Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs

Background: Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals. Methods: The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR. Results: PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells. Conclusion: These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells.Peer Reviewe

Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs

Background Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals. Methods The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR. Results PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells. Conclusion These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells

Origin of anomalously long interatomic distances in suspended gold chains

The discovery of long bonds in gold atom chains has represented a challenge for physical interpretation. In fact, interatomic distances frequently attain 3.0-3.6 A values and, distances as large as 5.0 A may be seldom observed. Here, we studied gold chains by transmission electron microscopy and performed theoretical calculations using cluster ab initio density functional formalism. We show that the insertion of two carbon atoms is required to account for the longest bonds, while distances above 3 A may be due to a mixture of clean and one C atom contaminated bonds.Comment: 4 pages, 4 Postscript figures, to be published in Physical Review Letter

Modification and preservation of environmental signals in speleothems

Speleothems are primarily studied in order to generate archives of climatic change and results have led to significant advances in identifying and dating major shifts in the climate system. However, the climatological meaning of many speleothem records cannot be interpreted unequivocally; this is particularly so for more subtle shifts and shorter time periods, but the use of multiple proxies and improving understanding of formation mechanisms offers a clear way forward. An explicit description of speleothem records as time series draws attention to the nature and importance of the signal filtering processes by which the weather, the seasons and longer-term climatic and other environmental fluctuations become encoded in speleothems. We distinguish five sources of variation that influence speleothem geochemistry: atmospheric, vegetation/soil, karstic aquifer, primary speleothem crystal growth and secondary alteration and give specific examples of their influence. The direct role of climate diminishes progressively through these five factors. \ud \ud We identify and review a number of processes identified in recent and current work that bear significantly on the conventional interpretation of speleothem records, for example: \ud \ud 1) speleothem geochemistry can vary seasonally and hence a research need is to establish the proportion of growth attributable to different seasons and whether this varies over time. \ud \ud 2) whereas there has traditionally been a focus on monthly mean Ã�´18O data of atmospheric moisture, current work emphasizes the importance of understanding the synoptic processes that lead to characteristic isotope signals, since changing relative abundance of different weather types might 1Corresponding author, fax +44(0)1214145528, E-mail: [email protected] control their variation on the longer-term. \ud \ud 3) the ecosystem and soil zone overlying the cave fundamentally imprint the carbon and trace element signals and can show characteristic variations with time. \ud \ud 4) new modelling on aquifer plumbing allows quantification of the effects of aquifer mixing. \ud \ud 5) recent work has emphasized the importance and seasonal variability of CO2-degassing leading to calcite precipitation upflow of a depositional site on carbon isotope and trace element composition of speleothems. \ud \ud 6) Although much is known about the chemical partitioning between water and stalagmites, variability in relation to crystal growth mechanisms and kinetics is a research frontier. \ud \ud 7) Aragonite is susceptible to conversion to calcite with major loss of chemical information, but the controls on the rate of this process are obscure. \ud \ud Analytical factors are critical to generate high-resolution speleothem records. A variety of methods of trace element analysis are available, but standardization is a common problem with the most rapid methods. New stable isotope data on Irish stalagmite CC3 compares rapid laser-ablation techniques with the conventional analysis of micromilled powders and ion microprobe methods. A high degree of comparability between techniques for Ã�´18O is found on the mm-cm scale, but a previously described high-amplitude oxygen isotope excursion around 8.3 ka is identified as an analytical artefact related to fractionation of the laser-analysis associated with sample cracking. High-frequency variability of not less than 0.5o/oo may be an inherent feature of speleothem Ã�´18O records

Revealing the pace of river landscape evolution during the Quaternary: recent developments in numerical dating methods

During the last twenty years, several technical developments have considerably intensified the use of numerical dating methods for the Quaternary. The study of fluvial archives has greatly benefited from these enhancements, opening new dating horizons for a range of archives at distinct time scales and thereby providing new insights into previously unanswered questions. In this contribution, we separately present the state of the art of five numerical dating methods that are frequently used in the fluvial context: radiocarbon, Luminescence, Electron Spin Resonance (ESR), 230Th/U and terrestrial cosmogenic nuclides (TCN) dating. We focus on the major recent developments for each technique that are most relevant for new dating applications in diverse fluvial environments and on explaining these for non-specialists. Therefore, essential information and precautions about sampling strategies in the field and/or laboratory procedures are provided. For each method, new and important implications for chronological reconstructions of Quaternary fluvial landscapes are discussed and, where necessary, exemplified by key case studies. A clear statement of the current technical limitations of these methods is included and forthcoming developments, which might possibly open new horizons for dating fluvial archives in the near future, are summarised

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

© 2008 Ebert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to searchfor astrophysical neutrino sources. It has so far provided compelling evidencefor a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observedin coincidence with the high-energy neutrino IceCube-170922A detected byIceCube. The detection of very-high-energy gamma rays (VHE, $\mathrm{E} >100\,\mathrm{GeV}$) from this source helped establish the coincidence andconstrained the modeling of the blazar emission at the time of the IceCubeevent. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) -FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program oftarget-of-opportunity observations of neutrino alerts sent by IceCube. Thisprogram has two main components. One are the observations of known gamma-raysources around which a cluster of candidate neutrino events has been identifiedby IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of singlehigh-energy neutrino candidate events of potential astrophysical origin such asIceCube-170922A. GFU has been recently upgraded by IceCube in collaborationwith the IACT groups. We present here recent results from the IACT follow-upprograms of IceCube neutrino alerts and a description of the upgraded IceCubeGFU system.<br