Free-breathing 3D phase-resolved functional lung MRI vs breath-hold hyperpolarized Xe ventilation MRI in patients with chronic obstructive pulmonary disease and healthy volunteers.

Objectives: 3D phase-resolved functional lung (PREFUL) MRI offers evaluation of pulmonary ventilation without inhalation of contrast agent. This study seeks to compare ventilation maps obtained from 3D PREFUL MRI with a direct ventilation measurement derived from Xe MRI in both patients with chronic obstructive pulmonary disease (COPD) and healthy volunteers.

Methods: Thirty-one patients with COPD and 12 healthy controls underwent free-breathing 3D PREFUL MRI and breath-hold Xe MRI at 1.

Feasibility, Repeatability, and Correlation to Lung Function of Phase-Resolved Functional Lung (PREFUL) MRI-derived Pulmonary Artery Pulse Wave Velocity Measurements.

Background: Pulse wave velocity (PWV) in the pulmonary arteries (PA) is a marker of vascular stiffening. Currently, only phase-contrast (PC) MRI-based options exist to measure PA-PWV.

Purpose: To test feasibility, repeatability, and correlation to clinical data of Phase-Resolved Functional Lung (PREFUL) MRI-based calculation of PA-PWV.

Comparison of Free-Breathing 3D Phase-Resolved Functional Lung (PREFUL) MRI With Dynamic F Ventilation MRI in Patients With Obstructive Lung Disease and Healthy Volunteers.

Background: Non-contrast-enhanced H magnetic resonance imaging (MRI) with full lung coverage shows promise for assessment of regional lung ventilation but a comparison with direct ventilation measurement using F MRI is lacking.

Purpose: To compare ventilation parameters calculated using 3D phase-resolved functional lung (PREFUL) MRI with F MRI.

Study Type: Prospective.

Walking bumblebees see faster.

The behavioural state of animals has profound effects on neuronal information processing. Locomotion changes the response properties of visual interneurons in the insect brain, but it is still unknown if it also alters the response properties of photoreceptors. Photoreceptor responses become faster at higher temperatures.

Artificially-generated consolidations and balanced augmentation increase performance of U-net for lung parenchyma segmentation on MR images.

Purpose: To improve automated lung segmentation on 2D lung MR images using balanced augmentation and artificially-generated consolidations for training of a convolutional neural network (CNN).

Materials And Methods: From 233 healthy volunteers and 100 patients, 1891 coronal MR images were acquired. Of these, 1666 images without consolidations were used to build a binary semantic CNN for lung segmentation and 225 images (187 without consolidations, 38 with consolidations) were used for testing.

Intratumoral delivery of TransCon TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction.

Background: Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events.

Methods: To address these limitations, TransCon TLR7/8 Agonist-an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod-was developed.

Inflammatory response of monocytes to ambient particles varies by highway proximity.

Epidemiological studies have demonstrated associations of chronic respiratory disease with near-roadway pollutant exposure, effects that were independent of those of regional air pollutants. However, there has been limited study of the potential mechanisms for near-roadway effects. Therefore, we examined the in vitro effect of respirable particulate matter (PM) collected adjacent to a major Los Angeles freeway and at an urban background location.

Structural determinants of RGS-RhoGEF signaling critical to Entamoeba histolytica pathogenesis.

G protein signaling pathways, as key components of physiologic responsiveness and timing, are frequent targets for pharmacologic intervention. Here, we identify an effector for heterotrimeric G protein α subunit (EhGα1) signaling from Entamoeba histolytica, the causative agent of amoebic colitis. EhGα1 interacts with this effector and guanosine triphosphatase-accelerating protein, EhRGS-RhoGEF, in a nucleotide state-selective fashion.

Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.

Heterotrimeric G-protein signaling pathways are vital components of physiology, and many are amenable to pharmacologic manipulation. Here, we identify functional heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent of amoebic colitis. The E.

Structural determinants of affinity enhancement between GoLoco motifs and G-protein alpha subunit mutants.

GoLoco motif proteins bind to the inhibitory G(i) subclass of G-protein α subunits and slow the release of bound GDP; this interaction is considered critical to asymmetric cell division and neuro-epithelium and epithelial progenitor differentiation. To provide protein tools for interrogating the precise cellular role(s) of GoLoco motif/Gα(i) complexes, we have employed structure-based protein design strategies to predict gain-of-function mutations that increase GoLoco motif binding affinity. Here, we describe fluorescence polarization and isothermal titration calorimetry measurements showing three predicted Gα(i1) point mutations, E116L, Q147L, and E245L; each increases affinity for multiple GoLoco motifs.

A homogeneous method to measure nucleotide exchange by α-subunits of heterotrimeric G-proteins using fluorescence polarization.

The mainstay of assessing guanosine diphosphate release by the α-subunit of a heterotrimeric G-protein is the [³⁵S]guanosine 5'-O-(3-thiotriphosphate) (GTPγS) radionucleotide-binding assay. This assay requires separation of protein-bound GTPγS from free GTPγS at multiple time points followed by quantification via liquid scintillation. The arduous nature of this assay makes it difficult to quickly characterize multiple mutants, determine the effects of individual variables (e.

A capture coupling method for the covalent immobilization of hexahistidine tagged proteins for surface plasmon resonance.

Surface plasmon resonance (SPR) is a robust method to detect and quantify macromolecular interactions; however, to measure binding interactions, one component must be immobilized on a sensor surface. This is typically achieved using covalent immobilization via free amines or thiols, or noncovalent immobilization using high-affinity interactions such as biotin/streptavidin or antibody/antigen. In this chapter we describe a robust method to covalently immobilize His(6) fusion proteins on the sensor surface for SPR analysis.

A high throughput fluorescence polarization assay for inhibitors of the GoLoco motif/G-alpha interaction.

The GoLoco motif is a short Galpha-binding polypeptide sequence. It is often found in proteins that regulate cell-surface receptor signaling, such as RGS12, as well as in proteins that regulate mitotic spindle orientation and force generation during cell division, such as GPSM2/LGN. Here, we describe a high throughput fluorescence polarization (FP) assay using fluorophore-labeled GoLoco motif peptides for identifying inhibitors of the GoLoco motif interaction with the G-protein alpha subunit Galpha (i1).