An ancient role for CYP73 monooxygenases in phenylpropanoid biosynthesis and embryophyte development.

The phenylpropanoid pathway is one of the plant metabolic pathways most prominently linked to the transition to terrestrial life, but its evolution and early functions remain elusive. Here, we show that activity of the t-cinnamic acid 4-hydroxylase (C4H), the first plant-specific step in the pathway, emerged concomitantly with the CYP73 gene family in a common ancestor of embryophytes. Through structural studies, we identify conserved CYP73 residues, including a crucial arginine, that have supported C4H activity since the early stages of its evolution. We further demonstrate that impairing C4H function via CYP73 gene inactivation or inhibitor treatment in three bryophyte species-the moss Physcomitrium patens, the liverwort Marchantia polymorpha and the hornwort Anthoceros agrestis-consistently resulted in a shortage of phenylpropanoids and abnormal plant development. The latter could be rescued in the moss by exogenous supply of p-coumaric acid, the product of C4H. Our findings establish the emergence of the CYP73 gene family as a foundational event in the development of the plant phenylpropanoid pathway, and underscore the deep-rooted function of the C4H enzyme in embryophyte biology.

Complete Genome Sequence of Microbacterium sp. Strain Nx66, Isolated from Waters Contaminated with Petrochemicals in El Saf-Saf Valley, Algeria.

Microbacterium sp. strain Nx66 was isolated from waters contaminated by petrochemical effluents collected in Algeria. Its genome was sequenced using Illumina MiSeq (2 × 150-bp read pairs) and Oxford Nanopore (long reads) technologies and was assembled using Unicycler. It is composed of one chromosome of 3.42 Mb and one plasmid of 34.22 kb.

Oral dysbiosis induced by Porphyromonas gingivalis is strain-dependent in mice.

Background: Porphyromonas gingivalis strain W83, one of the most widely investigated, is considered virulent in the context of periodontitis. The recently isolated P. gingivalis TDC60 has been reported to be highly pathogenic, although it has not yet been investigated in a mouse periodontitis model by oral gavage. Aim: Our aim was to compare the virulence of both strains by evaluating their impact on alveolar bone loss and the composition of oral microbiota. Methods: We inoculated by oral gavage C57BL/6 mice with either one of the two P. gingivalis strains and compared to a sham-treated group, without antibiotics pre-treatment. The mandibular alveolar bone of treated mice and controls were assessed, one month after the final inoculation, by microCT measurements. Moreover, at this time, we characterized their oral microbiota by 16S rRNA gene sequencing. Results: While P. gingivalis W83 successfully initiated periodontitis, TDC60-treated mice only experienced moderate lesions. Furthermore, only W83-treated mice exhibited a specific distinct microbiota, with significantly lower richness and evenness than other samples, and decreased proportions of taxa usually found in healthy individuals. Conclusion: This association between alveolar bone loss and a major persistent shift of the oral microbiota gives insights into virulence discrepancies among these bacterial strains.

Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.

Cause of complex dyskinesia remains elusive in some patients. A homozygous missense variant leading to drastic decrease of PDE2A enzymatic activity was reported in one patient with childhood-onset choreodystonia preceded by paroxysmal dyskinesia and associated with cognitive impairment and interictal EEG abnormalities. Here, we report three new cases with biallelic PDE2A variants identified by trio whole-exome sequencing. Mitochondria network was analyzed after Mitotracker™ Red staining in control and mutated primary fibroblasts. Analysis of retrospective video of patients' movement disorder and refinement of phenotype was carried out. We identified a homozygous gain of stop codon variant c.1180C>T; p.(Gln394*) in PDE2A in siblings and compound heterozygous variants in young adult: a missense c.446C>T; p.(Pro149Leu) and splice-site variant c.1922+5G>A predicted and shown to produce an out of frame transcript lacking exon 22. All three patients had cognitive impairment or developmental delay. The phenotype of the two oldest patients, aged 9 and 26, was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed as epilepsy due to interictal EEG abnormalities. The youngest patient showed a proven epilepsy at the age of 4 months and no paroxysmal dyskinesia at 15 months. Interestingly, analysis of the fibroblasts with the biallelic variants in PDE2A variants revealed mitochondria network morphology changes. Together with previously reported case, our three patients confirm that biallelic PDE2A variants are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy.