Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.

Background: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

Methods: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance.

A pragmatic clinical trial of cascade testing for familial hypercholesterolemia.

Purpose: We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology.

Methods: We enrolled 52 FH probands with a pathogenic variant (FH) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FH). After direct contact by the study team, family members (FMs) of FH probands could opt-in for genetic testing and FMs of FH probands were asked to provide a lipid profile.

Systematic Review of Aptamer Sequence Reporting in the Literature Reveals Widespread Unexplained Sequence Alterations.

Aptamers have been the subject of more than 144 000 papers to date. However, there has been a growing concern that discrepancies in the reporting of aptamer research limit the reliability of these reagents for research and other applications. These observations noting inconsistencies in the use of our RNA antilysozyme aptamer served as an impetus for our systematic review of the reporting of aptamer sequences in the literature.

Web-Based Tool (FH Family Share) to Increase Uptake of Cascade Testing for Familial Hypercholesterolemia: Development and Evaluation.

Background: Familial hypercholesterolemia, a prevalent genetic disorder, remains significantly underdiagnosed in the United States. Cascade testing, wherein individuals diagnosed with familial hypercholesterolemia- probands-contact their family members to inform them of their risk for familial hypercholesterolemia, has low uptake in the United States. Digital tools are needed to facilitate communication between familial hypercholesterolemia probands and their family members and to promote sharing of familial hypercholesterolemia-related risk information.

Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity.

In the mammalian brain, perivascular astrocytes (PAs) closely juxtapose blood vessels and are postulated to have important roles in the control of vascular physiology, including regulation of the blood-brain barrier (BBB). Deciphering specific functions for PAs in BBB biology, however, has been limited by the ability to distinguish these cells from other astrocyte populations. In order to characterize selective roles for PAs , a new mouse model has been generated in which the endogenous megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) gene drives expression of Cre fused to a mutated estrogen ligand-binding domain (Mlc1-T2A-CreERT2).

Genetic basis of hypercholesterolemia in adults.

We investigated monogenic and polygenic causes of hypercholesterolemia in a population-based cohort, excluding secondary hypercholesterolemia, and using an established framework to identify pathogenic variants. We studied 1682 individuals (50.2 ± 8.

Memory Reactivation during Learning Simultaneously Promotes Dentate Gyrus/CA Pattern Differentiation and CA Memory Integration.

Events that overlap with previous experience may trigger reactivation of existing memories. However, such reactivation may have different representational consequences within the hippocampal circuit. Computational theories of hippocampal function suggest that dentate gyrus and CA (DG/CA) are biased to differentiate highly similar memories, whereas CA may integrate related events by representing them with overlapping neural codes.