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811.
Beja-Pereira A Luikart G England PR Bradley DG Jann OC Bertorelle G Chamberlain AT Nunes TP Metodiev S Ferrand N Erhardt G 《Nature genetics》2003,35(4):311-313
Milk from domestic cows has been a valuable food source for over 8,000 years, especially in lactose-tolerant human societies that exploit dairy breeds. We studied geographic patterns of variation in genes encoding the six most important milk proteins in 70 native European cattle breeds. We found substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites (>5,000 years ago) and present-day lactose tolerance in Europeans. This suggests a gene-culture coevolution between cattle and humans. 相似文献
812.
Ueda H Howson JM Esposito L Heward J Snook H Chamberlain G Rainbow DB Hunter KM Smith AN Di Genova G Herr MH Dahlman I Payne F Smyth D Lowe C Twells RC Howlett S Healy B Nutland S Rance HE Everett V Smink LJ Lam AC Cordell HJ Walker NM Bordin C Hulme J Motzo C Cucca F Hess JF Metzker ML Rogers J Gregory S Allahabadia A Nithiyananthan R Tuomilehto-Wolf E Tuomilehto J Bingley P Gillespie KM Undlien DE Rønningen KS Guja C Ionescu-Tîrgovişte C Savage DA Maxwell AP Carson DJ Patterson CC Franklyn JA 《Nature》2003,423(6939):506-511
Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction. 相似文献
813.
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain 总被引:118,自引:0,他引:118
Cua DJ Sherlock J Chen Y Murphy CA Joyce B Seymour B Lucian L To W Kwan S Churakova T Zurawski S Wiekowski M Lira SA Gorman D Kastelein RA Sedgwick JD 《Nature》2003,421(6924):744-748
Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages. 相似文献
814.
De Joussineau C Soulé J Martin M Anguille C Montcourrier P Alexandre D 《Nature》2003,426(6966):555-559
Drosophila thoracic mechanosensory bristles originate from cells that are singled out from 'proneural' groups of competent epithelial cells. Neural competence is restricted to individual sensory organ precursors (SOPs) by Delta/Notch-mediated 'lateral inhibition', whereas other cells in the proneural field adopt an epidermal fate. The precursors of the large macrochaetes differentiate separately from individual proneural clusters that comprise about 20-30 cells or as heterochronic pairs from groups of more than 100 cells, whereas the precursors of the small regularly spaced microchaetes emerge from even larger proneural fields. This indicates that lateral inhibition might act over several cell diameters; it was difficult to reconcile with the fact that the inhibitory ligand Delta is membrane-bound until the observation that SOPs frequently extend thin processes offered an attractive hypothesis. Here we show that the extension of these planar filopodia--a common attribute of wing imaginal disc cells--is promoted by Delta and that their experimental suppression reduces Notch signalling in distant cells and increases bristle density in large proneural groups, showing that these membrane specializations mediate long-range lateral inhibition. 相似文献
815.
Lava erupts into cold sea water on the ocean floor at mid-ocean ridges (at depths of 2,500 m and greater), and the resulting flows make up the upper part of the global oceanic crust. Interactions between heated sea water and molten basaltic lava could exert significant control on the dynamics of lava flows and on their chemistry. But it has been thought that heating sea water at pressures of several hundred bars cannot produce significant amounts of vapour and that a thick crust of chilled glass on the exterior of lava flows minimizes the interaction of lava with sea water. Here we present evidence to the contrary, and show that bubbles of vaporized sea water often rise through the base of lava flows and collect beneath the chilled upper crust. These bubbles of steam at magmatic temperatures may interact both chemically and physically with flowing lava, which could influence our understanding of deep-sea volcanic processes and oceanic crustal construction more generally. We infer that vapour formation plays an important role in creating the collapse features that characterize much of the upper oceanic crust and may accordingly contribute to the measured low seismic velocities in this layer. 相似文献
816.
Memory consolidation resulting from sleep has been seen broadly: in verbal list learning, spatial learning, and skill acquisition in visual and motor tasks. These tasks do not generalize across spatial locations or motor sequences, or to different stimuli in the same location. Although episodic rote learning constitutes a large part of any organism's learning, generalization is a hallmark of adaptive behaviour. In speech, the same phoneme often has different acoustic patterns depending on context. Training on a small set of words improves performance on novel words using the same phonemes but with different acoustic patterns, demonstrating perceptual generalization. Here we show a role of sleep in the consolidation of a naturalistic spoken-language learning task that produces generalization of phonological categories across different acoustic patterns. Recognition performance immediately after training showed a significant improvement that subsequently degraded over the span of a day's retention interval, but completely recovered following sleep. Thus, sleep facilitates the recovery and subsequent retention of material learned opportunistically at any time throughout the day. Performance recovery indicates that representations and mappings associated with generalization are refined and stabilized during sleep. 相似文献
817.
818.
Daniel I. Arnon 《Cellular and molecular life sciences : CMLS》1966,22(5):273-287
Zusammenfassung Dieser kurze Überblick über das Gebiet der Photosynthese in isolierten Chloroplasten wäre unvollständig, würde nicht die Abhängigkeit des erzielten Fortschrittes von mindestens zwei «verbesserten analytischen Methoden» betont, welcheEmil Fischers
1 60 Jahre zurückliegende Prophezeiung erfüllen. Zur Entdeckung der Photophosphorylierung und der Kohlenhydratsynthese durch isolierte Chloroplasten war die Einführung der Isotopen-Technik in die Biologie durchvon Hevesy
107 und die Entwicklung der Papierchromatographie durchMartin undSynge
108 von besonderer Bedeutung.Untersuchungen an isolierten Chloroplasten führten zu einer Auffassung der Photosynthese, die sich von der herkömmlichen Ansicht — als eines CO2-Assimilationsprozesses — unterscheidet: Die Photosynthese scheint im wesentlichen ein Prozess zur Umwandlung der Strahlungsenergie des Sonnenlichtes in chemische Energie zu sein. Diese Umwandlung steht in engerer Beziehung zur Phosphorassimilation und zur Reduktion des Eisenproteids Ferredoxin als zur Kohlensäureassimilation. Die ersten, chemisch definierten Produkte dieser Energieumwandlungsreaktion in der Photosynthese erwiesen sich nicht als Zwischenprodukte der Kohlenstoffassimilation, sondern als ATP und reduziertes Ferredoxin.
Based, in part, on a paper presented at the Advanced Study Institute on the Biochemistry of the Chloroplasts, Aberystwyth, Wales, U.K., August 26, 1965. — The research work from the author's laboratory reported herein has been aided by grants from the National Institutes of Health, Office of Naval Research and the Charles F. Kettering Foundation. 相似文献
Based, in part, on a paper presented at the Advanced Study Institute on the Biochemistry of the Chloroplasts, Aberystwyth, Wales, U.K., August 26, 1965. — The research work from the author's laboratory reported herein has been aided by grants from the National Institutes of Health, Office of Naval Research and the Charles F. Kettering Foundation. 相似文献
819.
Zusammenfassung Papierchromatographisch wurde Murein in symbiontischen Bakteroiden derPeriplaneta americana nachgewiesen. Die Murein-Komponente Glukosamin und der Murein-Anzeiger Muramic-Säure wurden mittels Bakteroid-Hydrolysaten identifiziert. Das Vorhandensein von --Diaminopimelic-Säure jedoch konnte nicht einwandfrei festgestellt werden.
This is paper No. 6175, Scientific Journal Series, Minnesota Agricultural Experiment Station, St. Paul (Minnesota, USA). The work was supported by U.S. Public Health Service Research Grant No. AI 00961, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. 相似文献
This is paper No. 6175, Scientific Journal Series, Minnesota Agricultural Experiment Station, St. Paul (Minnesota, USA). The work was supported by U.S. Public Health Service Research Grant No. AI 00961, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. 相似文献
820.
Miguel Afonso Sellitto Guilherme Schreiber Pereira Rafael Marques Daniel Pacheco Lacerda 《Systemic Practice and Action Research》2018,31(5):479-494
The purpose of this article is to construct a systemic structure to explain the relations subjacent to the coopetitive behaviour observed in a Latin American technological park. The research method is qualitative modelling. The primary research technique is the in-depth interview with park experts. Systemic language organised the speeches. The systemic language uses symbols that represent the elements of a system, such as variables, relations, and feedback loops. Initially, we constructed two essential archetypes that describe how the need for coopetition emerged, triggered by failures in meeting customers´ demands and reduced sales. Then, we built an overall systemic structure relying on the essential archetypes, which explains how the coopetitive strategy emerged in the park. The main conclusion reached by the study is learning and public policies as desirable conditions; failure in meeting customers’ requirements as the trigger; and sustainability, knowledge and resource sharing, mitigation of risks and uncertainties, and increased sales by price reduction, as reinforcing feedback factors. The main contribution of the study is a systemic qualitative model that helps understanding how to implement or manage a coopetitive strategy in a network formed of companies mainly driven by technological factors. 相似文献