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81.
Characterization of Stachybotrys from water-damaged buildings based on morphology, growth, and metabolite production 总被引:1,自引:0,他引:1
Stachybotrys was found to be associated with idiopathic pulmonary hemorrhage in infants in Cleveland, Ohio. Since that time, considerable effort has been put into finding the toxic components responsible for the disease. The name Stachybotrys chartarum has been applied to most of these isolates, but inconsistent toxicity results and taxonomic confusion prompted the present study. In this study, 122 Stachybotrys isolates, mainly from water-damaged buildings, were characterized and identified by combining three different approaches: morphology, colony characteristics, and metabolite production. Two different Stachybotrys taxa, S. chartarum and one undescribed species, were found in water-damaged buildings regardless of whether the buildings were in Denmark, Finland, or the USA. Furthermore, two chemotypes could be distinguished in S. chartarum. One chemotype produced atranones, whereas the other was a macrocyclic trichothecene-producer. The second undescribed taxon produced atranones and could be differentiated from S. chartarum by its growth characteristics and pigment production. Our results correlate with different inflammatory and toxicological properties reported for these same isolates and show that the three taxa/chemotypes should be treated separately. The co-occurrence of these three taxa/chemotypes in water-damaged buildings explains the inconsistent results in the literature concerning toxicity of Stachybotrys isolated from that environment. 相似文献
82.
Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102 总被引:7,自引:0,他引:7
PDZ domains typically interact with the very carboxyl terminus of their binding partners. Type 1 PDZ domains usually require valine, leucine, or isoleucine at the very COOH-terminal (P(0)) position, and serine or threonine 2 residues upstream at P(-2). We quantitatively defined the contributions of carboxyl-terminal residues to binding selectivity of the prototypic interactions of the PDZ domains of postsynaptic density protein 95 (PSD-95) and its homolog synapse-associated protein 90 (SAP102) with the NR2b subunit of the N-methyl-d-aspartate-type glutamate receptor. Our studies indicate that all of the last five residues of NR2b contribute to the binding selectivity. Prominent were a requirement for glutamate or glutamine at P(-3) and for valine at P(0) for high affinity binding and a preference for threonine over serine at P(-2), in the context of the last 11 residues of the NR2b COOH terminus. This analysis predicts a COOH-terminal (E/Q)(S/T)XV consensus sequence for the strongest binding to the first two PDZ domains of PSD-95 and SAP102. A search of the human genome sequences for proteins with a COOH-terminal (E/Q)(S/T)XV motif yielded 50 proteins, many of which have not been previously identified as PSD-95 or SAP102 binding partners. Two of these proteins, brain-specific angiogenesis inhibitor 1 and protein kinase Calpha, co-immunoprecipitated with PSD-95 and SAP102 from rat brain extracts. 相似文献
83.
Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck 总被引:4,自引:0,他引:4
Schweimer K Hoffmann S Bauer F Friedrich U Kardinal C Feller SM Biesinger B Sticht H 《Biochemistry》2002,41(16):5120-5130
Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpesviral infection. We investigated the interaction of proline-rich Tip peptides with the LckSH3 domain starting with the structural characterization of the unbound interaction partners. The solution structure of the LckSH3 was determined by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy using 44 residual dipolar couplings in addition to the conventional experimental restraints. Circular dichroism spectroscopy proved that the polyproline helix of Tip is already formed prior to SH3 binding and is conformationally stable. NMR titration experiments point out three major regions of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical turn preceding the last strand of the beta-sheet. Further changes of the chemical shifts were observed for the N- and C-terminal beta-strands of the SH3 domain, indicating additional contacts outside the proline-rich segment or subtle structural rearrangements transmitted from the binding site of the proline helix. Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for Lyn, Hck, and Lck. 相似文献
84.
Sharma VM Prasanna P Seshu KV Renuka B Rao CV Kumar GS Narasimhulu CP Babu PA Puranik RC Subramanyam D Venkateswarlu A Rajagopal S Kumar KB Rao CS Mamidi NV Deevi DS Ajaykumar R Rajagopalan R 《Bioorganic & medicinal chemistry letters》2002,12(17):2303-2307
In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents. 相似文献
85.
Hereditary hemochromatosis (HH) is a common genetic disease with iron overload in certain organs, especially the liver. Most cases are homozygous for the C282Y mutation in the HFE gene; a few are C282Y heterozygous, compound C282Y/H63D heterozygous, or have no known mutation. A third mutation, S65C, has been associated with HH, but this finding is disputed. We have studied the clinical significance of various genotypes with the S65C mutation. In a population-based screening for HH in 65,238 persons, 613 had high serum transferrin saturation in two blood samples and were invited for HFE genotyping. In 556 persons with complete data sets, we studied the serum ferritin concentration and the risk of being diagnosed with phenotypic HH in the various genotypic groups. The phenotypic diagnosis was given without knowing the genotypic result. Except for the C282Y homozygotes, no differences in median serum ferritin concentrations were found between the various genotypic groups. However, the C282Y/S65C compound heterozygous group had a higher risk of being diagnosed with phenotypic HH than the wild-type group, as did the C282Y homozygous and the C282Y/H63D compound heterozygous groups. When combined with the C282Y mutation, the S65C mutation is associated with an increased risk of being diagnosed with phenotypic HH. 相似文献
86.
A recent computational study of gain control via shunting inhibition has shown that the slope of the frequency-versus-input (f-I) characteristic of a neuron can be decreased by increasing the noise associated with the inhibitory input (Neural Comput. 13, 227-248). This novel noise-induced divisive gain control relies on the concommittant increase of the noise variance with the mean of the total inhibitory conductance. Here we investigate this effect using different neuronal models. The effect is shown to occur in the standard leaky integrate-and-fire (LIF) model with additive Gaussian white noise, and in the LIF with multiplicative noise acting on the inhibitory conductance. The noisy scaling of input currents is also shown to occur in the one-dimensional theta-neuron model, which has firing dynamics, as well as a large scale compartmental model of a pyramidal cell in the electrosensory lateral line lobe of a weakly electric fish. In this latter case, both the inhibition and the excitatory input have Poisson statistics; noise-induced divisive inhibition is thus seen in f-I curves for which the noise increases along with the input I. We discuss how the variation of the noise intensity along with inputs is constrained by the physiological context and the class of model used, and further provide a comparison of the divisive effect across models. 相似文献
87.
Split-thickness skin grafts remain central to the strategy of burn wound treatment. The dressing used to cover the donor wound site has a significant effect on healing parameters. The purpose of this study was to compare split-thickness skin graft donor site reepithelialization under Xeroform and Jelonet dressings. A dermatome was used to cut two consecutive strips of skin from 25 paired donor sites on the thigh, calf, or back of 19 participants. Standardization of the harvest method was achieved by using the same surgeon to harvest the compared skin graft strips, with attention to consistency of dermatome skin-thickness setting, downward pressure, and angle of dermatome approach. A strip of Xeroform or Jelonet was applied to one of each pair of wounds. Epidermal and dermal thickness was measured from biopsy specimens cut at the midpoint of each split-thickness graft strip. The day of final dressing separation was declared the day of complete donor reepithelialization (healing). The mean healing time for Xeroform and Jelonet was 10.4 +/- 2.6 days (n = 25) and 10.6 +/- 2.8 days (n = 25) (p = 0.76) at sites cut to a mean depth of 0.23 +/- 0.08 mm and 0.23 +/- 0.09 mm (p = 0.89), respectively. There was no correlation between graft thickness and healing time for sites dressed with Xeroform (r = 0.17) or Jelonet (r = 0.02). Donors sites reharvested 10 to 21 days after a prior harvest healed an average of 3.1 days earlier than virgin sites (8.4 +/- 1.6 versus 11.5 +/- 2.6 days, p < 0.001), although reharvested grafts were on average 0.05 mm thicker (p = 0.10). The mean thickness of reepithelialized donor-site epidermis (0.13 +/- 0.04 mm, n = 30) was found to be twice the thickness of virgin epidermis from the same sites (0.06 +/- 0.02 mm, n = 38, p < 0.001). Thirty-six grafts harvested with dermatomes set to cut 8/1000 inch (0.20 mm) deep ranged from 0.12 to 0.42 mm thick, with only eight of these grafts measuring within +/-10 percent of the desired thickness setting. Before donor dressing separation, Xeroform and Jelonet dressings were judged to be more comfortable by nine patients and one patient, respectively, whereas no difference was detected by six patients. The authors now use Xeroform as the preferred donor dressing. 相似文献
88.
Plio-Pleistocene faunal assemblages from Swartkrans Cave (South Africa) preserve large numbers of primate remains. Brain, C.K., 1981. The Hunters or the Hunted? An Introduction to African Cave Taphonomy. University of Chicago Press, Chicago suggested that these primate subassemblages might have resulted from a focus by carnivores on primate predation and bone accumulation. Brain's hypothesis prompted us to investigate, in a previous study, this taphonomic issue as it relates to density-mediated destruction of primate bones (J. Archaeol. Sci. 29, 2002, 883). Here we extend our investigation of Brain's hypothesis by examining additional intrinsic qualities of baboon bones and their role as mediators of skeletal element representation in carnivore-created assemblages. Using three modern adult baboon skeletons, we collected data on four intrinsic bone qualities (bulk bone mineral density, maximum length, volume, and cross-sectional area) for approximately 81 bones per baboon skeleton. We investigated the relationship between these intrinsic bone qualities and a measure of skeletal part representation (the percentage minimum animal unit) for baboon bones in carnivore refuse and scat assemblages. Refuse assemblages consist of baboon bones not ingested during ten separate experimental feeding episodes in which individual baboon carcasses were fed to individual captive leopards and a spotted hyena. Scat assemblages consist of those baboon bones recovered in carnivore regurgitations and feces resulting from the feeding episodes. In refuse assemblages, volume (i.e., size) was consistently the best predictor of element representation, while cross-sectional area was the poorest predictor in the leopard refuse assemblage and bulk bone mineral density (i.e., a measure of the proportion of cortical to trabecular bone) was the poorest predictor in the hyena refuse assemblage. In light of previous documentation of carnivore-induced density-mediated destruction to bone assemblages, we interpret the current findings as suggestive of the secondary importance of bulk bone mineral density to other intrinsic qualities of skeletal elements (e.g., size, maximum dimension, and average cross-sectional area). It is only when skeletal elements are too large for consumption (e.g., many long bones) that they are fragmented following intra-element patterns of density-mediated carnivore destruction. There appears to be a size threshold beneath which bulk bone mineral density contributes little to mediating carnivore destruction of carcasses. Thus, depending on body size of the predator, body size of the prey, and specific size of the element, bulk bone mineral density may play little or no role of primary importance in mediating the destruction of skeletal elements. We compare patterns in modern comparative assemblages to patterns in primate fossil assemblages from Swartkrans. One of the fossil assemblages, Swartkrans Member 1, Hanging Remnant, most closely approximates a hyena (possibly refuse) assemblage pattern, while the Swartkrans Member 2 assemblage most closely approximates a leopard (possibly scat) assemblage pattern. The Swartkrans Member 1, Lower Bank, assemblage does not closely approximate any of our modern comparative assemblage patterns. 相似文献
89.
90.
Transcriptome analysis of root transporters reveals participation of multiple gene families in the response to cation stress 总被引:31,自引:4,他引:27