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51.
52.
Towers PR Lescure P Baban D Malek JA Duarte J Jones E Davies KE Ségalat L Sattelle DB 《Genomics》2006,88(5):642-649
The Caenorhabditis elegans genome contains a single dystrophin/utrophin orthologue, dys-1. Point mutations in this gene, dys-1(cx35) and dys-1(cx18), result in truncated proteins. Such mutants offer potentially valuable worm models of human Duchenne muscular dystrophy. We have used microarrays to examine genes expressed differentially between wild-type C. elegans and dys-1 mutants. We found 106 genes (115 probe sets) to be differentially expressed when the two mutants are compared to wild-type worms, 49 of which have been assigned to six functional categories. The main categories of regulated genes in C. elegans are genes encoding intracellular signalling, cell-cell communication, cell-surface, and extracellular matrix proteins; genes in these same categories have been shown by others to be differentially expressed in muscle biopsies of muscular dystrophy patients. The C. elegans model may serve as a convenient vehicle for future genetic and chemical screens to search for new drug targets. 相似文献
53.
Schmidt MG Attaway HH Terzieva S Marshall A Steed LL Salzberg D Hamoodi HA Khan JA Feigley CE Michels HT 《Current microbiology》2012,65(2):141-149
Microbial growth in heating ventilation and air-conditioning (HVAC) systems with the subsequent contamination of indoor air is of increasing concern. Microbes and the subsequent biofilms grow easily within heat exchangers. A comparative study where heat exchangers fabricated from antimicrobial copper were evaluated for their ability to limit microbial growth was conducted using a full-scale HVAC system under conditions of normal flow rates using single-pass outside air. Resident bacterial and fungal populations were quantitatively assessed by removing triplicate sets of coupons from each exchanger commencing the fourth week after their installation for the next 30 weeks. The intrinsic biofilm associated with each coupon was extracted and characterized using selective and differential media. The predominant organisms isolated from aluminum exchangers were species of Methylobacterium of which at least three colony morphologies and 11 distinct PFGE patterns we found; of the few bacteria isolated from the copper exchangers, the majority were species of Bacillus. The concentrations and type of bacteria recovered from the control, aluminum, exchangers were found to be dependent on the type of plating media used and were 11,411-47,257 CFU cm(-2) per coupon surface. The concentration of fungi was found to average 378 CFU cm(-2). Significantly lower concentrations of bacteria, 3 CFU cm(-2), and fungi, 1 CFU cm(-2), were recovered from copper exchangers regardless of the plating media used. Commonly used aluminum heat exchangers developed stable, mixed, bacterial/fungal biofilms in excess of 47,000 organisms per cm(2) within 4 weeks of operation, whereas the antimicrobial properties of metallic copper were able to limit the microbial load affiliated with the copper heat exchangers to levels 99.97 % lower during the same time period. 相似文献
54.
Christina M. Payne Jamil Baban Svein J. Horn Paul H. Backe Andrew S. Arvai Bj?rn Dalhus Magnar Bj?r?s Vincent G. H. Eijsink Morten S?rlie Gregg T. Beckham Gustav Vaaje-Kolstad 《The Journal of biological chemistry》2012,287(43):36322-36330
Degradation of recalcitrant polysaccharides in nature is typically accomplished by mixtures of processive and nonprocessive glycoside hydrolases (GHs), which exhibit synergistic activity wherein nonprocessive enzymes provide new sites for productive attachment of processive enzymes. GH processivity is typically attributed to active site geometry, but previous work has demonstrated that processivity can be tuned by point mutations or removal of single loops. To gain additional insights into the differences between processive and nonprocessive enzymes that give rise to their synergistic activities, this study reports the crystal structure of the catalytic domain of the GH family 18 nonprocessive endochitinase, ChiC, from Serratia marcescens. This completes the structural characterization of the co-evolved chitinolytic enzymes from this bacterium and enables structural analysis of their complementary functions. The ChiC catalytic module reveals a shallow substrate-binding cleft that lacks aromatic residues vital for processivity, a calcium-binding site not previously seen in GH18 chitinases, and, importantly, a displaced catalytic acid (Glu-141), suggesting flexibility in the catalytic center. Molecular dynamics simulations of two processive chitinases (ChiA and ChiB), the ChiC catalytic module, and an endochitinase from Lactococcus lactis show that the nonprocessive enzymes have more flexible catalytic machineries and that their bound ligands are more solvated and flexible. These three features, which relate to the more dynamic on-off ligand binding processes associated with nonprocessive action, correlate to experimentally measured differences in processivity of the S. marcescens chitinases. These newly defined hallmarks thus appear to be key dynamic metrics in determining processivity in GH enzymes complementing structural insights. 相似文献
55.
The putative capsule O-acetyltransferase gene wcjE is highly conserved across various Streptococcus pneumoniae serotypes, but the role of the gene in capsule biosynthesis and bacterial fitness remains largely unclear. Isolates expressing pneumococcal serotype 9A arise from precursors expressing wcjE-associated serotype 9V through loss-of-function mutation to wcjE. To define the biosynthetic role of 9V wcjE, we characterized the structure and serological properties of serotype 9V and 9A capsule polysaccharide (PS). NMR data revealed that both 9V and 9A PS are composed of an identical pentasaccharide repeat unit, as reported previously. However, in sharp contrast to previous studies on 9A PS being devoid of any O-acetylation, we identified O-acetylation of α-glucuronic acid and α-glucose in 9A PS. In addition, 9V PS also contained -CH(2) O-acetylation of β-N-acetylmannosamine, a modification that disappeared following in vitro recombinatorial deletion of wcjE. We also show that serotyping sera and monoclonal antibodies specific for 9V and 9A bound capsule PS in an O-acetate-dependent manner. Furthermore, IgG and to a lesser extent IgM from human donors immunized with serotype 9V PS displayed stronger binding to 9V compared with 9A PS. We conclude that serotype 9V wcjE mediates 6-O-acetylation of β-N-acetylmannosamine. This PS modification can be selectively targeted by antibodies in immunized individuals, identifying a potential selective advantage for wcjE inactivation and serotype 9A emergence. 相似文献
56.
Mutations in EDNRB gene have been reported to cause Waardenburg-Shah syndrome (WS4) in humans. We investigated 17 patients
with WS4 for identification of mutations in EDNRB gene using PCR and direct sequencing technique. Four genomic mutations were
detected in four patients; a G to C transversion in codon 335 (S335C) in exon 5 and a transition of T to C in codon (S361L)
in exon 5, a transition of A to G in codon 277 (L277L) in exon 4, a non coding transversion of T to A at −30 nucleotide position
of exon 5. None of these mutations were found in controls. One of the patients harbored two novel mutations (S335C, S361L)
in exon 5 and one in Intronic region (−30exon5 A>G). All of the mutations were homozygous and novel except the mutation observed
in exon 4. In this study, we have identified 3 novel mutations in EDNRB gene associated with WS4 in Pakistani patients. 相似文献
57.
Mohammad ZuberKhalid Mahmood Zia Ijaz Ahmad BhattiTahir Jamil Fazal-ur-RehmanAli Rizwan 《Carbohydrate polymers》2012,87(4):2439-2446
A series of aqueous solutions of poly(vinyl alcohol) of various commercial products were prepared and applied onto the surfaces of cotton and blends of cotton/polyester fabrics. Fourier transform infrared spectrophotometer was used to confirm the molecular structure of the polyvinyl alcohol used. Performance tests such as colorfastness to rubbing (dry and wet) and colorfastness to washing were determined. The controlling variables affecting the performance properties of the finished substrate such as post-treatment with poly(vinyl alcohol) of various commercial trades, concentration and dilutions were studied. Crocking, washing and hue change of the treated dyed and printed fabrics is accompanied by the formation of semi-inter-penetrated network structure due to the presence of the hydroxyl (-OH) groups which make feasible to a number of grafting and physical cross linking reactions of polymer backbone. 相似文献
58.
LF Chin SM Kong HL Seng YL Tiong KE Neo MJ Maah AS Khoo M Ahmad TS Hor HB Lee SL San SM Chye CH Ng 《Journal of biological inorganic chemistry》2012,17(7):1093-1105
Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50?% inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index. 相似文献
59.
60.
Cronin M Akin AR Collins SA Meganck J Kim JB Baban CK Joyce SA van Dam GM Zhang N van Sinderen D O'Sullivan GC Kasahara N Gahan CG Francis KP Tangney M 《PloS one》2012,7(1):e30940
The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation.In this study, the non-pathogenic commensal bacteria E. coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (i.v.) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and μCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations. 相似文献