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Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.
Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the leading cause of mortality in HIV infection. KSHV reactivation from latent- to lytic-stage infection initiates a cascade of viral gene expression. Here we show how these changes remodel the host cell proteome to enable viral replication. By undertaking a systematic and unbiased analysis of changes to the endothelial cell proteome following KSHV reactivation, we quantify >7,000 cellular proteins and 71 viral proteins and provide a temporal profile of protein changes during the course of lytic KSHV infection. Lytic KSHV induces >2-fold downregulation of 291 cellular proteins, including PKR, the key cellular sensor of double-stranded RNA. Despite the multiple episomes per cell, CRISPR-Cas9 efficiently targets KSHV genomes. A complementary KSHV genome-wide CRISPR genetic screen identifies K5 as the viral gene responsible for the downregulation of two KSHV targets, Nectin-2 and CD155, ligands of the NK cell DNAM-1 receptor.Horizon 2020/grant agreement no. 656511
Deutsche Forschungsgemeinschaft – SFB900/3 – 158989968; project C1
High-Resolution spectroscopy of the low-mass X-ray binary EXO 0748-67
We present initial results from observations of the low-mass X-ray binary EXO
0748-67 with the Reflection Grating Spectrometer on board the XMM-Newton
Observatory. The spectra exhibit discrete structure due to absorption and
emission from ionized neon, oxygen, and nitrogen. We use the quantitative
constraints imposed by the spectral features to develop an empirical model of
the circumsource material. This consists of a thickened accretion disk with
emission and absorption in the plasma orbiting high above the binary plane.
This model presents challenges to current theories of accretion in X-ray binary
systems.Comment: 5 pages, 4 figures, accepted by A&A letters, XMM special issu
A large-scale proteomic analysis of human embryonic stem cells
<p>Abstract</p> <p>Background</p> <p>Much of our current knowledge of the molecular expression profile of human embryonic stem cells (hESCs) is based on transcriptional approaches. These analyses are only partly predictive of protein expression however, and do not shed light on post-translational regulation, leaving a large gap in our knowledge of the biology of pluripotent stem cells.</p> <p>Results</p> <p>Here we describe the use of two large-scale western blot assays to identify over 600 proteins expressed in undifferentiated hESCs, and highlight over 40 examples of multiple gel mobility variants, which are suspected protein isoforms and/or post-translational modifications. Twenty-two phosphorylation events in cell signaling molecules, as well as potential new markers of undifferentiated hESCs were also identified. We confirmed the expression of a subset of the identified proteins by immunofluorescence and correlated the expression of transcript and protein for key molecules in active signaling pathways in hESCs. These analyses also indicated that hESCs exhibit several features of polarized epithelia, including expression of tight junction proteins.</p> <p>Conclusion</p> <p>Our approach complements proteomic and transcriptional analysis to provide unique information on human pluripotent stem cells, and is a framework for the continued analyses of self-renewal.</p
Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae
Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant Saccharomyces cerevisiae strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p(1-989)), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p(1-989) increased tolerance toward two other monoterpenes (beta-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p(1-989) is the first example of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C-10 alkenes in yeast
Ac hopping conduction at extreme disorder takes place on the percolating cluster
Simulations of the random barrier model show that ac currents at extreme
disorder are carried almost entirely by the percolating cluster slightly above
threshold; thus contradicting traditional theories contributions from isolated
low-activation-energy clusters are negligible. The effective medium
approximation in conjunction with the Alexander-Orbach conjecture leads to an
excellent analytical fit to the universal ac conductivity with no nontrivial
fitting parameters
App-based rehabilitation program after total knee arthroplasty: a randomized controlled trial
Introduction: New app-based programs for postoperative rehabilitation have been developed, but no long-term study has been published to date. Thus, a prospective randomized control trial with 2-year follow-up was performed to evaluate the effectiveness of app-based rehabilitation (GenuSport) compared to a control group after total knee arthroplasty (TKA).
Methods: Between April and October 2016, 60 patients were enrolled in the study. Twenty-five patients were lost to follow-up, leaving 35 patients undergoing TKA for inclusion. In this group, twenty patients received app-based exercise program and 15 were randomized to the control group. The mean age was 64.37 +/- 9.32 years with a mean follow-up of 23.51 +/- 1.63 months. Patients in the app group underwent an app-based knee training starting on the day of surgery; whereas, patients in the control group underwent regular physiotherapy. Functional outcome scores using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS) and VAS of pain were analyzed.
Results: In the short term, significant differences between the app group and control group in time of 10-m walk (19.66 +/- 7.80 vs. 27.08 +/- 15.46 s; p = 0.029), VAS pain at rest and activity (2.65 +/- 0.82 vs. 3.57 +/- 1.58, respectively 4.03 +/- 1.26 vs. 5.05 +/- 1.21; p < 0.05) were observed. In the long term, a variety of different tendencies was found, highest in KSS Function with 76.32 +/- 16.49 (app group) vs. 67.67 +/- 16.57 (control group) (p = 0.130). Additionally, patients in the app group required less painkillers (10.0% vs. 26.7%) and more likely to participate in sports (65.0% vs. 53.3%).
Conclusions: An app-based knee trainer is a promising tool in improving functional outcomes such as KSS function score and VAS after TKA
Discovery of Selective Inhibitors Against EBNA1 via High Throughput In Silico Virtual Screening
Background: Epstein-Barr Virus (EBV) latent infection is associated with several human malignancies and is a causal agent of lymphoproliferative diseases during immunosuppression. While inhibitors of herpesvirus DNA polymerases, like gancyclovir, reduce EBV lytic cycle infection, these treatments have limited efficacy for treating latent infection. EBNA1 is an EBVencoded DNA-binding protein required for viral genome maintenance during latent infection. Methodology: Here, we report the identification of a new class of small molecules that inhibit EBNA1 DNA binding activity. These compounds were identified by virtual screening of 90,000 low molecular mass compounds using computational docking programs with the solved crystal structure of EBNA1. Four structurally related compounds were found to inhibit EBNA1-DNA binding in biochemical assays with purified EBNA1 protein. Compounds had a range of 20–100 mM inhibition of EBNA1 in fluorescence polarization assays and were further validated for inhibition using electrophoresis mobility shift assays. These compounds exhibited no significant inhibition of an unrelated DNA binding protein. Three of these compounds inhibited EBNA1 transcription activation function in cell-based assays and reduced EBV genome copy number when incubated with a Burkitt lymphoma cell line. Conclusions: These experiments provide a proof-of-principle that virtual screening can be used to identify specific inhibitor
The NY-Ă…lesund TurbulencE Fiber Optic eXperiment (NYTEFOX): investigating the Arctic boundary layer, Svalbard
The NY-Ă…lesund TurbulencE Fiber Optic eXperiment (NYTEFOX) was a field experiment at the
Ny-Ă…lesund Arctic site (78.9â—¦ N, 11.9â—¦ E) and yielded a unique meteorological data set. These data describe the
distribution of heat, airflows, and exchange in the Arctic boundary layer for a period of 14 d from 26 February
to 10 March 2020. NYTEFOX is the first field experiment to investigate the heterogeneity of airflow and its
transport of temperature, wind, and kinetic energy in the Arctic environment using the fiber-optic distributed
sensing (FODS) technique for horizontal and vertical observations. FODS air temperature and wind speed were
observed at a spatial resolution of 0.127 m and a temporal resolution of 9 s along a 700 m horizontal array at
1 m above ground level (a.g.l.) and along three 7 m vertical profiles. Ancillary data were collected from three
sonic anemometers and an acoustic profiler (minisodar; sodar is an acronym for “sound detection and ranging”)
yielding turbulent flow statistics and vertical profiles in the lowest 300 m a.g.l., respectively. The observations
from this field campaign are publicly available on Zenodo (https://doi.org/10.5281/zenodo.4756836, Huss et al.,
2021) and supplement the meteorological data set operationally collected by the Baseline Surface Radiation
Network (BSRN) at Ny-Ă…lesund, Svalbard
New Types of Off-Diagonal Long Range Order in Spin-Chains
We discuss new possibilities for Off-Diagonal Long Range Order (ODLRO) in
spin chains involving operators which add or delete sites from the chain. For
the Heisenberg and Inverse Square Exchange models we give strong numerical
evidence for the hidden ODLRO conjectured by Anderson \cite{pwa_conj}. We find
a similar ODLRO for the XY model (or equivalently for free fermions in one
spatial dimension) which we can demonstrate rigorously, as well as numerically.
A connection to the singlet pair correlations in one dimensional models of
interacting electrons is made and briefly discussed.Comment: 13 pages, Revtex v3.0, 2 PostScript figures include
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