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141.
Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice. 总被引:8,自引:0,他引:8
M P Sch?n A Arya E A Murphy C M Adams U G Strauch W W Agace J Marsal J P Donohue H Her D R Beier S Olson L Lefrancois M B Brenner M J Grusby C M Parker 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(11):6641-6649
The mucosal lymphocyte integrin alpha E(CD103)beta 7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding alpha E, localized it to chromosome 11, and generated integrin alpha E-deficient mice. In alpha E-/- mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of alpha E beta 7 to E-cadherin expressed on epithelial cells. However, it was surprising that lamina propria T lymphocyte numbers were diminished, as E-cadherin is not expressed in the lamina propria. In contrast, peribronchial, intrapulmonary, Peyer's patch, and splenic T lymphocyte numbers were not reduced in alpha E-deficient mice. Thus, alpha E beta 7 was important for generating or maintaining the gut and vaginal T lymphocytes located diffusely within the epithelium or lamina propria but not for generating the gut-associated organized lymphoid tissues. Finally, the impact of alpha E deficiency upon intestinal IEL numbers was greater at 3-4 wk of life than in younger animals, and affected the TCR alpha beta+ CD8+ T cells more than the gamma delta T cells or the TCR alpha beta+ CD4+CD8- population. These findings suggest that alpha E beta 7 is involved in the expansion/recruitment of TCR alpha beta+ CD8+ IEL following microbial colonization. Integrin alpha E-deficient mice will provide an important tool for studying the role of alpha E beta 7 and of alpha E beta 7-expressing mucosal T lymphocytes in vivo. 相似文献
142.
Georgakopoulos A Marambaud P Efthimiopoulos S Shioi J Cui W Li HC Schütte M Gordon R Holstein GR Martinelli G Mehta P Friedrich VL Robakis NK 《Molecular cell》1999,4(6):893-902
In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations. 相似文献
143.
Markus Burgmer Maimu Alissa Rehbein Marco Wrenger Judith Kandil Gereon Heuft Christian Steinberg Bettina Pfleiderer Markus Jungh?fer 《PloS one》2013,8(8)
Background
In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC) activation at early processing stages (<100 ms). Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma.Methodology
The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain.Principal Findings
Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120–300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing.Conclusions
Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms. 相似文献144.
Dr. A. Gebauer Dr. T. Scheper Prof. Dr. K. Schügerl 《Bioprocess and biosystems engineering》1987,2(1):13-23
E. coli ATCC 11105 was cultivated in a 10-1 stirred tank reactor and in a 60-1 tower loop reactor in batch and continuous operation. By on-line measurements of O2 and CO2 concentrations in the outlet gas, pH, temperature, cell mass concentration X as well as dissolved O2 concentration along the tower in the broth, gas holdup, broth recirculation rate through the loop and by offline measurements of substrate concentration DOC and cell mass concentration along the tower, the maximum specific growth rate
m
, yield coefficients Y
X/S. Y
X/DOC and
were evaluated in stirred tank and tower loop in batch and continuous cultures with and without motionless mixers in the tower and at different broth circulation rates through the loop. To control the accuracy of the measurements the C balance was calculated and 95% of the C content was covered.The biological parameters determined depend on the mode of operation as well as on the reactor used. Furthermore, they depend on the recirculation rate of the broth and built-ins in the tower. The unstructured cell and reactor models are unable to explain these differences. Obviously, structured cell and reactor models are needed. The cell mass concentration can be determined on line by NADH fluorescence in balanced growth, if the model parameters are determined under the same operational conditions in the same reactor.List of Symbols
a, b
empirical parameters in Eq. (1)
- CPR kg/(m3 h)
CO2 production rate
-
C kg/m3
concentration
-
D l/h
dilution rate
- DOC kg/m3
dissolved organic carbon
-
I
net. fluorescence intensity
-
K
S
kg/m3
Monod constant
-
k
L
a l/h
volumetric mass transfer coefficient
- OTR kg/(m3 h)
oxygen transfer rate
- OUR kg/(m3 h)
oxygen utilization rate
- RQ = CPR/OUR
respiratory quotient
-
S kg/m3
substrate concentration
-
t h,min, s
time
-
t
u
min
recirculation time
-
t
M
min
mixing time
-
v m3/h
volumetric flow rate through the loop
-
X kg/m3
(dry) cell mass concentration
-
Y
X/S
yield coefficient of cell mass with regard to the consumed substrate
-
Y
X/DOC
yield coefficient of the cell mass with regard to the consumed DOC
-
Y
X/O
yield coefficient of the cell mass with regard to the consumed oxygen
-
Z
relative distance in the tower from the aerator with regard to the height of the aerated broth
-
l/h
specific growth rate
-
m
l/h
maximum specific growth rate
Indices
f
feed
-
e
outlet 相似文献
145.
B. Müller E. Schlichting L. Bischoff K. Schügerl 《Applied microbiology and biotechnology》1987,26(3):206-210
Summary Penicillin G was extracted from mycelfree fermentation broths by means of the carrier (Amberlite LA-2) in n-butylacetate at pH 5 in a 7.6 m high pilot plant Karr-column with degrees of extraction E=98–99% and penicillin enrichments up to 3. The reextraction was carried out with phosphate buffer at pH-values above 7.5 with degree of extractions E=86–88% and penicillin enrichments up to 3. The penicillin and carrier losses were negligible. The influence of the process variables on the extraction degree was investigated. The penicillin extraction of the model medium and the fermentation broths were compared. Recommendations are given for the optimal penicillin recovery with reactive extraction.Symbols a
specific interfacial area with regard to the volume of the continuous phase
- cA
concentration of carrier
- cAHP,O
concentration of complex in feed
- cP,cP,O
concentration of penicillin acid anion in theaqueous phase, in the feed
-
d
32
Sauter droplet diameter
-
E
degree of extraction
-
f
stroke frequency
-
V
aq
throughput of the aqueous phase
-
V
0
throughput of the organic phase
-
Z
dimensionsless longitudinal coordinate of the column with regard to its active length (4m)
-
holdup of the organic phase 相似文献
146.
Water permeability and composition of soluble cuticular lipids of isolated cuticular membranes from leaves of Citrus aurantium L. were investigated for 3 successive years. The average water permeability coefficient determined using 169 cuticular membranes was 1.09·10–7 cm s–1 with a standard deviation of 0.78·10–7 cm s–1. There were no significant differences in water permeability between years. Cuticular membranes are characterized by a great variability in water permeability both within and between years. Both water permeability of individual membranes and variability between membranes are shown to be determined by soluble cuticular lipids contained within the cuticular membranes. The soluble cuticular lipids of Citrus leaves are composed of fatty acids, primary alcohols, esters, and hydrocarbons. They occur in amounts of 9.84 g cm–2, which represents approx. 3% of the total mass of isolated cuticular membranes. The specific weight of cuticular membranes (365.4 g cm–1) and total amount of soluble cuticular lipids did not vary significantly between years. Significant differences were observed for the amounts and composition of the constituent classes of lipids. Six homologues comprise 86% of the fatty acids (C16; C18; C19; C21; C24; C26), 83% of the primary alcohols (C24; C26; C28; C30; C32; C34) and 88% of the esters (C36; C38; C40; C41; C42; C44). Eleven major homologues amount only to 62% of the total hydrocarbons (C16; C17; C18; C20; C26; C27; C29; C30; C31; C32; C33). Variability in the composition of soluble cuticular lipids between years was much smaller than variability of water permeability and, therefore, no relation between composition of soluble cuticular lipids and water permeability could be found. It is suggested that this may be due to the fact that the lipid composition observed represents the averages of 20 to 30 membranes analyzed so that differences between individual membranes may have been leveled out.Abbreviations CM
cuticular membranes
- MX
polymer matrix
- Pd
permeability coefficient for diffusion of water
- SCL
soluble cuticular lipids
- MES
morpholinoethane sulphonic acid 相似文献
147.
The monomeric homing endonuclease PI-SceI harbors two catalytic centers which cooperate in the cleavage of the two strands of its extended recognition sequence. Structural and biochemical data suggest that catalytic center I contains Asp218, Asp229, and Lys403, while catalytic center II contains Asp326, Thr341, and Lys301. The analogy with I-CreI, for which the cocrystal structure with the DNA substrate has been determined, suggests that Asp218 and Asp229 in catalytic center I and Asp326 and Thr341 in catalytic center II serve as ligands for Mg(2+), the essential divalent metal ion cofactor which can be replaced by Mn(2+) in vitro. We have carried out a mutational analysis of these presumptive Mg(2+) ligands. The variants carrying an alanine or asparagine substitution bind DNA, but (with the exception of the D229N variant) are inactive in DNA cleavage in the presence of Mg(2+), demonstrating that these residues are important for cleavage. Our finding that the PI-SceI variants carrying single cysteine substitutions at these positions are inactive in the presence of the oxophilic Mg(2+) but active in the presence of the thiophilic Mn(2+) suggests that the amino acid residues at these positions are involved in cofactor binding. From the fact that in the presence of Mn(2+) the D218C and D326C variants are even more active than the wild-type enzyme, it is concluded that Asp218 and Asp326 are the principal Mg(2+) ligands of PI-SceI. On the basis of these findings and the available structural information, a model for the composition of the two Mg(2+) binding sites of PI-SceI is proposed. 相似文献
148.
Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias 总被引:7,自引:0,他引:7
Barghorn S Zheng-Fischhöfer Q Ackmann M Biernat J von Bergen M Mandelkow EM Mandelkow E 《Biochemistry》2000,39(38):11714-11721
We have studied biochemical and structural parameters of several missense and deletion mutants of tau protein (G272V, N279K, DeltaK280, P301L, V337M, R406W) found in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The mutant proteins were expressed on the basis of both full-length tau (htau40) and constructs derived from the repeat domain. They were analyzed with respect to the capacity to enhance microtubule assembly, binding of tau to microtubules, secondary structure content, and aggregation into Alzheimer-like paired helical or straight filaments. We find that the mutations cause a moderate decrease in microtubule interactions and stabilization, and they show no gross structural changes compared with the natively unfolded conformation of the wild-type protein, but the aggregation into PHFs is strongly enhanced, particularly for the mutants DeltaK280 and P301L. This gain of pathological aggregation would be consistent with the autosomal dominant nature of the disease. 相似文献
149.
Julian Baur Jeannine Roy Martin A. Schfer Nalini Puniamoorthy Wolf U. Blanckenhorn Patrick T. Rohner 《Journal of evolutionary biology》2020,33(3):297-308
Sexual selection is generally held responsible for the exceptional diversity in secondary sexual traits in animals. Mating system evolution is therefore expected to profoundly affect the covariation between secondary sexual traits and mating success. Whereas there is such evidence at the interspecific level, data within species remain scarce. We here investigate sexual selection acting on the exaggerated male fore femur and the male wing in the common and widespread dung flies Sepsis punctum and S. neocynipsea (Diptera: Sepsidae). Both species exhibit intraspecific differences in mating systems and variation in sexual size dimorphism (SSD) across continents that correlates with the extent of male–male competition. We predicted that populations subject to increased male–male competition will experience stronger directional selection on the sexually dimorphic male foreleg. Our results suggest that fore femur size, width and shape were indeed positively associated with mating success in populations with male‐biased SSD in both species, which was not evident in conspecific populations with female‐biased SSD. However, this was also the case for wing size and shape, a trait often assumed to be primarily under natural selection. After correcting for selection on overall body size by accounting for allometric scaling, we found little evidence for independent selection on any of these size or shape traits in legs or wings, irrespective of the mating system. Sexual dimorphism and (foreleg) trait exaggeration is therefore unlikely to be driven by direct precopulatory sexual selection, but more so by selection on overall size or possibly selection on allometric scaling. 相似文献
150.
Impact of selective genotyping in the training population on accuracy and bias of genomic selection 总被引:1,自引:0,他引:1
Zhao Y Gowda M Longin FH Würschum T Ranc N Reif JC 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,125(4):707-713
Estimating marker effects based on routinely generated phenotypic data of breeding programs is a cost-effective strategy to implement genomic selection. Truncation selection in breeding populations, however, could have a strong impact on the accuracy to predict genomic breeding values. The main objective of our study was to investigate the influence of phenotypic selection on the accuracy and bias of genomic selection. We used experimental data of 788 testcross progenies from an elite maize breeding program. The testcross progenies were evaluated in unreplicated field trials in ten environments and fingerprinted with 857 SNP markers. Random regression best linear unbiased prediction method was used in combination with fivefold cross-validation based on genotypic sampling. We observed a substantial loss in the accuracy to predict genomic breeding values in unidirectional selected populations. In contrast, estimating marker effects based on bidirectional selected populations led to only a marginal decrease in the prediction accuracy of genomic breeding values. We concluded that bidirectional selection is a valuable approach to efficiently implement genomic selection in applied plant breeding programs. 相似文献