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51.
Hannah T Baddock Sanja Brolih Yuliana Yosaatmadja Malitha Ratnaweera Marcin Bielinski Lonnie
P Swift Abimael Cruz-Migoni Haitian Fan Jeremy R Keown Alexander P Walker Garrett
M Morris Jonathan
M Grimes Ervin Fodor Christopher
J Schofield Opher Gileadi Peter
J McHugh 《Nucleic acids research》2022,50(3):1484
The SARS-CoV-2 coronavirus is the causal agent of the current global pandemic. SARS-CoV-2 belongs to an order, Nidovirales, with very large RNA genomes. It is proposed that the fidelity of coronavirus (CoV) genome replication is aided by an RNA nuclease complex, comprising the non-structural proteins 14 and 10 (nsp14–nsp10), an attractive target for antiviral inhibition. Our results validate reports that the SARS-CoV-2 nsp14–nsp10 complex has RNase activity. Detailed functional characterization reveals nsp14–nsp10 is a versatile nuclease capable of digesting a wide variety of RNA structures, including those with a blocked 3′-terminus. Consistent with a role in maintaining viral genome integrity during replication, we find that nsp14–nsp10 activity is enhanced by the viral RNA-dependent RNA polymerase complex (RdRp) consisting of nsp12–nsp7–nsp8 (nsp12–7–8) and demonstrate that this stimulation is mediated by nsp8. We propose that the role of nsp14–nsp10 in maintaining replication fidelity goes beyond classical proofreading by purging the nascent replicating RNA strand of a range of potentially replication-terminating aberrations. Using our developed assays, we identify drug and drug-like molecules that inhibit nsp14–nsp10, including the known SARS-CoV-2 major protease (Mpro) inhibitor ebselen and the HIV integrase inhibitor raltegravir, revealing the potential for multifunctional inhibitors in COVID-19 treatment. 相似文献
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Dubin G Popowicz G Krajewski M Potempa J Dubin A Holak TA 《Journal of biomolecular NMR》2004,28(3):295-296
The increasing antibiotic resistance of an important human pathogen Staphylococcus aureus calls for the development of new therapeutic strategies. Staphylococcal cysteine proteases have been suggested as targets for such therapies. The recent discovery of staphostatins, specific protein inhibitors of these enzymes, gives prospects for the design and production of synthetic, low molecular weight analogs which might become drugs. We have decided to structurally characterize staphostatin A, a representative inhibitor of staphylococcal cysteine proteases, and to assess its binding mode to the target protease with the view of clarifying the specificity determinants. Here we report the (1)H, (15)N and (13)C NMR resonance assignments of staphostatin A. 相似文献
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55.
A number of in planta transformation protocols that avoid long culture under sterile conditions were developed for Arabidopsis thaliana. The most widely used methods are based on vacuum infiltration and floral dip. These methods were adapted for transformation
of other species as well. Successful in planta transformations of alfalfa, radish, pakchoi and petunia were reported recently. In this short review we present several modified
procedures originally developed for Arabidopsis thaliana and in some cases adapted to other species. We emphasize the crucial parameters involved in in planta transformation. We also describe here the studies attempting to shed light on the mechanisms and estimating the cellular
target of transformation, which may help in transforming new plant species. 相似文献
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Lewczuk B Nowicki M Prusik M Przybylska-Gornowicz B 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2004,42(3):155-163
The study was conducted to investigate diurnal changes in pinealocyte ultrastructure, pineal serotonin content and plasma melatonin concentration in the domestic pig. The immature pigs (n=24) were kept under a cycle of 12 h light : 12 h dark, with a photophase between 0800 and 2000. During the photophase the animals were exposed to direct sunlight. After four weeks the gilts were slaughtered at 0900, 1400, 2100 and 0200. The pineals were removed and divided into two parts - one for quantitative ultrastructural study (by a point count method) and one for serotonin assay. Simultaneously, blood samples were taken for melatonin assay. The relative volume of mitochondria in pinealocyte perikarya was significantly higher at 1400 than at 0200 and 0900 as well as at 2100 than at 0200. The relative volume of Golgi apparatus was higher at 0900 and 1400 than at 0200. The relative volume of dense bodies of the MBB-1 type in pinealocyte perikarya was significantly lower at 1400 and 2100 than at 0900. In contrast, the relative volume of MBB-2 was higher at 1400 than at 0900 and 0200. The numerical density of DCV in perikarya was significantly higher at 0200 than at 1400. No significant differences were found in rough endoplasmic reticulum, lysosomes and multivesicular bodies. The pineal serotonin content showed a prominent rhythm with the maximum at 1400. The plasma melatonin concentration was significantly higher at 0200 than at 0900, 1400 and 2100. The obtained results demonstrate that both pinealocyte ultrastructure and pineal biochemistry in the pig undergo significant changes in the course of the diurnal rhythm. 相似文献
58.
Czarnik U Zabolewicz T Galiński M Pareek CS Walawski K 《Journal of applied genetics》2004,45(1):73-76
We report on a PCR-RFLP procedure for recognising of a silent point mutation of ITGB2 CD18 subunit gene in cattle. Polymorphism screening was performed in a Polish Black-and-White cattle population (n=210). The genotype and allele frequencies were established in the sires and cows. Further research is needed to explain the possible applications of the CD18 silent point mutation as a potential molecular marker for high milk productivity. 相似文献
59.
Nosratollah?Ale-Agha Adrien?Bolay Uwe?BraunEmail author Benno?Feige Horst?Jage Volker?Kummer Ale??Lebeda Marcin?Pi?tek Hyeon-Dong?Shin Katarína?Zimmermannová-Pastir?aková 《Mycological Progress》2004,3(4):291-296
The recent epidemic spread of the North American powdery mildew Erysiphe elevata in Europe is described and discussed. Since 2002, this plant pathogenic fungus has been collected on Catalpa bignonioides, C. erubescens and C. speciosa in the Czech Republic, Germany, Hungary, Slovakia and Switzerland. The diagnostically important anamorph of E. elevata, so far unknown, is described and illustrated in detail. Type material of Erysiphe catalpae and two specimens of E. catalpae recently collected in Poland have been examined and compared with E. elevata. The anamorph as well as the teleomorph of E. catalpae proved to be easily distinguishable from E. elevata. The supposition that E. catalpae, introduced in Armenia, was based on immature ascomata of E. elevata proved to be wrong. The origin and distribution of E. catalpae are discussed, and a key to powdery mildew fungi on Catalpa spp. in Europe is provided. 相似文献
60.
The aim of our studies was to establish which enzymes constitute the "cGMP pathway" in rat and guinea pig peritoneal macrophages (PM). We found that in guinea pig PM synthesis of the nucleotide was significantly enhanced in response to activators of soluble guanylyl cyclase (sGC) and it was only slightly stimulated by specific activators of particulate guanylyl cyclases (pGC). In contrast, rat PM responded strongly to atrial natriuretic peptide (ANP), the activator of pGC type A. The rat cells synthesized about three-fold more cGMP than an equal number of the guinea pig cells. The activity of phosphodiesterases (PDE) hydrolyzing cGMP was apparently regulated by cGMP itself in PM of both species and again it was higher in the rat cells than in those isolated from guinea pig. However, guinea pig PM revealed an activity of Ca(2+)/calmodulin-dependent PDE1, which was absent in the rat cells. Using Western blotting analysis we were unable to detect the presence of cGMP-dependent protein kinase 1 (PKG1) in PM isolated from either species. In summary, our findings indicate that particulate GC-A is the main active form of GC in the rat PM, while in guinea pig macrophages the sGC activity dominates. Since the profiles of the PDE activities in rat and guinea pig PM are also different, we conclude that the mechanisms regulating cGMP metabolism in PM are species-specific. Moreover, our results suggest that targets for cGMP other than PKG1 should be present in PM of both species. 相似文献