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81.
Daniela Josa Elaine F.F. da Cunha Teodorico C. Ramalho Thais C.S. Souza Melissa S. Caetano 《Journal of biomolecular structure & dynamics》2013,31(4):373-376
Abstract Rifamicyns (Rifs) are antibiotic widely used for the treatment of tuberculosis (TB); nevertheless, their efficacy has been limited by a high percentage of mutations, principally in the rpoB gene. In this work, the first three-dimensional molecular model of the hypothetical structures for the wild-type and D516V and H526L mutants of Mycobacterium tuberculosis (mtRNAP) were elucidated by a homology modeling method. In addition, the orientations and binding affinities of some Rifs with those new structures were investigated. Our findings could be helpful for the design of new more potent rifamycin analogs. 相似文献
82.
Elaine F. F. da Cunha Edilaine F. Barbosa Aline A. Oliveira Teodorico C. Ramalho 《Journal of biomolecular structure & dynamics》2013,31(5):619-625
Abstract Mycobacterium tuberculosis (Mt) is a leading cause of infectious disease in the world today. This outlook is aggravated by a growing number of Mt infections in individuals who are immunocompromised as a result of HIV infections. Thus, new and more potent anti-tuberculosis agents are necessary. Therefore, DNA gyrase was selected as a target enzyme to combat Mt. In this work, the first three-dimensional molecular model of the hypothetical structures for the Mycobacterium tuberculosis DNA gyrase (mtDNAg) was elucidated by a homology modeling method. In addition, the orientations and binding affinities of some gatifloxacin analogs with those new structures were investigated. Our findings could be helpful for the design of new more potent gatifloxacin analogs. 相似文献
83.
84.
Mark E. Lauer Tibor T. Glant Katalin Mikecz Paul L. DeAngelis F. Michael Haller M. Elaine Husni Vincent C. Hascall Anthony Calabro 《The Journal of biological chemistry》2013,288(1):205-214
The covalent transfer of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC donor. In the present study, we show that transfer of HCs to low molecular weight HA oligosaccharides is an irreversible event where subsequent shuffling does not occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can serve as HC acceptors, but are unable to function as HC donors. We show that the HC-HA complex is present in the synovial fluid of mice subjected to systemic and monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA matrices from the inflamed joint to their normal state, unmodified with HCs. This process was also effective for HC-HA in the synovial fluid of human rheumatoid arthritis patients (in vitro). 相似文献
85.
Despina Soteriou Banu Iskender Adam Byron Jonathan D. Humphries Simon Borg-Bartolo Marie-Claire Haddock Melissa A. Baxter David Knight Martin J. Humphries Susan J. Kimber 《The Journal of biological chemistry》2013,288(26):18716-18731
Human embryonic stem cells (hESCs) are pluripotent cells that have indefinite replicative potential and the ability to differentiate into derivatives of all three germ layers. hESCs are conventionally grown on mitotically inactivated mouse embryonic fibroblasts (MEFs) or feeder cells of human origin. In addition, feeder-free culture systems can be used to support hESCs, in which the adhesive substrate plays a key role in the regulation of stem cell self-renewal or differentiation. Extracellular matrix (ECM) components define the microenvironment of the niche for many types of stem cells, but their role in the maintenance of hESCs remains poorly understood. We used a proteomic approach to characterize in detail the composition and interaction networks of ECMs that support the growth of self-renewing hESCs. Whereas many ECM components were produced by supportive and unsupportive MEF and human placental stromal fibroblast feeder cells, some proteins were only expressed in supportive ECM, suggestive of a role in the maintenance of pluripotency. We show that identified candidate molecules can support attachment and self-renewal of hESCs alone (fibrillin-1) or in combination with fibronectin (perlecan, fibulin-2), in the absence of feeder cells. Together, these data highlight the importance of specific ECM interactions in the regulation of hESC phenotype and provide a resource for future studies of hESC self-renewal. 相似文献
86.
Marina Azevêdo Souza Susana Johann Luciana Alves Rodrigues dos Santos Lima Fernanda Fraga Campos Isolda Castro Mendes Heloisa Beraldo Elaine Maria de Souza-Fagundes Patrícia Silva Cisalpino Carlos Augusto Rosa Tania Maria de Almeida Alves Nívea Pereira de Sá Carlos Leomar Zani 《Memórias do Instituto Oswaldo Cruz》2013,108(3):342-351
Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes. 相似文献
87.
John A. Martignetti Lifeng Tian Dong Li Maria Celeste M. Ramirez Olga Camacho-Vanegas Sandra Catalina Camacho Yiran Guo Dina J. Zand Audrey M. Bernstein Sandra K. Masur Cecilia E. Kim Frederick G. Otieno Cuiping Hou Nada Abdel-Magid Ben Tweddale Denise Metry Jean-Christophe Fournet Eniko Papp Elizabeth W. McPherson Carrie Zabel Guy Vaksmann Cyril Morisot Brendan Keating Patrick M. Sleiman Jeffrey A. Cleveland David B. Everman Elaine Zackai Hakon Hakonarson 《American journal of human genetics》2013
88.
Naiara Akizu Nuri?M. Shembesh Tawfeg Ben-Omran Laila Bastaki Asma Al-Tawari Maha?S. Zaki Roshan Koul Emily Spencer Rasim?Ozgur Rosti Eric Scott Elizabeth Nickerson Stacey Gabriel Gilberto da?Gente Jiang Li Matthew?A. Deardorff Laura?K. Conlin Margaret?A. Horton Elaine?H. Zackai Elliott?H. Sherr Joseph?G. Gleeson 《American journal of human genetics》2013,92(3):392-400
The corpus callosum is the principal cerebral commissure connecting the right and left hemispheres. The development of the corpus callosum is under tight genetic control, as demonstrated by abnormalities in its development in more than 1,000 genetic syndromes. We recruited more than 25 families in which members affected with corpus callosum hypoplasia (CCH) lacked syndromic features and had consanguineous parents, suggesting recessive causes. Exome sequence analysis identified C12orf57 mutations at the initiator methionine codon in four different families. C12orf57 is ubiquitously expressed and encodes a poorly annotated 126 amino acid protein of unknown function. This protein is without significant paralogs but has been tightly conserved across evolution. Our data suggest that this conserved gene is required for development of the human corpus callosum. 相似文献
89.
Anita Kulukian Elaine Fuchs 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2013,368(1629)
Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stem cells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis. 相似文献
90.
Bridgett M. vonHoldt John P. Pollinger Dent A. Earl Heidi G. Parker Elaine A. Ostrander Robert K. Wayne 《Mammalian genome》2013,24(1-2):80-88
The ability to detect recent hybridization between dogs and wolves is important for conservation and legal actions, which often require accurate and rapid resolution of ancestry. The availability of a genetic test for dog–wolf hybrids would greatly support federal and legal enforcement efforts, particularly when the individual in question lacks prior ancestry information. We have developed a panel of 100 unlinked ancestry-informative SNP markers that can detect mixed ancestry within up to four generations of dog–wolf hybridization based on simulations of seven genealogical classes constructed following the rules of Mendelian inheritance. We establish 95 % confidence regions around the spatial clustering of each genealogical class using a tertiary plot of allele dosage and heterozygosity. The first- and second-backcrossed-generation hybrids were the most distinct from parental populations, with >90 % correctly assigned to genealogical class. In this article we provide a tool kit with population-level statistical quantification that can detect recent dog–wolf hybridization using a panel of dog–wolf ancestry-informative SNPs with divergent allele frequency distributions. 相似文献