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11.
A. Rapp H. Steffen H. Ullemeyer G. Rilling 《Cellular and molecular life sciences : CMLS》1972,28(4):493-495
Summary A fluid-measuring tube with separate cell measuring and counting chamber, is described with which metabolic transposition of small amounts of biological materials can be examined within an enclosed system. Tests were carried out on the course of the expiration of sucrose through phylloxers weighing 20 mg, and also on the fixation in the dark of CO2 by 8 green grapes. Tests were also carreied out on the expiration of sucrose and malic acid by yeast in fermentation. The course of metabolism can easily be seen by means of the radioactivity curves. 相似文献
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Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma 总被引:3,自引:0,他引:3
Schwartzentruber J Korshunov A Liu XY Jones DT Pfaff E Jacob K Sturm D Fontebasso AM Quang DA Tönjes M Hovestadt V Albrecht S Kool M Nantel A Konermann C Lindroth A Jäger N Rausch T Ryzhova M Korbel JO Hielscher T Hauser P Garami M Klekner A Bognar L Ebinger M Schuhmann MU Scheurlen W Pekrun A Frühwald MC Roggendorf W Kramm C Dürken M Atkinson J Lepage P Montpetit A Zakrzewska M Zakrzewski K Liberski PP Dong Z Siegel P Kulozik AE Zapatka M Guha A Malkin D Felsberg J Reifenberger G 《Nature》2012,482(7384):226-231
Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis. 相似文献
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Across the Greenland-Scotland ridge there is a continuous flow of cold dense water, termed 'overflow', from the Nordic seas to the Atlantic Ocean. This is a main contributor to the production of North Atlantic Deep Water that feeds the lower limb of the Atlantic meridional overturning circulation, which has been predicted to weaken as a consequence of climate change. The two main overflow branches pass the Denmark Strait and the Faroe Bank channel. Here we combine results from direct current measurements in the Faroe Bank channel for 1995-2005 with an ensemble hindcast experiment for 1948-2005 using an ocean general circulation model. For the overlapping period we find a convincing agreement between model simulations and observations on monthly to interannual timescales. Both observations and model data show no significant trend in volume transport. In addition, for the whole 1948-2005 period, the model indicates no persistent trend in the Faroe Bank channel overflow or in the total overflow transport, in agreement with the few available historical observations. Deepening isopycnals in the Norwegian Sea have tended to decrease the pressure difference across the Greenland-Scotland ridge, but this has been compensated for by the effect of changes in sea level. In contrast with earlier studies, we therefore conclude that the Faroe Bank channel overflow, and also the total overflow, did not decrease consistently from 1950 to 2005, although the model does show a weakening total Atlantic meridional overturning circulation as a result of changes south of the Greenland-Scotland ridge. 相似文献
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Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. 总被引:17,自引:0,他引:17
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Muzny DM Scherer SE Kaul R Wang J Yu J Sudbrak R Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Wei S Wheeler DA Wright MW Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clendenning J Clerc-Blankenburg KP Chen R Chen Z Davis C Delgado O Dinh HH Dong W 《Nature》2006,440(7088):1194-1198
After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. 相似文献
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Rafael Andrés Posada-Duque Omar Ramirez Steffen Härtel Nibaldo C. Inestrosa Felipe Bodaleo Christian González-Billault Alfredo Kirkwood Gloria Patricia Cardona-Gómez 《Cellular and molecular life sciences : CMLS》2017,74(1):153-172
CDK5 is a serine/threonine kinase that is involved in the normal function of the adult brain and plays a role in neurotransmission and synaptic plasticity. However, its over-regulation has been associated with Tau hyperphosphorylation and cognitive deficits. Our previous studies have demonstrated that CDK5 targeting using shRNA-miR provides neuroprotection and prevents cognitive deficits. Dendritic spine morphogenesis and forms of long-term synaptic plasticity—such as long-term potentiation (LTP)—have been proposed as essential processes of neuroplasticity. However, whether CDK5 participates in these processes remains controversial and depends on the experimental model. Using wild-type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased LTP and recovered the PPF in deficient LTP of APPswe/PS1Δ9 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased dendritic protrusion morphogenesis, which was dependent on Rac activity. In addition, silencing of CDK5 increased BDNF expression, temporarily increased phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in neurites. Together, our data suggest that CDK5 downregulation induces synaptic plasticity in mature neurons involving Ca2+ signaling and BDNF/CREB activation. 相似文献
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Ross MT Grafham DV Coffey AJ Scherer S McLay K Muzny D Platzer M Howell GR Burrows C Bird CP Frankish A Lovell FL Howe KL Ashurst JL Fulton RS Sudbrak R Wen G Jones MC Hurles ME Andrews TD Scott CE Searle S Ramser J Whittaker A Deadman R Carter NP Hunt SE Chen R Cree A Gunaratne P Havlak P Hodgson A Metzker ML Richards S Scott G Steffen D Sodergren E Wheeler DA Worley KC Ainscough R Ambrose KD Ansari-Lari MA Aradhya S Ashwell RI Babbage AK Bagguley CL Ballabio A Banerjee R Barker GE Barlow KF 《Nature》2005,434(7031):325-337
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. 相似文献
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Steffen Ducheyne 《Archive for History of Exact Sciences》2011,65(2):181-227
This article seeks to provide a historically well-informed analysis of an important post-Newtonian area of research in experimental
physics between 1798 and 1898, namely the determination of the mean density of the earth and, by the end of the nineteenth
century, the gravitational constant. Traditionally, research on these matters is seen as a case of “puzzle solving.” In this
article, the author shows that such focus does not do justice to the evidential significance of eighteenth- and nineteenth-century
experimental research on the mean density of the earth and the gravitational constant. As Newton’s theory of universal gravitation
was mainly based on astronomical observation, it remained to be shown that Newton’s law of universal gravitation did not break
down at terrestrial distances. In this context, Cavendish’ experiment and related nineteenth-century experiments played a
decisive role, for they provided converging and increasingly stronger evidence for the universality of Newton’s theory of
gravitation. More precisely, the author shall argue that, as the accuracy and precision of the experimental apparatuses and
the procedures to eliminate external disturbances involved increasingly improved, the empirical support for the universality
of Newton’s theory of gravitation improved correspondingly. 相似文献