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101.
Jason E. Chung Hannah R. Joo Jiang Lan Fan Daniel F. Liu Alex H. Barnett Supin Chen Charlotte Geaghan-Breiner Mattias P. Karlsson Magnus Karlsson Kye Y. Lee Hexin Liang Jeremy F. Magland Jeanine A. Pebbles Angela C. Tooker Leslie F. Greengard Vanessa M. Tolosa Loren M. Frank 《Neuron》2019,101(1):21-31.e5
102.
Purkis Sam J. Gleason Arthur C. R. Purkis Charlotte R. Dempsey Alexandra C. Renaud Philip G. Faisal Mohamed Saul Steven Kerr Jeremy M. 《Coral reefs (Online)》2019,38(3):467-488
Coral Reefs - With compelling evidence that half the world’s coral reefs have been lost over the last four decades, there is urgent motivation to understand where reefs are located and their... 相似文献
103.
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
104.
Stuart G. Fisher Nancy B. Grimm Eugènia Martí Robert M. Holmes Jeremy B. Jones Jr. 《Ecosystems》1998,1(1):19-34
Stream ecosystems consist of several subsystems that are spatially distributed concentrically, analogous to the elements
of a simple telescope. Subsystems include the central surface stream, vertically and laterally arrayed saturated sediments
(hyporheic and parafluvial zones), and the most distal element, the riparian zone. These zones are hydrologically connected;
thus water and its dissolved and suspended load move through all of these subsystems as it flows downstream. In any given
subsystem, chemical transformations result in a change in the quantity of materials in transport. Processing length is the length of subsystem required to “process” an amount of substrate equal to advective input. Long processing lengths
reflect low rates of material cycling. Processing length provides the length dimension of each cylindrical element of the
telescope and is specific to subsystem (for example, the surface stream), substrate (for instance, nitrate), and process (denitrification,
for example). Disturbance causes processing length to increase. Processing length decreases during succession following disturbance.
The whole stream-corridor ecosystem consists of several nested cylindrical elements that extend and retract, much as would
a telescope, in response to disturbance regime. This telescoping ecosystem model (TEM) can improve understanding of material
retention in running water systems; that is, their “nutrient filtration” capacity. We hypothesize that disturbance by flooding
alters this capacity in proportion to both intensity of disturbance and to the relative effect of disturbance on each subsystem.
We would expect more distal subsystems (for example, the riparian zone) to show the highest resistance to floods. In contrast,
we predict that postflood recovery of functions such as material processing (that is, resilience) will be highest in central
elements and decrease laterally. Resistance and resilience of subsystems are thus both inversely correlated and spatially
separated. We further hypothesize that cross-linkages between adjacent subsystems will enhance resilience of the system as
a whole. Whole-ecosystem retention, transformation, and transport are thus viewed as a function of subsystem extent, lateral
and vertical linkage, and disturbance regime.
Received 15 April 1997; accepted 1 September 1997. 相似文献
105.
Catherine L. Malone Charles R. Knapp Jeremy F. Taylor Scott K. Davis 《Conservation Genetics》2003,4(1):1-15
Pleistocene fragmentation of the Great BahamaBank resulted in one large and several smallpopulations of rock iguanas (Cycluracychlura). We explore patterns of geneticvariation within and among these islandpopulations using mitochondrial sequence data(partial ND4 to tRNALeu) in combinationwith eight polymorphic microsatellite loci (2to 10 alleles). Genetic data support twophylogeographically distinct groups, AndrosIsland and the Exuma cays. This resultconflicts with current subspecific taxonomy inwhich three subspecies are described. Analysesof allelic data indicate that most islandpopulations are currently demographicallyindependent. Pairwise Fst values between eightisland populations range from 0.18 to 0.63, and6 of 135 individuals are misassigned in anassignment test. Population-genetic diversityis characterized using standard measures suchas number of alleles and heterozygosity (H) inaddition to a normalized Shannon-Weaver indexof diversity (D). We find genetic diversity inthe Andros Island population comparable to thatin other non-piscine animals (avg. # ofalleles = 5, avg. H = 0.56, avg. D = 0.66) while inthe Exuma cays populations these measures aremuch lower (avg. # of alleles = 2.75–1.625, avg.H = 0.43–0.17, avg. D = 0.45–0.18). These dataare used to discuss conservation managementstrategies, including prioritization andtranslocation. 相似文献
106.
Nagy T Nurizzo D Davies GJ Biely P Lakey JH Bolam DN Gilbert HJ 《The Journal of biological chemistry》2003,278(22):20286-20292
alpha-Glucuronidases are key components of the ensemble of enzymes that degrade the plant cell wall. They hydrolyze the alpha1,2-glycosidic bond between 4-O-methyl-d-glucuronic acid (4-O-MeGlcA) and the xylan or xylooligosaccharide backbone. Here we report the crystal structure of an inactive mutant (E292A) of the alpha-glucuronidase, GlcA67A, from Cellvibrio japonicus in complex with its substrate. The data show that the 4-O-methyl group of the substrate is accommodated within a hydrophobic sheath flanked by Val-210 and Trp-160, whereas the carboxylate moiety is located within a positively charged region of the substrate-binding pocket. The carboxylate side chains of Glu-393 and Asp-365, on the "beta-face" of 4-O-MeGlcA, form hydrogen bonds with a water molecule that is perfectly positioned to mount a nucleophilic attack at the anomeric carbon of the target glycosidic bond, providing further support for the view that, singly or together, these amino acids function as the catalytic base. The capacity of reaction products and product analogues to inhibit GlcA67A shows that the 4-O-methyl group, the carboxylate, and the xylose sugar of aldobiouronic acid all play an important role in substrate binding. Site-directed mutagenesis informed by the crystal structure of enzyme-ligand complexes was used to probe the importance of highly conserved residues at the active site of GlcA67A. The biochemical properties of K288A, R325A, and K360A show that a constellation of three basic amino acids (Lys-288, Arg-325, and Lys-360) plays a critical role in binding the carboxylate moiety of 4-O-MeGlcA. Disruption of the apolar nature of the pocket created by Val-210 (V210N and V210S) has a detrimental effect on substrate binding, although the reduction in affinity is not reflected by an inability to accommodate the 4-O-methyl group. Replacing the two tryptophan residues that stack against the sugar rings of the substrate with alanine (W160A and W543A) greatly reduced activity. 相似文献
107.
Jeremy Savian 《American anthropologist》1998,100(2):573-573
The Arbitrary Indian: The Indian Arts and Crafts Act of 1990. Gail K. Sheffield. Norman: University of Oklahoma Press, 1997. 223 pp. 相似文献
108.
The peptidyl-prolyl isomerase (PPIase) cyclophilin A (Cpr1p) is conserved from eubacteria to mammals, yet its biological function has resisted elucidation. Unable to identify a phenotype that is suggestive of Cpr1p's function in a cpr1Delta Saccharomyces cerevisiae strain, we screened for CPR1-dependent strains. In all cases, dependence was conferred by mutations in ZPR1, a gene encoding an essential zinc finger protein. CPR1 dependence was suppressed by overexpression of EF1alpha (a translation factor that binds Zpr1p), Cpr6p (another cyclophilin), or Fpr1p (a structurally unrelated PPIase). Suppression by a panel of cyclophilin A mutants correlated with PPIase activity, confirming the relevance of this activity in CPR1-dependent strains. In CPR1(+) cells, wild-type Zpr1p was distributed equally between the nucleus and cytoplasm. In contrast, proteins encoded by CPR1-dependent alleles of ZPR1 accumulated in the nucleus, as did wild-type Zpr1p in cpr1Delta cells. Transport kinetic studies indicated that nuclear export of Zpr1p was defective in cpr1Delta cells, and rescue of this defect correlated with PPIase activity. Our results demonstrate a functional interaction between Cpr1p, Zpr1p, and EF1alpha, a role for Cpr1p in Zpr1p nuclear export, and a biological function for Cpr1p PPIase activity. 相似文献
109.
Meprin A and B are highly regulated, secreted and cell-surface homo- and hetero-oligomeric enzymes. Meprins are abundantly expressed in kidney and intestine. The multidomain alpha and beta subunits have high sequence identity, however they have very different substrate specificities, oligomerization potentials and are differentially regulated. Here we describe that meprin subunit activities are modulated differently by physico-chemical factors. Homo-oligomeric meprin B had an acidic pH optimum. The low pH protonation indicated the existence of at least two ionizable groups. An additional ionizable group generated a shoulder in the basic pH range. Homo-oligomeric meprin A had a neutral pH optimum and the activity curve revealed that two ionizable groups might be protonated at acidic pH similar to meprin B. Increasing the concentration of salt generally inhibited meprin B activity. Meprin A was inhibited at low salt concentrations but activated as salt was increased. This work has important implications in the elucidation of the catalytic mechanisms of meprins and other metalloproteases. In addition, the activity of meprin oligomers that arise in tissues will be affected by variations in pH and NaCl. This could have profound implications because meprins are exposed to a range of conditions in the extracellular milieu of renal and intestinal tissues and in inflammation and cancer. 相似文献
110.
Mahdi Saatchi Robert D Schnabel Megan M Rolf Jeremy F Taylor Dorian J Garrick 《遗传、选种与进化》2012,44(1):38