The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance., P. Soucek, V. Hlavac, K. Elsnerova, R. Vaclavikova, R. Kozevnikovova, K. Raus., and Obsahuje bibliografii
Purkinje fibers were the first discovered component of the cardiac conduction system. Origin ally described in sheep in 1839 as pale subendocardial cells, they were found to be present, although with different morphology, in all mammalian and avian hearts. Here we review differences in their appearance and extent in different species, summarize the current state of knowledge of their function, and provide an update on markers for these cells. Special emphasis is given to popular model species and human anatomy., D. Sedmera, R. G. Gourdie., and Obsahuje bibliografii a bibliografické odkazy
Metabolic syndrome is a prevalent, complex condition. The search for genetic determinants of the syndrome is currently undergoing a paradigm enhancement by adding systems genetics approaches to association studies. We summarize the current evidence on relations between an emergent new candidate, zinc finger and BTB domain containing 16 (ZBTB16) transcription factor and the major components constituting the metabolic syndrome. Information stemming from studies on experimental models with altered Zbtb16 expression clearly shows its effect on adipogenesis, cardiac hypertrophy and fibrosis, lipid levels and insulin sensitivity. Based on current evidence, we provide a network view of relations between ZBTB16 and hallmarks of metabolic syndrome in order to elucidate the potential functional links involving the ZBTB16 node. Many of the identified genes interconnecting ZBTB16 with all or most metabolic syndrome components are linked to immune function, inflammation or oxidative stress. In summary, ZBTB16 represents a promising pleiotropic candidate node for metabolic syndrome., O. Šeda, L. Šedová, J. Včelák, M. Vaňková, F. Liška, B. Bendlová., and Obsahuje bibliografii
The data derived from rat models and the preliminary results of human studies provide strong indices of involvement of common ZBTB16 variants in a range of cardiovascular and metabolic traits. This cross-sectional study in the Caucasian cohort of 1517 Czech adults aimed to verify the hypothesis that ZBTB16 gene variation directly affects obesity and serum lipid levels. Genotyping of nine polymorphisms of the ZBTB16 gene (rs11214863, rs593731, rs763857, rs2846027, rs681200, rs686989, rs661223, rs675044, rs567057) was performed. A multivariate bidirectional regression with the reduction of dimensionality (O2PLS model) revealed relationships between basal lipid levels and anthropometric parameters and some minor ZBTB16 alleles. In men, the predictors - age and presence of minor ZBTB16 alleles of rs686989, rs661223, rs675044, rs567057 - were associated with significantly higher body mass index, waist to hip ratio, body adiposity index, waist and abdominal circumferences, higher total cholesterol and LDL cholesterol and explained 20 % of variability of these variables. In women, the predictors - age and presence of the rs686989 minor T allele - were also associated with increased anthropometric parameters and total cholesterol and LDL cholesterol but the obtained O2PLS model explained only 7.8 % of the variability of the explained variables. Our study confirmed that the selected gene variants of the transcription factor ZBTB16 influence the obesity-related parameters and lipid levels. This effect was more pronounced in men., B. Bendlová, M. Vaňková, M. Hill, G. Vacínová, P. Lukášová, D. Vejražková, L. Šedová, O. Šeda, J. Včelák., and Obsahuje bibliografii
One of the most abundant immunologic cell types in early decidua is the uterine natural killer (UNK) cell that despite the presence of cytoplasmic granules rich in perforin and granzymes does not degranulate in normal pregnancy. UNK cells are important producers of angiogenic factors that permit normal dilation of uterine arteries to provide increased blood flow for the growing feto-placental unit. Gram-negative bacteria lipopolysaccharide (LPS) administration can trigger an imbalance of pro-inflammatory and anti-inflammatory cytokines impairing the normal immune cells activity as well as uterine homeostasis. The present study aimed to evaluate by immunohistochemistry the reactivity of perforin and α-actin on UNK cell from LPStreated pregnant mice. For the first time, we demonstrate that LPS injection in pregnant mice causes α-actin down regulation, concomitantly with perforin loss in UNK cells. This suggests that LPS alters UNK cell migration and activates cytotoxic granule release., B. Zavan, A. M. do Amarante-Paffaro, V. A. Paffaro Jr., and Obsahuje bibliografii