Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing.

Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, low efficiencies or low specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples the programmability of prime editing with the ability of recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases. Evolved and engineered Bxb1 recombinase variants (evoBxb1 and eeBxb1) mediated up to 60% donor integration (3.

Trans- and Multigenerational Maternal Social Isolation Stress Programs the Blood Plasma Metabolome in the F3 Generation.

Metabolic risk factors are among the most common causes of noncommunicable diseases, and stress critically contributes to metabolic risk. In particular, social isolation during pregnancy may represent a salient stressor that affects offspring metabolic health, with potentially adverse consequences for future generations. Here, we used proton nuclear magnetic resonance (H NMR) spectroscopy to analyze the blood plasma metabolomes of the third filial (F3) generation of rats born to lineages that experienced either transgenerational or multigenerational maternal social isolation stress.

Identifying Core Values with a Hierarchical, Ipsative, Preference Assessment.

Values provide a foundation for decision making, behavior, and emotional reaction; they are often used by practitioners to design effective interventions for self-awareness and personal growth. This report describes a novel, user-friendly method that identifies core values with a hierarchical ipsatization procedure (HIP) that is transparent and efficient. Response bias, validity, and user satisfaction were examined in a study in which 602 respondents completed a survey asking them to rate 80 values and use HIP to identify their 4 most inspiring and motivating values.

Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus.

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long-Evans rats exposed to social isolation stress (SIS) during preconception and pregnancy across four generations (F0-F3).

Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation.

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8 T cells during early stages of activation. Mice receiving tumor-specific CD8 T cells treated with CDK4/6 inhibitors displayed increased T-cell persistence and immunologic memory.