Towards optimizing diversifying base editors for high-throughput studies of single- nucleotide variants.

Determining the phenotypic effects of single nucleotide variants is critical for understanding the genome and interpreting clinical sequencing results. Base editors, including diversifying base editors that create C>N mutations, are potent tools for installing point mutations in mammalian genomes and studying their effect on cellular function. Numerous base editor options are available for such studies, but little information exists on how the composition of the editor (deaminase, recruitment method, and fusion architecture) affects editing.

Mesh-associated complications in minimally invasive ventral mesh rectopexy: a systematic review.

Background: Ventral mesh rectopexy (laparoscopic and robotic) is a common and well established treatment of rectal prolapse. Although described as safe and effective, complications, especially mesh-associated ones are often mentioned. Additionally, there is no consensus regarding the mesh type and fixation method as well as the materials used for this purpose.

Activation of 5-HT receptors in the mouse dentate gyrus does not affect theta-burst-induced plasticity at the perforant path synapse.

Background: The study examined the effects of 5-HT receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input.

Methods: Immunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells-two glutamatergic neuron types present in the dentate gyrus.

Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.

Transcriptional effectors are protein domains known to activate or repress gene expression; however, a systematic understanding of which effector domains regulate transcription across genomic, cell type and DNA-binding domain (DBD) contexts is lacking. Here we develop dCas9-mediated high-throughput recruitment (HT-recruit), a pooled screening method for quantifying effector function at endogenous target genes and test effector function for a library containing 5,092 nuclear protein Pfam domains across varied contexts. We also map context dependencies of effectors drawn from unannotated protein regions using a larger library tiling chromatin regulators and transcription factors.

A High-Throughput Screen for Antiproliferative Peptides in Mammalian Cells Identifies Key Transcription Factor Families.

Transcription factors (TFs) are a promising therapeutic target for a multitude of diseases. TFs perform their cellular roles by participating in multiple specific protein-protein interactions. For example, homo- or heterodimerization of some TFs controls DNA binding, while interactions between TFs and components of basal transcriptional machinery or chromatin modifiers can also be critical.