Protein-mediated Fatty Acid Uptake in the Heart

Long chain fatty acids (LCFAs) provide 70-80% of the energy for cardiac contractile activity. LCFAs are also essential for many other cellular functions, such as transcriptional regulation of proteins involved in lipid metabolism, modulation of intracellular signalling pathways, and as substrates for membrane constituents. When LCFA uptake exceeds the capacity for their cardiac utilization, the intracellular lipids accumulate and are thought to contribute to contractile dysfunction, arrhythmias, cardiac myocyte apoptosis and congestive heart failure. Moreover, increased cardiac myocyte triacylglycerol, diacylglycerol and ceramide depots are cardinal features associated with obesity and type 2 diabetes. In recent years considerable evidence has accumulated to suggest that, the rate of entry of long chain fatty acids (LCFAs) into the cardiac myocyte is a key factor contributing to a) regulating cardiac LCFA metabolism and b) lipotoxicity in the obese and diabetic heart. In the present review we i) examine the evidence indicating that LCFA transport into the heart involves a protein-mediated mechanism, ii) discuss the proteins involved in this process, including FAT/CD36, FABPpm and FATP1, iii) discuss the mechanisms involved in regulating LCFA transport by some of these proteins (including signaling pathways), as well as iv) the possible interactions of these proteins in regulating LCFA transport into the heart. In addition, v) we discuss how LCFA transport and transporters are altered in the obese/diabetic heart

Inactivation of Numb and Numblike in Embryonic Dorsal Forebrain Impairs Neurogenesis and Disrupts Cortical Morphogenesis

AbstractNumb and Numblike, conserved homologs of Drosophila Numb, have been implicated in cortical neurogenesis; however, analysis of their involvement in later stages of cortical development has been hampered by early lethality of double mutants in previous studies. Using Emx1IREScre to induce more restricted inactivation of Numb in the dorsal forebrain of numblike null mice beginning at E9.5, we have generated viable double mutants that displayed striking brain defects. It was thus possible to examine neurogenesis during the later peak phase (E12.5–E16.5). Loss of Numb and Numblike in dorsal forebrain resulted in neural progenitor hyperproliferation, delayed cell cycle exit, impaired neuronal differentiation, and concomitant defects in cortical morphogenesis. These findings reveal novel and essential function of Numb and Numblike during the peak period of cortical neurogenesis. Further, these double mutant mice provide an unprecedented viable animal model for severe brain malformations due to defects in neural progenitor cells

Galaxy Zoo: The large-scale spin statistics of spiral galaxies in the Sloan Digital Sky Survey

We re-examine the evidence for a violation of large-scale statistical isotropy in the distribution of projected spin vectors of spiral galaxies. We have a sample of $\sim 37,000$ spiral galaxies from the Sloan Digital Sky Survey, with their line of sight spin direction confidently classified by members of the public through the online project Galaxy Zoo. After establishing and correcting for a certain level of bias in our handedness results we find the winding sense of the galaxies to be consistent with statistical isotropy. In particular we find no significant dipole signal, and thus no evidence for overall preferred handedness of the Universe. We compare this result to those of other authors and conclude that these may also be affected and explained by a bias effect.Comment: Accepted for publication in MNRAS. 8 pages, 5 figure

The Araucaria Project: A study of the classical Cepheid in the eclipsing binary system OGLE LMC562.05.9009 in the Large Magellanic Cloud

We present a detailed study of the classical Cepheid in the double-lined, highly eccentric eclipsing binary system OGLE-LMC562.05.9009. The Cepheid is a fundamental mode pulsator with a period of 2.988 days. The orbital period of the system is 1550 days. Using spectroscopic data from three 4-8-m telescopes and photometry spanning 22 years, we were able to derive the dynamical masses and radii of both stars with exquisite accuracy. Both stars in the system are very similar in mass, radius and color, but the companion is a stable, non-pulsating star. The Cepheid is slightly more massive and bigger (M_1 = 3.70 +/- 0.03M_sun, R_1 = 28.6 +/- 0.2R_sun) than its companion (M_2 = 3.60 +/- 0.03M_sun, R_2 = 26.6 +/- 0.2R_sun). Within the observational uncertainties both stars have the same effective temperature of 6030 +/- 150K. Evolutionary tracks place both stars inside the classical Cepheid instability strip, but it is likely that future improved temperature estimates will move the stable giant companion just beyond the red edge of the instability strip. Within current observational and theoretical uncertainties, both stars fit on a 205 Myr isochrone arguing for their common age. From our model, we determine a value of the projection factor of p = 1.37 +/- 0.07 for the Cepheid in the OGLE-LMC562.05.9009 system. This is the second Cepheid for which we could measure its p-factor with high precision directly from the analysis of an eclipsing binary system, which represents an important contribution towards a better calibration of Baade-Wesselink methods of distance determination for Cepheids.Comment: Accepted to be published in Ap

Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism

<p>Abstract</p> <p>Background</p> <p>The variable penetrance of ovarian cancer in <it>BRCA1 </it>mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (<it>PHB</it>) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring <it>BRCA1 </it>mutations.</p> <p>Methods</p> <p>To investigate whether the <it>PHB </it>3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and <it>BRCA1 </it>mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.</p> <p>Results</p> <p>A comparison of the genotype frequencies between cases and controls revealed no association of the <it>PHB </it>3'UTR _CT+TT genotypes with ovarian cancer risk (OR_adj1.34; 95% CI, 0.59–3.11).</p> <p>Conclusion</p> <p>Our data suggest that the <it>PHB </it>3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish <it>BRCA1 </it>founder mutations.</p

Aerobic Training in Rats Increases Skeletal Muscle Sphingomyelinase and Serine Palmitoyltransferase Activity, While Decreasing Ceramidase Activity

Sphingolipids are important components of cell membranes that may also serve as cell signaling molecules; ceramide plays a central role in sphingolipid metabolism. The aim of this study was to examine the effect of 5 weeks of aerobic training on key enzymes and intermediates of ceramide metabolism in skeletal muscles. The experiments were carried out on rats divided into two groups: (1) sedentary and (2) trained for 5 weeks (on a treadmill). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), neutral and alkaline ceramidases (nCDase and alCDase) and the content of sphingolipids was determined in three types of skeletal muscle. We also measured the fasting plasma insulin and glucose concentration for calculating HOMA-IR (homeostasis model assessment) for estimating insulin resistance. We found that the activities of aSMase and SPT increase in muscle in the trained group. These changes were followed by elevation in the content of sphinganine. The activities of both isoforms of ceramidase were reduced in muscle in the trained group. Although the activities of SPT and SMases increased and the activity of CDases decreased, the ceramide content did not change in any of the studied muscle. Although ceramide level did not change, we noticed increased insulin sensitivity in trained animals. It is concluded that training affects the activity of key enzymes of ceramide metabolism but also activates other metabolic pathways which affect ceramide metabolism in skeletal muscles

Phage Therapy:What Have We Learned?

In this article we explain how current events in the field of phage therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances in the research and application of the therapy. In addition, we discuss methods to obtain optimal phage preparations and suggest the potential of novel applications of phage therapy extending beyond its anti-bacterial action

Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

Genetic deletion of murine Esco2 (an acetylase known to establish cohesin during S-phase and genetically linked to Roberts syndrome) results in embryonic lethality that can be molecularly linked to novel and specific functions of Esco2 at pericentric heterochromatin

The influence of physical exercise on the generation of TGF-β1, PDGF-AA, and VEGF-A in adipose tissue

Adipose tissue is an important organ that produces and secretes hormones and cytokines, including TGF-β1, PDGF-AA, and VEGF-A. The goal of the present study was to investigate the influence of a single session of acute exercise, as well as the prolonged endurance training on the production of TGF-β1, PDGF-AA, and VEGF-A in the subcutaneous white adipose tissue in rats. Rats were randomly divided into two groups: untrained (UT, n = 30) and trained rats (T, subjected to 6-week endurance training with increasing load, n = 29). Both groups were subjected to an acute exercise session with the same work load. The rats were killed before (UTpre, Tpre), immediately after (UT0h, T0h), or 3 h (UT3h, T3h) after exercise and adipose tissue samples collected. Growth factor mRNA was evaluated using RT-PCR; the protein levels were measured before and after training (UTpre and Tpre) using the immunoenzymatic method. TGF-β1 and PDGF-AA mRNA levels were decreased in the UT3h rats compared to the UTpre rats (P = 0.0001 and P = 0.03, respectively), but the VEGF-A mRNA level remained unchanged in the UT0h and UT3h rats compared to UTpre rats. TGF-β1, PDGF-AA and VEGF-A mRNA levels were decreased in the T3h rats compared to Tpre (P = 0.0002, P = 0.02, and P = 0.03, respectively). TGF-β1, PDGF-AA and VEGF-A mRNA levels significantly increased in the Tpre rats compared to UTpre (all P = 0.0002). However, the protein levels remained constant. In conclusion, prolonged physical exercise increases growth factor mRNA in adipose tissue but not protein levels