HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.     

Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome

We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.     

Do experts' adjustments on model‐based SKU‐level forecasts improve forecast quality?

Model‐based SKU‐level forecasts are often adjusted by experts. In this paper we propose a statistical methodology to test whether these expert forecasts improve on model forecasts. Application of the methodology to a very large database concerning experts in 35 countries who adjust SKU‐level forecasts for pharmaceutical products in seven distinct categories leads to the general conclusion that expert forecasts are equally good at best, but are more often worse than model‐based forecasts. We explore whether this is due to experts putting too much weight on their contribution, and this indeed turns out to be the case. Copyright © 2009 John Wiley & Sons, Ltd.     

TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy

We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.     

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.     

Über die Ursache des gegensätzlichen geotropischen Verhaltens von Sproß und Wurzel

Ohne Zusammenfassung     

Hypoxanthin,ein Zusatzwachstumsfaktor für Mucorineen

Summary In case ofAbsidia coerulea, Mucor mucedo, Rhizopus nodosus, Rhizopus oryzae andRhizopus suinus (auxoautotroph), Hypoxanthine effects, as well as in case ofPhycomyces Blakesleeanus (auxo-heterotroph), by acceleration of the germinating of the spores a temporary increased growth in contrary to controls without this additional growth factor.     

地扪:时光边缘 古风依旧

正侗寨中缓缓流淌的世俗生活笼罩在蓝色的薄雾里,一如它千百年来的样子,此时此刻,天地澄明,心门顿开有这样一个地方,人与自然相融共生;有这样一个地方,可以治愈灵魂的思乡病。地扪,是根据侗语音译的地名,意为泉水不断涌出的地方。这个贵州黔东南重重山谷中的偏远村落群,千年来依然延续着自给自足的农耕生活,时光在这里似乎有意放慢了脚步,以保留这片与世隔绝的世外田园。