH). We tested the hypothesis that saroglitazar, a PPAR α/γ agonist would improve NASH in the diet-induced animal model of NAFLD. Mice received chow diet and normal water (CDNW) or high fat western diet and ad lib sugar water (WDSW). After 12 weeks, WDSW fed mice were randomized to receive (1) WDSW alone, (2) WDSW + vehicle, (3) WDSW + pioglitazone or (4) WDSW + saroglitazar for an additional 12 weeks. Compared to mice on WDSW and vehicle controls, mice receiving WDSW + saroglitazar had lower weight, lower HOMA-IR, triglycerides, total cholesterol, and ALT. Saroglitazar improved steatosis, lobular inflammation, hepatocellular ballooning and fibrosis stage. NASH resolved in all mice receiving saroglitazar. These effects were at par with or superior to pioglitazone. Molecular analyses confirmed target engagement and reduced oxidative stress, unfolded protein response and fibrogenic signaling. Transcriptomic analysis further confirmed increased PPAR-target expression and an anti-inflammatory effect with saroglitazar. Lipidomic analyses demonstrated that saroglitazar also reduced triglycerides, diglycerides, sphingomyelins and ceramides. These preclinical data provide a strong rationale for developing saroglitazar for the treatment of NASH in humans

ENGAGEMENT IN ORGANIZATIONAL BEHAVIOUR PLANE

Örgütlere rekabet üstünlüğü sağlayan birincil ve hayati unsur insandır. Psikolojik ve sosyal bir varlık olan insanın örgüt için üretken hale getirilmesinde örgütsel davranış disiplinine önemli görevler düşmektedir. Örgütsel davranışın ilgilendiği konulardan biri olan adanmışlık, örgüt başarısında etkili bir durumdur. Adanmışlık durumu, birey ve örgüt yapısı çerçevesinde birçok unsurla etkileşim göstermektedir. Tutumlar, davranışlar ve oluşan örgüt kültürü çalışanların adanmışlık seviyesini etkileyen unsurlardandır. Adanmışlık konusununun teorik bir yaklaşımla ortaya konulmaya çalışıldığı bu araştırmada farklı adanmışlık unsurları ve boyutları, adanmışlık durumları, adanmışlığın önemi, adanmışlığı ortaya çıkaran ve arttıran unsurlar irdelenip adanmışlığın tükenmişlikle ilişkisi ortaya konulmaya çalışılmıştır.The major and vital factor providing competitive advantage to the organizations is person. Organizational behavior discipline plays a crucial role in rendering a person that is both psychological and social entity to an efficient being in the organization. Commitment which is one of the issues examined by organizational behavior is an effective condition in the way of reaching to organizational success. The condition of commitment is related to several factors within the frame of individual and organizational structure. Attitudes, behaviors and developing organizational culture affect the commitment degree of workers. In this research, it is aimed to establish a frame on the relation between commitment and burn-out by examining particular commitment factors and dimensions, commitment conditions, the importance of commitment and the factors revealing and increasing the commitmen