Examining the Relationship between Aptamer Complexity and Molecular Discrimination of a Low-Epitope Target.

Aptamers are oligonucleotide-based affinity reagents that are increasingly being used in various applications. Systematic evolution of ligands by exponential enrichment (SELEX) has been widely used to isolate aptamers for small-molecule targets, but it remains challenging to generate aptamers with high affinity and specificity for targets with few functional groups. To address this challenge, we have systematically evaluated strategies for optimizing the isolation of aptamers for (+)-methamphetamine, a target for which previously reported aptamers have weak or no binding affinity.

TASOR expression in naive embryonic stem cells safeguards their developmental potential.

The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs.

Bypassing Prescribers and Pharmacists: Online Purchasing of Semaglutide and Tirzepatide "For Research Purposes".

Unscrupulous manufacturers provide consumers with ways to circumvent access controls by purchasing drug products outside the legitimate prescription drug supply chain. Manufacturers are selling vials containing semaglutide and tirzepatide to consumers without a prescription for "research purposes only" and/or "not for human consumption," but frequently without the supplies and knowledge they would need to dissolve the active ingredient, draw it up into a syringe, and inject it into the body. Avoiding prescribers allows consumer access to products where the risk may outweigh the benefits and quality standards may not be met.

Micronuclear collapse from oxidative damage.

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood.