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1.
Reinhard Told Stefan Palkovits Helmuth Haslacher Sophie Frantal Doreen Schmidl Agnes Boltz Michael Lasta Semira Kaya René M. Werkmeister Gerhard Garh?fer Leopold Schmetterer 《PloS one》2013,8(4)
A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis. 相似文献
2.
High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans 总被引:1,自引:0,他引:1
We compared male-reproductive-tract polypeptides of Drosophila melanogaster
and D. simulans by using two-dimensional gel electrophoresis. Approximately
64% of male-reproductive-tract polypeptides were identical between two
randomly chosen isofemale lines from these two species, compared with 83%
identity for third-instar imaginal wing-disc polypeptides. Qualitatively
similar differences were found between reproductive tracts and imaginal
discs when D. sechellia was compared with D. melanogaster and with D.
simulans. When genic polymorphism was taken into account, approximately 10%
of male- reproductive-tract polypeptides were apparently fixed for
different alleles between D. melanogaster and D. simulans; this proportion
is the same as that found for soluble enzymes by one-dimensional gel
electrophoresis. Strikingly, approximately 20% of male-reproductive- tract
polypeptides of either D. melanogaster or D. simulans had no detectable
homologue in the other species. We propose that proteins of the Drosophila
male reproductive tract may have diverged more extensively between species
than have other types of proteins and that much of this divergence may
involve large changes in levels of polypeptide expression.
相似文献
3.
The Distribution and Biochemical Properties of a Cdc2-Related Kinase, KKIALRE, in Normal and Alzheimer Brains 总被引:2,自引:0,他引:2
Shu-Hui Yen Agnes Kenessey Sunhee C. Lee Dennis W. Dickson 《Journal of neurochemistry》1995,65(6):2577-2584
Abstract: The biochemical properties and distribution of a Cdc2-related kinase, KKIALRE, were studied in brain tissues and cultured cells with antibodies to a subregion of KKIALRE protein deduced from cDNA. In adult human brain, the KKIALRE-immunoreactive protein consisted of four or five isoforms having a molecular size of 40–52 kDa, whereas in fetal brain, there was one protein of ∼48 kDa. Cultured astrocytes, neuroblastoma cells, and mouse brains contained the fetal form of KKIALRE protein. KKIALRE-immunoreactive proteins were capable of phosphorylating histone and synthetic peptides with the X-Ser-Pro-X motif, indicating that these proteins belong to the proline-directed Ser/Thr protein kinase family. The KKIALRE immunoreactivity was detected primarily in fibrous astrocytes in white matter and perivascular and subpial spaces, as well as in Bergmann glia in the cerebellum. In fetal brains radial glia were weakly immunoreactive. Reactive astrocytes were more intensely labeled than other glia. Neurons in normal brains and brains with Alzheimer's disease (AD) displayed no KKIALRE immunoreactivity. KKIALRE immunoreactivity was similar in neurons with and without neurofibrillary tangles. The results indicate that in CNS, the KKIALRE protein is mainly a glial protein that is up-regulated in gliosis and that it probably plays no role in the hyperphosphorylation of τ in AD brains. 相似文献
4.
Ventilation and metabolism among rat strains 总被引:3,自引:0,他引:3
Strohl Kingman P.; Thomas Agnes J.; St. Jean Pamela; Schlenker Evelyn H.; Koletsky Richard J.; Schork Nicholas J. 《Journal of applied physiology》1997,82(1):317-323
Strohl, Kingman P., Agnes J. Thomas, Pamela St. Jean, EvelynH. Schlenker, Richard J. Koletsky, and Nicholas J. Schork. Ventilation and metabolism among rat strains. J. Appl. Physiol. 82(1): 317-323, 1997.We examinedventilation and metabolism in four rat strains with variation in traitsfor body weight and/or blood pressure regulation.Sprague-Dawley [SD; 8 males (M), 8 females (F)], BrownNorway (BN; 10 M, 11 F), and Zucker (Z; 11 M, 12 F) rats were comparedwith Koletsky (K; 11 M, 11 F) rats. With the use of noninvasiveplethysmography, frequency, tidal volume, minute ventilation(E),O2 consumption, andCO2 production were derived atrest during normoxia (room air) and during the 5th minute of exposureto each of the following: hyperoxia (100% O2), hypoxia (10%O2-balanceN2), and hypercapnia (7%CO2-balance O2). Statistical methods probedfor strain and sex effects, with covariant analysis by body weight,length, and body mass. During resting breathing, strain effects werefound with respect to both frequency (BN, Z > K, SD) and tidal volume(SD > BN, Z) but not to E. Sexinfluenced frequency (F > M) alone. Z rats had higher values forO2 consumption,CO2 production, and respiratoryquotient than the other three strains, with no independent effect bysex. During hyperoxia, frequency was greater in BN and Z than in SD orK rats; SD rats had a larger tidal volume than BN or Z rats; Z rats hada greater E than K rats; and M had alarger tidal volume than F. Strain differences persisted duringhypercapnia, with Z rats exhibiting the highest frequency andE values. During hypoxic exposure,strain effects were found to influenceE (SD > K, Z), frequency (BN > K), and tidal volume (SD > BN, K, Z). Body mass was only amodest predictor of E during normoxia, of both E and tidal volume withhypoxia, hypercapnia, or hyperoxia, and of frequency duringhypercapnia. We conclude that strain of rats, more than their body massor sex, has major and different influences on metabolism, the patternand level of ventilation during air breathing, and ventilation duringacute exposure to hypercapnia or hypoxia. 相似文献
5.
Identification by in vitro complementation of regions required for cell-invasive activity of Bordetella pertussis adenylate cyclase toxin 总被引:2,自引:0,他引:2
The adenylate cyclase toxin (CyaA) of Bordetella pertussis is a 1706-residue protein composed of an amino-terminal adenylate cyclase (AC) domain linked to a 1300-residue channel-forming RTX ( r epeats in t o x in) haemolysin. The toxin delivers its AC domain into a variety of eukaryotic cells and impairs cellular functions by catalysing unregulated synthesis of cAMP from intracellular ATP. We have examined toxin activities of a set of deletion derivatives of CyaA. The results indicate that CyaA does not have a dedicated target cell-binding domain and that structural integrity and co-operation of all domains, as well as the post-translational fatty acylation mediated by an accessory protein CyaC, are all essential for target cell association and toxin activity of CyaA. When tested individually, all toxin derivatives were inactive and impaired in the tight association with the target cell surface. However, pairs of constructs with non-overlapping deletions complemented each other in vitro and exhibited a partially restored cytotoxic activity. This suggests that at least a part of the active toxin may act in the form of dimers or higher oligomers. The complementation analysis revealed that the last 217 residues of CyaA, containing the unprocessed secretion signal, form an autonomous domain essential for toxin activity, and that the region from residue 624 to 780 may be directly involved in delivery of the AC toxin into cells. 相似文献
6.
Incorporation of the gene for a cell-cell channel protein into transformed cells leads to normalization of growth 总被引:13,自引:0,他引:13
Parmender P. Mehta Agnes Hotz-Wagenblatt Birgit Rose David Shalloway Warner R. Loewenstein 《The Journal of membrane biology》1991,124(3):207-225
Summary Incorporation of the gene for connexin 43, a cell-cell channel protein of gap junction, into the genome of communication-deficient transformed mouse 10T1/2 cells restored junctional communication and inhibited growth. Growth was slowed, saturation density reduced and focus formation suppressed, and these effects were contingent on overexpression of the exogenous gene and the consequent enhancement of communication. In coculture with normal cells the growth of the connexin overexpressors was completely arrested, as these cells established strong communication with the normal ones. Thus, in culture by themselves or in coculture, the connexin overexpressor cells grew like normal cells. These results demonstrate that the cell-cell channel is instrumental in growth control; they are the expected behavior if the channel transmits cytoplasmic growth-regulatory signals. 相似文献
7.
Summary Following the observation of a close sequence homology between the N-terminal moiety of the -chain of fibrinogen with large parts of-casein, the occurrence of a keratin domain in the middle section of the Achain is suggested. 相似文献
8.
9.
Crystal structure of a secreted insect ferritin reveals a symmetrical arrangement of heavy and light chains 总被引:2,自引:0,他引:2
Hamburger AE West AP Hamburger ZA Hamburger P Bjorkman PJ 《Journal of molecular biology》2005,349(3):558-569
Ferritins are iron storage proteins made of 24 subunits forming a hollow spherical shell. Vertebrate ferritins contain varying ratios of heavy (H) and light (L) chains; however, known ferritin structures include only one type of chain and have octahedral symmetry. Here, we report the 1.9A structure of a secreted insect ferritin from Trichoplusia ni, which reveals equal numbers of H and L chains arranged with tetrahedral symmetry. The H/L-chain interface includes complementary features responsible for ordered assembly of the subunits. The H chain contains a ferroxidase active site resembling that of vertebrate H chains with an endogenous, bound iron atom. The L chain lacks the residues that form a putative iron core nucleation site in vertebrate L chains. Instead, a possible nucleation site is observed at the L chain 3-fold pore. The structure also reveals inter- and intrasubunit disulfide bonds, mostly in the extended N-terminal regions unique to insect ferritins. The symmetrical arrangement of H and L chains and the disulfide crosslinks reflect adaptations of insect ferritin to its role as a secreted protein. 相似文献
10.
Stockton JC Howson JM Awomoyi AA McAdam KP Blackwell JM Newport MJ 《FEMS immunology and medical microbiology》2004,41(2):157-160
The nucleotide oligomerization binding domain 2 gene (NOD2) encodes an intracellular receptor for bacterial components, which is expressed in monocytes and is associated with Crohn's Disease (CD). This finding, along with epidemiological evidence, supports a role for infection in the pathogenesis of CD. Speculation that mycobacteria are involved in CD led us to investigate NOD2 in susceptibility to tuberculosis (TB), a global public health problem caused by Mycobacterium tuberculosis. CD-associated NOD2 variants were absent in a case-control study of 640 Gambians, where CD is rare. Novel NOD2 promoter polymorphisms were identified but showed no association with TB in this African population sample. 相似文献