Distinct origins of dura mater graft-associated Creutzfeldt-Jakob disease: past and future problems

Dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) can be divided into two subgroups that exhibit distinct clinical and neuropathological features, with the majority represented by a non-plaque-type of dCJD (np-dCJD) and the minority by a plaque-type of dCJD (p-dCJD). The two distinct phenotypes of dCJD had been considered to be unrelated to the genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP gene or type (type 1 or type 2) of abnormal isoform of prion protein (PrP(Sc)) in the brain, while these are major determinants of clinicopathological phenotypes of sporadic CJD (sCJD). The reason for the existence of two distinct subgroups in dCJD had remained elusive. Recent progress in research of the pathogenesis of dCJD has revealed that two distinct subgroups of dCJD are caused by infection with different PrP(Sc) strains from sCJD, i.e., np-dCJD caused by infection with sCJD-MM1/MV1, and p-dCJD caused by infection with sCJD-VV2 or -MV2. These studies have also revealed previously unrecognized problems as follows: (i) the numbers of p-dCJD patients may increase in the future, (ii) the potential risks of secondary infection from dCJD, particularly from p-dCJD, may be considerable, and (iii) the effectiveness of the current PrP(Sc) decontamination procedures against the PrP(Sc) from p-dCJD is uncertain. To prevent secondary infection from p-dCJD, the establishment of effective decontamination procedures is an urgent issue. In this review, we summarize the past and future problems surrounding dCJD

Intraspecies Prion Transmission Results in Selection of Sheep Scrapie Strains

Background: Sheep scrapie is caused by multiple prion strains, which have been classified on the basis of their biological characteristics in inbred mice. The heterogeneity of natural scrapie prions in individual sheep and in sheep flocks has not been clearly defined. Methodology/Principal Findings: In this study, we intravenously injected 2 sheep (Suffolk and Corriedale) with material from a natural case of sheep scrapie (Suffolk breed). These 3 sheep had identical prion protein (PrP) genotypes. The protease-resistant core of PrP (PrPres) in the experimental Suffolk sheep was similar to that in the original Suffolk sheep. In contrast, PrPres in the Corriedale sheep differed from the original PrPres but resembled the unusual scrapie isolate, CH1641. This unusual PrPres was not detected in the original sheep. The PrPres distributions in the brain and peripheral tissues differed between the 2 breeds of challenged sheep. A transmission study in wild-type and TgBoPrP mice, which overexpressing bovine PrP, led to the selection of different prion strains. The pathological features of prion diseases are thought to depend on the dominantly propagated strain. Conclusions/Significance: Our results indicate that prion strain selection occurs after both inter- and intraspecie

Sulfated Dextrans Enhance In Vitro Amplification of Bovine Spongiform Encephalopathy PrPSc and Enable Ultrasensitive Detection of Bovine PrPSc

Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrP(Sc), a protease-resistant misfolded isoform of the cellular prion protein PrP(C). Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrP(Sc). However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrP(Sc) in BSE-affected cattle therefore remains unknown.We report here that PrP(Sc) derived from BSE-affected cattle can be amplified ultra-efficiently by PMCA in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrP(Sc) from the saliva, palatine tonsils, lymph nodes, ileocecal region, and muscular tissues of BSE-affected cattle. Individual differences in the distribution of PrP(Sc) in spleen and cerebrospinal fluid samples were observed in terminal-stage animals. However, the presence of PrP(Sc) in blood was not substantiated in the BSE-affected cattle examined.The distribution of PrP(Sc) is not restricted to the nervous system and can spread to peripheral tissues in the terminal disease stage. The finding that PrP(Sc) could be amplified in the saliva of an asymptomatic animal suggests a potential usefulness of this technique for BSE diagnosis. This highly sensitive method also has other practical applications, including safety evaluation or safety assurance of products and byproducts manufactured from bovine source materials

Pacemaker Inhibition During Cardioplegia in Open Heart Surgery

A 53-year-old patient underwent mitral valve replacement after implantation of permanent pacemaker. During cardioplegia in open heart surgery, we performed the inhibition of permanent pacemaker to obtain complete myocardial preservation and quiet heart, using stimulations of an external pulse generator. This procedure is considered available, when the patient who has had a permanent pacemaker undergoes open heart surgery more safely

A 100 W-Class Water-Vapor Hall Thruster for Constellations and Space Explorations by SmallSats

The laboratory models of a water-vapor Hall thruster and LaB6 thermionic cathode were developed and tested. To optimize the thruster design to water-vapor propellant, the geometrical investigation was conducted. After testing six different models, the smallest thruster, with an outer diameter of 20 mm, was found to be the most suitable for 100-W class operation. This thruster was able to be operated less than 100 W at 200 V. In addition, the discharge power was suppressed to 200 W even at 300 V. Based on the plume diagnostics, the thrust force of 2.9 mN, specific impulse of 650 s, and anode efficiency of 4.6 % were obtained as a representative performance of this 300 V operating point. After the thruster operation was achieved, the cathode coupling test was conducted to demonstrate electron emission under water-vapor plasma existence. As a result of this experiment, the effective increase in electron current compared to the previous stand-alone tests was confirmed as well as the compatability to the water-vapor plasma plume. On the other hand, the electron emission current has not achieved 100 mA-class yet and the required heating power was predicted over 100 W; thus, further improvement is progressing

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

Atypical bovine spongiform encephalopathy (BSE) has recently been identified in Europe, North America, and Japan. It is classified as H-type and L-type BSE according to the molecular mass of the disease-associated prion protein (PrPSc). To investigate the topographical distribution and deposition patterns of immunolabeled PrPSc, H-type BSE isolate was inoculated intracerebrally into cattle. H-type BSE was successfully transmitted to 3 calves, with incubation periods between 500 and 600 days. Moderate to severe spongiform changes were detected in the cerebral and cerebellar cortices, basal ganglia, thalamus, and brainstem. H-type BSE was characterized by the presence of PrP-immunopositive amyloid plaques in the white matter of the cerebrum, basal ganglia, and thalamus. Moreover, intraglial-type immunolabeled PrPSc was prominent throughout the brain. Stellate-type immunolabeled PrPSc was conspicuous in the gray matter of the cerebral cortex, basal ganglia, and thalamus, but not in the brainstem. In addition, PrPSc accumulation was detected in the peripheral nervous tissues, such as trigeminal ganglia, dorsal root ganglia, optic nerve, retina, and neurohypophysis. Cattle are susceptible to H-type BSE with a shorter incubation period, showing distinct and distinguishable phenotypes of PrPSc accumulation

Strukturierung des Unterrichts anhand der Lehrer:innenfragen. Perspektiven der Jugyo Kenkyu

Analog zum Leipziger Ansatz der qualitativen Unterrichtsforschung stellt das Team der Hiroshima Universität sein spezifisches Vorgehen der Lesson Study vor. Auf der Basis der normativen Lesson Study mit Fokus auf die Gruppenbildung im Klassenzimmer zeigt die Analyse ihre Praxisnähe und moniert ein gewisses Defizit der Untersuchungsmaterialien, die aus dem Kontext der qualitativen Unterrichtsforschung bereitgestellt wurden. Die forschungsmethodologische Differenz zeigt sich darin, dass der Fokus auf die Lehrer:innenfrage im qualitativen Zugang Prozesse der Offenheit und Lenkung und in der Jugyo Kenkyu Strukturen der Gruppenbildung in den Blick rückt. (DIPF/Orig.

Ultrasensitive detection of SARS-CoV-2 nucleocapsid protein using large gold nanoparticle-enhanced surface plasmon resonance

The COVID-19 pandemic has created urgent demand for rapid detection of the SARS-CoV-2 coronavirus. Herein, we report highly sensitive detection of SARS-CoV-2 nucleocapsid protein (N protein) using nanoparticle-enhanced surface plasmon resonance (SPR) techniques. A crucial plasmonic role in significantly enhancing the limit of detection (LOD) is revealed for exceptionally large gold nanoparticles (AuNPs) with diameters of hundreds of nm. SPR enhanced by these large nanoparticles lowered the LOD of SARS-CoV-2 N protein to 85 fM, resulting in the highest SPR detection sensitivity ever obtained for SARS-CoV-2 N protein