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991.
Thermotoga neapolitana Homotetrameric Xylose Isomerase Is Expressed as a Catalytically Active and Thermostable Dimer in Escherichia coli 总被引:1,自引:0,他引:1 下载免费PDF全文
J. Michael Hess Vladimir Tchernajenko Claire Vieille J. Gregory Zeikus Robert M. Kelly 《Applied microbiology》1998,64(7):2357-2360
The xylA gene from Thermotoga neapolitana 5068 was expressed in Escherichia coli. Gel filtration chromatography showed that the recombinant enzyme was both a homodimer and a homotetramer, with the dimer being the more abundant form. The purified native enzyme, however, has been shown to be exclusively tetrameric. The two enzyme forms had comparable stabilities when they were thermoinactivated at 95°C. Differential scanning calorimetry revealed thermal transitions at 99 and 109.5°C for both forms, with an additional shoulder at 91°C for the tetramer. These results suggest that the association of the subunits into the tetrameric form may have little impact on the stability and biocatalytic properties of the enzyme. 相似文献
992.
993.
Osteoporosis is one of the most prevalent skeletal disorders and has enormous public health consequences due to the morbidity and mortality of the resulting fractures. This article discusses the developmental origins of osteoporosis and outlines some of the modifiable and non-modifiable risk factors in both intrauterine and postnatal life that contribute to the later onset of osteoporosis. Evidence for the effects of birth size and early growth in both preterm and term born infants are discussed and the role of epigenetics within the programming hypothesis is highlighted. This review provides compelling evidence for the developmental origins of osteoporosis and highlights the importance of osteoporosis prevention at all stages of the life course. 相似文献
994.
Altered permeability and modulatory character of connexin channels during mammary gland development 总被引:2,自引:0,他引:2
Locke D Stein T Davies C Morris J Harris AL Evans WH Monaghan P Gusterson B 《Experimental cell research》2004,298(2):643-660
Abrupt developmental changes occur in structural form and function of connexin (Cx) channels in the mouse mammary gland. Microarray study shows that the principal connexin isoform in epithelial cells during pregnancy is Cx26, up-regulated and persisting from the virgin. After parturition, there is rapid induction of Cx32. In epithelial plasma membranes, size exclusion chromatography reveals that Cx32 organizes initially with Cx26 as heteromeric (Cx26-Cx32) hemichannels and later in heteromeric and homomeric Cx32 channels. Dramatic alterations of connexin channel function following these developmental changes in channel composition are characterized using native channels reconstituted into liposomes. Changes to channel stoichiometry increase the allowable physical size limits of permeant after parturition; the new Cx32 channels are wider than channels containing Cx26. Most remarkably, heteromeric Cx26-Cx32 channels are selectively permeability to adenosine 3',5' cyclic phosphate (cAMP), guanosine 3',5' cyclic phosphate (cGMP), and inositol 1,4,5-triphosphate (IP(3)), whereas homomeric channels are not. Homomeric Cx26 and heteromeric channels with high Cx26/Cx32 stoichiometry are also inhibited by taurine, an osmolyte playing a key role in milk protein synthesis. Taurine effect is reduced where heteromeric channels contain Cx32 > Cx26 and eliminated when channels contain only Cx32. Connexin channel stoichiometry, permeability, and chemical gating character change in precisely the desired fashion after parturition to maximize molecular and electrical coupling to support coordinated milk secretion. 相似文献
995.
Faraz M. Alam Colin Bateman Claire E. Turner Siouxsie Wiles Shiranee Sriskandan 《PloS one》2013,8(11)
Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 105 bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines. 相似文献
996.
Child DF Hudson PR Hunter-Lavin C Mukhergee S China S Williams CP Williams JH 《Cell stress & chaperones》2006,11(1):101-105
Abstract It has been suggested that induction of the heat shock response in the mammalian embryo during the critical period of organogenesis can result in anatomical malformation. We measured serum heat shock protein 70 (Hsp70), anti-Hsp70, and anti-Hsp60 in samples taken from expectant mothers at 16 weeks gestation. Samples from women whose babies were born with a birth defect (n = 30) were compared with controls who gave birth to healthy babies (n = 46). Anti-Hsp70 levels were significantly elevated in patients who later gave birth to babies with cleft lip or palate or neurological abnormalities (n = 10): 260 (223-406) microg/mL compared to 150 (88-207) microg/mL in controls (P < 0.001). No significant differences were found in serum Hsp70 and anti-Hsp60 levels between cases and controls. This finding of increased maternal anti-Hsp70 in patients who later gave birth to babies with these abnormalities suggests a previous stressful event may have contributed to the pathogenesis. Further work is required to determine whether Hsp70 has a direct or indirect role in this pathogenesis or whether anti-Hsp70 is simply a marker of a prior increase in Hsp70 due to a physiological stress that itself resulted in the damage. This work is consistent with previous studies showing a buffering role for Hsps in evolution. 相似文献
997.
Vincent Battesti Muriel Gros-Balthazard Clémence Ogéron Sarah Ivorra Jean-Frédéric Terral Claire Newton 《Human ecology: an interdisciplinary journal》2018,46(4):529-546
We evaluate date palm (Phoenix dactylifera L.) agrobiodiversity of Siwa oasis, Egypt, located at the crossroads of ancient Trans-Saharan routes, focusing on diversity both as expressed and maintained by the folk categorization system of Siwa inhabitants (through an ethnographic analysis) and as described by genetic sciences and a morphometric tool based on size and geometry of seeds. We verified that some named types are true cultivars, sharing not only a formal identity, important for Isiwan people, but also a genetic identity. However, we also confirm the existence of “ethnovarieties,” i.e., voluntary collections of multiple clones sharing phenotypic characteristics with the same local name, suggesting the genetic richness is higher than the apparent agrobiodiversity estimated by a superficial ethnobotanical approach. Finally, our research offers new insights on the relative importance of feral and cultivated date palms. 相似文献
998.
Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping 总被引:1,自引:0,他引:1
Richardson CM Nunns CL Williamson DS Parratt MJ Dokurno P Howes R Borgognoni J Drysdale MJ Finch H Hubbard RE Jackson PS Kierstan P Lentzen G Moore JD Murray JB Simmonite H Surgenor AE Torrance CJ 《Bioorganic & medicinal chemistry letters》2007,17(14):3880-3885
Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode. 相似文献
999.
Menear KA Adcock C Alonso FC Blackburn K Copsey L Drzewiecki J Fundo A Le Gall A Gomez S Javaid H Lence CF Martin NM Mydlowski C Smith GC 《Bioorganic & medicinal chemistry letters》2008,18(14):3942-3945
We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors. 相似文献
1000.
Robin Faillettaz Agathe Blandin Claire B. Paris Philippe Koubbi Jean-Olivier Irisson 《PloS one》2015,10(8)
Mortality is very high during the pelagic larval phase of fishes but the factors that determine recruitment success remain unclear and hard to predict. Because of their bipartite life history, larvae of coastal species have to head back to the shore at the end of their pelagic episode, to settle. These settlement-stage larvae are known to display strong sensory and motile abilities, but most work has been focused on tropical, insular environments and on the influence of coast-related cues on orientation. In this study we quantified the in situ orientation behavior of settlement-stage larvae in a temperate region, with a continuous coast and a dominant along-shore current, and inspected both coast-dependent and independent cues. We tested six species: one Pomacentridae, Chromis chromis, and five Sparidae, Boops boops, Diplodus annularis, Oblada melanura, Spicara smaris and Spondyliosoma cantharus. Over 85% of larvae were highly capable of keeping a bearing, which is comparable to the orientation abilities of tropical species. Sun-related cues influenced the precision of bearing-keeping at individual level. Three species, out of the four tested in sufficient numbers, oriented significantly relative to the sun position. These are the first in situ observations demonstrating the use of a sun compass for orientation by wild-caught settlement-stage larvae. This mechanism has potential for large-scale orientation of fish larvae globally. 相似文献