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101.
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Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (β3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals’ fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming β3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that β3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for β3GalT6 in multiple major developmental and pathophysiological processes.  相似文献   
103.
Protein misfolding, self-assembly, and aggregation are an essential problem in cell biology, biotechnology, and biomedicine. The protein aggregates are very different morphologically varying from soluble amorphous aggregates to highly ordered amyloid-like fibrils. The objective of this study was to elucidate the role of the amino acid l-arginine (Arg), a widely used suppressor of protein aggregation, in the regulation of transformations of soluble aggregation-prone proteins into supramolecular structures of higher order. However, a striking potential of Arg to govern the initial events in the process of protein aggregation has been revealed under environment conditions where the protein aggregation in its absence was not observed. Using dynamic light scattering we have demonstrated that Arg (10–100 mM) dramatically accelerated the dithiothreitol-induced aggregation of acidic model proteins. The inhibitory effect on the protein aggregation was revealed at higher concentrations of Arg. Using atomic force microscopy it was shown that aggregation of α-lactalbumin from bovine milk induced upon addition of Arg reached a state of formation of supramolecular structures of non-fibrillar species profoundly differing from those of the individual protein in type, size, and shape. The interaction of another positively charged amino acid l-lysine with α-lactalbumin also resulted in profound acceleration of the aggregation process and transformation of supramolecular structures of the aggregates.  相似文献   
104.

This study proposed to investigate the effect of azurin on the major stages of pathogenesis (adhesion and invasion) of intestinal bacterial pathogens (Salmonella spp. and Escherichia coli) and epithelial pathogens (Staphylococcus aureus and Pseudomonas aeruginosa) on the human colorectal adenocarcinoma (Caco-2) cell line. Azurin protein was produced by cloning the azurin gene into pET21a and heterologous expression in E. coli BL21. The protein was purified using affinity chromatography and confirmed by Western blotting. The purified protein was evaluated by three experiments of adhesion and invasion assays, including exclusion, competition, and replacement. Azurin was observed to significantly inhibit the attachment and invasion of S. aureus, Salmonella spp., and E. coli, while no such inhibitory effects were observed on P. aeruginosa. In fact, the protein increased the adhesion of P. aeruginosa to the cell. In conclusion, our study proposes that azurin is a potential prophylactic or preventive helper candidate to inhibit the attachment and invasion of pathogenic bacteria to host cells and reduce the progression of the infection process. Our study also reveals the involvement of azurin in bacteria-host cell interactions, providing novel and important insights toward the elucidation of its biological function in this field. Thus, this study provides new opportunities to use azurin as an adjunct therapy against critical stages of infection by a wide range of pathogenic bacteria.

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In 1998–2000 a monitoring of the spectrum of Fusarium species on winter wheat was carried out in the Rhineland. The epidemic spread ofFusarium spp. on wheat plants during growing season was investigated as well as the grain contamination after harvest.F avenaceum was the Fusarium species isolated most frequently followed byF culmorum, F poae andF graminearum. Microdochium nivale occurred considerably only in 1998. Both, susceptibility and plant height of the cultivars were correlated to the incidence of Fusarium species /M nivale on harvested kernels; interactions with cropping intensities were detected. The incidence ofF poae seemed to be independent of the cultivar-specific Fusarium susceptibility. Despite the lack of disease symptoms, between growth stages 45–85 mycelium ofFusarium spp. was detectable in the leaves as well as conidia on the leaf surfaces.  相似文献   
107.
The inoculation of wheat ears with 27 isolates ofFusarium culmorum in growth stage 65 reduced 1000-grain weights by 14 to 61%. For the phytopathological characterisation of isolates the virulence on primary wheat leaves and the growth rate an potato-dextrose-agar were assessed. Deoxynivalenol-producing isolates ofF. culmorum reduced the 1000-grain weight more than nivalenol-producing isolates.  相似文献   
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OBJECTIVE: To evaluate the specificity and sensitivity of brush cytology and biopsy in colorectal malignancies. STUDY DESIGN: The study was performed over 3 years, 1998-2000. Seventy-six patients with any colorectal lesion on colonoscopy were selected, and in all of them brush cytology and biopsy were done at the same time. The cytologic smears and biopsies were reviewed separately. The cytologic smears were categorized as negative, suspicious, suggestive or positive for malignancy. The results of cytology and biopsy were compared based on sensitivity and specificity. The gold standard for positive cases was the tissue specimen after surgery; negative cases were followed for at least 1 year. Cases with 1 year of disease-free survival were considered negative. RESULTS: Among 76 cases, 4 were excluded because of unsatisfactory cytologic smears. Of the remaining 72 cases, 31 were male and 41 female. The age range was 19-80 years. Cytology showed 23 positive and 49 negative cases (1 false positive and 3 false negative). Biopsy showed 24 positive and 48 negative cases (no false positives and 1 false negative). There were 47 negative cases, followed for at least 1 year, and after that we considered them definitively negative for malignancy. Sensitivity of cytology and biopsy was 88% and 96%; specificity was 98% and 100%, respectively. Combined use of brush cytology and biopsy had the highest sensitivity, 100%. CONCLUSION: Brush cytology of the colon is a safe, fast and reliable method for the diagnosis of colorectal cancer. We recommend performing it in conjunction with biopsy. It is also reasonable to perform a repeat biopsy in patients with negative biopsy and positive cytology for a definitive diagnosis.  相似文献   
110.

Background  

The availability of interaction databases provides an opportunity for researchers to utilize immense amounts of data exclusively in silico. Recently there has been an emphasis on studying the global properties of biological interactions using network analysis. While this type of analysis offers a wide variety of global insights it has surprisingly not been used to examine more localized interactions based on mechanism. In as such we have particular interest in the role of key topological components in signal transduction cascades as they are vital regulators of healthy and diseased cell states.  相似文献   
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