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81.
82.
Weiss J Pyrski M Jacobi E Bufe B Willnecker V Schick B Zizzari P Gossage SJ Greer CA Leinders-Zufall T Woods CG Wood JN Zufall F 《Nature》2011,472(7342):186-190
Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell. 相似文献
83.
High-resolution carbon dioxide concentration record 650,000-800,000 years before present 总被引:6,自引:0,他引:6
Lüthi D Le Floch M Bereiter B Blunier T Barnola JM Siegenthaler U Raynaud D Jouzel J Fischer H Kawamura K Stocker TF 《Nature》2008,453(7193):379-382
Changes in past atmospheric carbon dioxide concentrations can be determined by measuring the composition of air trapped in ice cores from Antarctica. So far, the Antarctic Vostok and EPICA Dome C ice cores have provided a composite record of atmospheric carbon dioxide levels over the past 650,000 years. Here we present results of the lowest 200 m of the Dome C ice core, extending the record of atmospheric carbon dioxide concentration by two complete glacial cycles to 800,000 yr before present. From previously published data and the present work, we find that atmospheric carbon dioxide is strongly correlated with Antarctic temperature throughout eight glacial cycles but with significantly lower concentrations between 650,000 and 750,000 yr before present. Carbon dioxide levels are below 180 parts per million by volume (p.p.m.v.) for a period of 3,000 yr during Marine Isotope Stage 16, possibly reflecting more pronounced oceanic carbon storage. We report the lowest carbon dioxide concentration measured in an ice core, which extends the pre-industrial range of carbon dioxide concentrations during the late Quaternary by about 10 p.p.m.v. to 172-300 p.p.m.v. 相似文献
84.
Microfluidic diagnostic technologies for global public health 总被引:2,自引:0,他引:2
The developing world does not have access to many of the best medical diagnostic technologies; they were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive, but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world. 相似文献
85.
K. Bernhard 《Cellular and molecular life sciences : CMLS》1948,4(2):79-80
Ohne Zusammenfassung 相似文献
86.
Kent SC Chen Y Bregoli L Clemmings SM Kenyon NS Ricordi C Hering BJ Hafler DA 《Nature》2005,435(7039):224-228
In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing beta-islet cells. Identification of the autoantigens involved in triggering this process is a central question. Here we examined T cells from pancreatic draining lymph nodes, the site of islet-cell-specific self-antigen presentation. We cloned single T cells in a non-biased manner from pancreatic draining lymph nodes of subjects with type 1 diabetes and from non-diabetic controls. A high degree of T-cell clonal expansion was observed in pancreatic lymph nodes from long-term diabetic patients but not from control subjects. The oligoclonally expanded T cells from diabetic subjects with DR4, a susceptibility allele for type 1 diabetes, recognized the insulin A 1-15 epitope restricted by DR4. These results identify insulin-reactive, clonally expanded T cells from the site of autoinflammatory drainage in long-term type 1 diabetics, indicating that insulin may indeed be the target antigen causing autoimmune diabetes. 相似文献
87.
Karrai K Warburton RJ Schulhauser C Högele A Urbaszek B McGhee EJ Govorov AO Garcia JM Gerardot BD Petroff PM 《Nature》2004,427(6970):135-138
The self-assembly of semiconductor quantum dots has opened up new opportunities in photonics. Quantum dots are usually described as 'artificial atoms', because electron and hole confinement gives rise to discrete energy levels. This picture can be justified from the shell structure observed as a quantum dot is filled either with excitons (bound electron-hole pairs) or with electrons. The discrete energy levels have been most spectacularly exploited in single photon sources that use a single quantum dot as emitter. At low temperatures, the artificial atom picture is strengthened by the long coherence times of excitons in quantum dots, motivating the application of quantum dots in quantum optics and quantum information processing. In this context, excitons in quantum dots have already been manipulated coherently. We show here that quantum dots can also possess electronic states that go far beyond the artificial atom model. These states are a coherent hybridization of localized quantum dot states and extended continuum states: they have no analogue in atomic physics. The states are generated by the emission of a photon from a quantum dot. We show how a new version of the Anderson model that describes interactions between localized and extended states can account for the observed hybridization. 相似文献
88.
89.
Oxygenic photosynthesis in plants, algae and cyanobacteria is initiated at photosystem II, a homodimeric multisubunit protein-cofactor complex embedded in the thylakoid membrane. Photosystem II captures sunlight and powers the unique photo-induced oxidation of water to atmospheric oxygen. Crystallographic investigations of cyanobacterial photosystem II have provided several medium-resolution structures (3.8 to 3.2 A) that explain the general arrangement of the protein matrix and cofactors, but do not give a full picture of the complex. Here we describe the most complete cyanobacterial photosystem II structure obtained so far, showing locations of and interactions between 20 protein subunits and 77 cofactors per monomer. Assignment of 11 beta-carotenes yields insights into electron and energy transfer and photo-protection mechanisms in the reaction centre and antenna subunits. The high number of 14 integrally bound lipids reflects the structural and functional importance of these molecules for flexibility within and assembly of photosystem II. A lipophilic pathway is proposed for the diffusion of secondary plastoquinone that transfers redox equivalents from photosystem II to the photosynthetic chain. The structure provides information about the Mn4Ca cluster, where oxidation of water takes place. Our study uncovers near-atomic details necessary to understand the processes that convert light to chemical energy. 相似文献
90.
Mutations in a novel gene,NPHP3, cause adolescent nephronophthisis,tapeto-retinal degeneration and hepatic fibrosis 总被引:12,自引:0,他引:12
Olbrich H Fliegauf M Hoefele J Kispert A Otto E Volz A Wolf MT Sasmaz G Trauer U Reinhardt R Sudbrak R Antignac C Gretz N Walz G Schermer B Benzing T Hildebrandt F Omran H 《Nature genetics》2003,34(4):455-459
Nephronophthisis (NPHP), a group of autosomal recessive cystic kidney disorders, is the most common genetic cause of progressive renal failure in children and young adults. NPHP may be associated with Leber congenital amaurosis, tapeto-retinal degeneration, cerebellar ataxia, cone-shaped epiphyses, congenital oculomotor apraxia and hepatic fibrosis. Loci associated with an infantile type of NPHP on 9q22-q31 (NPHP2), juvenile types of NPHP on chromosomes 2q12-q13 (NPHP1) and 1p36 (NPHP4) and an adolescent type of NPHP on 3q21-q22 (NPHP3) have been mapped. NPHP1 and NPHP4 have been identified, and interaction of the respective encoded proteins nephrocystin and nephrocystin-4 has been shown. Here we report the identification of NPHP3, encoding a novel 1,330-amino acid protein that interacts with nephrocystin. We describe mutations in NPHP3 in families with isolated NPHP and in families with NPHP with associated hepatic fibrosis or tapeto-retinal degeneration. We show that the mouse ortholog Nphp3 is expressed in the node, kidney tubules, retina, respiratory epithelium, liver, biliary tract and neural tissues. In addition, we show that a homozygous missense mutation in Nphp3 is probably responsible for the polycystic kidney disease (pcy) mouse phenotype. Interventional studies in the pcy mouse have shown beneficial effects by modification of protein intake and administration of methylprednisolone, suggesting therapeutic strategies for treating individuals with NPHP3. 相似文献