Fot1, a new family of fungal transposable elements

Summary We report here the discovery of a family of transposable elements, which we refer to as Fotl elements, in the fungal plant pathogen Fusarium oxysporum. The first element was identified as an insertion in the gene encoding nitrate reductase. It is 1928 by long, has 44 by inverted terminal repeats, contains a large open reading frame and is flanked by a 2 by (TA) target site duplication. This element shares significant structural similarities with a class of transposons that includes Tc1 from Caenorhabditis elegans and therefore represents a new class of transposable elements in fungi.     

ArchAlign: coordinate-free chromatin alignment reveals novel architectures

To facilitate identification and characterization of genomic functional elements, we have developed a chromatin architecture alignment algorithm (ArchAlign). ArchAlign identifies shared chromatin structural patterns from high-resolution chromatin structural datasets derived from next-generation sequencing or tiled microarray approaches for user defined regions of interest. We validated ArchAlign using well characterized functional elements, and used it to explore the chromatin structural architecture at CTCF binding sites in the human genome. ArchAlign is freely available at http://www.acsu.buffalo.edu/~mjbuck/ArchAlign.html.     

Chronic TNFα and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis

We examined the effects of chronic TNFα and dibutyryl-cAMP (Db-cAMP) pre-treatment on the lipolytic machinery of human hMADS adipocytes. TNFα decreased adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin (PLIN) protein content. Conversely, Db-cAMP increased ATGL and HSL protein content but prevented PLIN phosphorylation, the net result being accentuated basal lipolysis. In forskolin-stimulated conditions, TNFα and Db-cAMP pre-treatment decreased stimulated TG-hydrolase activity and impaired PLIN phosphorylation. Together, this resulted in a severely attenuated response to forskolin-stimulated lipolysis.     

Molecular Analysis of a Large Subtelomeric Nucleotide-Binding-Site–Leucine-Rich-Repeat Family in Two Representative Genotypes of the Major Gene Pools of Phaseolus vulgaris

In common bean, the B4 disease resistance (R) gene cluster is a complex cluster localized at the end of linkage group (LG) B4, containing at least three R specificities to the fungus Colletotrichum lindemuthianum. To investigate the evolution of this R cluster since the divergence of Andean and Mesoamerican gene pools, DNA sequences were characterized from two representative genotypes of the two major gene pools of common bean (BAT93: Mesoamerican; JaloEEP558: Andean). Sequences encoding 29 B4-CC nucleotide-binding-site–leucine-rich-repeat (B4-CNL) genes were determined—12 from JaloEEP558 and 17 from BAT93. Although sequence exchange events were identified, phylogenetic analyses revealed that they were not frequent enough to lead to homogenization of B4-CNL sequences within a haplotype. Genetic mapping based on pulsed-field gel electrophoresis separation confirmed that the B4-CNL family is a large family specific to one end of LG B4 and is present at two distinct blocks separated by 26 cM. Fluorescent in situ hybridization on meiotic pachytene chromosomes revealed that two B4-CNL blocks are located in the subtelomeric region of the short arm of chromosome 4 on both sides of a heterochromatic block (knob), suggesting that this peculiar genomic environment may favor the proliferation of a large R gene cluster.     

Obesity‐related Polymorphisms and Their Associations With the Ability to Regulate Fat Oxidation in Obese Europeans: The NUGENOB Study

Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single‐nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, ?178 A>C CD36 (rs2232169) (P = 0.02), ?22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with ?174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.     

CIDEA interacts with liver X receptors in white fat cells

Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) is endogenously expressed in human but not rodent white adipocytes. We performed a bioinformatic analysis of the human CIDEA sequence and found conserved amino-acid motifs involved in binding to nuclear receptors. Protein-protein binding experiments and transactivation assays confirmed that CIDEA binds to liver X receptors and regulates their activity in vitro. Cell fractionation demonstrated that CIDEA localizes to both the cytoplasm and the nucleus in human white adipocytes. The interaction between CIDEA and nuclear receptors could therefore be of importance for the regulation of metabolic processes in human adipose tissue.     

Influence of shape-memory stent grafts on local aortic compliance

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

     

Millennium fat-cell lipolysis reveals unsuspected novel tracks.

Adipose tissue lipolysis, i.e., the catabolic process leading to the breakdown of triglycerides into fatty acids and glycerol, is often considered as a simple and well-understood metabolic pathway. However, progress on the hormonal regulation and molecular mechanism of fat-cell lipolysis is opening new avenues and points to a number of unanswered questions. Recent studies on the lipolytic beta- and antilipolytic alpha2-adrenergic control of lipolysis has allowed a better understanding of the relative contribution of the two types of receptors and provide strong evidence for the in vivo implication of alpha2-adrenoceptors in the physiological control of subcutaneous adipose-tissue lipolysis. A novel lipolytic system has been characterized in human fat cells. Natriuretic peptides stimulate lipolysis through a cGMP-dependent pathway. The molecular details of the lipolytic reaction are not fully understood. Translocation of hormone-sensitive lipase, the rate-limiting enzyme of lipolysis, to the lipid droplet seems to be an important step during lipolytic activation. Reorganization of the lipid droplet coating by perilipins may also facilitate the access of the enzyme. Unexpectedly, hormone-sensitive lipase-deficient mice are not obese and show residual adipose-tissue lipolysis, which suggests the existence of another triglyceride lipase. Whether the expression of this uncharacterized neutral lipase is compensatory for the lack of hormone-sensitive lipase is an important question yet to be resolved. In humans, alterations of hormone-sensitive lipase expression are associated with changes in lipolysis in various physiological and pathological states. Genetic studies show that beta2-adrenoceptor and hormone-sensitive lipase genes may participate in the polygenic background of obesity.