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131.
Smith CM Wilson NS Waithman J Villadangos JA Carbone FR Heath WR Belz GT 《Nature immunology》2004,5(11):1143-1148
Several studies have indicated that CD8(+) T cells require CD4(+) T cell help for memory formation. Evidence suggests that such help can be antigen independent, challenging whether the 'licensing' of dendritic cells (DCs) by CD4(+) T cells is ever required for cytotoxic T lymphocyte (CTL) responses. We show here that help is essential for the generation of CTL immunity to herpes simplex virus 1 and that CD4(+) T cells mediate help in a cognate, antigen-specific way. We provide direct in vivo evidence for DC licensing by helper T cells and show that licensing is rapid and essential for the formation of effector and memory CTLs. In situations in which DCs are poorly licensed by pathogen-derived signals, our findings suggest that CTL immunity may be heavily dependent on cognate DC licensing. 相似文献
132.
On the ERN and the significance of errors 总被引:3,自引:0,他引:3
The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring. 相似文献
133.
Jason R Spence Juan-Carlos Aycinena Katia Del Rio-Tsonis 《Developmental dynamics》2007,236(5):1161-1174
The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration. 相似文献
134.
Leonard A. Jason Steven B. Pokorny Mazna Patka Monica Adams Taylor Morello 《Journal of community psychology》2007,35(8):967-979
Two primary outlets for community psychology research, the American Journal of Community Psychology and the Journal of Community Psychology, were assessed to rank institutions based on publication frequency and scientific influence of publications over a 32‐year period. Three specific periods were assessed (1973–1983, 1984–1994, 1995–2004). Findings indicate that there were a large group of institutions that published articles during these periods. Those academic institutions that had the most published articles as well as the largest influence, based on citations by other authors, were identified. Using archival data from the community psychology literature represents one approach for identifying those settings that made substantial contributions to the development and growth of the field. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 967–979, 2007. 相似文献
135.
Kennedy J Jackson G Ramsden S Taylor J Newman W Wright MJ Donnai D Elles R Briggs MD 《European journal of human genetics : EJHG》2005,13(5):547-555
The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making. 相似文献
136.
Kennedy J Jackson GC Barker FS Nundlall S Bella J Wright MJ Mortier GR Neas K Thompson E Elles R Briggs MD 《Human mutation》2005,25(6):593-594
Pseudoachondroplasia (PSACH) and some forms of multiple epiphyseal dysplasia (MED) result from mutations in the gene encoding cartilage oligomeric matrix protein (COMP). COMP is a large pentameric glycoprotein found predominantly in the extracellular matrix of cartilage, tendon, and ligament. As a modular protein, it is composed of a coiled-coil domain, four type II (T2) repeats, eight type III (T3) repeats, and a large globular C-terminal domain (CTD). The majority (>85%) of COMP mutations causing PSACH or MED are found in the exons encoding the T3 repeats, and the disease mechanism has been characterised in detail. Much less is known about disease-causing mutations in the CTD; in 10 years only seven mutations have been identified. In this study, we describe eight novel and two recurrent mutations that we have recently identified in patients with PSACH or MED. Interestingly, these mutations result in a spectrum of disease, ranging from mild MED to severe PSACH. Mapping of all known COMP CTD mutations on a three-dimensional model of the C-terminal domain shows that the CTD mutations cluster in two distinct regions. These regions are probably important in stabilising the T3-CTD structure and mediating intra- or intermolecular interactions. 相似文献
137.
Taki Y Goto R Evans A Zijdenbos A Neelin P Lerch J Sato K Ono S Kinomura S Nakagawa M Sugiura M Watanabe J Kawashima R Fukuda H 《Neurobiology of aging》2004,25(4):455-463
The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter. 相似文献
138.
Jason B. Mattingley Louise A. Corben John L. Bradshaw Judy A. Bradshaw Jim G. Phillips Malcolm K. Horne 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,120(2):243-256
Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets.
To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli,
we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control
subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional
or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable
or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at
the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional
targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy
controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment
2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to
move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same
direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements
towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements.
Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional
targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose
that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional
events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged
right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events.
Received: 1 October 1996 / Accepted: 21 October 1997 相似文献
139.
Hemodynamic Conditions Alter Axial and Circumferential Remodeling of Arteries Engineered <Emphasis Type="Italic">Ex Vivo</Emphasis> 总被引:3,自引:0,他引:3
We previously demonstrated that growth and remodeling was stimulated in arteries elongated ex vivo using step increases in axial strain. Viability and vasoactivity were similar to fresh arteries, however there was a substantial decrease in the ultimate circumferential stress. To test the hypothesis that the subphysiological perfusion conditions (i.e., low pressure and flow) previously used caused the reduction, arteries were subjected to the identical elongation protocol (50% increase over 9 days) while being perfused with physiological levels of flow, viscosity and pulsatile pressure. A significant increase in unloaded length was achieved by elongation under both perfusion conditions, although the increase was less under physiological (7 ± 1%) than under subphysiological conditions (19 ± 2%, p < 0.005). When length at physiological stress was estimated using mechanical testing data the values were similar. The ultimate circumferential stress of arteries elongated under physiological conditions was increased (33%), whereas the ultimate axial stress was decreased (50%) as compared with arteries elongated under subphysiological conditions. Elongated arteries under both perfusion conditions showed significant increases in proliferation and collagen mass, and similar viability and appearance to fresh arteries. These data suggest that there is substantial cross-talk between perfusion conditions and axial strain that modulates arterial remodeling and length. 相似文献
140.
M Shohat V Herman S Melmed N Neufeld R Schreck S Pulst J M Graham D L Rimoin J R Korenberg 《American journal of medical genetics》1991,39(1):56-63
Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p 11.23)], we have excluded the growth hormone-releasing hormone (GHRH) gene from the region 20p11.23----pter. The patient had minor facial anomalies. Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23----qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p. 相似文献