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Background and purpose: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD‐related genes and determine the mutational spectrum of early‐onset PD in ethnic Chinese. Methods: In this study, whole‐exome sequencing and/or gene dosage analysis were performed in 704 early‐onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty‐six PD‐related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. Results: Eighty‐two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD‐related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi‐allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein‐truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late‐onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. Conclusions: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD. [ABSTRACT FROM AUTHOR]

Considering that I GBA i , I TMEM175 i , and I SNCA i are risk genes for both LBD and PD, it is noteworthy to investigate whether I BIN1 i and I APOE i are also associated with the risk of PD. Keywords: APOE; BIN1; Parkinson's disease; rare variant EN APOE BIN1 Parkinson's disease rare variant 698 701 4 04/15/22 20220501 NES 220501 Abbreviations GWAS genome-wide association study LBD Lewy body dementia PD Parkinson's disease Dear Editor, Recently, Chia et al. identified five risk genes for Lewy body dementia (LBD) in a genome-wide association study (GWAS) [1]. Similarly, a previous study identified that the I BIN1 i variant rs13403026 was associated with later AAO in I GBA i -associated PD [4], suggesting the potential role of I BIN1 i in regulating AAO in PD. [Extracted from the article]

Background and Purpose Experimental approach Key Results Conclusion and Implications The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5‐HT in the antidepressant effects of ketamine remains unclear.The chronic restraint stress procedure was performed to induce depression‐like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant‐like effects of ketamine. Tph2 knockout or depletion of 5‐HT by PCPA and 5,7‐DHT were used to manipulate the brain 5‐HT system. ELISA and fibre photometry recordings were used to measure extracellular 5‐HT levels in the brain.60 min after injection, ketamine (10 mg·kg−1, i.p.) produced rapid antidepressant‐like effects and increased brain 5‐HT levels. After 24 h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5‐HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24 h) but not rapid (60 min) antidepressant‐like effects of ketamine were abrogated by PCPA and 5,7‐DHT, or by Tph2 knockout. Importantly, NBQX (10 mg·kg−1, i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5‐HT levels and abolished the sustained antidepressant‐like effects of ketamine in naïve or CRS‐treated mice.This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant‐like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets. [ABSTRACT FROM AUTHOR]

Chinese mahogany (Toona sinensis) is a woody plant that is widely cultivated in China and Malaysia. Toona sinensis is important economically, including as a nutritious food source, as material for traditional Chinese medicine and as a high‐quality hardwood. However, the absence of a reference genome has hindered in‐depth molecular and evolutionary studies of this plant. In this study, we report a high‐quality T. sinensis genome assembly, with scaffolds anchored to 28 chromosomes and a total assembled length of 596 Mb (contig N50 = 1.5 Mb and scaffold N50 = 21.5 Mb). A total of 34,345 genes were predicted in the genome after homology‐based and de novo annotation analyses. Evolutionary analysis showed that the genomes of T. sinensis and Populus trichocarpa diverged ~99.1–103.1 million years ago, and the T. sinensis genome underwent a recent genome‐wide duplication event at ~7.8 million years and one more ancient whole genome duplication event at ~71.5 million years. These results provide a high‐quality chromosome‐level reference genome for T. sinensis and confirm its evolutionary position at the genomic level. Such information will offer genomic resources to study the molecular mechanism of terpenoid biosynthesis and the formation of flavour compounds, which will further facilitate its molecular breeding. As the first chromosome‐level genome assembled in the family Meliaceae, it will provide unique insights into the evolution of members of the Meliaceae. [ABSTRACT FROM AUTHOR]