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Pre-existence and emergence of drug resistance in a generalized model of intra-host viral dynamics
(2012)EpidemicsUnderstanding the source of drug resistance emerging within a treated patient is an important problem, from both clinical and basic evolutionary perspectives. Resistant mutants may arise de novo either before or after treatment is initiated, with different implications for prevention. Here we investigate this problem in the context of chronic viral diseases, such as human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and ...Journal Article -
Advanced radiometry measurements and Earth science applications with the Airborne Prism Experiment (APEX)
(2015)Remote Sensing of EnvironmentWe present the Airborne Prism Experiment (APEX), its calibration and subsequent radiometric measurements as well as Earth science applications derived from this data. APEX is a dispersive pushbroom imaging spectrometer covering the solar reflected wavelength range between 372 and 2540 nm with nominal 312 (max. 532) spectral bands. APEX is calibrated using a combination of laboratory, in-flight and vicarious calibration approaches. These ...Journal Article -
Vaccinia Virus Entry Is Followed by Core Activation and Proteasome-Mediated Release of the Immunomodulatory Effector VH1 from Lateral Bodies
(2013)Cell ReportsHost cell entry of vaccinia virus, the prototypic poxvirus, involves a membrane fusion event delivering the viral core and two proteinaceous lateral bodies (LBs) into the cytosol. Uncoating of viral cores is poorly characterized, and the composition and function of LBs remains enigmatic. We found that cytosolic cores rapidly dissociated from LBs and expanded in volume, which coincided with reduction of disulfide-bonded core proteins. We ...Journal Article -
Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve
(2013)Cell ReportsSchwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the ...Journal Article -
The RNA methyltransferase dnmt2 is required for efficient dicer-2-dependent siRNA pathway activity in Drosophila
(2013)Cell ReportsTransfer RNA (tRNA) fragmentation in response to stress conditions has been described in many organisms. tRNA fragments have been found in association with small interfering RNA (siRNA) components, but the biological role of these interactions remains unclear. We report here that the tRNA methyltransferase Dnmt2 is essential for efficient Dicer-2 (Dcr-2) function in Drosophila. Using small RNA (sRNA) sequencing, we confirmed that Dnmt2 ...Journal Article -
Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues
(2014)Cell ReportsOne promising approach for in vivo studies of cell proliferation is the FUCCI system (fluorescent ubiquitination-based cell cycle indicator). Here, we report the development of a Drosophila-specific FUCCI system (Fly-FUCCI) that allows one to distinguish G1, S, and G2 phases of interphase. Fly-FUCCI relies on fluorochrome-tagged degrons from the Cyclin B and E2F1 proteins, which are degraded by the ubiquitin E3-ligases APC/C and CRL4Cdt2, ...Journal Article -
TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy
(2013)Cell ReportsVery long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell’s metabolic demand remains unknown. The goal of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated ...Journal Article -
PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts
(2013)Cell Death & DiseasePrimary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstand high doses of irradiation and to prevent irradiation-induced apoptosis. However, the underlying regulatory basis for this ...Journal Article -
Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis
(2014)Cell ReportsResolution of inflammation reduces pathological tissue destruction and restores tissue homeostasis. Here, we used a proteomic protease substrate discovery approach, terminal amine isotopic labeling of substrates (TAILS), to analyze the role of the macrophage-specific matrix metalloproteinase-12 (MMP12) in inflammation. In murine peritonitis, MMP12 inactivates antithrombin and activates prothrombin, prolonging the activated partial ...Journal Article -
Antiviral RNA Silencing in Mammals: No News Is Not Good News
(2014)Cell ReportsOther Journal Item