Transient Reversal of Episome Silencing Precedes VP16-Dependent Transcription during Reactivation of Latent HSV-1 in Neurons

Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Identification of a Cessna Citation II Model Based on Flight Test Data

As a result of new aviation legislation, from 2019 on all air-carrier pilots are obliged to go through flight simulator-based stall recovery training. For this reason the Control and Simulation division at Delft University of Technology has set up a task force to develop a new methodology for high-fidelity aircraft stall behavior modeling and simulation. As part of this research project, the development of a new high-fidelity Cessna II simulation model, valid throughout the normal, pre-stall flight envelope, is presented in this paper. From an extensive collection of flight test data, aerodynamic model identification was performed using the Two-Step Method. New in this approach is the use of the Unscented Kalman Filter for an improved accuracy and robustness of the state estimation step. Also, for the first time an explicit data-driven model structure selection is presented for the Citation II by making use of an orthogonal regression scheme. This procedure has indicated that most of the six non-dimensional forces and moments can be parametrized sufficiently by a linear model structure. It was shown that only the translational and lateral aerodynamic force models would benefit from the addition of higher order terms, more specifically the squared angle of attack and angle of sideslip. The newly identified aerodynamic model was implemented into an upgraded version of the existing simulation framework and will serve as a basis for the integration of a stall and post-stall model.Control & Simulatio