MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells

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DNp73 improves generation efficiency of human induced pluripotent stem cells

<p>Abstract</p> <p>Background</p> <p>Recent studies have found that p53 and its' associated cell cycle pathways are major inhibitors of human induced pluripotent stem (iPS) cell generation. In the same family as p53 is p73, which shares sequence similarities with p53. However, p73 also has distinct properties of its own, such as two alternative promoters to express transactivation of p73 (TAp73) and N terminal deleted p73 (DNp73). Functionally, TAp73 acts similarly to p53 in tumor suppression. However, DNp73, on the other hand acts as an oncogene to suppress p53 and p73 induced apoptosis. Therefore, how can p73 have opposing roles in human iPS cell generation?</p> <p>Results</p> <p>Transcription factors, Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) are used as basal conditions to generate iPS cells. In addition, the factor of DNp73(actually alpha splicing DNp73, DNp73α) is used to generate iPS cells. The experiment found that the addition of DNp73 gene increases human iPS cell generation efficiency by 12.6 folds in comparison to human fibroblast cells transduced with only the basal conditions. Also, iPS cells generated with DNp73 expression are more resistant to <it>in vitro </it>and <it>in vivo </it>differentiation.</p> <p>Conclusions</p> <p>This study found DNp73, a family member of p53, is also involved in the human iPS cell generation. Specifically, that the involvement of DNp73 generates iPS cells that are more resistant to <it>in vitro </it>and <it>in vivo </it>differentiation. Therefore, this data may prove to be useful in future developmental studies and cancer researches.</p

ITCH Deficiency Protects From Diet-Induced Obesity

This study was funded in part by Fondazione Roma 2008, ESFD/Lilly 2012, AIRC 2012 Project IG 13163, FP7-Health-241913 FLORINASH, FP-7 EURHYTHDIA, and PRIN 2009FATXW3_002 to M.Fe.; SAF-2012-33014 from Ministerio de Economía y Competitividad, Spain, to B.P.; and Medical Research Council, U.K., grants ACC12, MIUR/PRIN (20078P7T3K_001)/FIRB (RBIP06LCA9_0023, RBIP06LCA9_0C), AIRC (2011-IG11955), and AIRC 5xmille (MCO #9979), Telethon grant GGPO9133, Ministero della Salute, and IDI-IRCCS (RF08 c.15, RF07 c.57) to G.M

Biosynthesis and Cellular Functions of Tartaric Acid in Grapevines

Tartaric acid (TA) is an obscure end point to the catabolism of ascorbic acid (Asc). Here, it is proposed as a “specialized primary metabolite”, originating from carbohydrate metabolism but with restricted distribution within the plant kingdom and lack of known function in primary metabolic pathways. Grapes fall into the list of high TA-accumulators, with biosynthesis occurring in both leaf and berry. Very little is known of the TA biosynthetic pathway enzymes in any plant species, although recently some progress has been made in this space. New technologies in grapevine research such as the development of global co-expression network analysis tools and genome-wide association studies, should enable more rapid progress. There is also a lack of information regarding roles for this organic acid in plant metabolism. Therefore this review aims to briefly summarize current knowledge about the key intermediates and enzymes of TA biosynthesis in grapes and the regulation of its precursor, ascorbate, followed by speculative discussion around the potential roles of TA based on current knowledge of Asc metabolism, TA biosynthetic enzymes and other aspects of fruit metabolism

Global mapping of cancers: The Cancer Genome Atlas and beyond

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole-genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan-Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine-learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning

Genome sequence of the Trifolium rueppellianum -nodulating Rhizobium leguminosarum bv. trifolii strain WSM2012

Rhizobium leguminosarum bv. trifolii WSM2012 (syn. MAR1468) is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an ineffective root nodule recovered from the roots of the annual clover Trifolium rueppellianum Fresen. growing in Ethiopia. WSM2012 has a narrow, specialized host range for N2-fixation. Here we describe the features of R. leguminosarum bv. trifolii strain WSM2012, together with genome sequence information and annotation. The 7,180,565 bp high-quality-draft genome is arranged into 6 scaffolds of 68 contigs, contains 7,080 protein-coding genes and 86 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Progra

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

p73: A Multifunctional Protein in Neurobiology

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, ΔNp73 shows a survival function in mature cortical neurons as selective ΔNp73 null mice have reduced cortical thickness. Recent evidence has also suggested that p73 isoforms are deregulated in neurodegenerative pathologies such as Alzheimer’s disease, with abnormal tau phosphorylation. Thus, in addition to its increasingly accepted contribution to tumorigenesis, the p73 subfamily also plays a role in neuronal development and neurodegeneration

The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73

The transcription factor p73, a member of the p53 family, mediates cell-cycle arrest and apoptosis in response to DNA damage-induced cellular stress, acting thus as a proapoptotic gene. Similar to p53, p73 activity is regulated by post-translational modification, including phosphorylation, acetylation and ubiquitylation. In C. elegans, the F-box protein FSN-1 controls germline apoptosis by regulating CEP-1, the single ancestral p53 family member. Here we report that FBXO45, the human ortholog of FSN-1, binds specifically to p73 triggering its proteasome-dependent degradation. Importantly, SCF(FBXO45) ubiquitylates p73 both in vivo and in vitro. Moreover, siRNA-mediated depletion of FBXO45 stabilizes p73 and concomitantly induces cell death in a p53-independent manner. All together, these results show that the orphan F-box protein FBXO45 regulates the stability of p73, highlighting a conserved pathway evolved from nematode to human by which the p53 members are regulated by an SCF-dependent mechanism

Genome sequence of the Ornithopus/Lupinus-nodulating Bradyrhizobium sp. strain WSM471

Bradyrhizobium sp. strain WSM471 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen- (N2) fixing root nodule formed on the annual legume Ornithopus pinnatus (Miller) Druce growing at Oyster Harbour, Albany district, Western Australia in 1982. This strain is in commercial production as an inoculant for Lupinus and Ornithopus. Here we describe the features of Bradyrhizobium sp. strain WSM471, together with genome sequence information and annotation. The 7,784,016 bp high-quality-draft genome is arranged in 1 scaffold of 2 contigs, contains 7,372 protein-coding genes and 58 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program.Wayne Reeve ... Vanessa Melino ... et al