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Biology subjects

Kleiman, E.

Publications and source records attributed to Kleiman, E..

3 recordsLinked to original sources

Chromosomal-Level Whole Genome Assemblies of Crassostrea Virginica

The eastern oyster, Crassostrea virginica, is an ecologically important foundation species and a valuable aquaculture organism. To support genomic studies and future breeding applications, we generated PacBio HiFi, Illumina, and Hi-C sequencing data from wild adult oysters, collected from Long Island Sound and assembled a chromosome-level reference genome. The final assembly spans 529.0 Mb and consists of 10 chromosomes with a scaffold N50 of 55.46 Mb and a contig N50 of 16.0 Mb. The resulting reference genome achieved 99.7% genome completeness and reduced duplicated universal single-copy ortholog content from 18.7% to 1.1%. Genome annotation identified 33,259 protein-coding genes and revealed that 43.2% of the genome is composed of repetitive elements. All sequencing data underwent stringent quality control, and the assembly results were validated through multiple technical evaluations. These dataset and resources of oyster genomics provided future studies such as effective breeding and sustainable farming.

genomics↗

An Igh novel enhancer modulates antigen receptor diversity by determining locus conformation

The Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of novel enhancers (NEs) that collaborate to configure the locus, determine transcriptional potential in over a hundred functional VH genes and their usage in V(D)J recombination. NE1 engages in a network of long-range interactions that interconnect the subTADs and the recombination center at the DHJH gene cluster. Deletion of NE1 alters discrete chromatin loops, higher order locus conformation, locus-wide VH gene transcription and regional V gene utilization that is linked to a greatly reduced splenic B1 B cell compartment. NE1 blocks long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant VH genes to the recombination center. NE1 is a critical architectural element that coordinates chromatin conformational states that favor VH gene transcription or V(D)J rearrangement.

immunology↗

Antigen-Specific T Cell Recall Assay To Screen Drugs For Off-Target Effects

Extracellular adenosine suppresses T cell immunity in the tumor microenvironment. We have developed an in vitro recall assay utilizing a sequential adenosine dosing regimen guide for testing drug off-target effects on memory T cell expansion/function. As a proof of principle, we show low dose adenosine analog GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8+ T cells. Parent drug GS-445124 at high dosage interferes with antigen-specific T cell recall without cellular toxicity. Despite similar chemical structure, these drugs displayed opposing effects on memory T cell expansion. This assay platform has broad utility in screening memory T cell off-target effects.

immunology↗