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111.
Obesity is the driving force behind the worldwide increase in the prevalence of type 2 diabetes mellitus. Hyperglycaemia is a hallmark of diabetes and is largely due to increased hepatic gluconeogenesis. The medial hypothalamus is a major integrator of nutritional and hormonal signals, which play pivotal roles not only in the regulation of energy balance but also in the modulation of liver glucose output. Bidirectional changes in hypothalamic insulin signalling therefore result in parallel changes in both energy balance and glucose metabolism. Here we show that activation of ATP-sensitive potassium (K(ATP)) channels in the mediobasal hypothalamus is sufficient to lower blood glucose levels through inhibition of hepatic gluconeogenesis. Finally, the infusion of a K(ATP) blocker within the mediobasal hypothalamus, or the surgical resection of the hepatic branch of the vagus nerve, negates the effects of central insulin and halves the effects of systemic insulin on hepatic glucose production. Consistent with these results, mice lacking the SUR1 subunit of the K(ATP) channel are resistant to the inhibitory action of insulin on gluconeogenesis. These findings suggest that activation of hypothalamic K(ATP) channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycaemia.  相似文献   
112.
Ji Y  Chung Y  Sprinzak D  Heiblum M  Mahalu D  Shtrikman H 《Nature》2003,422(6930):415-418
Double-slit electron interferometers fabricated in high mobility two-dimensional electron gases are powerful tools for studying coherent wave-like phenomena in mesoscopic systems. However, they suffer from low visibility of the interference patterns due to the many channels present in each slit, and from poor sensitivity to small currents due to their open geometry. Moreover, these interferometers do not function in high magnetic fields--such as those required to enter the quantum Hall effect regime--as the field destroys the symmetry between left and right slits. Here we report the fabrication and operation of a single-channel, two-path electron interferometer that functions in a high magnetic field. This device is the first electronic analogue of the optical Mach-Zehnder interferometer, and opens the way to measuring interference of quasiparticles with fractional charges. On the basis of measurements of single edge state and closed geometry transport in the quantum Hall effect regime, we find that the interferometer is highly sensitive and exhibits very high visibility (62%). However, the interference pattern decays precipitously with increasing electron temperature or energy. Although the origin of this dephasing is unclear, we show, via shot-noise measurements, that it is not a decoherence process that results from inelastic scattering events.  相似文献   
113.
Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.  相似文献   
114.
Correlation of DNA adduct levels in human lung with cigarette smoking   总被引:8,自引:0,他引:8  
D H Phillips  A Hewer  C N Martin  R C Garner  M M King 《Nature》1988,336(6201):790-792
Lung cancer is the most common cancer in men in the United Kingdom and the second most common in women, accounting for between 25 and 40% of all cancer deaths. Cigarette smoking is widely accepted as the major cause of lung cancer and linear relationships have been established between the number of cigarettes smoked and lung cancer risk. Although approximately 50 carcinogenic chemicals have been identified in cigarette smoke, a causal link between specific compounds and lung cancer has yet to be made. Studies on cigarette smokers' urine, blood and placenta have provided indications of carcinogen exposure, and although the presence of covalently-bound adducts in human DNA provides evidence of exposure to carcinogens, there have been no reports of systematic studies on the levels of DNA adducts in human lung. We report here, using the 32P-post-labelling technique, that cigarette smokers have higher adduct levels than non-smokers, that there is a linear relationship between adduct levels and daily or lifetime cigarette consumption, and that people who have given up smoking for at least five years have adduct levels similar to those of non-smokers.  相似文献   
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117.
中国西南地区地壳运动的GPS监测   总被引:31,自引:0,他引:31  
通过1991 ̄1997年期间对中国西南地区GPS(全球定位系统)载波相位测量,建立了青藏高原东部及相邻地区现代地壳运动的速度场,相对于成都,川滇地块及其以西的速度大多为5 ̄10mm/a,鲜水河-小江断裂以东的川青地块和扬子地块运动微弱,约为0 ̄7mm/a,2个地区都表现为顺时钟的涡旋运动,而没有明显的地壳物质向东挤出或逃逸,地壳变形主要型式为顺时针旋卷构造和块体边界断裂的非均一滑动。  相似文献   
118.
Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.  相似文献   
119.
Metallothionein (MT) expression is rapidly up-regulated following CNS injury, and there is a strong correlation between the presence or absence of MTand improved or impaired (respectively) recovery from such trauma.We now report that a distinct subset of NG2-positive, GFAP-negative glial cells bordering the injury tract express MT following focal injury to the adult rat neocortex. To confirm the ability of these NG2 glial cells to express MT, we have isolated and cultured them and identified that they can express MT following stimulation with zinc. To investigate the functional importance of MT expression by NG2 glial cells, we plated cortical neurons onto these cells and found that expression of MT enhanced the permissivity of NG2 glial cells to neurite outgrowth. Our data suggest that expression of MT by NG2 glial cells may contribute to the overall permissiveness of these cells to axon regeneration.  相似文献   
120.
Silicone coatings have been used in this study. The method adopted was the liquid drop analysis on the coated fabrics. The contact angle between a liquid drop and the fabric surface was measured with two liquids continuously and recorded by a computer. The surface energy was calculated by means of Owens method. Kinetic measurement was adopted. The contact angle of liquids on the fabric coated silicone decreased with time was found. A compound solution DX has been found, so that the contact angle of the liquids on the fabric washed with DX becomes constant, and the surface energy of the fabric can be reduced to below 15 mJ/m2.  相似文献   
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