Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry.

Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

USP10 inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity.

Nrf2 is an antioxidant transcriptional activator in many types of cells, and its dysfunction plays key roles in a variety of human disorders, including Parkinson's disease (PD). PD is characterized by the selective loss of dopaminergic neurons in PD-affected brain regions. Dopamine treatment of neuronal cells stimulates the production of reactive oxygen species (ROS) and increases ROS-dependent neuronal apoptosis. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Taken together, these results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including PD.

G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10.

The aberrant accumulation of ubiquitinated protein aggregates in cells plays a critical role in the pathogenesis of several degenerative diseases, including Parkinson disease (PD) and cystic fibrosis (CF). In this study, we found that Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits ubiquitinated protein aggregations induced by p62 and USP10 in cultured cells. p62 is a ubiquitin receptor, and p62 and its binding partner USP10 have been shown to augment ubiquitinated protein aggregation. G3BP1 interacted with p62 and USP10 and inhibited p62/USP10-induced protein aggregation. The G3BP1 inhibition of protein aggregations targeted two aggregation-prone proteins, α-synuclein and CFTR-ΔF508, which are causative factors of PD and CF, respectively. G3BP1 depletion increased the amounts of ubiquitinated α-synuclein and CFTR-ΔF508 protein. A proteasome reporter indicated that G3BP1 depletion inhibits the proteasome activity. We herein present evidence that G3BP1, p62 and USP10 together control ubiquitinated protein toxicity by controlling both ubiquitination and aggregation. Taken together, these results suggest that G3BP1, p62 and USP10 could be therapeutic targets for ubiquitinated protein aggregation disorders, including PD and CF.

Interface dynamics: Mechanisms of stabilization and destabilization and structure of flow fields.

Interfacial mixing and transport are nonequilibrium processes coupling kinetic to macroscopic scales. They occur in fluids, plasmas, and materials over celestial events to atoms. Grasping their fundamentals can advance a broad range of disciplines in science, mathematics, and engineering. This paper focuses on the long-standing classic problem of stability of a phase boundary-a fluid interface that has a mass flow across it. We briefly review the recent advances in theoretical and experimental studies, develop the general theoretical framework directly linking the microscopic interfacial transport to the macroscopic flow fields, discover mechanisms of interface stabilization and destabilization that have not been discussed before for both inertial and accelerated dynamics, and chart perspectives for future research.

Tuned Mullins-Sekerka instability: exact results.

Mullins-Sekerka's instability at 3D self-similar growth of a spherical seed crystal in an undercooled fluid is discussed. The exact solution of the linearized stability problem is obtained. It is quite different from the conventional results of the quasisteady approximation. The instability occurs much weaker, so that instead of exponential growth in time, unstable modes exhibit just power-law-growth. The relative growth rates of different modes vary in time and depend on their initial amplitudes. It allows control over the growth of each mode individually and tailoring the instability, to obtain a desired shape of the growing crystal at a given time.

What is certain and what is not so certain in our knowledge of Rayleigh-Taylor mixing?

Past decades significantly advanced our understanding of Rayleigh-Taylor (RT) mixing. We briefly review recent theoretical results and numerical modelling approaches and compare them with state-of-the-art experiments focusing the reader's attention on qualitative properties of RT mixing.