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91.
Nelson JF da Silveira Helen A Arcuri Carlos E Bonalumi Fátima P de Souza Isabel MVGC Mello Paula Rahal Jo?o RR Pinho Walter F de Azevedo 《BMC structural biology》2005,5(1):1
Background
Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. 相似文献92.
Thomas R. Pisanic II Pornpat Athamanolap Weijie Poh Chen Chen Alicia Hulbert Malcolm V. Brock James G. Herman Tza-Huei Wang 《Nucleic acids research》2015,43(22):e154
Many cancers comprise heterogeneous populations of cells at primary and metastatic sites throughout the body. The presence or emergence of distinct subclones with drug-resistant genetic and epigenetic phenotypes within these populations can greatly complicate therapeutic intervention. Liquid biopsies of peripheral blood from cancer patients have been suggested as an ideal means of sampling intratumor genetic and epigenetic heterogeneity for diagnostics, monitoring and therapeutic guidance. However, current molecular diagnostic and sequencing methods are not well suited to the routine assessment of epigenetic heterogeneity in difficult samples such as liquid biopsies that contain intrinsically low fractional concentrations of circulating tumor DNA (ctDNA) and rare epigenetic subclonal populations. Here we report an alternative approach, deemed DREAMing (Discrimination of Rare EpiAlleles by Melt), which uses semi-limiting dilution and precise melt curve analysis to distinguish and enumerate individual copies of epiallelic species at single-CpG-site resolution in fractions as low as 0.005%, providing facile and inexpensive ultrasensitive assessment of locus-specific epigenetic heterogeneity directly from liquid biopsies. The technique is demonstrated here for the evaluation of epigenetic heterogeneity at p14ARF and BRCA1 gene-promoter loci in liquid biopsies obtained from patients in association with non-small cell lung cancer (NSCLC) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively. 相似文献
93.
D. E. Delaney S. Nasuda T. R. Endo B. S. Gill S. H. Hulbert 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1995,91(5):780-782
Cytologically based physical maps for the group 3 chromosomes of wheat were constructed by mapping 25 Triticum aestivum deletion lines with 29 T. tauschii and T. aestivum RFLP probes. The deletion lines divide chromosomes 3A, 3B, and 3D into 31 discrete intervals, of which 18 were tagged by marker loci. The comparison of the consensus physical map with a consensus RFLP linkage map of the group 3 chromosomes of wheat revealed a fairly even distribution of marker loci on the long arm, and higher recombination in the distal region. 相似文献
94.
WT Ismaya A Efthyani DS Retnoningrum X Lai BW Dijkstra RR Tjandrawinata 《Biotechnic & histochemistry》2017,92(6):411-416
The light subunit of mushroom, Agaricus bisporus, tyrosinase (LSMT), has been identified as an extrinsic component of the enzyme. Its function is unknown, but it can cross an epithelial cell layer, which suggests that it can be absorbed by the intestine. A similar capability has been demonstrated for the HA-33 component of the progenitor toxin from Clostridium botulinum, which is the closest structural homolog of LSMT. Unlike HA-33, LSMT appears to be non-immunogenic as shown by preliminary tests in Swiss Webster mice. We investigated the immunogenicity and histopathology of LSMT in mice to determine its safety in vivo. LSMT did not evoke generation of antibodies after prolonged periods of intraperitoneal administration. Histopathological observations confirmed the absence of responses in organs after twelve weekly administrations of LSMT. We found that LSMT is not toxic and is less immunogenic than the C. botulinum HA-33 protein, which supports further research and development for pharmaceutical application. 相似文献
95.
MG Mullender NA Blom M De Kleuver JM Fock WMGC Hitters AMC Horemans CJ Kalkman JEH Pruijs RR Timmer PJ Titarsolej NC Van Haasteren Tol-de MJ Van Jager AJ Van Vught BJ Van Royen 《Scoliosis》2008,3(1):1-14
Background
Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.Methods
The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.Results
For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.Conclusion
In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders. 相似文献96.
Turner N Hulbert AJ Else PL 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2005,175(2):77-85
Previous research has shown that the lower sodium pump molecular activity observed in tissues of ectotherms compared to endotherms, is largely related to the lower levels of polyunsaturates and higher levels of monounsaturates found in the cell membranes of ectotherms. Marine-based ectotherms, however, have very polyunsaturated membranes, and in the current study, we measured molecular activity and membrane lipid composition in tissues of two disparate ectothermic species, the octopus (Octopus vulgaris) and the bearded dragon lizard (Pogona vitticeps), to determine whether the high level of membrane polyunsaturation generally observed in marine-based ectotherms is associated with an increased sodium pump molecular activity relative to other ectotherms. Phospholipids from all tissues of the octopus were highly polyunsaturated and contained high concentrations of the omega-3 polyunsaturate, docosahexaenoic acid (22:6 (n–3)). In contrast, phospholipids from bearded dragon tissues contained higher proportions of monounsaturates and lower proportions of polyunsaturates. Sodium pump molecular activity was only moderately elevated in tissues of the octopus compared to the bearded dragon, despite the much greater level of polyunsaturation in octopus membranes. When the current data were combined with data for the ectothermic cane toad, a significant (P=0.003) correlation was observed between sodium pump molecular activity and the content of 22:6 (n–3) in the surrounding membrane. These results are discussed in relation to recent work which shows a similar relationship in endotherms. 相似文献
97.
In maize, the Rp3 gene confers resistance to common rust caused by Puccinia sorghi. Flanking marker analysis of rust-susceptible rp3 variants suggested that most of them arose via unequal crossing over, indicating that rp3 is a complex locus like rp1. The PIC13 probe identifies a nucleotide binding site-leucine-rich repeat (NBS-LRR) gene family that maps to the complex. Rp3 variants show losses of PIC13 family members relative to the resistant parents when probed with PIC13, indicating that the Rp3 gene is a member of this family. Gel blots and sequence analysis suggest that at least 9 family members are at the locus in most Rp3-carrying lines and that at least 5 of these are transcribed in the Rp3-A haplotype. The coding regions of 14 family members, isolated from three different Rp3-carrying haplotypes, had DNA sequence identities from 93 to 99%. Partial sequencing of clones of a BAC contig spanning the rp3 locus in the maize inbred line B73 identified five different PIC13 paralogues in a region of approximately 140 kb. 相似文献
98.
Satellite-linked radio telemetry was used to study the geographic movements and vertical movement behaviour of the Pacific sleeper shark Somniosus pacificus . The fish were tagged near Steller sea lion Eumetopias jubatus rookeries in the Gulf of Alaska during periods when Steller sea lions pups were most vulnerable to predation; when Steller sea lion pups first enter the water (July to August) and when Steller sea lion pups are weaned (April to May). Final locations recovered from most Pacific sleeper sharks (76%) were within 100 km of release locations, 16% were within 100–250 km and 8% were within 250–500 km. The most striking behavioural feature was their extensive, nearly continuous vertical movements. Median daily depth range was 184 m; the most time (61%) was spent between 150 and 450 m, but ascents above 100 m were common (58% of days). Median vertical movement rate was 6 km day−1 and steady. The longest period of continuous vertical movement (> 60 m h−1 ) was 330 h. Systematic vertical oscillations were most common (60%), followed by diel vertical migrations (25%) and irregular vertical movements (15%). The Pacific sleeper sharks travelled below the photic zone during the day and approached the surface at night. Pacific sleeper sharks appear to employ a stealth and ambush hunting strategy that incorporates slow vertical oscillations to search for prey, and cryptic colouration and cover of darkness to avoid detection by potential prey. The depth and geographic range of Pacific sleeper shark and Steller sea lions overlap near four important Steller sea lion rookeries in the northern Gulf of Alaska, so the potential exists for predation to occur. None of the tissues in the stomachs of the 198 Pacific sleeper sharks collected during a companion diet study, however, were identified as Steller sea lion. 相似文献
99.
Genomic mapping of defense response genes in wheat 总被引:12,自引:2,他引:10
W. L. Li J. D. Faris J. M. Chittoor J. E. Leach S. H. Hulbert D. J. Liu P. D. Chen B. S. Gill 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(2):226-233
Defense response (DR) genes are a broad class involved in plant defense. In this study we mapped 36 probes representing seven
classes of defense response genes. This collection of probes represents genes involved in the hypersensitive response (HR),
pathogenesis-related (PR) genes, genes for the flavonoid metabolic pathway, genes encoding proline/glycine-rich proteins,
ion channel regulators, lipoxygenase, lectin, and others. Using nullisomic-tetrasomic lines of ‘Chinese Spring’, we were able
to assign at least 167 loci to the 21 chromosomes of wheat. Homoeologous group 7 chromosomes possessed the most DR loci followed
by group 2. Sixty-two loci were placed on existing genetic linkage maps of wheat. Map locations indicated that the DR gene
loci are not randomly distributed throughout the wheat genome, but rather are located in clusters and/or in distal gene-rich
regions of the chromosomes. Knowledge of the chromosomal locations and genome organization of DR genes will be useful for
candidate gene analysis of quantitative trait loci.
Received: 12 June 1998 / Accepted: 24 July 1998 相似文献
100.
Turner N Haga KL Hulbert AJ Else PL 《American journal of physiology. Regulatory, integrative and comparative physiology》2005,288(1):R301-R310
We investigated the relationship between body size, Na(+)-K(+)-ATPase molecular activity, and membrane lipid composition in the kidney of five mammalian and eight avian species ranging from 30-g mice to 280-kg cattle and 13-g zebra finches to 35-kg emus, respectively. Na(+)-K(+)-ATPase activity was found to be higher in the smaller species of both groups. In small mammals, the higher Na(+)-K(+)-ATPase activity was primarily the result of an increase in the molecular activity (turnover rate) of individual enzymes, whereas in small birds the higher Na(+)-K(+)-ATPase activity was the result of an increased enzyme concentration. Phospholipids from both mammals and birds contained a relatively constant percentage of unsaturated fatty acids; however, phospholipids from the smaller species were generally more polyunsaturated, and a complementary significant allometric increase in monounsaturate content was observed in the larger species. In particular, the relative content of the highly polyunsaturated docosahexaenoic acid [22:6(n-3)] displayed the greatest variation with body mass, scaling with allometric exponents of -0.21 and -0.26 in the mammals and birds, respectively. This allometric variation in fatty acid composition was correlated with Na(+)-K(+)-ATPase molecular activity in mammals, whereas in birds molecular activity only correlated with membrane cholesterol content. These relationships are discussed with respect to the metabolic intensity of different-sized animals. 相似文献