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1.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
2.
Recognition of protein structure in leukocyte chemotaxis 总被引:5,自引:0,他引:5
P C Wilkinson 《Nature》1973,244(5417):512-513
3.
Fromhold TM Patanè A Bujkiewicz S Wilkinson PB Fowler D Sherwood D Stapleton SP Krokhin AA Eaves L Henini M Sankeshwar NS Sheard FW 《Nature》2004,428(6984):726-730
Understanding how complex systems respond to change is of fundamental importance in the natural sciences. There is particular interest in systems whose classical newtonian motion becomes chaotic as an applied perturbation grows. The transition to chaos usually occurs by the gradual destruction of stable orbits in parameter space, in accordance with the Kolmogorov-Arnold-Moser (KAM) theorem--a cornerstone of nonlinear dynamics that explains, for example, gaps in the asteroid belt. By contrast, 'non-KAM' chaos switches on and off abruptly at critical values of the perturbation frequency. This type of dynamics has wide-ranging implications in the theory of plasma physics, tokamak fusion, turbulence, ion traps, and quasicrystals. Here we realize non-KAM chaos experimentally by exploiting the quantum properties of electrons in the periodic potential of a semiconductor superlattice with an applied voltage and magnetic field. The onset of chaos at discrete voltages is observed as a large increase in the current flow due to the creation of unbound electron orbits, which propagate through intricate web patterns in phase space. Non-KAM chaos therefore provides a mechanism for controlling the electrical conductivity of a condensed matter device: its extreme sensitivity could find applications in quantum electronics and photonics. 相似文献
4.
5.
In occupational therapy education in South Africa, community service (CS) focuses learning opportunities during fieldwork
placements. CS therefore enabled the researcher to utilise successive small scale research projects to guide learning of students
during fieldwork while simultaneously developing the occupational therapy service at a residential care facility. This community
setting provided a powerful environment through which research, in combination with opportunities for reflection, contributed
to nurturing skills needed by these future health professionals. A technical action research (AR) approach incorporated AR
cycles and opportunities for structured reflection. Therefore situations were created for the students to embrace experiential
learning. Experiential learning in the form of anticipatory reflection, reflection-in-action, reflection on reflection and
retrospective reflection impacted on the quality of the students’ work. Besides encouraging unique leaning opportunities for
students when engaging in research during their fieldwork placement, engagement in AR cycles simultaneously improved service
delivery to residents in the facility. Key benefits of this investigation were that fieldwork education utilising AR cycles
within a CS situation promoted students to identify voids in their theoretical background as well as practice skills; to apply
reflective practice that could contribute to their personal and professional development; and to utilize learning opportunities
optimally. Despite positive gains showed by this study, the role of power relations between the researcher as fieldwork educator
and the students prohibited the AR cycles from being more emancipatory in nature and should be addressed in follow-up studies. 相似文献
6.
Characterization of the chemotactic activity of casein for neutrophil leucocytes and macrophages 总被引:2,自引:0,他引:2
P C Wilkinson 《Experientia》1972,28(9):1051-1052
7.
A single point mutation has been engineered in the tyrosyl-tRNA synthetase that improves its affinity (KM) for its substrate ATP by a factor of 100. In the crystal structure of the tyrosyl tRNA synthetase (of Bacillus stearothermophilus), the side-chain hydroxyl of Thr 51 appears to make a weak hydrogen bond with the AMP moiety of the substrate intermediate, tyrosyl adenylate. In the absence of substrate, however, the hydroxyl group should make a strong hydrogen bond with water which would favour dissociation of the enzyme-substrate complex. We have used oligodeoxynucleotide-directed mutagenesis to construct two point mutants at this site: one to remove the hydroxyl group (Thr 51 leads to Ala 51) and the other, in addition, to distort the local polypeptide backbone (Thr 51 leads to Pro 51). We report here that both mutants have increased activity (kcat/KM for ATP) but one mutant (Pro 51) shows a massive 25-fold increase due mainly to a lowered KM for ATP. This demonstrates dramatically the potential of in vitro mutagenesis for improving the affinity of an enzyme for its substrate. 相似文献
8.
Summary The effect of dilutional hyponatraemia on cerebral blood flow and oxygen consumption, and net transfer of K+ to the circulation from brain tissue drained by the sagittal sinus was investigated in anaesthetized calves. Cerebral blood flow decreased, and net transfer of K+ to the circulation increased during hyponatraemia.Acknowledgments. The expert assistance of Miss B.N. O'Connor, Miss D. McNaughton and Mr P.M.M. Bircham is gratefully acknowledged. 相似文献
9.
In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. 总被引:10,自引:0,他引:10
The restriction of intermingling between specific cell populations is crucial for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing between segments in the insect epidermis and the vertebrate hindbrain that may enable each segment to maintain a distinct identity. In the hindbrain, this is a result of different adhesive properties of odd- and even-numbered segments (rhombomeres), but an adhesion molecule with alternating segmental expression has not been found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells. Eph receptors and their membrane-bound ligands, ephrins, are expressed in complementary rhombomeres and, by analogy with their roles in axon pathfinding, could mediate cell repulsion at boundaries. Remarkably, transmembrane ephrins can themselves transduce signals, raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor-expressing cells. We report here that mosaic activation of Eph receptors leads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numbered rhombomeres. These data implicate Eph receptors and ephrins in the segmental restriction of cell intermingling. 相似文献
10.
Inoue K Khajavi M Ohyama T Hirabayashi S Wilson J Reggin JD Mancias P Butler IJ Wilkinson MF Wegner M Lupski JR 《Nature genetics》2004,36(4):361-369
The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes. 相似文献