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11.
At central excitatory synapses, N-methyl-D-aspartate (NMDA) receptors, which have a high affinity for glutamate, produce a slowly rising synaptic current in response to a single transmitter pulse and an additional current after a second, closely timed stimulus. Here we show, by examining the kinetics of transmitter binding and channel gating in single-channel currents from recombinant NR1/NR2A receptors, that the synaptic response to trains of impulses is determined by the molecular reaction mechanism of the receptor. The rate constants estimated for the activation reaction predict that, after binding neurotransmitter, receptors hesitate for approximately 4 ms in a closed high-affinity conformation before they either proceed towards opening or release neurotransmitter, with about equal probabilities. Because only about half of the initially fully occupied receptors become active, repetitive stimulation elicits currents with distinct waveforms depending on pulse frequency. This high-affinity/low-efficiency activation mechanism might serve as a link between stimulation frequency and the directionality of the ensuing synaptic plasticity. 相似文献
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Pluchino S Zanotti L Rossi B Brambilla E Ottoboni L Salani G Martinello M Cattalini A Bergami A Furlan R Comi G Constantin G Martino G 《Nature》2005,436(7048):266-271
In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection. 相似文献
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Gabriela Brumatti Marika Salmanidis Paul G. Ekert 《Cellular and molecular life sciences : CMLS》2010,67(10):1619-1630
Cytokines and growth factors play a crucial role in the maintenance of haematopoietic homeostasis. They transduce signals
that regulate the competing commitments of haematopoietic stem cells, quiescence or proliferation, retention of stem cell
pluripotency or differentiation, and survival or demise. When the balance between these commitments and the requirements of
the organisms is disturbed, particularly when it favours survival and proliferation, cancer may result. Cell death provoked
by loss of growth factor signalling is regulated by the Bcl-2 family of apoptosis regulators, and thus survival messages transduced
by growth factors must regulate the activity of these proteins. Many aspects of direct interactions between cytokine signalling
and regulation of apoptosis remain elusive. In this review, we explore the mechanisms by which cytokines, in particular Interleukin-3
and granulocyte–macrophage colony-stimulating factor, promote cell survival and suppress apoptosis as models of how cytokine
signalling and apoptotic pathways intersect. 相似文献
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The thermal structure of the crust strongly influences deformation, metamorphism and plutonism. Models for the geothermal gradient in stable crust predict a steady increase of temperature with depth. This thermal structure, however, is incompatible with observations from high-temperature metamorphic terranes exhumed in orogens. Global compilations of peak conditions in high-temperature metamorphic terranes define relatively narrow ranges of peak temperatures over a wide range in pressure, for both isothermal decompression and isobaric cooling paths. Here we develop simple one-dimensional thermal models that include the effects of melt migration. These models show that long-lived plutonism results in a quasi-steady-state geotherm with a rapid temperature increase in the upper crust and nearly isothermal conditions in the middle and lower crust. The models also predict that the upward advection of heat by melt generates granulite facies metamorphism, and widespread andalusite-sillimanite metamorphism in the upper crust. Once the quasi-steady-state thermal profile is reached, the middle and lower crust are greatly weakened due to high temperatures and anatectic conditions, thus setting the stage for gravitational collapse, exhumation and isothermal decompression after the onset of plutonism. Near-isothermal conditions in the middle and lower crust result from the thermal buffering effect of dehydration melting reactions that, in part, control the shape of the geotherm. 相似文献
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Vladislav Valentinov Martina Bolečeková Gabriela Vaceková 《Systemic Practice and Action Research》2017,30(6):651-661
The present paper discusses the response of the Austrian and Slovak nonprofits to the recent migration crisis. In both countries, nonprofits delivered crucial problem-solving contributions but faced serious challenges related to scaling up, capacity building, and improving coordination. Drawing on the Luhmannian systems-theoretic approach, the paper argues that these challenges gave a boost to the systemic identity of nonprofits. Triggered by the substantial inflows of public money, the systemic identity explains why nonprofits can successfully operate in the polarized societal environment and develop unique expertise which is valuable to the public sector. At the same time, the systemic identity lowers the responsiveness of nonprofits to the societal environment. The major policy implication is that this responsiveness has to be continually improved through rational discourses and stakeholder dialogues. 相似文献
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Wetlands are one of the most valuable natural resources, providing a number of ecosystem services and socio-economic values. Small ponds sustain a rich aquatic biodiversity and because of their short hydrological regimen and small size are excellent environments for population studies of microcrustaceans such as ostracods. This study describes the population dynamics of the Ostracoda fauna in three temporary shallow lakes during one hydroperiod in Argentine Patagonia. Three cosmopolitan species were determined: Cypris pubera, Tonnacypris lutaria and Eucypris virens. Among them, T. lutaria is here reported for the first time from the Neotropical region. Multivariate ordination techniques were used to examine the relationships among environmental variables and ostracod density on each sampling site. High values of conductivity, absorption at 320 nm (as a measure of dissolved organic matter), dissolved oxygen concentration, temperature and chlorophyll a concentration correlated positively with ostracod density. All the populations studied reproduced parthenogenetically, and the life cycles of E.virens and C. pubera were followed in detail by weekly sampling of their populations. The former displayed continuous reproduction, whereas the latter showed a multivoltine strategy. The life history of C. pubera was affected by the seasonality of the habitat. The development rate correlated positively with water temperature; conductivity and temperature had a positive effect on adult size in C. pubera, while conductivity had a negative effect on adult size in E. virens. In this study, we present the first data set on the development and life history of ostracods in Patagonian freshwater environments. However, several questions remain and encourage us to further investigate the relative importance of ostracods in food webs, as well as the importance of inter-specific interactions between ostracods and other taxa. 相似文献
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Amaiden MR Santander VS Monesterolo NE Campetelli AN Rivelli JF Previtali G Arce CA Casale CH 《Cellular and molecular life sciences : CMLS》2011,68(10):1755-1768
The presence of tubulin in human erythrocytes was demonstrated using five different antibodies. Tubulin was distributed among
three operationally distinguishable pools: membrane, sedimentable structure and soluble fraction. It is known that in erythrocytes
from hypertensive subjects (HS), the Na+, K+-ATPase (NKA) activity is partially inhibited as compared with erythrocytes from normal subjects (NS). In erythrocytes from
HS the membrane tubulin pool is increased by ~150%. NKA was found to be forming a complex with acetylated tubulin that results
in inhibition of enzymes. This complex was also increased in erythrocytes from HS. Treatment of erythrocytes from HS with
nocodazol caused a decrease of acetylated tubulin in the membrane and stimulation of NKA activity, whereas taxol treatment
on erythrocytes from NS had the opposite effect. These results suggest that, in erythrocytes from HS, tubulin was translocated
to the membrane, where it associated with NKA with the consequent enzyme inhibition. 相似文献
20.
Rothman N Garcia-Closas M Chatterjee N Malats N Wu X Figueroa JD Real FX Van Den Berg D Matullo G Baris D Thun M Kiemeney LA Vineis P De Vivo I Albanes D Purdue MP Rafnar T Hildebrandt MA Kiltie AE Cussenot O Golka K Kumar R Taylor JA Mayordomo JI Jacobs KB Kogevinas M Hutchinson A Wang Z Fu YP Prokunina-Olsson L Burdett L Yeager M Wheeler W Tardón A Serra C Carrato A García-Closas R Lloreta J Johnson A Schwenn M Karagas MR Schned A Andriole G Grubb R Black A Jacobs EJ Diver WR Gapstur SM 《Nature genetics》2010,42(11):978-984
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?11) and a tag SNP for NAT2 acetylation status (P = 4 × 10?11), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis. 相似文献