bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Challenge-Protective Vaccine Concept by Modification of the Viral RNA-Dependent RNA Polymerase of Canine Distemper Virus
Authors: Silin D. , Lyubomska O. , Ludlow M. , Duprex W. P. , Rima B. K. 
Published: September 2007

ABSTRACTWe demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a “quick response” in vaccine development against well-known and “new” viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.
The Mre11/Rad50/Nbs1 Complex Limits Adeno-Associated Virus Transduction and Replication
Authors: Schwartz Rachel A. , Palacios Jose Alejandro , Cassell Geoffrey D. , Adam Sarah , Giacca Mauro , Weitzman Matthew D. 
Published: September 2007

ABSTRACT
Adeno-associated virus (AAV) is a parvovirus with a small single-stranded DNA genome that relies on cellular replication machinery together with functions supplied by coinfecting helper viruses. The impact of host factors on AAV infection is not well understood. We explored the connection between AAV helper functions supplied by adenovirus and cellular DNA repair proteins. The adenoviral E1b55K/E4orf6 proteins induce degradation of the cellular Mre11 repair complex (MRN) to promote productive adenovirus infection. These viral proteins also augment recombinant AAV transduction and provide crucial helper functions for wild-type AAV replication. Here, we show that MRN poses a barrier to AAV and that the helper function provided by E1b55K/E4orf6 involves MRN degradation. Using a fluorescent method to visualize the viral genome, we show an effect at the viral DNA level. MRN components accumulate at AAV replication centers and recognize the viral inverted terminal repeats. Together, our data suggest that AAV is targeted by MRN and has evolved to exploit adenoviral proteins that degrade these cellular factors.
A Novel Virus Detected in Papillomas and Carcinomas of the Endangered Western Barred Bandicoot (
Perameles bougainville
) Exhibits Genomic Features of both the
Papillomaviridae
and
Polyomaviridae
Authors: Woolford Lucy , Rector Annabel , Van Ranst Marc , Ducki Andrea , Bennett Mark D. , Nicholls Philip K. , Warren Kristin S. , Swan Ralph A. , Wilcox Graham E. , O'Hara Amanda J. 
Published: September 2007

ABSTRACT

Conservation efforts to prevent the extinction of the endangered western barred bandicoot (
Perameles bougainville
) are currently hindered by a progressively debilitating cutaneous and mucocutaneous papillomatosis and carcinomatosis syndrome observed in captive and wild populations. In this study, we detected a novel virus, designated the bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1), in lesional tissue from affected western barred bandicoots using multiply primed rolling-circle amplification and PCR with the cutaneotropic papillomavirus primer pairs FAP59/FAP64 and AR-L1F8/AR-L1R9. Sequencing of the BPCV1 genome revealed a novel prototype virus exhibiting genomic properties of both the
Papillomaviridae
and the
Polyomaviridae
. Papillomaviral properties included a large genome size (∼7.3 kb) and the presence of open reading frames (ORFs) encoding canonical L1 and L2 structural proteins. The genomic organization in which structural and nonstructural proteins were encoded on different strands of the double-stranded genome and the presence of ORFs encoding the nonstructural proteins large T and small t antigens were, on the other hand, typical polyomaviral features. BPCV1 may represent the first member of a novel virus family, descended from a common ancestor of the papillomaviruses and polyomaviruses recognized today. Alternatively, it may represent the product of ancient recombination between members of these two virus families. The discovery of this virus could have implications for the current taxonomic classification of
Papillomaviridae
and
Polyomaviridae
and can provide further insight into the evolution of these ancient virus families.
Cytoskeletal rearrangement and cell death induced by Bothrops alternatus snake venom in cultured Madin–Darby canine kidney cells
Authors: Nascimento Juliana Minardi , Franchi Gilberto Carlos , Nowill Alexandre Eduardo , Collares-Buzato Carla Beatriz , Hyslop Stephen 
Published: September 2007

Bothrops snake venoms cause renal damage, with renal failure being the main cause of death in humans bitten by these snakes. In this work, we investigated the cytoskeletal rearrangement and cytotoxicity caused by Bothrops alternatus venom in cultured Madin–Darby canine kidney (MDCK) cells. Incubation with venom (10 and 100 µg/mL) significantly (p <0.05) decreased the cellular uptake of neutral red dye after 1 and 3 h. Venom (100 µg/mL) also markedly decreased the transepithelial electrical resistance (RT) across MDCK monolayers. Staining with rhodamine-conjugated phalloidin revealed disarray of the cytoskeleton that involved the stress fibers at the basal cell surface and focal adhesion-associated F-actin in the cell–matrix contact region. Feulgen staining showed a significant decrease in the number of cells undergoing mitosis and an increase in the frequency of altered nuclei. Scanning electron microscopy revealed a decrease in the number of microvilli and the presence of cells with a fusiform format. Flow cytometry with annexin V and propidium iodide showed that cell death occurred by necrosis, with little apoptosis, a conclusion supported by the lack of DNA fragmentation characteristic of apoptosis. Pretreating the cells with catalase significantly attenuated the venom-induced loss of viability, indicating a possible involvement of H2O2 in the cellular damage; less protection was observed with superoxide dismutase or Nω-nitro-l-arginine methyl ester. These results indicate that Bothrops alternatus venom is cytotoxic to cultured MDCK cells, possibly via the action of reactive oxygen species. This cytotoxicity could contribute to nephrotoxicity after envenoming by this species.
Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation
Authors: Newsome Anthony L. , Johnson Jon Paul , Seipelt Rebecca L. , Thompson Michael W. 
Published: September 2007

Lactoferrin (LTF) is a multifunctional iron-binding protein that is also capable of binding other divalent metal cations, especially Zn2+. Recent investigations indicate that lactoferrin levels are elevated in many disease conditions in which matrix metalloproteinases (MMPs), particularly MMP-2, are also elevated, suggesting that the 2 proteins may interact. This possibility was examined by determining the effect of LTF in its holo (metal-bound) and apo (metal-free) forms on the proteolytic activity of MMP-2 and other similar zinc metalloproteases. Pre-incubation with apolactoferrin, but not hololactoferrin, greatly reduced the hydrolysis of a peptide substrate by MMP-2, but not by MMP-1, -8, -9, or -13. This inhibition was specific for the 42 kDa catalytic domain fragment of MMP-2 lacking the hemopexin domain, since the 66 kDa form was poorly inhibited by apolactoferrin. The inhibition of the MMP-2 catalytic domain was strongly temperature sensitive, indicating that the conformation of one or both proteins is crucial to this interaction. To ascertain the mechanism of inhibition, increasing concentrations of ZnCl2and FeCl2were added to the reaction. While addition of Fe2+did not reverse inhibition, the addition of Zn2+resulted in a recovery of MMP-2 activity, and furthermore, zinc-saturated LTF did not inhibit MMP-2. Together, these data strongly suggest that apolactoferrin is capable of removing the catalytic zinc from the active site of MMP-2, although an exosite-based interaction between the 2 proteins cannot be fully ruled out. This inhibitory activity suggests a novel function for LTF and may represent a novel regulatory mechanism that regulates proteolysis by MMP-2 in vivo.
Hydrogen peroxide affects abscisic acid binding to ABAP1 in barley aleurones
Authors: Razem Fawzi A. , Hill Robert D. 
Published: September 2007

Dramatic increases in H2O2 levels have been observed following abscisic acid (ABA) treatment of plant tissues. Following ABA treatment in aleurone cells, H2O2 reached transient levels of approximately 115 µmol/L H2O2. To determine whether ABA perception was modified by such changes, the effect of H2O2 on a recently characterized ABA-binding protein (ABAP1), cloned from barley aleurone layers, was examined. ABA binding to the protein was weakened by H2O2 in a concentration-dependent manner. A concentration of 75 µmol/L H2O2 gave a 50% decline in ABA binding in a reaction following first-order kinetics, indicative of binding-site susceptibility to its microenvironment. We monitored the unfolding of ABAP1 using steady-state and time-resolved tryptophan fluorescence, while following the capacity of ABAP1 to bind ABA. ABA binding decreased by 50% following ABAP1 denaturation with 1 mol/L guanidine hydrochloride or 2 mol/L urea, while the maximum emission spectra (λemi) red shifted from 338 to 347 nm at 3.5 mol/L guanidine hydrochloride and 5 mol/L urea. However, only a slight blue shift of λemi was observed following either ABAP1 incubation with H2O2 or binding to (+)-ABA (physiologically active ABA). The equilibrium ABA dissociation rate accelerated in the presence of 250 µmol/L H2O2, with the half-time dissociation reduced to 8 min. A comparison of inactivation kinetics and conformational changes shows that inactivation of ABAP1 occurs before any noticeable conformational change. This suggests that the ABA binding site is highly responsive to its microenvironment and is situated in a region that is more flexible than the protein molecule as a whole. The results demonstrate that H2O2, generated by ABA treatment of aleurone layers, is sufficient to affect the ABA-binding capacity of ABAP1, suggesting that this may be another level of control of ABA signal transduction.
Onset–potency relationship of nondepolarizing muscle relaxants: a reexamination using simulations
Authors: Bhatt S.B. , Amann A. , Nigrovic V. 
Published: September 2007

Nondepolarizing muscle relaxants (MRs) display an inverse onset–potency relationship, that is, less potent MRs display a more rapid onset. We have conducted the current investigation to estimate the impact of variable pharmacokinetic or pharmacodynamic properties of the MRs on potency and onset time, and on the onset–potency relationship. Using a model of neuromuscular transmission, we changed either the affinity of MRs for the postsynaptic receptors or the pharmacokinetic properties of the MRs. The elimination rate constant, k10, which defines the systemic clearance, was assigned one of 9 values and the transport rate constant, k12, one of 5 values. The transport rate constant into the effect compartment was constant (ke1 = 0.2 min–1). Only one parameter was altered at a time. With constant pharmacokinetics, a 100-fold decrease in affinity caused a proportional decrease in potency, but little change (0.02 min) in onset time. With constant affinity, increasing the clearance from 1 to 250 mL·kg–1·min–1 shortened the onset time from 7.2 to 0.7 min and decreased the potency 12-fold. In a double logarithmic plot, the onset–potency relationship was linear. Lesser affinities produce a nearly parallel rightward shift of the regression lines. The inverse onset–potency relationship may be explained by the pharmacokinetic factors producing changes in both the potency and onset times.
Reduction of asymmetric dimethylarginine involved in the cardioprotective effect of losartan in spontaneously hypertensive rats
Authors: Li Dai , Xia Ke , Li Nian-Sheng , Luo Dan , Wang Shan , Jiang De-Jian , Deng Han-Wu , Li Yuan-Jian 
Published: September 2007

Previous studies have indicated that nitric oxide synthase (NOS) inhibitors can induce an increase of blood pressure and exacerbate myocardial injury induced by ischemia and reperfusion, whereas angiotensin II receptor antagonists protect the myocardium against injury induced by ischemia and reperfusion. Isolated hearts from male spontaneously hypertensive rats (SHR) or male Wistar-Kyoto rats (WKY) were subjected to 20 min global ischemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure, and its first derivatives (±dP/dtmax) were recorded, and serum concentrations of asymmetric dimethylarginine (ADMA) and NO and the release of creatine kinase in coronary effluent were measured. The level of ADMA was significantly increased and the concentration of NO was decreased in SHR. Ischemia and reperfusion significantly inhibited the recovery of cardiac function and increased the release of creatine kinase, and ischemia and reperfusion-induced myocardial injury in SHR was aggravated compared with WKY. Vasodilation responses to acetylcholine of aortic rings were decreased in SHR. Treatment with losartan (30 mg/kg) for 14 days significantly lowered blood pressure, elevated the plasma level of NO, and decreased the plasma concentration of ADMA in SHR. Treatment with losartan significantly improved endothelium-dependent relaxation and cardiac function during ischemia and reperfusion in SHR. Exogenous ADMA also aggravated myocardial injury induced by ischemia and reperfusion in isolated perfused heart of WKY, as shown by increasing creatine kinase release and decreasing cardiac function. The present results suggest that the protective effect of losartan on myocardial injury induced by ischemia and reperfusion is related to the reduction of ADMA levels.
Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection
Authors: Muchova Lucie , Wong Ronald J. , Hsu Mark , Morioka Ichiro , Vitek Libor , Zelenka Jaroslav , Schröder Henning , Stevenson David K. 
Published: September 2007

Heme oxygenase (HO) has a central role in cellular antioxidant defences and vascular protection, and it may mediate pleiotropic actions of drugs used in cardiovascular therapy. We investigated whether long-term use of statins upregulates HO activity and increases carbon monoxide (CO) and bilirubin levels in vivo. Adult FvB mice were given atorvastatin or rosuvastatin (5 mg/kg) daily by i.p. injections for 1, 2, or 3 weeks. HO activity, tissue CO, bilirubin, and antioxidant levels, total plasma bilirubin, and carboxyhemoglobin (COHb) were measured. Fold changes in heart HO activity significantly increased after 1, 2, and 3 weeks of atorvastatin (1.24 ± 0.06 (p ≤ 0.05); 1.29 ± 0.26 (p ≤ 0.03); 1.33 ± 0.08 (p < 0.01), respectively) and 2 and 3 weeks of rosuvastatin (1.23 ± 0.20 (p ≤ 0.03); 1.63 ± 0.42 (p < 0.01), respectively). Heart tissue CO and COHb levels also increased after 3 weeks with atorvastatin (1.30 ± 0.24 (p ≤ 0.05); 1.92 ± 0.17 (p ≤ 0.001), respectively) and rosuvastatin (1.47 ± 0.13 (p ≤ 0.004); 1.63 ± 0.12 (p ≤ 0.001), respectively). Significant increases in heart antioxidant levels were observed after statin treatment and corroborated by heart bilirubin content elevations. Antioxidant level increases were abolished by treatment with an HO inhibitor. These findings suggest that the induction of HO and the production of its products, CO and bilirubin, may be a mechanism by which statins exert antioxidant actions and confer cardioprotection in vivo.
The history of attempts to establish a quantitative time-scale
Authors: Wager L. R. 
Published: September 2007

Summary
The great age of the Earth was first scientifically argued by Hutton in the eighteenth century. Next, a world-wide time-order scale of geological events was established using the biostratigraphic methods of William Smith. In the second half of the last century ‘hour-glass’ methods, based on salinity of the oceans and the maximum thickness of sediment, provided a framework for a rough time-scale, measured in years. The development of a reasonably detailed and satisfactory time-scale for geology is, however, an achievement of the present century and has been accomplished by using as an hour-glass method the rate of radioactive decay of certain elements present in rocks and minerals of known position in the time-order scale.
In 1913, from tentative radiometrically established ages, Holmes produced a quantitative Phanerozoic time-scale, and he and others have gradually refined it. In linking the isolated dates obtained by radiometric methods with the biostratigraphic time-scale, use has usually also been made of the maximum thicknesses of sediments accumulated in the various intervals of the time-order scale, and this is believed to be still the most useful method.
Sedimentation rates in relation to the Phanerozoic time-scale
Authors: Hudson J. D. 
Published: September 2007

Summary
Sedimentation rates combined with stratigraphical correlation provided the earliest reasonably objective geological time-scales, but these were at best crude approximations. Later, sedimentation rates were used only to interpolate between radiometrically determined ages. The hypothesis that average maximum rates of sedimentation (or subsidence) have increased during Phanerozoic time is discussed and it is concluded that the evidence for it is unsatisfactory.
The relationship between radiometric ages obtained from plutonic complexes and stratigraphical time
Authors: Lambert R. St J. 
Published: September 2007

Summary
For most of Phanerozoic time errors in radio- metric ages are usually approximately 3 per cent. except for Rb-Sr results from Mesozoic and Tertiary minerals, which must have high Rb/Sr ratios to give such low errors. Rates of uplift appear to be of the order of 10 cm/100 years for sustained movement; in consequence, uplift will normally take place within the error of an age except for post-Jurassic examples. The age obtained for a plutonic complex marks the time of closure of radiogenic systems: the available data indicate that this effectively takes place at about 200°C for the most retentive minerals, but this figure is subject to considerable uncer- tainty. Closure of systems at low temperatures poses several problems, which are discussed. It is concluded that there is much uncertainty about the stratigraphical meaning of ages obtained from minerals from large plutonic complexes.
Potassium—argon ages of sedimentary and pyroclastic rocks
Authors: Baadsgaard Halfdan , Dodson Martin Henry 
Published: September 2007

Summary
It is rarely possible to obtain reliable potassiumargon ages from sedimentary rocks. Glauconites generally give dates that are too low and very scattered, though the largest of a group of such measurements may be useful to define minimum ages of sediments that cannot be dated in any other way. Illite dates are subject to opposing systematic errors: because of this they may coincide roughly with the age of the sediment, but they cannot be regarded as reliable. Sylvines lose argon easily, though they may give good potassium-calcium dates.
From bentonites and volcanic ashes biotite, sanidine, and low-potassium feldspars have all been successfully dated. Contamination by old detritus is sometimes a problem, but the dates obtained from different minerals generally agree well, showing that the results are reliable. The wide geographical distribution of bentonites gives them a special value for time-scale work.
Glauconite dates from the Upper Jurassic and Lower Cretaceous
Authors: Dodson Martin Henry , Rex David Charles , Casey Raymond , Allen Percival 
Published: September 2007

Summary
Few dates are available from stratigraphically well-documented igneous materials of late Jurassic and early Cretaceous age. Glauconite dates therefore have a special interest despite the geochronological limitations of the mineral. Evidence from the Albian and Cenomanian, moreover, shows that some Mesozoic glauconites give results only slightly lower than the probable correct dates.
New glauconite determinations from sedimentary rocks near the Jurassic–Cretaceous boundary include four English dates close to 130 m.y. Those from Greenland and Russia are lower, ranging between 107 and 117 m.y. Published information concerning comparable stratigraphical horizons also includes low values and several near 130 m.y.
Our results suggest that the Jurassic–Cretaceous boundary (sensu borealis) is a little older than 130 m.y. They are thus consistent with the figure of 135 m.y. assigned to the boundary by Holmes and Kulp.
The age of the paroxysmal Variscan orogeny in England
Authors: Fitch Frank Joseph , Miller John Alfred 
Published: September 2007

Summary
Potassium–argon age-determinations on 10 basic igneous rocks from the English Midlands indicate two distinct episodes of magmatic intrusion. Geological evidence and Permo-Carboniferous isotopic age data from Britain confirm the well-known close relationship between magmatism and earth-movements. It is concluded that the paroxysmal phase of the Variscan orogeny in England occurred in the early Stephanian (Asturic phase), and that late-tectonic granitic magmatism in the active zone was penecontemporaneous with basaltic magmatism on the foreland around 295 m.y. A further period of basaltic magmatism close to 265 m.y. is equated with Saalic movements, and it is suggested that a primary mineralization event at 225 m.y. is of widespread occurrence and might be used to fix the Permo-Triassic boundary in Britain.
The Cretaceous period
Authors: Casey Raymond 
Published: September 2007

Summary
Fifty significant items from the large body of radiometric data on the Cretaceous period are reviewed and the following dates are acceptedas a basis for discussion: Jurassic-Cretaceous (Volgian-Ryazanian) boundary: 136 m.y.; Lower Cretaceous-Upper Cretaceous (Albian-Cenomanian) boundary: 100 m.y.; Upper Cretaceous-Tertiary (Maestrichtian-Danian) boundary: 64 m.y. A precise scale of geochronology for this period is impeded by inadequate stratigraphical dating of igneous events, unreliability of results from sedimentary sources (glauconite), and lack of international agreement on the limits of the Cretaceous System.
The Jurassic period
Authors: Howarth Michael Kingsley 
Published: September 2007

Summary
Seven critical biotite ages and five minimum glauconite ages for the Jurassic are discussed in relation to the time-scales of Holmes (1959) and Kulp (1961). It is proposed that the date for the base of the system should be amended to 190-5 m.y., the date for the end of the period remaining at 135 m.y.; the estimate for the length of the Jurassic is thus increased by 10 or 15 m.y. to 55–60 m.y.
The Carboniferous period
Authors: Francis Edward Howel , Woodland Austin William 
Published: September 2007

Summary
It is estimated that the duration of Carboniferous time was 65 m.y., extending from 345 to 280 m.y. ago. Using age-determinations made on sediments, contemporaneous volcanic rocks, and intrusive rocks that have varying degrees ofstratigraphical control, a provisional Carboniferous time-scale is proposed. In terms of the standard European succession, to which most of the critical data pertains or can be related, it is as follows: