Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer

CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.     

MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion

The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main clinical presentations: myopathic (OMIM 609560) and hepatocerebral (OMIM 251880). Known mutant genes, including TK2, SUCLA2, DGUOK and POLG, account for only a fraction of MDDS cases. We found a new locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on this locus using a new integrative genomics strategy. One of the top-scoring candidates was the human ortholog of the mouse kidney disease gene Mpv17. We found disease-segregating mutations in three families with hepatocerebral MDDS and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and mtDNA depletion, not only in affected individuals but also in Mpv17-/- mice.     

Interactions between VEGFR and Notch signaling pathways in endothelial and neural cells

Notch cell interaction mechanism governs cell fate decisions in many different cell contexts throughout the lifetime of all Metazoan species. It links the fate of one cell to that of its neighbors through cell-to-cell contacts, and binding of Notch receptors expressed on one cell to their membrane bound ligands on an adjacent cell. Environmental cues, such as growth factors and extracellular matrix molecules, superimpose a dynamic regulation on this canonical Notch signaling pathway. In this review, we will focus on Notch signaling in the vertebrate vascular and nervous systems and examine its role in angiogenesis, neurogenesis, and neurovascular interactions. We will also highlight the molecular relationships of the Notch pathway with vascular endothelial growth factors (VEGFs) and their high-affinity tyrosine kinase VEGF receptors, key regulators of both angiogenesis and neurogenesis.     

Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.     

Are plants cognitive? A reply to Adams

According to F. Adams [this journal, vol. 68, 2018] cognition cannot be realized in plants or bacteria. In his view, plants and bacteria respond to the here-and-now in a hardwired, inflexible manner, and are therefore incapable of cognitive activity. This article takes issue with the pursuit of plant cognition from the perspective of an empirically informed philosophy of plant neurobiology. As we argue, empirical evidence shows, contra Adams, that plant behavior is in many ways analogous to animal behavior. This renders plants suitable to be described as cognitive agents in a non-metaphorical way. Sections two to four review the arguments offered by Adams in light of scientific evidence on plant adaptive behavior, decision-making, anticipation, as well as learning and memory. Section five introduces the ‘phyto-nervous’ system of plants. To conclude, section six resituates the quest for plant cognition into a broader approach in cognitive science, as represented by enactive and ecological schools of thought. Overall, we aim to motivate the idea that plants may be considered genuine cognitive agents. Our hope is to help propel public awareness and discussion of plant intelligence once appropriately stripped of anthropocentric preconceptions of the sort that Adams' position appears to exemplify.     

Exopolysaccharide production byVolcaniella eurihalina

The application of microbial extracellular polymers began in the 1960s, and since then there has been a remarkable increase in their commercial use. They are used in the food, textile, pharmaceutical, agricultural, paint and petroleum industries.Volcaniella eurihalina, a moderately halophilic eubacterium, produces an extracellular polysaccharide whose physical and chemical properties could be of interest for various industrial applications. The aim of this investigation is to analyze the different environmental parameters which influence the production of polysaccharide, and to study its chemical composition and the rheological properties of its solutions.     

融合双通道音节特征的藏文La格例句自动分类模型

基于藏文La格(??????)例句的自动分类在藏语自然语言处理领域的重要性,根据藏文La格的用法和添接规则,在对藏文La格例句进行分类并定义分类概念的基础上,提出一种融合双通道音节特征的藏文La格例句自动分类模型.该模型首先使用word2vec和Glove构建双通道藏文音节嵌入,分别在每路卷积中融合双通道音节特征,丰富...     

高校计算机课程教学与改革探讨

以计算机为核心的多媒体教学在我国高校已经蓬勃兴起。文章针对现在教育面临的新形式,进行了高校计算机课程的教学与改革探讨。针对电子科技大学已经开展的多媒体式、专周式教学,就如何培养学生技能、提高动手能力,为最后的就业打下坚实基础提出了一些想法和建议。并对一些教学方法的效果进行了统计分析,通过分析和探讨,结合教学实际,提出了一些措施与建议,希望对探讨高校计算机专业教学、学习、就业有所帮助。     

Glycogenolytic effect of vasoactive intestinal peptide in the rat in vivo

Summary The effects of VIP (300 pmol/kg), injected via the portal vein, on the glycogen content of the liver and on glycemia, were studied in the rat in vivo. VIP enhanced glycogenolysis and caused hyperglycemia in a time-dependent manner.