Localization of the UsProtein Kinase of Equine Herpesvirus Type 1 Is Affected by the Cytoplasmic Structures Formed by the Novel IR6 Protein

AbstractPrevious work revealed that the Us(unique short) segment of equine herpesvirus type-1 (EHV-1), like that of other alphaherpesviruses, encodes a serine/threonine protein kinase (PK). Experiments were carried out to identify the PK encoded by the EHV-1 EUS2 gene (ORF 69) and to ascertain its time course of synthesis and cellular localization. Western blot and immunoprecipitation analyses of EHV-1-infected cell extracts using a PK-specific polyclonal antibody generated against a bacterially expressed TrpE/PK fusion protein identified the UsPK as a 42- to 45-kDa phosphoprotein. The PK protein is first synthesized at 3 hr postinfection, is produced throughout the infection cycle, and is incorporated into EHV-1 virions. Interestingly, immunoprecipitation analyses revealed that the PK protein within the cytoplasm is associated with the 33-kDa IR6 novel protein of EHV-1, is expressed abundantly as an early protein, and is present in the large rod-like structures formed by the IR6 protein (ORF67 protein) within the cytoplasm of infected cells. Confocal microscopic examination of cells stained with fluorescein-labeled antibody clearly showed that the PK protein colocalized with the cytoplasmic IR6 rod-like structures and remained associated with these unique structures during infection. In contrast, in cells infected with the EHV-1 RacM strain in which the IR6 protein harbors four amino acid substitutions that prevent formation of the rod-like structures (Osterriederet al.,1996,Virology217, 442–451), the PK protein localized predominantly to the nucleus. The possible significance of the association of the IR6 and PK proteins in EHV-1 replication is discussed

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0·0086). We quantified the risk of perinatal transmission and the age-dependent rate of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers

nutritional cancer care slowly evolving clinical practice reveals regional and professional hcp variability

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Direct identification of extended defects as vortex pinning centers in melt textured YBa2Cu3O7-Y2BaCuO5 composites

Single domain YBa2Cu3O7-Y2BaCuO5 melt textured ceramic composites have revealed a very rich microstructure, which has usually impeded, by using standard measurements, to evaluate the contribution of each defect to the enhancement of the critical current. We have measured the inplane magnetoresistance anisotropy and the anisotropic in-plane inductive critical currents and we show that together with the microstructural TEM analysis, the contribution of the different extended pinning centers can be separated. These results have allowed us to infer the kind of microstructure modifications required to improve the critical current. In particular, we present an isostatic pressing deformation technique as a very promising post-processing treatment to strongly increase the critical currents of these composites.Peer Reviewe

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

Magnetic field sensitivity of variable thickness microbridges in tbcco, bscco and ybco.

We describe results of a study comparing the magnetic field sensitivities of variable thickness bridge (VTB) arrays fabricated in TBCCO, BSCCO, and YBCO thin films. Identical structures were patterned in a variety of films, and the bridges were thinned by four different methods. Analysis of the data yields experimental evidence as to the suitability of these types of films for devices such as the superconducting flux flow transistor (SFFT) which is based on this geometry. The volt-ampere characteristics of the arrays were measured in low uniform magnetic fields (⩽130 G) and in nonuniform fields (⩽5 G) produced by a nearby control line. For these films in this geometry, no measurable effect of the control line magnetic field was observed. Large values of transresistance and current gain could only be attained through a thermal mechanism when the control line was driven normal. Upper bounds for (magnetically generated) transresistance (⩽5 mΩ) and current gains (⩽0.005) have been inferred from the uniform field data assuming a standard best-case device geometry. All volt-ampere curves followed closely a power law relationship (V~I n), with exponent n ~1.2-10. We suggest materials considerations that may yield improved device performancePeer Reviewe

Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population

BACKGROUND The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR

Seeking String Theory in the Cosmos

We review the existence, formation and properties of cosmic strings in string theory, the wide variety of observational techniques that are being employed to detect them, and the constraints that current observations impose on string theory models.Comment: 25 pages; contribution for String Cosmology issue of Classical and Quantum Gravity. References added and other improvements. Matches journal versio