An Unusual Presentation of Immunoglobulin G4-Related Disease (IgG4-RD) Causing Subglottic Stenosis

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that is known to involve multiple organs and was first described as an entity in 2003. It is characterized by lesions with a dense lymphoplasmacytic infiltrate, IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Organs that are commonly involved include the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, retroperitoneum, lungs, pleura, thyroid, aorta, and lymph nodes. Rarer manifestations of IgG4-RD include central nervous system (CNS) involvement, prostatitis, mastitis, midline destructive disease, and nasopharyngeal disease. In this report, we discuss an atypical case of a young woman with laryngeal subglottic involvement leading to stenosis and airway obstruction, which was ultimately successfully managed with systemic immunosuppression

Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy

To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration’s role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist’s role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy

Involvement of a Toxoplasma gondii Chromatin Remodeling Complex Ortholog in Developmental Regulation

The asexual cycle of the parasite Toxoplasma gondii has two developmental stages: a rapidly replicating form called a tachyzoite and a slow growing cyst form called a bradyzoite. While the importance of ATP-independent histone modifications for gene regulation in T. gondii have been demonstrated, ATP-dependent chromatin remodeling pathways have not been examined. In this study we characterized C9, an insertional mutant showing reduced expression of bradyzoite differentiation marker BAG1, in cultured human fibroblasts. This mutant contains an insertion in the gene encoding TgRSC8, which is homologous to the Saccharomyces cerevisiae proteins Rsc8p (remodel the structure of chromatin complex subunit 8) and Swi3p (switch/sucrose non-fermentable [SWI/SNF]) of ATP-dependent chromatin-remodeling complexes. In the C9 mutant, TgRSC8 is the downstream open reading frame on a dicistronic transcript. Though protein was expressed from the downstream gene of the dicistron, TgRSC8 levels were decreased in C9 from those of wild-type parasites, as determined by western immunoblot and flow cytometry. As TgRSC8 localized to the parasite nucleus, we postulated a role in gene regulation. Transcript levels of several markers were assessed by quantitative PCR to test this hypothesis. The C9 mutant displayed reduced steady state transcript levels of bradyzoite-induced genes BAG1, LDH2, SUSA1, and ENO1, all of which were significantly increased with addition of TgRSC8 to the mutant. Transcript levels of some bradyzoite markers were unaltered in C9, or unable to be increased by complementation with TgRSC8, indicating multiple pathways control bradyzoite-upregulated genes. Together, these data suggest a role for TgRSC8 in control of bradyzoite-upregulated gene expression. Thus chromatin remodeling, by both ATP-independent and dependent mechanisms, is an important mode of gene regulation during stage differentiation in parasites

A facile and fast method for the functionalization of polymersomes by photoinduced cycloaddition chemistry

Polymersomes are promising platforms for use in biosensing, where their stability may be crucial over that of liposomes. For the introduction of the desired functionality multiple strategies have been reported for functionalization of polymersomes. However, none of them have combined readily available starting materials, facility and in situ quantification. We show a simple 4-step method for functionalization of polymersomes starting from commercially available materials. For the key conjugation step a recently explored light induced cycloaddition was used which is relatively fast (15 min) and allows in situ quantification by the intrinsic fluorescence of the conjugate. The facility of the protocol, the ease of preparation and quantification make this ‘click’-type conjugation method a promising alternative to the established strained cycloadditions

Self-assembled architectures with multiple aqueous compartments

A vital organizational feature of living cells is that of compartmentalization. This allows cells to run concurrently incompatible metabolic processes and to regulate these processes by selective trans-membrane transport. Although strategies that effectively mimic cell function in simple architectures have been researched extensively, soft matter systems with membranes that delineate distinct and multiple aqueous environments have only recently caught attention. We highlight a range of multi-compartmentalized soft matter systems including vesosomes, capsosomes, polymersomes, double emulsions, and their combinations, and demonstrate that the unique properties of the multi-compartmentalized architectures have the potential to add value to application areas such as drug-delivery and multi-enzyme biosynthesis

Conformational antibody binding to a native, cell-free expressed GPCR in block copolymer membranes.

G-protein coupled receptors (GPCRs) play a key role in physiological processes and are attractive drug targets. Their biophysical characterization is, however, highly challenging because of their innate instability outside a stabilizing membrane and the difficulty of finding a suitable expression system. We here show the cell-free expression of a GPCR, CXCR4, and its direct embedding in diblock copolymer membranes. The polymer-stabilized CXCR4 is readily immobilized onto biosensor chips for label-free binding analysis. Kinetic characterization using a conformationally sensitive antibody shows the receptor to exist in the correctly folded conformation, showing binding behaviour that is commensurate with heterologously expressed CXCR4

A hydrogel-based enzyme-loaded polymersome reactor

In this study we report the immobilization of enzyme-containing polymersomes into a macromolecular hydrogel. Whereas free enzyme shows progressive leakage from the hydrogel in a period of days, leakage of the polymersome-protected enzyme is virtually absent. The preparation of the hydrogel occurs under mild conditions and does not inhibit the activity of the encapsulated enzymes nor does it affect the structure of the polymersomes. The stability of the polymersome hydrogel architecture is demonstrated by the facile recycling of the polymersomes and their use in repeated reaction cycles. A ‘continuous-flow polymersome reactor’ is constructed in which substrate is added to the top of the reactor and product is collected at the bottom. This set-up allows the use of different enzymes and the processing of multiple substrates, as is demonstrated by the conversion of 2-methoxyphenyl acetate to tetraguaiacol in a reactor loaded with polymersome hydrogels containing the enzymes Candida antarcticalipase B (CALB) and glucose oxidase (GOx).\ud \ud \ud \u

In Vitro Expressed GPCR Inserted in Polymersome Membranes for Ligand-Binding Studies

The dopamine receptor D2 (DRD2), a G-protein coupled receptor is expressed into PBd22-PEO13 and PMOXA20-PDMS54-PMOXA20 block copolymer vesicles (see scheme). The conformational integrity of the receptor is confirmed by antibody- and ligand-binding assays. Replacement of bound dopamine is demonstrated on surface-immobilized polymersomes, thus making this a promising platform for drug screening