Non-structural proteins of arthropod-borne bunyaviruses: roles and functions

Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod

Aticaprant: (a κ-opioid receptor antagonist) for major depressive disorder

INTRODUCTION: Major depression is a common, disabling mental health condition associated with the highest disease burden for any neuropsychiatric disorder worldwide, according to the WHO. Due to the imperfect efficacy and tolerability profiles of existing treatments, investigational compounds in novel treatment classes are needed. Opioid-receptor antagonists are a potential new class of treatments currently under investigation.AREAS COVERED: Major depressive disorder is first overviewed. Existing treatments, both their mechanisms of action and their place within the antidepressant space, are discussed herein. Then, the profile of Aticaprant and the wider context of kappa-opioid antagonism for depression are discussed in focus.EXPERT OPINION: Early evidence indicates that Aticaprant may possess desirable pharmacodynamic and pharmacokinetic properties. A lack of convincing efficacy data at the time of writing precludes any definitive statement on its potential as an antidepressant.</p

Exploiting Equivariance in the Design of Tracking Controllers for Euler-Poincare Systems on Matrix Lie Groups

The trajectory tracking problem is a fundamental control task in the study of mechanical systems. A key construction in tracking control is the error or difference between an actual and desired trajectory. This construction also lies at the heart of observer design and recent advances in the study of equivariant systems have provided a template for global error construction that exploits the symmetry structure of a group action if such a structure exists. Hamiltonian systems are posed on the cotangent bundle of configuration space of a mechanical system and symmetries for the full cotangent bundle are not commonly used in geometric control theory. In this paper, we propose a group structure on the cotangent bundle of a Lie group and leverage this to define momentum and configuration errors for trajectory tracking drawing on recent work on equivariant observer design. We show that this error definition leads to error dynamics that are themselves ``Euler-Poincare like'' and use these to derive simple, almost global trajectory tracking control for fully-actuated Euler-Poincare systems on a Lie group state space

Exploiting Equivariance in the Design of Tracking Controllers for Euler-Poincare Systems on Matrix Lie Groups

The trajectory tracking problem is a fundamental control task in the study of mechanical systems. A key construction in tracking control is the error or difference between an actual and desired trajectory. This construction also lies at the heart of observer design and recent advances in the study of equivariant systems have provided a template for global error construction that exploits the symmetry structure of a group action if such a structure exists. Hamiltonian systems are posed on the cotangent bundle of configuration space of a mechanical system and symmetries for the full cotangent bundle are not commonly used in geometric control theory. In this paper, we propose a group structure on the cotangent bundle of a Lie group and leverage this to define momentum and configuration errors for trajectory tracking drawing on recent work on equivariant observer design. We show that this error definition leads to error dynamics that are themselves ``Euler-Poincare like'' and use these to derive simple, almost global trajectory tracking control for fully-actuated Euler-Poincare systems on a Lie group state space.Comment: Preprint for LHMNC202

Exploiting Different Symmetries for Trajectory Tracking Control with Application to Quadrotors

High performance trajectory tracking control of quadrotor vehicles is an important challenge in aerial robotics. Symmetry is a fundamental property of physical systems and offers the potential to provide a tool to design high-performance control algorithms. We propose a design methodology that takes any given symmetry, linearises the associated error in a single set of coordinates, and uses LQR design to obtain a high performance control; an approach we term Equivariant Regulator design. We show that quadrotor vehicles admit several different symmetries: the direct product symmetry, the extended pose symmetry and the pose and velocity symmetry, and show that each symmetry can be used to define a global error. We compare the linearised systems via simulation and find that the extended pose and pose and velocity symmetries outperform the direct product symmetry in the presence of large disturbances. This suggests that choices of equivariant and group affine symmetries have improved linearisation error

A role for SSU72 in balancing RNA polymerase II transcription elongation and termination

Interactions of pre-mRNA 3&prime;end factors and the CTD of RNA polymerase II (RNAP II) are required for transcription termination and 3&prime;end processing. Here, we demonstrate that Ssu72p is stably associated with yeast cleavage and polyadenylation factor CPF and provide evidence that it bridges the CPF subunits Pta1p and Ydh1p/Cft2p, the general transcription factor TFIIB, and RNAP II via Rpb2p. Analyses of ssu72-2 mutant cells in the absence and presence of the nuclear exosome component Rrp6p revealed defects in RNAP II transcription elongation and termination. 6-azauracil, that reduces transcription elongation rates, suppressed the ssu72-2 growth defect at 33&deg;C. The sum of our analyses suggests a negative influence of Ssu72p on RNAP II during transcription that affects the commitment to either elongation or termination.<br /