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51.
Quantitative trait loci for susceptibility to tapeworm infection in the red flour beetle 总被引:2,自引:0,他引:2
Parasites have profound effects on host ecology and evolution, and the effects of parasites on host ecology are often influenced by the magnitude of host susceptibility to parasites. Many parasites have complex life cycles that require intermediate hosts for their transmission, but little is known about the genetic basis of the intermediate host's susceptibility to these parasites. This study examined the genetic basis of susceptibility to a tapeworm (Hymenolepis diminuta) in the red flour beetle (Tribolium castaneum) that serves as an intermediate host in its transmission. Quantitative trait loci (QTL) mapping experiments were conducted with two independent segregating populations using amplified fragment length polymorphism (AFLP) markers and randomly amplified polymorphic DNA (RAPD) markers. A total of five QTL that significantly affected beetle susceptibility were identified in the two reciprocal crosses. Two common QTL on linkage groups 3 and 6 were identified in both crosses with similar effects on the phenotype, and three QTL were unique to each cross. In one cross, the three main QTL accounted for 29% of the total phenotypic variance and digenic epistasis explained 39% of the variance. In the second cross, the four main QTL explained 62% of the variance and digenic epistasis accounted for only 5% of the variance. The actions of these QTL were either overdominance or underdominance. Our results suggest that the polygenic nature of beetle susceptibility to the parasites and epistasis are important genetic mechanisms for the maintenance of variation within or among beetle strains in susceptibility to tapeworm infection. 相似文献
52.
Sidjanin DJ Miller B Kijas J McElwee J Pillardy J Malek J Pai G Feldblyum T Fraser C Acland G Aguirre G 《Genomics》2003,81(2):138-148
53.
54.
D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis 总被引:3,自引:0,他引:3
During Drosophila oogenesis, asymmetrically localized Gurken activates the EGF receptor (Egfr) and determines dorsal follicle cell fates. Using a mosaic follicle cell system we have identified a mutation in the D-cbl gene which causes hyperactivation of the Egfr pathway. Cbl proteins are known to downregulate activated receptors. We find that the abnormal Egfr activation is ligand dependent. Our results show that the precise regulation of Egfr activity necessary to establish different follicle cell fates requires two levels of control. The localized ligand Gurken activates Egfr to different levels in different follicle cells. In addition, Egfr activity has to be repressed through the activity of D-cbl to ensure the absence of signaling in the ventral most follicle cells. 相似文献
55.
Penicillopepsin-JT2, a recombinant enzyme from Penicillium janthinellum and the contribution of a hydrogen bond in subsite S3 to k(cat) 下载免费PDF全文
Cao QN Stubbs M Ngo KQ Ward M Cunningham A Pai EF Tu GC Hofmann T 《Protein science : a publication of the Protein Society》2000,9(5):991-1001
The nucleotide sequence of the gene (pepA) of a zymogen of an aspartic proteinase from Penicillium janthinellum with a 71% identity in the deduced amino acid sequence to penicillopepsin (which we propose to call penicillopepsin-JT1) has been determined. The gene consists of 60 codons for a putative leader sequence of 20 amino acid residues, a sequence of about 150 nucleotides that probably codes for an activation peptide and a sequence with two introns that codes for the active aspartic proteinase. This gene, inserted into the expression vector pGPT-pyrG1, was expressed in an aspartic proteinase-free strain of Aspergillus niger var. awamori in high yield as a glycosylated form of the active enzyme that we call penicillopepsin-JT2. After removal of the carbohydrate component with endoglycosidase H, its relative molecular mass is between 33,700 and 34,000. Its kinetic properties, especially the rate-enhancing effects of the presence of alanine residues in positions P3 and P2' of substrates, are similar to those of penicillopepsin-JT1, endothiapepsin, rhizopuspepsin, and pig pepsin. Earlier findings suggested that this rate-enhancing effect was due to a hydrogen bond between the -NH- of P3 and the hydrogen bond accepting oxygen of the side chain of the fourth amino acid residue C-terminal to Asp215. Thr219 of penicillopepsin-JT2 was mutated to Ser, Val, Gly, and Ala. Thr219Ser showed an increase in k(cat) when a P3 residue was present in the substrate, which was similar to that of the wild-type, whereas the mutants Thr219Val, Thr219Gly, and Thr219Ala showed no significant increase when a P3 residue was added. The results show that the putative hydrogen bond alone is responsible for the increase. We propose that by locking the -NH- of P3 to the enzyme, the scissile peptide bond between P1 and P1' becomes distorted toward a tetrahedral conformation and becomes more susceptible to nucleophilic attack by the catalytic apparatus without the need of a conformational change in the enzyme. 相似文献
56.
Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. The RNA genome of HDV encodes two proteins, the small delta antigen and the large delta antigen, which differ only with the latter having an additional 19 amino acids at the C-terminus. Previously, we have shown that dAg24-50, a synthetic peptide corresponding to residues 24-50 of the N-terminal leucine-repeat region of hepatitis delta antigen, binds to the viral RNA and forms an alpha-helical conformation in TFE-containing solution. However, it exhibited low alpha-helicity (less than 5%) in the absence of TFE. In order to obtain biologically active delta antigen peptides with higher structural stability in solution, an N-capping 21-residue polypeptide corresponding to residues 24-38 of hepatitis delta antigen (dAg(Cap24-38am)) was synthesized and, surprisingly, its solution structure was found to be a stable alpha-helix (64%) by circular dichroism and 1H NMR techniques. Moreover, the structure of the capping box shows the characteristic L-shaped bend perpendicular to the helix axis. This structural knowledge provides a molecular basis for understanding the role of the N-terminal leucine-repeat region of hepatitis delta antigen and has a significant potential for the development of diagnostic and therapeutic methods for HDV. 相似文献
57.
Hui Chen Pai Sunil Kumar Chien-Chang Shen Jing Ping Liou Shiow Lin Pan Che Ming Teng 《PloS one》2015,10(4)
Objective
In this study, the anticancer mechanisms of MT-4 were examined in A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines.Methods
To evaluate the activity of MT-4, we performed in vitro cell viability and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin polymerization was determined using a tubulin binding assay.Results
MT-4 (2-Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M arrest followed by caspase-mediated apoptosis. Further studies indicated that MT-4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In addition, we found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. Treatment of cells with SB203580 or overexpression of dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT-4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI-ADR/res cell growth in vitro and in vivo.Conclusion
These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer. 相似文献58.
While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant. In this study, we examine the extent of alternative splicing in human cells using deep RNA sequencing and de novo identification of splice junctions. We demonstrate the existence of a large class of low abundance isoforms, encompassing approximately 150,000 previously unannotated splice junctions in our data. Newly-identified splice sites show little evidence of evolutionary conservation, suggesting that the majority are due to erroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites. We estimate that the average intron has a splicing error rate of approximately 0.7% and show that introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisy splicing as an important property of genome evolution. 相似文献
59.
Magnesium translocation across cell membranes is essential for numerous physiological processes. Three recently reported crystal structures of the CorA magnesium transport system revealed a surprising architecture, with a bundle of giant α-helices forming a 60-Å-long pore that extends beyond the membrane before widening into a funnel-shaped cytosolic domain. The presence of divalent cations in putative intracellular regulation sites suggests that these structures correspond to the closed conformation of CorA. To examine the nature of the conduction pathway, we performed 110-ns molecular-dynamics simulations of two of these structures in a lipid bilayer with and without regulatory ions. The results show that a 15-Å-long hydrophobic constriction straddling the membrane-cytosol interface constitutes a steric bottleneck whose location coincides with an electrostatic barrier opposing cation translocation. In one of the simulations, structural relaxation after the removal of regulatory ions led to concerted changes in the tilt of the pore helices, resulting in iris-like dilation and spontaneous hydration of the hydrophobic neck. This simple and robust mechanism is consistent with the regulation of pore opening by intracellular magnesium concentration, and explains the unusual architecture of CorA. 相似文献
60.
Enhanced G2 chromatid radiosensitivity in dyskeratosis congenita fibroblasts. 总被引:2,自引:0,他引:2 下载免费PDF全文
Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Although excessive spontaneous chromatid breakage has been reported in DC, it is not a consistent cytological marker for this disorder. We examined the frequency and specificity of X-irradiation-induced G2 chromatid breakage in fibroblasts from three unrelated DC patients (two males and one female). Metaphase cells from DC patients had significantly more chromatid breaks (16-18-fold and 17-26-fold at 50 and 100 rad X-irradiation, respectively) and chromatid gaps (10-12-fold and 6-7-fold at 50 and 100 rad, respectively) than those from two different controls. Analysis of banded chromosomes revealed a nonrandom distribution of chromatid aberrations in DC but not in controls, a distribution corresponding to some of the known breakpoints for cancer-specific rearrangements, constitutive fragile sites, and/or loci for cellular proto-oncogenes. The significance of this finding for cancer predisposition in DC patients is uncertain, but the increased susceptibility of X-irradiation-induced chromatid breakage may serve as a cellular marker of diagnostic value. 相似文献