SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

Metabolic Engineering of Corynebacterium glutamicum for High-Level Production of 1,5-Pentanediol, a C5 Diol Platform Chemical.

The biobased production of chemicals is essential for advancing a sustainable chemical industry. 1,5-Pentanediol (1,5-PDO), a five-carbon diol with considerable industrial relevance, has shown limited microbial production efficiency until now. This study presents the development and optimization of a microbial system to produce 1,5-PDO from glucose in Corynebacterium glutamicum via the l-lysine-derived pathway.

In situ forming and self-crosslinkable protein hydrogels for localized cancer therapy and topical wound healing.

Proteins, inherently biocompatible and biodegradable, face a challenge in forming stable hydrogels without external chemical crosslinkers. Here, we construct a ring-shaped trimeric SpyTag-fused Proliferating Cell Nuclear Antigen Protein (ST-PCNA) as a core protein building block, and a dumbbell-shaped tandem dimeric SpyCatcher (SC-SC) as a bridging component. Self-crosslinked PCNA/SC-SC Protein (2SP) hydrogels are successfully formed by simply mixing the solutions of ST-PCNA and SC-SC, without chemical crosslinkers.