Predictions are made of the equilibrium genetic variances and responses in a metric trait under the joint effects of directional selection, mutation and linkage in a finite population. The "infinitesimal model" is analyzed as the limiting case of many mutants of very small effect, otherwise Monte Carlo simulation is used. If the effects of mutant genes on the trait are symmetrically distributed and they are unlinked, the variance of mutant effects is not an important parameter. If the distribution is skewed, unless effects or the population size is small, the proportion of mutants that have increasing effect is the critical parameter. With linkage the distribution of genotypic values in the population becomes skewed downward and the equilibrium genetic variance and response are smaller as disequilibrium becomes important. Linkage effects are greater when the mutational variance is contributed by many genes of small effect than few of large effect, and are greater when the majority of mutants increase rather than decrease the trait because genes that are of large effect or are deleterious do not segregate for long. The most likely conditions for "Muller's ratchet" are investigated.
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http://dx.doi.org/10.1093/genetics/117.3.573 | DOI Listing |
ACS Nano
January 2025
Department of Bioengineering, University of Washington, Seattle, Washington 98195-5061, United States.
The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.
View Article and Find Full Text PDFTo assess whether spinal manipulative therapy (SMT) application procedures (ie, target, thrust, and region) impacted changes in pain and disability for adults with spine pain. Systematic review with network meta-analysis. We searched PubMed and Epistemonikos for systematic reviews indexed up to February 2022 and conducted a systematic search of 5 databases (MEDLINE, EMBASE, CENTRAL [Cochrane Central Register of Controlled Trials], PEDro [Physiotherapy Evidence Database], and Index to Chiropractic Literature) from January 1, 2018, to September 12, 2023.
View Article and Find Full Text PDFPLoS Biol
January 2025
Institute of Applied and Computational Mathematics, Foundation for Research and Technology Hellas, Heraklion, Crete, Greece.
Goal-directed behavior requires the effective suppression of distractions to focus on the task at hand. Although experimental evidence suggests that brain areas in the prefrontal and parietal lobe contribute to the selection of task-relevant and the suppression of task-irrelevant stimuli, how conspicuous distractors are encoded and effectively ignored remains poorly understood. We recorded neuronal responses from 2 regions in the prefrontal and parietal cortex of macaques, the frontal eye fields (FEFs) and the lateral intraparietal (LIP) area, during a visual search task, in the presence and absence of a salient distractor.
View Article and Find Full Text PDFJ Proteome Res
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Discovery Research, AbbVie, Inc., 1 North Waukegan Rd., North Chicago, Illinois 60064, United States.
Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small-molecule target selectivity and engagement. However, the tedious sample preparation steps and time-consuming MS acquisition process have limited its use in a high-throughput format. Here, we report an automated workflow employing biotinylated probes and streptavidin magnetic beads for small-molecule target enrichment in the 96-well plate format, ending with direct sampling from EvoSep Solid Phase Extraction tips for liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis.
View Article and Find Full Text PDFHormones (Athens)
January 2025
LABIOEX-Exercise Biology Lab, Department of Health Sciences, UFSC-Federal University of Santa Catarina, Araranguá, SC, Brazil.
The endocannabinoid system (ECS), regulating such processes as energy homeostasis, inflammation, and muscle function, centers around cannabinoid receptors, including CB1. These receptors are mainly located in the central nervous system and skeletal muscles. Hyperactivity of CB1 receptors is linked to metabolic disorders and chronic inflammation, highlighting their potential as therapeutic targets for muscle hypertrophy and metabolic health.
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