Ecogenomics (Japan)

MutationAssessor (MA) helps researchers evaluate the likely functional impact of somatic and germline mutations in cancer. It provides an evolution-based functional impact score (FIS) to classify mutations based on their likely effect on protein function. FIS scores are based on analysis of patterns of conservation in protein families (conserved residues) and subfamilies (specificity residues). In this new version (r4) we have (1) refined the combinatorial entropy analysis of conservation patterns, (2) recalculated full-length protein multiple sequence alignments covering a larger fraction of human proteins and making use of the explosive growth of protein sequence data, (3) compared predicted functional impact with the pathogenic-benign classification of sequence variants in curated knowledge bases, such as ClinVar, (4) observed the inverse relationship between predicted high functional impact and variant frequency in germline genome sequences and (5) explore the evaluation of switch-of-function mutational effects. Functional impact of ~4 million somatic amino-acid changing mutations across more than 320K human tumor samples are now available in the widely used cBioPortal for Cancer Genomics.

Koala populations in Australia face a barrage of threats, chiefly, habitat degradation and the effects of climate change including drought and bushfire. Further, high rates of chlamydiosis, linked to koala retrovirus (KoRV) viral load, is a major contributing factor to northern population decline. However, recent work by Yu et al., (Cell, 2024) has provided a glimmer of hope: some koalas have evolved 'adaptive genome immunity', which is able to actively suppress endogenous KoRV transcription. A single KoRV-A provirus insertion within MAP4K4 gene's 3' UTR is shown to be the trigger for production of sense and anti-sense piRNAs, and that MAP4K4 KoRV integration is linked to both a 20% reduction in proviral genome integrations and 10-fold reduction of KoRV transcription within male germline tissue. Here we discuss how this finding offers the potential to reduce koala disease burden and can be incorporated into conservation management to help save this iconic species.

Relata-se no presente trabalho, o caso de uma paciente da espécie felina, com queixa clínica de aumento de volume abdominal e secreção vulvar, avaliada por meio dos exames clínico, hematológico, ultrassonográfico e histopatológico. Ao exame sanguíneo pode-se observar leucopenia, trombocitopenia, aumento do valor de ureia, diminuição da albumina e soro ictérico. Ao exame ultrassonográfico foi constatado aumento de cornos uterinos, com paredes espessas, apresentando em seu lúmen imagens ecogênicas de formato alongado, verticalizadas e discreto conteúdo anecogênico (líquido) de permeio. A paciente foi submetida à ovariossalpingo-histerectomia, e o material enviado para histopatologia. O diagnóstico foi de endometrite piogranulomatosa séptica, uma condição ainda não documentada na literatura veterinária, se tratando de um caso inédito.

The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC. The primary endpoint was differences in CD4+ and CD8+ T-cell infiltrate in 8-week versus baseline bone metastasis biopsies; secondary endpoints were safety, radiographic progression-free survival (rPFS), and overall survival (OS). Of the 42 treated patients (29 R223+P, 13 R223), 18 R223+P and 8 R223 patients had evaluable paired tumor biopsies. Median fold-change of CD4+ T cells was -0.7 (range: -9.3 to 4.7) with R223+P and 0.1 (-11.1 to 3.7) with R223 (P = 0.66); for CD8+ T cells, median fold-change was -0.6 (-7.4 to 5.3) with R223+P and -1.3 (-3.1 to 4.8) with R223 (P = 0.66). Median rPFS and OS was 6.1 (95% confidence interval: 2.7-11.0) and 16.9 months [12.7-not reached (NR)], respectively, with R223+P and 5.7 (2.6-NR) and 16.0 (9.0-NR), respectively, with R223. Although R223+P was well tolerated with no unexpected toxicity, the combination did not improve efficacy. High-dimensional flow cytometry demonstrated minimal immune modulation with R223, whereas R223+P induced CTLA-4 expression on circulating CD4+ T cells. Clinical responders possessed lower circulating frequencies of Ki67+ T and myeloid cells at baseline and higher circulating frequencies of TIM-3+ T and myeloid cells by week 9. Although R223+P did not induce T-cell infiltration into the tumor microenvironment, exhaustion of induced peripheral T-cell immune responses may dampen the combination's clinical activity.

Cold desert soil microbiomes thrive despite severe moisture and nutrient limitations. In Eastern Antarctic soils, bacterial primary production is supported by trace gas oxidation and the light-independent RuBisCO form IE. This study aims to determine if atmospheric chemosynthesis is widespread within Antarctic, Arctic and Tibetan cold deserts, to identify the breadth of trace gas chemosynthetic taxa and to further characterize the genetic determinants of this process. H2 oxidation was ubiquitous, far exceeding rates reported to fulfill the maintenance needs of similarly structured edaphic microbiomes. Atmospheric chemosynthesis occurred globally, contributing significantly (p < 0.05) to carbon fixation in Antarctica and the high Arctic. Taxonomic and functional analyses were performed upon 18 cold desert metagenomes, 230 dereplicated medium-to-high-quality derived metagenome-assembled genomes (MAGs) and an additional 24,080 publicly available genomes. Hydrogenotrophic and carboxydotrophic growth markers were widespread. RuBisCO IE was discovered to co-occur alongside trace gas oxidation enzymes in representative Chloroflexota, Firmicutes, Deinococcota and Verrucomicrobiota genomes. We identify a novel group of high-affinity [NiFe]-hydrogenases, group 1m, through phylogenetics, gene structure analysis and homology modeling, and reveal substantial genetic diversity within RuBisCO form IE (rbcL1E), and high-affinity 1h and 1l [NiFe]-hydrogenase groups. We conclude that atmospheric chemosynthesis is a globally-distributed phenomenon, extending throughout cold deserts, with significant implications for the global carbon cycle and bacterial survival within environmental reservoirs.

The Ceylon Journal of Science is published by the University of Peradeniya, Sri Lanka. Full text available. The journal also has its own website. The Ceylon Journal of Science is a continuation of the Ceylon Journal of Science (Biological Sciences) which is no longer being published as a separate journal. The history of the journal can be found here.From May 2020, Ceylon Journal of Science is indexed in DOAJ.