Expression of Foxm1 Transcription Factor in Cardiomyocytes Is Required for Myocardial Development

Forkhead Box M1 (Foxm1) is a transcription factor essential for organ morphogenesis and development of various cancers. Although complete deletion of Foxm1 in Foxm1−/− mice caused embryonic lethality due to severe abnormalities in multiple organ systems, requirements for Foxm1 in cardiomyocytes remain to be determined. This study was designed to elucidate the cardiomyocyte-autonomous role of Foxm1 signaling in heart development. We generated a new mouse model in which Foxm1 was specifically deleted from cardiomyocytes (Nkx2.5-Cre/Foxm1fl/f mice). Deletion of Foxm1 from cardiomyocytes was sufficient to disrupt heart morphogenesis and induce embryonic lethality in late gestation. Nkx2.5-Cre/Foxm1fl/fl hearts were dilated with thinning of the ventricular walls and interventricular septum, as well as disorganization of the myocardium which culminated in cardiac fibrosis and decreased capillary density. Cardiomyocyte proliferation was diminished in Nkx2.5-Cre/Foxm1fl/fl hearts owing to altered expression of multiple cell cycle regulatory genes, such as Cdc25B, Cyclin B1, Plk-1, nMyc and p21cip1. In addition, Foxm1 deficient hearts displayed reduced expression of CaMKIIδ, Hey2 and myocardin, which are critical mediators of cardiac function and myocardial growth. Our results indicate that Foxm1 expression in cardiomyocytes is critical for proper heart development and required for cardiomyocyte proliferation and myocardial growth

Hierarchical structure of cascade of primary and secondary periodicities in Fourier power spectrum of alphoid higher order repeats

<p>Abstract</p> <p>Background</p> <p>Identification of approximate tandem repeats is an important task of broad significance and still remains a challenging problem of computational genomics. Often there is no single best approach to periodicity detection and a combination of different methods may improve the prediction accuracy. Discrete Fourier transform (DFT) has been extensively used to study primary periodicities in DNA sequences. Here we investigate the application of DFT method to identify and study alphoid higher order repeats.</p> <p>Results</p> <p>We used method based on DFT with mapping of symbolic into numerical sequence to identify and study alphoid higher order repeats (HOR). For HORs the power spectrum shows equidistant frequency pattern, with characteristic two-level hierarchical organization as signature of HOR. Our case study was the 16 mer HOR tandem in AC017075.8 from human chromosome 7. Very long array of equidistant peaks at multiple frequencies (more than a thousand higher harmonics) is based on fundamental frequency of 16 mer HOR. Pronounced subset of equidistant peaks is based on multiples of the fundamental HOR frequency (multiplication factor <it>n </it>for <it>n</it>mer) and higher harmonics. In general, <it>n</it>mer HOR-pattern contains equidistant secondary periodicity peaks, having a pronounced subset of equidistant primary periodicity peaks. This hierarchical pattern as signature for HOR detection is robust with respect to monomer insertions and deletions, random sequence insertions etc. For a monomeric alphoid sequence only primary periodicity peaks are present. The 1/<it>f</it>^{<it>β </it>}– noise and periodicity three pattern are missing from power spectra in alphoid regions, in accordance with expectations.</p> <p>Conclusion</p> <p>DFT provides a robust detection method for higher order periodicity. Easily recognizable HOR power spectrum is characterized by hierarchical two-level equidistant pattern: higher harmonics of the fundamental HOR-frequency (secondary periodicity) and a subset of pronounced peaks corresponding to constituent monomers (primary periodicity). The number of lower frequency peaks (secondary periodicity) below the frequency of the first primary periodicity peak reveals the size of <it>n</it>mer HOR, i.e., the number <it>n </it>of monomers contained in consensus HOR.</p

Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus. This study investigated the impact of Hatha yoga and conventional physical training (PT) exercise regimens on biochemical, oxidative stress indicators and oxidant status in patients with type 2 diabetes.</p> <p>Methods</p> <p>This prospective randomized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups. Biochemical parameters such as fasting blood glucose (FBG), serum total cholesterol (TC), triglycerides, low-density lipoprotein (LDL), very low-density lipoproteins (VLDL) and high-density lipoprotein (HDL) were determined at baseline and at two consecutive three monthly intervals. The oxidative stress indicators (malondialdehyde – MDA, protein oxidation – POX, phospholipase A2 – PLA2 activity) and oxidative status [superoxide dismutase (SOD) and catalase activities] were measured.</p> <p>Results</p> <p>The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48% and 27.43% respectively (P < 0.0001) and there was a significant reduction in serum TC in both groups (P < 0.0001). The concentrations of VLDL in the managed groups after six months differed significantly from baseline values (P = 0.036). Lipid peroxidation as indicated by MDA significantly decreased by 19.9% and 18.1% in the Hatha yoga and conventional PT exercise groups respectively (P < 0.0001); whilst the activity of SOD significantly increased by 24.08% and 20.18% respectively (P = 0.031). There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68% and 13.19% in the Hatha yoga and conventional PT exercise groups respectively (P = 0.144).</p> <p>Conclusion</p> <p>The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose, lipid profile, oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12608000217303</p

Detailed Analysis of a Contiguous 22-Mb Region of the Maize Genome

Most of our understanding of plant genome structure and evolution has come from the careful annotation of small (e.g., 100 kb) sequenced genomic regions or from automated annotation of complete genome sequences. Here, we sequenced and carefully annotated a contiguous 22 Mb region of maize chromosome 4 using an improved pseudomolecule for annotation. The sequence segment was comprehensively ordered, oriented, and confirmed using the maize optical map. Nearly 84% of the sequence is composed of transposable elements (TEs) that are mostly nested within each other, of which most families are low-copy. We identified 544 gene models using multiple levels of evidence, as well as five miRNA genes. Gene fragments, many captured by TEs, are prevalent within this region. Elimination of gene redundancy from a tetraploid maize ancestor that originated a few million years ago is responsible in this region for most disruptions of synteny with sorghum and rice. Consistent with other sub-genomic analyses in maize, small RNA mapping showed that many small RNAs match TEs and that most TEs match small RNAs. These results, performed on ∼1% of the maize genome, demonstrate the feasibility of refining the B73 RefGen_v1 genome assembly by incorporating optical map, high-resolution genetic map, and comparative genomic data sets. Such improvements, along with those of gene and repeat annotation, will serve to promote future functional genomic and phylogenomic research in maize and other grasses

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Phytoserotonin: A review

Serotonin (5-hydroxytryptamine; SER) is one of the well-studied indoleamine neurotransmitters in vertebrates. Recently SER has also been reported in wide range of plant species. The precise function of SER at the physiological level, particularly growth regulation, flowering, xylem sap exudation, ion permeability and plant morphogenesis in plant system has not been clear. Though SER is found in different parts of plant species including leaves, stems, roots, fruits and seeds, the quantity of SER within plant tissues varies widely. SER has been recently shown as a plant hormone in view of its auxin-like activity. This brief review provides an overview of SER biosynthesis, localization, its role in plant morphogenesis and possible physiological functions in plants. This would certainly help to elucidate further the multiple roles of SER in plant morphogenesis. In the future it may form the basis for studies on involvement of SER in cellular signaling mechanisms in plants. Apart from these gaps in understanding the role of SER in ontogeny of plant physiology and ecological, adaptations have been emphasized. Thus, overall perspectives in this area of research and its possible implications have been presented