Comparative Study of T-Cell Repertoires after COVID-19 Immunization with Homologous or Heterologous Vaccine Booster.

Sequencing of the T-cell repertoire is an innovative method to assess the cellular responses after immunization. The purpose of this study was to compare T-cell repertoires after COVID-19 immunization with homologous (HOB) and heterologous (HEB) boosting. The study included 20 participants with a median age of 27.

Computational modeling identifies multitargeted kinase inhibitors as effective therapies for metastatic, castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC) is an advanced subtype of prostate cancer with limited therapeutic options. Here, we applied a systems-based modeling approach called kinome regularization (KiR) to identify multitargeted kinase inhibitors (KIs) that abrogate CRPC growth. Two predicted KIs, PP121 and SC-1, suppressed CRPC growth in two-dimensional in vitro experiments and in vivo subcutaneous xenografts.

KiRNet: Kinase-centered network propagation of pharmacological screen results.

The ever-increasing size and scale of biological information have popularized network-based approaches as a means to interpret these data. We develop a network propagation method that integrates kinase-inhibitor-focused functional screens with known protein-protein interactions (PPIs). This method, dubbed KiRNet, uses an a edge-weighting strategy based on node degree to establish a pipeline from a kinase inhibitor screen to the generation of a predictive PPI subnetwork.

KInhibition: A Kinase Inhibitor Selection Portal.

Protein kinases constitute a large class of signaling molecules frequently targeted in research and clinical uses. However, kinase inhibitors are notoriously non-specific, making it difficult to select an appropriate inhibitor for a given kinase. Available data from large-scale kinase inhibitor screens are often difficult to query.

Semi-automated quantification and neuroanatomical mapping of heterogeneous cell populations.

Background: Our group studies the interactions between cells of the brain and the neurotropic parasite Toxoplasma gondii. Using an in vivo system that allows us to permanently mark and identify brain cells injected with Toxoplasma protein, we have identified that Toxoplasma-injected neurons (TINs) are heterogeneously distributed throughout the brain. Unfortunately, standard methods to quantify and map heterogeneous cell populations onto a reference brain atlas are time consuming and prone to user bias.

A comprehensive evaluation of increasing temporal resolution with multiband-accelerated protocols and effects on statistical outcome measures in fMRI.

Accelerated functional Magnetic Resonance Imaging (fMRI) with 'multiband' protocols is now relatively widespread. These protocols can be used to dramatically reduce the repetition time (TR) and produce a time-series sampled at a higher temporal resolution, which may produce benefits in the statistical methods typically used to analyse fMRI data. We tested the effects of higher temporal resolutions for fMRI on statistical outcome measures in a comprehensive manner on two different MRI scanner platforms.

Inducible CRISPR genome editing platform in naive human embryonic stem cells reveals JARID2 function in self-renewal.

To easily edit the genome of naïve human embryonic stem cells (hESC), we introduced a dual cassette encoding an inducible Cas9 into the AAVS1 site of naïve hESC (iCas9). The iCas9 line retained karyotypic stability, expression of pluripotency markers, differentiation potential, and stability in 5iLA and EPS pluripotency conditions. The iCas9 line induced efficient homology-directed repair (HDR) and non-homologous end joining (NHEJ) based mutations through CRISPR-Cas9 system.

Identifying host regulators and inhibitors of liver stage malaria infection using kinase activity profiles.

Plasmodium parasites have extensive needs from their host hepatocytes during the obligate liver stage of infection, yet there remains sparse knowledge of specific host regulators. Here we assess 34 host-targeted kinase inhibitors for their capacity to eliminate Plasmodium yoelii-infected hepatocytes. Using pre-existing activity profiles of each inhibitor, we generate a predictive computational model that identifies host kinases, which facilitate Plasmodium yoelii liver stage infection.

Comparison of two fecal egg recovery techniques and larval culture for cyathostomins in horses.

Objective: To compare the McMaster and centrifugal flotation techniques and larval culture for recovery of cyathostomin (small strongyle) eggs from the feces of horses.

Sample Population: Fecal samples from 101 horses.

Procedures: In experiment I, homogenized fresh feces from a single horse were randomly subsampled by use of each technique for 10 replicates.