Algebraic characteristic classes for idempotent matrices

This paper contains the algebraic analog for idempotent matrices of the Chern-Weil theory of characteristic classes. This is used to show, algebraically, that the canonical line bundle on the complex projective space is not stably trivial. Also a theorem is proved saying that for any smooth manifold there is a canonical epimorphism from the even dimensional algebraic de Rham cohomology of its algebra of smooth functions onto the standard even dimensional de Rham cohomology of the manifold

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

AbstractAutosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids

Pyruvate kinase synthesis and degradation by normal and pathologic cells during erythroid maturation

Abstract Mature erythrocytes contain a specific isozyme of pyruvate kinase (R- PK) while immature erythroblasts coexpress R-PK and another isozyme, M2- PK. To determine what roles degradation and decreasing of synthesis played in the disappearance of M2-PK during erythroid maturation, M2-PK and R-PK synthesis and degradation were studied in erythroblasts from fetal liver and blood BFU-E-derived erythroblasts from healthy subjects, an erythroleukemic patient, and a patient with an erythrocyte PK hyperactivity associated with M2-PK persistence in mature erythrocytes. In normal erythroblasts, R-PK synthesis was constant throughout erythroid maturation, whereas M2-PK synthesis decreased to the point of becoming undetectable. R-PK degradation was very low, while M2-PK degradation was more pronounced and steady during erythroid maturation. In leukemic erythroblasts, total protein turnover was higher than in normal cells, but the M2-PK degradation rate was lower. In erythroblasts from the patient with M2-PK persistence in mature erythrocytes, M2-PK synthesis did not decline with cell maturation. In conclusion, our results emphasize the importance of the decrease of M2- PK synthesis in the disappearance of M2-PK during erythroid maturation. Further studies of patients with pathologic persistence of M2-PK synthesis will help in the understanding of this event involved in erythroid maturation.</jats:p