Thermodynamic Stability Is a Poor Indicator of Cocrystallization in Models of Organic Molecules.

Cocrystallizing a given molecule with another can be useful for adjusting the physical properties of molecules in the solid state. However, most combinations of molecules do not readily cocrystallize but form either one-component crystals or amorphous solids. Computational methods of crystal structure prediction can, in principle, identify the thermodynamically stable cocrystal and thus predict if molecules will cocrystallize or not.

Pre-Nucleation Clusters Predict Crystal Structures in Models of Chiral Molecules.

Kinetics can play an important role in the crystallization of molecules and can give rise to polymorphism, the tendency of molecules to form more than one crystal structure. Current computational methods of crystal structure prediction, however, focus almost exclusively on identifying the thermodynamically stable polymorph. Kinetic factors of nucleation and growth are often neglected because the underlying microscopic processes can be complex and accurate rate calculations are numerically cumbersome.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case.

Varicella Vaccine Meningitis as a Complication of Herpes Zoster in Twice-Immunized Immunocompetent Adolescents.

Varicella-zoster virus vaccination is recommended for virtually all young children in the United States, Canada, and several other countries. Varicella vaccine is a live attenuated virus that retains some of its neurotropic properties. Herpes zoster caused by vaccine virus still occurs in immunized children, although the rate is much lower than in children who had wild-type varicella.

Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment.

The literature on the egress of different herpesviruses after secondary envelopment is contradictory. In this report, we investigated varicella-zoster virus (VZV) egress in a cell line from a child with Pompe disease, a glycogen storage disease caused by a defect in the enzyme required for glycogen digestion. In Pompe cells, both the late autophagy pathway and the mannose-6-phosphate receptor (M6PR) pathway are interrupted.

Heterogeneous Interactions Promote Crystallization and Spontaneous Resolution of Chiral Molecules.

Predicting the crystallization of chiral molecules from solution is a major challenge in the chemical sciences. In this paper, we use molecular dynamics computer simulations to study the crystallization of a family of coarse-grained models of chiral molecules with a broad range of molecular shapes and interactions. Our simulations reproduce the experimental crystallization behavior of real chiral molecules, including racemic and enantiopure crystals, as well as amorphous solids.

Responsive Nanoporous Membranes with Size Selectivity and Charge Rejection from Self-Assembly of Polyelectrolyte "Hairy" Nanoparticles.

We report the preparation and characterization of charged nanoporous membranes by self-assembly of "hairy" silica nanoparticles (HNPs) functionalized with polyelectrolyte copolymer brushes. We show that HNP membranes possess high water flux, have well-defined pore sizes, and rejection up to 80% of charged species in solution. The properties of these membranes can be tuned by controlling the length and composition of polymer brushes and the electrolyte concentration in solution.

Cellular Stress Response to Varicella-Zoster Virus Infection of Human Skin Includes Highly Elevated Interleukin-6 Expression.

Background: The infectious cycle of varicella-zoster virus (VZV) after reactivation from the dorsal root ganglia includes replication and assembly of complete enveloped virions in the human skin to cause the characteristic herpes zoster (shingles).

Methods: To pursue studies of innate immunity to VZV infection, we have adapted a fetal skin organ culture model to a human neonatal foreskin explant model.

Results: Abundant expression of VZV IE62, gE, and gC was visualized by confocal microscopy while numerous enveloped virions were observed by electron microscopy in infected skin organ cultures.

How Hot are Your Ions Really? A Threshold Collision-Induced Dissociation Study of Substituted Benzylpyridinium "Thermometer" Ions.

The first absolute experimental bond dissociation energies (BDEs) for the main heterolytic bond cleavages of four benzylpyridinium "thermometer" ions are measured using threshold collision-induced dissociation in a guided ion beam tandem mass spectrometer. In this experiment, substituted benzylpyridinium ions are introduced into the apparatus using an electrospray ionization source, thermalized, and collided with Xe at varied kinetic energies to determine absolute cross-sections for these reactions. Various effects are accounted for, including kinetic shifts, multiple collisions, and internal and kinetic energy distributions.

Varicella-Zoster Virus Infectious Cycle: ER Stress, Autophagic Flux, and Amphisome-Mediated Trafficking.

Varicella-zoster virus (VZV) induces abundant autophagy. Of the nine human herpesviruses, the VZV genome is the smallest (~124 kbp), lacking any known inhibitors of autophagy, such as the herpes simplex virus neurovirulence gene. Therefore, this review assesses the evidence for VZV-induced cellular stress, endoplasmic-reticulum-associated degradation (ERAD), and autophagic flux during the VZV infectious cycle.

Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways.

Unlabelled: Varicella-zoster virus (VZV) is an extremely cell-associated herpesvirus with limited egress of viral particles. The induction of autophagy in VZV-infected monolayers is easily detectable; inhibition of autophagy leads to decreased VZV glycoprotein biosynthesis and diminished viral titers. To explain how autophagic flux could exert a proviral effect on the VZV infectious cycle, we postulated that the VZV exocytosis pathway following secondary envelopment may converge with the autophagy pathway.

Defensive Perimeter in the Central Nervous System: Predominance of Astrocytes and Astrogliosis during Recovery from Varicella-Zoster Virus Encephalitis.

Unlabelled: Varicella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system.

The pros and cons of autophagic flux among herpesviruses.

Autophagy has been intensively studied in herpes simplex virus type 1 (HSV-1), a human alphaherpesvirus. The HSV-1 genome encodes a well-known neurovirulence protein called ICP34.5.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis.

Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA).

Methods: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining.

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection.

Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux.

Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells.

Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. The virus then establishes latency in the nervous system and re-emerges, typically decades later, as zoster or shingles. We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression.

Focal encephalitis following varicella-zoster virus reactivation without rash in a healthy immunized young adult.

Herein we describe an episode of focal varicella-zoster virus (VZV) encephalitis in a healthy young man with neither rash nor radicular pain. The symptoms began with headaches and seizures, after which magnetic resonance imaging detected a single hyperintense lesion in the left temporal lobe. Because of the provisional diagnosis of a brain tumor, the lesion was excised and submitted for pathological examination.

Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity.

Autophagy and the effects of its inhibition or induction were investigated during the entire infectious cycle of varicella-zoster virus (VZV), a human herpesvirus. As a baseline, we first enumerated the number of autophagosomes per cell after VZV infection compared with the number after induction of autophagy following serum starvation or treatment with tunicamycin or trehalose. Punctum induction by VZV was similar in degree to punctum induction by trehalose in uninfected cells.

Aberrant virion assembly and limited glycoprotein C production in varicella-zoster virus-infected neurons.

Highly pure (>95%) terminally differentiated neurons derived from pluripotent stem cells appear healthy at 2 weeks after infection with varicella-zoster virus (VZV), and the cell culture medium contains no infectious virus. Analysis of the healthy-appearing neurons revealed VZV DNA, transcripts, and proteins corresponding to the VZV immediate early, early, and late kinetic phases of replication. Herein, we further characterized virus in these neuronal cells, focusing on (i) transcription and expression of late VZV glycoprotein C (gC) open reading frame 14 (ORF14) and (ii) ultrastructural features of virus particles in neurons.

The attenuated genotype of varicella-zoster virus includes an ORF0 transitional stop codon mutation.

Varicella-zoster virus (VZV) is the first of the human herpesviruses to be attenuated and subsequently approved as a live vaccine to prevent varicella and herpes zoster. Both the attenuated VZV vaccine, called vaccine Oka or vOka, and the parental strain pOka have been completely sequenced. Yet the specific determinants of attenuation are uncertain.

Overview of varicella-zoster virus glycoproteins gC, gH and gL.

The VZV genome is smaller than the HSV genome and only encodes nine glycoproteins. This chapter provides an overview of three VZV glycoproteins: gH (ORF37), gL (ORF60), and gC (ORF14). All three glycoproteins are highly conserved among the alpha herpesviruses.

Enumeration of an extremely high particle-to-PFU ratio for Varicella-zoster virus.

Varicella-zoster virus (VZV) is renowned for its low titers. Yet investigations to explore the low infectivity are hampered by the fact that the VZV particle-to-PFU ratio has never been determined with precision. Herein, we accomplish that task by applying newer imaging technology.

Discordant varicella-zoster virus glycoprotein C expression and localization between cultured cells and human skin vesicles.

Because of its very low titer, varicella-zoster virus (VZV) infectivity is usually transferred by passage of trypsin dispersed infected cells. Previously, we observed that gC biosynthesis was markedly delayed in monolayers inoculated with cell free virus. In this report, we investigated the kinetics of gC expression in more detail and included studies of monolayers inoculated with trypsin dispersed infected cells, the more traditional method of VZV infection.