MATERIALS AND METHODS: Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.
RESULTS: The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of B. longum 379 and B. bifidum 791. A feature of the B. bifidum 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The B. bifidum 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication in vitro up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6·106 CFU/ml.
CONCLUSION: The analysis of complete genomes of B. longum 379, B. bifidum 1, and B. bifidum 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of B. longum 379 and B. bifidum 791 strains, in contrast to B. bifidum 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of B. bifidum 791 strain determines its pronounced antiviral activity.
METHODS: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview.
RESULTS: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan.
CONCLUSION: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.
METHODS: Twenty-eight patients with severe TBI (GCS ≤ 8, three patients had initial GCS = 9-10, but rapidly deteriorated to ≤8) were recruited. CSF was collected from admission to day 5 post-injury. TRP, kynurenine (KYN), kynurenic acid (KYNA), QUIN, anthranilic acid (AA) and 3-hydroxyanthranilic acid (3HAA) were measured in CSF. The Glasgow Outcome Scale Extended (GOSE) score was assessed at 6 months post-TBI. Post-mortem brains were obtained from the Australian Neurotrauma Tissue and Fluid Bank and used in qPCR for quantitating expression of KP enzymes (indoleamine 2,3-dioxygenase-1 (IDO1), kynurenase (KYNase), kynurenine amino transferase-II (KAT-II), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyl transferase (QPRTase) and IDO1 immunohistochemistry.
RESULTS: In CSF, KYN, KYNA and QUIN were elevated whereas TRP, AA and 3HAA remained unchanged. The ratios of QUIN:KYN, QUIN:KYNA, KYNA:KYN and 3HAA:AA revealed that QUIN levels were significantly higher than KYN and KYNA, supporting increased neurotoxicity. Amplified IDO1 and KYNase mRNA expression was demonstrated on post-mortem brains, and enhanced IDO1 protein coincided with overt tissue damage. QUIN levels in CSF were significantly higher in patients with unfavourable outcome and inversely correlated with GOSE scores.
CONCLUSION: TBI induced a striking activation of the KP pathway with sustained increase of QUIN. The exceeding production of QUIN together with increased IDO1 activation and mRNA expression in brain-injured areas suggests that TBI selectively induces a robust stimulation of the neurotoxic branch of the KP pathway. QUIN's detrimental roles are supported by its association to adverse outcome potentially becoming an early prognostic factor post-TBI.