Lasting differential gene expression of circulating CD8 T cells in chronic HCV infection with cirrhosis identifies a role for Hedgehog signaling in cellular hyperfunction.

Background: The impact of chronic hepatic infection on antigen non-specific immune cells in circulation remains poorly understood. We reported lasting global hyperfunction of peripheral CD8 T cells in HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known.

SARS-CoV-2 antigen-carrying extracellular vesicles activate T cell responses in a human immunogenicity model.

Extracellular vesicles (EVs) are entering the clinical arena as novel biologics for infectious diseases, potentially serving as the immunogenic components of next generation vaccines. However, relevant human assays to evaluate the immunogenicity of EVs carrying viral antigens are lacking, contributing to challenges in translating rodent studies to human clinical trials. Here, we engineered EVs to carry SARS-CoV-2 Spike to evaluate the immunogenicity of antigen-carrying EVs using human peripheral blood mononuclear cells (PBMCs).

Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition.

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates.

Synthesis and characterization of thermally responsive N-isopropylacrylamide hydrogels copolymerized with novel hydrophobic polyphenolic crosslinkers.

Two series of thermosensitive hydrogels were synthesized by copolymerizing N-isopropylacrylamide (NIPAAm) with various contents of novel hydrophobic crosslinkers, curcumin multiacrylate (CMA) and quercetin multiacrylate (QMA). The compositions of the resulting hydrogels were characterized using solid state-NMR (ss-NMR), and the temperature dependent swelling behavior and lower critical solution temperature (LCST) were characterized using swelling studies and differential scanning calorimetry (DSC). Increasing the crosslinker content resulted in a significant decrease in the LCST and swelling ratio of hydrogels, which could be attributed to the increased hydrophobicity introduced by CMA or QMA.

Characterization of Synthesized and Commercial Forms of Magnesium Stearate Using Differential Scanning Calorimetry, Thermogravimetric Analysis, Powder X-Ray Diffraction, and Solid-State NMR Spectroscopy.

Magnesium stearate is the salt of a complex mixture of fatty acids, with the majority being stearate and palmitate. It has multiple crystalline forms and, potentially, an amorphous form. Magnesium stearate is used in the pharmaceutical manufacturing industry as a powder lubricant, and typically is added at low levels (∼1%) during the manufacturing process and blended for a relatively short time (∼5 min).

Terahertz spectroscopy and computational investigation of the flufenamic acid/nicotinamide cocrystal.

Terahertz spectroscopy probes the low-frequency vibrations that are sensitive to both the intermolecular and intramolecular interactions of molecules in the solid state. Thus, terahertz spectroscopy can be a useful tool in the investigation of crystalline pharmaceutical compounds, where slight changes in the packing arrangement can modify the overall effectiveness of a drug formulation. This is especially true for cases of polymorphic systems, hydrates/solvates, and cocrystals.

The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease, best characterized by the formation of proliferative nodules that express smooth muscle and melanocytic antigens within the lung parenchyma, leading to progressive destruction of lung tissue and function. The pathological basis of LAM is associated with Tuberous Sclerosis Complex (TSC), a multi-system disorder marked by low-grade tumors in the brain, kidneys, heart, eyes, lung and skin, arising from inherited or spontaneous germ-line mutations in either of the TSC1 or TSC2 genes. LAM can develop either in a patient with TSC (TSC-LAM) or spontaneously (S-LAM), and it is clear that the majority of LAM lesions of both forms are characterized by an inactivating mutation in either TSC1 or TSC2, as in TSC.

Terahertz vibrational modes of the rigid crystal phase of succinonitrile.

Succinonitrile (N ≡ C-CH2-CH2-C ≡ N), an orientationally disordered molecular plastic crystal at room temperature, exhibits rich phase behavior including a solid-solid phase transition at 238 K. In cooling through this phase transition, the high-temperature rotational disorder of the plastic crystal phase is frozen out, forming a rigid crystal that is both spatially and orientationally ordered. Using temperature-dependent terahertz time-domain spectroscopy, we characterize the vibrational modes of this low-temperature crystalline phase for frequencies from 0.

Using terahertz spectroscopy and solid-state density functional theory to characterize a new polymorph of 5-(4-pyridyl)tetrazole.

A new high-temperature polymorph of 5-(4-pyridyl)tetrazole has been discovered and characterized using X-ray crystallography and terahertz (THz) spectroscopy. The THz spectrum of the new polymorph was compared to the previously published form and was replicated by means of solid-state density functional theory. Terahertz spectroscopy was used to determine the influence of the different packing motifs on the molecular and low energy lattice vibrations displayed in the region from 10 to 100 cm(-1).

Investigating tautomeric polymorphism in crystalline anthranilic acid using terahertz spectroscopy and solid-state density functional theory.

Terahertz spectroscopy is sensitive to the interactions between molecules in the solid-state and recently has emerged as a new analytical tool for investigating polymorphism. Here, this technique is applied for the first time to the phenomenon of tautomeric polymorphism where the crystal structures of anthranilic acid (2-aminobenzoic acid) have been investigated. Three polymorphs of anthranilic acid (denoted Forms I, II and III) were studied using terahertz spectroscopy and the vibrational modes and relative polymorph stabilities analyzed using solid-state density functional theory calculations augmented with London dispersion force corrections.