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901.
Tschumperlin DJ Dai G Maly IV Kikuchi T Laiho LH McVittie AK Haley KJ Lilly CM So PT Lauffenburger DA Kamm RD Drazen JM 《Nature》2004,429(6987):83-86
Physical forces elicit biochemical signalling in a diverse array of cells, tissues and organisms, helping to govern fundamental biological processes. Several hypotheses have been advanced that link physical forces to intracellular signalling pathways, but in many cases the molecular mechanisms of mechanotransduction remain elusive. Here we find that compressive stress shrinks the lateral intercellular space surrounding epithelial cells, and triggers cellular signalling via autocrine binding of epidermal growth factor family ligands to the epidermal growth factor receptor. Mathematical analysis predicts that constant rate shedding of autocrine ligands into a collapsing lateral intercellular space leads to increased local ligand concentrations that are sufficient to account for the observed receptor signalling; direct experimental comparison of signalling stimulated by compressive stress versus exogenous soluble ligand supports this prediction. These findings establish a mechanism by which mechanotransduction arises from an autocrine ligand-receptor circuit operating in a dynamically regulated extracellular volume, not requiring induction of force-dependent biochemical processes within the cell or cell membrane. 相似文献
902.
There has been considerable debate about changes in the temperature of the troposphere measured using the Microwave Sounding Unit (MSU) instrument or radiosondes. Fu et al. linearly combine time series from two MSU channels to estimate vertically integrated 850-300-hPa temperatures and claim consistency between surface and free-troposphere warming for one MSU record. We believe that their approach overfits the data, produces trends that overestimate warming and gives overly optimistic uncertainty estimates. There still remain large differences between observed tropospheric temperature trends and those simulated by a climate model. 相似文献
903.
A jet of fluid flowing down a partially wetting, inclined plane usually meanders but--by maintaining a constant flow rate--meandering can be suppressed, leading to the emergence of a beautiful braided structure. Here we show that this flow pattern can be explained by the interplay between surface tension, which tends to narrow the jet, and fluid inertia, which drives the jet to widen. These observations dispel misconceptions about the relationship between braiding and meandering that have persisted for over 20 years. 相似文献
904.
The 2004 Olympic women's 100-metre sprint champion, Yuliya Nesterenko, is assured of fame and fortune. But we show here that--if current trends continue--it is the winner of the event in the 2156 Olympics whose name will be etched in sporting history forever, because this may be the first occasion on which the race is won in a faster time than the men's event. 相似文献
905.
A high-speed silicon optical modulator based on a metal-oxide-semiconductor capacitor 总被引:1,自引:0,他引:1
Liu A Jones R Liao L Samara-Rubio D Rubin D Cohen O Nicolaescu R Paniccia M 《Nature》2004,427(6975):615-618
Silicon has long been the optimal material for electronics, but it is only relatively recently that it has been considered as a material option for photonics. One of the key limitations for using silicon as a photonic material has been the relatively low speed of silicon optical modulators compared to those fabricated from III-V semiconductor compounds and/or electro-optic materials such as lithium niobate. To date, the fastest silicon-waveguide-based optical modulator that has been demonstrated experimentally has a modulation frequency of only approximately 20 MHz (refs 10, 11), although it has been predicted theoretically that a approximately 1-GHz modulation frequency might be achievable in some device structures. Here we describe an approach based on a metal-oxide-semiconductor (MOS) capacitor structure embedded in a silicon waveguide that can produce high-speed optical phase modulation: we demonstrate an all-silicon optical modulator with a modulation bandwidth exceeding 1 GHz. As this technology is compatible with conventional complementary MOS (CMOS) processing, monolithic integration of the silicon modulator with advanced electronics on a single silicon substrate becomes possible. 相似文献
906.
A remarkable feature of prion biology is the strain phenomenon wherein prion particles apparently composed of the same protein lead to phenotypically distinct transmissible states. To reconcile the existence of strains with the 'protein-only' hypothesis of prion transmission, it has been proposed that a single protein can misfold into multiple distinct infectious forms, one for each different strain. Several studies have found correlations between strain phenotypes and conformations of prion particles; however, whether such differences cause or are simply a secondary manifestation of prion strains remains unclear, largely due to the difficulty of creating infectious material from pure protein. Here we report a high-efficiency protocol for infecting yeast with the [PSI+] prion using amyloids composed of a recombinant Sup35 fragment (Sup-NM). Using thermal stability and electron paramagnetic resonance spectroscopy, we demonstrate that Sup-NM amyloids formed at different temperatures adopt distinct, stably propagating conformations. Infection of yeast with these different amyloid conformations leads to different [PSI+] strains. These results establish that Sup-NM adopts an infectious conformation before entering the cell--fulfilling a key prediction of the prion hypothesis--and directly demonstrate that differences in the conformation of the infectious protein determine prion strain variation. 相似文献
907.
Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves 总被引:2,自引:0,他引:2
Court FA Sherman DL Pratt T Garry EM Ribchester RR Cottrell DF Fleetwood-Walker SM Brophy PJ 《Nature》2004,431(7005):191-195
Nerve impulses are propagated at nodes of Ranvier in the myelinated nerves of vertebrates. Internodal distances have been proposed to affect the velocity of nerve impulse conduction; however, direct evidence is lacking, and the cellular mechanisms that might regulate the length of the myelinated segments are unknown. Ramón y Cajal described longitudinal and transverse bands of cytoplasm or trabeculae in internodal Schwann cells and suggested that they had a nutritive function. Here we show that internodal growth in wild-type nerves is precisely matched to nerve extension, but disruption of the cytoplasmic bands in Periaxin-null mice impairs Schwann cell elongation during nerve growth. By contrast, myelination proceeds normally. The capacity of wild-type and mutant Schwann cells to elongate is cell-autonomous, indicating that passive stretching can account for the lengthening of the internode during limb growth. As predicted on theoretical grounds, decreased internodal distances strikingly decrease conduction velocities and so affect motor function. We propose that microtubule-based transport in the longitudinal bands of Cajal permits internodal Schwann cells to lengthen in response to axonal growth, thus ensuring rapid nerve impulse transmission. 相似文献
908.
As in other competitive sports, the famous Grand National steeplechase, which is held at Aintree in the United Kingdom and is watched by 600 million people worldwide, sometimes results in injury. By analysing data from the past 15 Grand National races (consisting of 560 starts by horses), we are able to identify several factors that are significantly associated with failure to complete the race: no previous experience of the course and its unique obstacles, unfavourable ground conditions (too soft or too hard), a large number of runners, and the length of the odds ('starting price'). We also find that there is an increased risk of falling at the first fence and at the jump known as Becher's Brook, which has a ditch on the landing side. Our findings indicate ways in which the Grand National could be made safer for horses and illustrate how epidemiological analysis might contribute to preventing injury in competitive sport. 相似文献
909.
Mumby PJ Edwards AJ Arias-González JE Lindeman KC Blackwell PG Gall A Gorczynska MI Harborne AR Pescod CL Renken H Wabnitz CC Llewellyn G 《Nature》2004,427(6974):533-536
Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs. 相似文献
910.