Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis)

<p>Abstract</p> <p>Background</p> <p>Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease.</p> <p>Results</p> <p>Cynomolgus macaques (<it>Macaca fasicularis</it>) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the <it>basis pontis </it>and <it>vermis cerebelli </it>of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques.</p> <p>Conclusions</p> <p>We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.</p

Nodal liquid and s-wave superconductivity in transition metal dichalcogenides

We explore the physical properties of a unified microscopic theory for the coexistence of superconductivity and charge density waves in two-dimensional transition metal dichalcogenides. In the case of particle-hole symmetry the elementary particles are Dirac fermions at the nodes of the charge density wave gap. When particle-hole symmetry is broken electron (hole) pockets are formed around the Fermi surface. The superconducting ground state emerges from the pairing of nodal quasi-particles mediated by acoustic phonons via a piezoelectric coupling. We calculate several properties in the s-wave superconducting phase, including specific heat, ultra-sound absorption, nuclear magnetic relaxation, thermal, and optical conductivities. In the case with particle-hole symmetry, the specific heat jump at the transition deviates strongly from ordinary superconductors. The nuclear magnetic response shows an anomalous anisotropy due to the broken time-reversal symmetry of the superconducting gap, induced by the triple charge density wave state. The loss of lattice inversion symmetry in the charge density wave phase leads to anomalous coherence factors in the optical conductivity and to the appearance of an absorption edge at the optical gap energy. Furthermore, optical and thermal conductivities display anomalous peaks in the infrared when particle-hole symmetry is broken.Comment: 23 pages, 16 figures. Published versio

Engineering the semiconductor/oxide interaction for stacking twin suppression in single crystalline epitaxial silicon(111)/insulator/Si(111) heterostructures

The integration of alternative semiconductor layers on the Si material platform via oxide heterostructures is of interest to increase the performance and/or functionality of future Si-based integrated circuits. The single crystalline quality of epitaxial (epi) semiconductor-insulator-Si heterostructures is however limited by too high defect densities, mainly due to a lack of knowledge about the fundamental physics of the heteroepitaxy mechanisms at work. To shed light on the physics of stacking twin formation as one of the major defect mechanisms in (111)-oriented fcc-related heterostructures on Si(111), we report a detailed experimental and theoretical study on the structure and defect properties of epi-Si(111)/Y2O 3/Pr2O3/Si(111) heterostructures. Synchrotron radiation-grazing incidence x-ray diffraction (SR-GIXRD) proves that the engineered Y2O3/Pr2O3 buffer dielectric heterostructure on Si(111) allows control of the stacking sequence of the overgrowing single crystalline epi-Si(111) layers. The epitaxy relationship of the epi-Si(111)/insulator/Si(111) heterostructure is characterized by a type A/B/A stacking configuration. Theoretical ab initio calculations show that this stacking sequence control of the heterostructure is mainly achieved by electrostatic interaction effects across the ionic oxide/covalent Si interface (IF). Transmission electron microscopy (TEM) studies detect only a small population of misaligned type B epi-Si(111) stacking twins whose location is limited to the oxide/epiSi IF region. Engineering the oxide/semiconductor IF physics by using tailored oxide systems opens thus a promising approach to grow heterostructures with well-controlled properties. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

The Spectrum of the Dirac Operator on Coset Spaces with Homogeneous Gauge Fields

The spectrum and degeneracies of the Dirac operator are analysed on compact coset spaces when there is a non-zero homogeneous background gauge field which is compatible with the symmetries of the space, in particular when the gauge field is derived from the spin-connection. It is shown how the degeneracy of the lowest Landau level in the recently proposed higher dimensional quantum Hall effect is related to the Atiyah-Singer index theorem for the Dirac operator on a compact coset space.Comment: 25 pages, typeset in LaTeX, uses youngtab.st

The impact of surgical site infection—a cost analysis

Purpose: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. Methods: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 euro; 19.703 USD (IQR 21.638 euro; 25.552 USD) vs. median 11.235 euro; 13.276 USD (IQR 11.564 euro; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 euro; 7.870 USD with SSI vs. median 5.040 euro; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 euro; 9.924 USD with SSI vs. median 4.690 euro; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 euro; 14.237 USD vs. median 12.793 euro; 15.107 USD in the polyhexanide group (p = 0.52). Conclusion: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide

Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection

Background: The human genome contains multiple LTR elements including human endogenous retroviruses (HERVs) that together account for approximately 8–9% of the genomic DNA. At least 40 different HERV groups have been assigned to three major HERV classes on the basis of their homologies to exogenous retroviruses. Although most HERVs are silenced by a variety of genetic and epigenetic mechanisms, they may be reactivated by environmental stimuli such as exogenous viruses and thus may contribute to pathogenic conditions. The objective of this study was to perform an in-depth analysis of the influence of HIV-1 infection on HERV activity in different cell types. Results: A retrovirus-specific microarray that covers major HERV groups from all three classes was used to analyze HERV transcription patterns in three persistently HIV-1 infected cell lines of different cellular origins and in their uninfected counterparts. All three persistently infected cell lines showed increased transcription of multiple class I and II HERV groups. Up-regulated transcription of five HERV taxa (HERV-E, HERV-T, HERV-K (HML-10) and two ERV9 subgroups) was confirmed by quantitative reverse transcriptase PCR analysis and could be reversed by knock-down of HIV-1 expression with HIV-1-specific siRNAs. Cells infected de novo by HIV-1 showed stronger transcriptional up-regulation of the HERV-K (HML-2) group than persistently infected cells of the same origin. Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells. Conclusions: Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production. Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

A new approach to the assessment of lumen visibility of coronary artery stent at various heart rates using 64-slice MDCT

Coronary artery stent lumen visibility was assessed as a function of cardiac movement and temporal resolution with an automated objective method using an anthropomorphic moving heart phantom. Nine different coronary stents filled with contrast fluid and surrounded by fat were scanned using 64-slice multi-detector computed tomography (MDCT) at 50–100 beats/min with the moving heart phantom. Image quality was assessed by measuring in-stent CT attenuation and by a dedicated tool in the longitudinal and axial plane. Images were scored by CT attenuation and lumen visibility and compared with theoretical scoring to analyse the effect of multi-segment reconstruction (MSR). An average increase in CT attenuation of 144 ± 59 HU and average diminished lumen visibility of 29 ± 12% was observed at higher heart rates in both planes. A negative correlation between image quality and heart rate was non-significant for the majority of measurements (P > 0.06). No improvement of image quality was observed in using MSR. In conclusion, in-stent CT attenuation increases and lumen visibility decreases at increasing heart rate. Results obtained with the automated tool show similar behaviour compared with attenuation measurements. Cardiac movement during data acquisition causes approximately twice as much blurring compared with the influence of temporal resolution on image quality

Fibroblast Growth Factor-2 Primes Human Mesenchymal Stem Cells for Enhanced Chondrogenesis

Human mesenchymal stem cells (hMSCs) are multipotent cells capable of differentiating into a variety of mature cell types, including osteoblasts, adipocytes and chondrocytes. It has previously been shown that, when expanded in medium supplemented with fibroblast growth factor-2 (FGF-2), hMSCs show enhanced chondrogenesis (CG). Previous work concluded that the enhancement of CG could be attributed to the selection of a cell subpopulation with inherent chondrogenic potential. In this study, we show that FGF-2 pretreatment actually primed hMSCs to undergo enhanced CG by increasing basal Sox9 protein levels. Our results show that Sox9 protein levels were elevated within 30 minutes of exposure to FGF-2 and progressively increased with longer exposures. Further, we show using flow cytometry that FGF-2 increased Sox9 protein levels per cell in proliferating and non-proliferating hMSCs, strongly suggesting that FGF-2 primes hMSCs for subsequent CG by regulating Sox9. Indeed, when hMSCs were exposed to FGF-2 for 2 hours and subsequently differentiated into the chondrogenic lineage using pellet culture, phosphorylated-Sox9 (pSox9) protein levels became elevated and ultimately resulted in an enhancement of CG. However, small interfering RNA (siRNA)-mediated knockdown of Sox9 during hMSC expansion was unable to negate the prochondrogenic effects of FGF-2, suggesting that the FGF-2-mediated enhancement of hMSC CG is only partly regulated through Sox9. Our findings provide new insights into the mechanism by which FGF-2 regulates predifferentiation hMSCs to undergo enhanced CG