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1.
MEASUREMENT of the absolute value of absorption by water vapour at microwave frequencies is difficult because the effect is so small. Far in the wings of the absorption lines, in the so-called 'windows' of the spectrum, it is especially difficult to achieve high accuracy in the free atmosphere. But it is in these windows that the behaviour of the absorption is important from both applied and scientific points of view. Satellite communications, remote sensing of the atmosphere, and radioastronomy, are all influenced by this behaviour. Measurements on an Earth-space path are reported here; the results indicate a nonlinear relationship between absorption and water-vapour content. 相似文献
2.
Comparative study of two immunoglobulin G Fd-fragments 总被引:4,自引:0,他引:4
3.
Subtypes of medulloblastoma have distinct developmental origins 总被引:2,自引:0,他引:2
Gibson P Tong Y Robinson G Thompson MC Currle DS Eden C Kranenburg TA Hogg T Poppleton H Martin J Finkelstein D Pounds S Weiss A Patay Z Scoggins M Ogg R Pei Y Yang ZJ Brun S Lee Y Zindy F Lindsey JC Taketo MM Boop FA Sanford RA Gajjar A Clifford SC Roussel MF McKinnon PJ Gutmann DH Ellison DW Wechsler-Reya R Gilbertson RJ 《Nature》2010,468(7327):1095-1099
Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer. 相似文献
4.
Coltman DW O'Donoghue P Jorgenson JT Hogg JT Strobeck C Festa-Bianchet M 《Nature》2003,426(6967):655-658
Phenotype-based selective harvests, including trophy hunting, can have important implications for sustainable wildlife management if they target heritable traits. Here we show that in an evolutionary response to sport hunting of bighorn trophy rams (Ovis canadensis) body weight and horn size have declined significantly over time. We used quantitative genetic analyses, based on a partly genetically reconstructed pedigree from a 30-year study of a wild population in which trophy hunting targeted rams with rapidly growing horns, to explore the evolutionary response to hunter selection on ram weight and horn size. Both traits were highly heritable, and trophy-harvested rams were of significantly higher genetic 'breeding value' for weight and horn size than rams that were not harvested. Rams of high breeding value were also shot at an early age, and thus did not achieve high reproductive success. Declines in mean breeding values for weight and horn size therefore occurred in response to unrestricted trophy hunting, resulting in the production of smaller-horned, lighter rams, and fewer trophies. 相似文献
5.
Disulphide bonds in secreted proteins are considered to be inert because of the oxidizing nature of the extracellular milieu. An exception to this rule is a reductase secreted by tumour cells that reduces disulphide bonds in the serine proteinase plasmin. Reduction of plasmin initiates proteolytic cleavage in the kringle 5 domain and release of the tumour blood vessel inhibitor angiostatin. New blood vessel formation or angiogenesis is critical for tumour expansion and metastasis. Here we show that the plasmin reductase isolated from conditioned medium of fibrosarcoma cells is the glycolytic enzyme phosphoglycerate kinase. Recombinant phosphoglycerate kinase had the same specific activity as the fibrosarcoma-derived protein. Plasma of mice bearing fibrosarcoma tumours contained several-fold more phosphoglycerate kinase, as compared with mice without tumours. Administration of phosphoglycerate kinase to tumour-bearing mice caused an increase in plasma levels of angiostatin, and a decrease in tumour vascularity and rate of tumour growth. Our findings indicate that phosphoglycerate kinase not only functions in glycolysis but is secreted by tumour cells and participates in the angiogenic process as a disulphide reductase. 相似文献
6.
7.
H.-T. Zhao S. Endo S. Ishikura R. Chung P. J. Hogg A. Hara O. El-Kabbani 《Cellular and molecular life sciences : CMLS》2009,66(9):1570-1579
l-Xylulose reductase (XR) is involved in water re-absorption and cellular osmoregulation. The crystal structure of human XR
complemented with site-directed mutagenesis (Cys138Ala) indicated that the disulfide bond in the active site between Cys138
and Cys150 is unstable and may affect the reactivity of the enzyme. The effects of reducing agents on the activities of the
wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease
in catalytic efficiency. Furthermore, the addition of cysteine (>2 mM) inactivated human XR and was accompanied by a 10-fold
decrease in catalytic efficiency. TOF-MS analysis of the inactivated enzyme showed the S-cysteinylation of Cys138 in the wild-type
and Cys150 in the mutant enzymes. Thus, the action of human XR may be regulated by cellular redox conditions through reversible
disulfide-bond formation and by S-cysteinylation.
Received 25 January 2009; received after revision 12 February 2009; accepted 16 February 2009
H.-T. Zhao, S. Endo: These two authors contribute equally to this work. 相似文献
8.
Phagocyte recognition of cells that have undergone apoptosis (programmed cell death) is an event of broad biological significance. Characterized by endogenous endonuclease activation, which results in chromatin fragmentation and nuclear condensation, apoptosis leads to swift ingestion of intact but 'senescent' or 'unwanted' cells by phagocytes in processes as diverse as the physiological involution of organs, the remodelling of embryonic tissues, and metamorphosis. The cell-surface mechanisms by which macrophages recognize apoptotic cells as 'senescent-self' have remained obscure. Here we report that macrophage recognition of apoptotic cells (both neutrophils and lymphocytes) is mediated by the vitronectin receptor, a heterodimer belonging to the beta 3 or cytoadhesin family of the integrins. Previously, the functions of the vitronectin receptor were believed to be limited to cell anchorage, but our findings indicate that the receptor has a novel and direct role in self-senescent-self intercellular recognition leading to macrophage phagocytosis of cells undergoing apoptosis. 相似文献
9.
Regional insolation forcing of late Quaternary climate change in the Southern Hemisphere 总被引:2,自引:0,他引:2
Vandergoes MJ Newnham RM Preusser F Hendy CH Lowell TV Fitzsimons SJ Hogg AG Kasper HU Schlüchter C 《Nature》2005,436(7048):242-245
In agreement with the Milankovitch orbital forcing hypothesis it is often assumed that glacial-interglacial climate transitions occurred synchronously in the Northern and Southern hemispheres of the Earth. It is difficult to test this assumption, because of the paucity of long, continuous climate records from the Southern Hemisphere that have not been dated by tuning them to the presumed Northern Hemisphere signals. Here we present an independently dated terrestrial pollen record from a peat bog on South Island, New Zealand, to investigate global and local factors in Southern Hemisphere climate changes during the last two glacial-interglacial cycles. Our record largely corroborates the Milankovitch model of orbital forcing but also exhibits some differences: in particular, an earlier onset and longer duration of the Last Glacial Maximum. Our results suggest that Southern Hemisphere insolation may have been responsible for these differences in timing. Our findings question the validity of applying orbital tuning to Southern Hemisphere records and suggest an alternative mechanism to the bipolar seesaw for generating interhemispheric asynchrony in climate change. 相似文献
10.
Mutations in SUFU predispose to medulloblastoma 总被引:8,自引:0,他引:8
Taylor MD Liu L Raffel C Hui CC Mainprize TG Zhang X Agatep R Chiappa S Gao L Lowrance A Hao A Goldstein AM Stavrou T Scherer SW Dura WT Wainwright B Squire JA Rutka JT Hogg D 《Nature genetics》2002,30(3):306-310
Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma. The extent of skeletal involvement is variable in enchondromatosis and may include dysplasia that is not directly attributable to enchondromas. Enchondromatosis is rare, obvious inheritance of the condition is unusual and no candidate loci have been identified. Enchondromas are usually in close proximity to, or in continuity with, growth-plate cartilage. Consequently, they may result from abnormal regulation of proliferation and terminal differentiation of chondrocytes in the adjoining growth plate. In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH). PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis that signals abnormally in vitro and causes enchondroma-like lesions in transgenic mice. The mutant receptor constitutively activates Hedgehog signaling, and excessive Hedgehog signaling is sufficient to cause formation of enchondroma-like lesions. 相似文献