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611.
Harjunmaa E Kallonen A Voutilainen M Hämäläinen K Mikkola ML Jernvall J 《Nature》2012,483(7389):324-327
One of the fascinating aspects of the history of life is the apparent increase in morphological complexity through time, a well known example being mammalian cheek tooth evolution. In contrast, experimental studies of development more readily show a decrease in complexity, again well exemplified by mammalian teeth, in which tooth crown features called cusps are frequently lost in mutant and transgenic mice. Here we report that mouse tooth complexity can be increased substantially by adjusting multiple signalling pathways simultaneously. We cultured teeth in vitro and adjusted ectodysplasin (EDA), activin A and sonic hedgehog (SHH) pathways, all of which are individually required for normal tooth development. We quantified tooth complexity using the number of cusps and a topographic measure of surface complexity. The results show that whereas activation of EDA and activin A signalling, and inhibition of SHH signalling, individually cause subtle to moderate increases in complexity, cusp number is doubled when all three pathways are adjusted in unison. Furthermore, the increase in cusp number does not result from an increase in tooth size, but from an altered primary patterning phase of development. The combination of a lack of complex mutants, the paucity of natural variants with complex phenotypes, and our results of greatly increased dental complexity using multiple pathways, suggests that an increase may be inherently different from a decrease in phenotypic complexity. 相似文献
612.
A new atmospherically relevant oxidant of sulphur dioxide 总被引:2,自引:0,他引:2
RL Mauldin T Berndt M Sipilä P Paasonen T Petäjä S Kim T Kurtén F Stratmann VM Kerminen M Kulmala 《Nature》2012,488(7410):193-196
Atmospheric oxidation is a key phenomenon that connects atmospheric chemistry with globally challenging environmental issues, such as climate change, stratospheric ozone loss, acidification of soils and water, and health effects of air quality. Ozone, the hydroxyl radical and the nitrate radical are generally considered to be the dominant oxidants that initiate the removal of trace gases, including pollutants, from the atmosphere. Here we present atmospheric observations from a boreal forest region in Finland, supported by laboratory experiments and theoretical considerations, that allow us to identify another compound, probably a stabilized Criegee intermediate (a carbonyl oxide with two free-radical sites) or its derivative, which has a significant capacity to oxidize sulphur dioxide and potentially other trace gases. This compound probably enhances the reactivity of the atmosphere, particularly with regard to the production of sulphuric acid, and consequently atmospheric aerosol formation. Our findings suggest that this new atmospherically relevant oxidation route is important relative to oxidation by the hydroxyl radical, at least at moderate concentrations of that radical. We also find that the oxidation chemistry of this compound seems to be tightly linked to the presence of alkenes of biogenic origin. 相似文献
613.
614.
F Odoardi C Sie K Streyl VK Ulaganathan C Schläger D Lodygin K Heckelsmiller W Nietfeld J Ellwart WE Klinkert C Lottaz M Nosov V Brinkmann R Spang H Lehrach M Vingron H Wekerle C Flügel-Koch A Flügel 《Nature》2012,488(7413):675-679
The blood–brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease. 相似文献
615.
616.
H Pälike MW Lyle H Nishi I Raffi A Ridgwell K Gamage A Klaus G Acton L Anderson J Backman J Baldauf C Beltran SM Bohaty P Bown W Busch JE Channell CO Chun M Delaney P Dewangan T Dunkley Jones KM Edgar H Evans P Fitch GL Foster N Gussone H Hasegawa EC Hathorne H Hayashi JO Herrle A Holbourn S Hovan K Hyeong K Iijima T Ito S Kamikuri K Kimoto J Kuroda L Leon-Rodriguez A Malinverno TC Moore BH Murphy DP Murphy H Nakamura K Ogane C Ohneiser C Richter R Robinson EJ Rohling O Romero K Sawada H Scher 《Nature》2012,488(7413):609-614
Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth. 相似文献
617.
B Lu T Nakamura K Inouye J Li Y Tang P Lundbäck SI Valdes-Ferrer PS Olofsson T Kalb J Roth Y Zou H Erlandsson-Harris H Yang JP Ting H Wang U Andersson DJ Antoine SS Chavan GS Hotamisligil KJ Tracey 《Nature》2012,488(7413):670-674
The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation. 相似文献
618.
Freshwater gastropods (Basommatophora and Prosobranchia) harbor a variety of mating systems. In particular, apomictic parthenogenesis in prosobranchs and self-fertilization in the hermaphrodite pulmonates may be viable alternatives to outcrossing sexuality in a number of species. The coexistence of different mating systems in extant populations provides opportunities to examine the forces directing their evolution. We review the models analyzing and predicting genetic variability in subdivided populations, with an emphasis on the effects of inbreeding. Population genetic data on freshwater pulmonates are examined in the context of selfing rates and the loss of variability under selfing. Furthermore, the genetic and demographic factors thought to influence mating system evolution are considered, and we highlight the different approaches available to estimate mating system parameters, in particular the selfing rate. Recent population biological studies on polyploid species (Bulinus truncatus, Ancylus fluviatilis) indicate that selfing is the predominant mating system. These studies have contributed to a deeper understanding of conceptual issues in the evolution of selfing rates. Throughout, we emphasize the need for further carefully designed studies. 相似文献
619.
The Jurassic floras of Romania occur in the Carpathian Mountains and in Dobrogea (Eastern Romania). In the South Carpathians, diverse and well preserved floras have been recorded since the middle of the 19th Century in the Resita, Sirinia, Presacina, CernaJiu, Holbav and Cristian Basins. The ages of these floras range between Hettangian and Sinemurian, with representatives belonging to Bryophytes, Pteridophytes and Gymnosperms. Excellent preservation and diversity were recorded in Anina, in the central area of the Resita Basin, a possible fossile-Lagerst?tte locality. The 3D collecting opportunities due to underground coal mining permitted detailed phytostratigraphical studies. These studies showed a floral change at the Hettangian-Sinemurian boundary, related to climate change. The Jurassic coal basins of the South Carpathians show both intramontainous and paralic features. The Resita Basin is a typical intramountainous depression basin, while the other basins are influenced by the marine realm. From a paleogeographical point of view, the Romanian Early and Middle Jurassic floras occurred on the northern frame of the Tethys realm, floristic features indicating the Eurosinian Province. One of the closest floras in terms of floristic similarities is the Iranian Early Jurassic flora. In the Apuseni Mountains, the HettangianSinemurian flora is less well-preserved and diverse than those of the South Carpathians. The Middle Jurassic flora of Romania is confined to Dobrogea (Eastern Romania), where a bennettite-dominated assemblage with low diversity and preservation was recorded. 相似文献
620.
In the first clear mathematical treatment of natural selection, Müller proposed that a shared warning signal (mimicry) would benefit defended prey species by sharing out the per capita mortality incurred during predator education. Although mimicry is a mainstay of adaptationist thinking, there has been repeated debate on whether there is a mutualistic or a parasitic relationship between unequally defended co-mimic species. Here we show that the relationship between unequally defended species is mutualistic. We examined this in a 'novel world' of artificial prey with wild predators (great tit, Parus major). We kept the abundance of a highly defended prey ('model') constant and increased the density of a moderately defended prey ('defended mimic') of either perfect or imperfect mimetic resemblance to the model. Both model and defended mimic showed a net benefit from a density-dependent decrease in their per capita mortality. Even when the effect of dilution through density was controlled for, defended mimics did not induce additional attacks on the model, but we found selection for accurate signal mimicry. In comparison, the addition of fully edible (batesian) mimics did increase additional attacks on the model, but as a result of dilution this resulted in no overall increase in per capita mortality. By ignoring the effects of density, current theories may have overestimated the parasitic costs imposed by less defended mimics on highly defended models. 相似文献