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Elena S Kotova,1 Yulia A Savochkina,2 Yuriy V Doludin,3 Alexander O Vasilyev,4 Elena A Prilepskay,4 Natalia V Potoldykova,3 Konstantin A Babalyan,1 Alexandra V Kanygina,1 Andrey O Morozov,3 Alexander V Govorov,4 Dmitry V Enikeev,3 Elena S Kostryukova,1 Elena N Ilina,1 Vadim M Govorun,1 Dmitry Y Pushkar,4 Elena I Sharova1 1Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia; 2Lytech Ltd, Moscow, Russia; 3Sechenov First Moscow State Medical University, Moscow, Russia; 4Department of Urology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, RussiaCorrespondence:Elena S KotovaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya 1a, Moscow 119992, RussiaTel +7 910 464 56 55Fax +7 499 246 44 09Email potamanthus@gmail.comPurpose: Preclinical evaluation of PCA3 and AMACR transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥ 7) in a Russian cohort.Patients and Methods: We analyzed urine samples of patients with a total serum PSA ≥ 2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort). PCA3, AMACR, PSA and GPI transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis.Results: There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy p=0.0088, prebiopsy cohort p=0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511– 0.752), the AMACR score AUC was 0.711 (95%CI: 0.617– 0.806) and AUC of classification model based on the PCA3 score, the AMACR score and total PSA was 0.72 (95%CI: 0.58– 0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347, p=6.542e– 09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use.Conclusion: The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.Keywords: prostatic neoplasms, early diagnosis, neoplasm grading, alpha-methylacyl-CoA racemase, RNA

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive eye disease. GDLD is characterized by the loss of barrier function in corneal epithelial cells (CECs) and amyloid deposition due to pathogenic variants in the TACSTD2 gene. Limbal stem cell transplantation (LSCT) has been suggested as an effective therapeutic alternative for patients with GDLD. However, despite LSCT, amyloid deposition recurs in some patients. The pathogenesis of recurrence is poorly studied. We present the case of a patient with GDLD. Genetic analysis revealed a homozygous deletion, NM_002353.3:c.653del, in the TACSTD2 gene. Functional analysis in a cell model system revealed the loss of the transmembrane domain and subcellular protein mislocalization. The patient with GDLD underwent direct allogeneic LSCT with epithelial debridement followed by deep anterior lamellar keratoplasty 10 months later due to amyloid deposition and deterioration of vision. Taken together, the results of transcriptome analysis and immunofluorescence staining of post-LSCT corneal sample with amyloid deposits obtained during keratoplasty demonstrated complete restoration of wild-type TACSTD2 expression, indicating that donor CECs replaced host CECs. Our study provides experimental evidence that amyloid deposition can recur after LSCT despite complete restoration of wild-type TACSTD2 expression., (© 2024. The Author(s).)

We report the draft genome sequence of a type strain Acidiplasma cupricumulans Strain BH2 T , isolated from a pregnant leachate solution of industrial-scale chalcocite bioleach heap (Monywa, Myanmar). The genome is 1.7 Mbp long with a GC content of 34.2%., Competing Interests: The authors declare no conflict of interest.

We report the draft genome sequence of Acidiplasma aeolicum strain V1 T , isolated from a hydrothermal pool (Vulcano Island, Italy). The genome is 1.8 Mbp long with a GC content of 34%. The genome sequence was found to be closely related to those of other known strains of Acidiplasma genus.

Here, we report the draft genome sequences of the green sulfur bacterium Chlorobium phaeovibrioides strains GrTcv12 and PhvTcv-s14, isolated from the chemocline zone from meromictic Lake Trekhtzvetnoe, separated from the White Sea, in Russia. This is the first report showing the presence of plasmids containing antiphage systems in the Chlorobium sp. genome., (Copyright © 2020 Boldyreva et al.)

Prostate cancer (PCa) is the most frequently diagnosed among men malignant disease that remains poorly characterized at the molecular level. Advanced PCa is not curable, and the current treatment methods can only increase the life expectancy by several months. Identification of the genetic aberrations in tumor cells provides clues to understanding the mechanisms of PCa pathogenesis and the basis for developing new therapeutic approaches. Here we present data on somatic mutations, namely single nucleotide variations (SNVs), small insertions and deletions, detected in prostate tumor tissue obtained from Russian patients with PCa. Moreover, we provide a raw dataset on the whole exome and targeted DNA sequencing of tumor and non-tumor prostate tissue obtained from Russian patients with PCa and benign prostatic hyperplasia (BPH). This data is available at NCBI Sequence Read Archive under Accession No. PRJNA506922.

Background: Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated., Methods: We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability., Results: The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes., Conclusions: The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.

Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.

Background: Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related., Results: We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons., Conclusions: Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.

Results of genome analysis of a member of the family Ferroplasmaceae, Acidiplasma sp. strain MBA-1, an extremely acidophilic, moderately thermophilic archaeon oxidizing ferrous iron under oxic conditions and utilizing organic compounds. This strain was previously shown to predominate in the community carrying out biooxidation of pyrite-arsenopyrite gold-bearing concentrate. The genome was sequenced using the Illumina HiSeq 2000 platform. A total of 2306800 pairwise reads were obtained, corresponding to 300-fold coverage. Assembly was carried out by three programs in parallel. The optimal assembly contained nine contigs, the genome size was 1747364 bp, and N50 was 446845 bp. Annotation of the genome revealed 1749 protein-encoding sequences, as well as 46 tRNA genes and one rRNA gene copy. The results of genome analysis confirmed the previous data on the physiology of this organism. The gene of sulfocyanin (TZ01_06185), a blue copper-containing protein playing the key role in the iron-oxidizing electron transport chain, was identified in the genome. The genes encoding sulfur oxidoreductase (TZ01_04750) and sulfateadenilyl transferase (TZ01_04545), the enzymes of sulfur oxidation, were also identified. The genes involved in the transport and catabolism of organic compounds and the genes of the 3-hydroxypropionate/4-hydroxybutyrate cycle were revealed. The genome of Acidiplasma sp. MBA-1 is the first genome of this genus deposited to a public database DDBJ/EMBL/GenBank (accession no. JYHS00000000) and is of interest for further investigation of Acidiplasma archaea.

Optochin-resistant pneumococci can be rarely caught in clinical microbiology laboratories because of the routine identification of all such strains as viridans group non-pneumococci. We were lucky to find four non-typeable Streptococcus pneumoniae clones demonstrating the different susceptibilities to optochin: one of them (Spn_13856) was resistant to optochin, while the other three (Spn_1719, Spn_27, and Spn_2298) were susceptible. Whole genome nucleotide sequences of these strains were compared to reveal the differences between the optochin-resistant and optochin-susceptible strains. Two adjacent genes coding maltose O-acetyltransferase and uridine phosphorylase which were presented in the genomes of all optochin-susceptible strains and missed in the optochin-resistant strain were revealed. Non-synonymous substitutions in 14 protein-coding genes were discovered, including the Ala49Ser mutation in the C-subunit of the F0 part of the ATP synthase rotor usually associated with pneumococcal optochin resistance. Modeling of a process of optochin interaction with the F0 part of the ATP synthase rotor indicates that the complex of optochin with "domain C" composed by wild-type C-subunits is more stable than the same complex composed of Ala49Ser mutant C-subunits.