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PNAS Papers on Parkinson's Expression, Bacterial Engineering, Transcription-Coupled DNA Repair

Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.

A team from Sweden and Portugal explores early transcriptomic shifts found in cell lines originating in individuals with Parkinson's disease or multiple system atrophy (MSA), conditions known as synucleinopathies involving potential alpha-synuclein protein effects on oligodendrocyte central nervous system cells. Using patient-induced pluripotent stem cells, the team generated oligodendrocyte lineage cells that they assessed through array-based gene expression profiling, gene set enrichment analyses, and other approaches. Compared to control cell lines, the Parkinson's and MSA lines were marked by an impaired maturation phenotype, the authors report, along with human leukocyte antigen and other immune system-related shifts with apparent ties to alpha-synuclein protein activity. "Our results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes in the alpha-synucleinopathies Parkinson's disease and multiple system atrophy," they write.

Researchers at the Chinese Academy of Sciences and the Korea Advanced Institute of Science and Technology present a genetic system designed for boosting metabolic engineering and synthetic biology options in the model organism Bacillus subtilis, a gram-positive bacterial species that is missing genetic elements found in some other bacteria. The team's "malO-based genetic toolbox" allows for promoter-based mutagenesis and other targeted genetic changes using a malA promoter-driven operator box — an approach the group applied to come up with several bacterial mutants capable of expressing proteins originating in other organisms based on exposure to maltose. "It is expected that this scalable approach will pave a new way forward to generate more flexible and orthogonal operator-based genetics devices and parts," the authors conclude. "The availability of such toolboxes will help expedite our attempts to solve complex biological problems and expand the applications of B. subtilis."

A team from the University of Massachusetts Chan Medical School, Jagiellonian University in Poland, and elsewhere share findings from a CRISPR gene editing-based analysis of the transcription-coupled repair component UVSSA — a transcription-coupled repair protein that interacts with CSA and CSB proteins that are altered in individuals with a photosensitivity- and aging-related neurocutaneous condition called Cockayne syndrome. Based on their gene editing and other experiments in a human embryonic kidney cell line, the researchers considered the functional effects of removing UVSSA, which has been linked to a rare photosensitivity condition that is milder than Cockayne syndrome. While some features of cells missing UVSSA did resemble those in CSA- or CSB-deficient cells, they explain, the UVSSA knockout cells did not show sensitivity to oxidative damage or PARP inhibitors. More broadly, the authors note, "[w]e anticipate that this [UVSSA] knockout cell line will advance understanding of this and possibly related transcription-coupled DNA repair diseases."

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