MMP14 expression and collagen remodelling support uterine leiomyosarcoma aggressiveness.

Fibrillar collagen deposition, stiffness and downstream signalling support the development of leiomyomas (LMs), common benign mesenchymal tumours of the uterus, and are associated with aggressiveness in multiple carcinomas. Compared with epithelial carcinomas, however, the impact of fibrillar collagens on malignant mesenchymal tumours, including uterine leiomyosarcoma (uLMS), remains elusive. In this study, we analyse the network morphology and density of fibrillar collagens combined with the gene expression within uLMS, LM and normal myometrium (MM). We find that, in contrast to LM, uLMS tumours present low collagen density and increased expression of collagen-remodelling genes, features associated with tumour aggressiveness. Using collagen-based 3D matrices, we show that matrix metalloproteinase-14 (MMP14), a central protein with collagen-remodelling functions that is particularly overexpressed in uLMS, supports uLMS cell proliferation. In addition, we find that, unlike MM and LM cells, uLMS proliferation and migration are less sensitive to changes in collagen substrate stiffness. We demonstrate that uLMS cell growth in low-stiffness substrates is sustained by an enhanced basal yes-associated protein 1 (YAP) activity. Altogether, our results indicate that uLMS cells acquire increased collagen remodelling capabilities and are adapted to grow and migrate in low collagen and soft microenvironments. These results further suggest that matrix remodelling and YAP are potential therapeutic targets for this deadly disease.

Fungal community diversity of heavy metal contaminated soils revealed by metagenomics.

The inappropriate disposal of toxic compounds generated by industrial activity has been impacting the environment considerably. Microbial communities inhabiting contaminated sites may represent interesting ecological alternatives for the decontamination of environments. The present work aimed to investigate the fungal diversity and its functionality contained in stream sediments with industrial waste contaminated with heavy metals by using metagenomic approach. A total of 12 fungal orders were retrieved from datasets and, at phylum level, Ascomycota was the most abundant, followed by Basidiomycota, Chytridiomycota and Blastocladiomycota. Higher abundance of sequences was encountered within the less contaminated site, while the lower abundance was found in the sample with the higher contamination with lead. Gene sequences related to DNA repair and heavy metals biosorption processes were found in the four samples analyzed. The genera Aspergillus and Chaetomium, and Saccharomycetales order were highly present within all samples, showing their potential to be used for bioremediation studies. The present work demonstrated the importance of using the metagenomic approach to understand the dynamics and the possible metabolic pathways associated with fungal communities related to environmental samples containing heavy metals, as well as evidenced the importance of improving culturomics techniques for isolating strains with potential application in bioremediation processes of environments contaminated with heavy metals.

A decision tree to improve identification of pathogenic mutations in clinical practice.

BACKGROUND: A variant of unknown significance (VUS) is a variant form of a gene that has been identified through genetic testing, but whose significance to the organism function is not known. An actual challenge in precision medicine is to precisely identify which detected mutations from a sequencing process have a suitable role in the treatment or diagnosis of a disease. The average accuracy of pathogenicity predictors is 85%. However, there is a significant discordance about the identification of mutational impact and pathogenicity among them. Therefore, manual verification is necessary for confirming the real effect of a mutation in its casuistic. METHODS: In this work, we use variables categorization and selection for building a decision tree model, and later we measure and compare its accuracy with four known mutation predictors and seventeen supervised machine-learning (ML) algorithms. RESULTS: The results showed that the proposed tree reached the highest precision among all tested variables: 91% for True Neutrals, 8% for False Neutrals, 9% for False Pathogenic, and 92% for True Pathogenic. CONCLUSIONS: The decision tree exceptionally demonstrated high classification precision with cancer data, producing consistently relevant forecasts for the sample tests with an accuracy close to the best ones achieved from supervised ML algorithms. Besides, the decision tree algorithm is easier to apply in clinical practice by non-IT experts. From the cancer research community perspective, this approach can be successfully applied as an alternative for the determination of potential pathogenicity of VOUS.

Draft Whole-Genome Sequence of Leishmania (Viannia) braziliensis Presenting Leishmania RNA Virus 1, from Western Amazon, Brazil.

Leishmania (Viannia) braziliensis is the main etiological agent of tegumentary leishmaniasis in the neotropics. Here, we report a draft genome sequence (31.2 Mb) of an L. braziliensis strain from the western Amazon region of Brazil. This genome sequence will complement those available for other Leishmania species and contribute to further studies focusing on this parasite and the neglected diseases associated with it.

Draft genome assembly of Colletotrichum musae, the pathogen of banana fruit.

Colletotrichum musae is an important cosmopolitan pathogenic fungus that causes anthracnose in banana fruit. The entire genome of C. musae isolate GM20 (CMM 4420), originally isolated from infected banana fruit from Alagoas State, Brazil, was sequenced and annotated. The pathogen genomic DNA was sequenced on HiSeq Illumina platform. The C. musae GM20 genome has 50,635,197 bp with G + C content of 53.74% and in its present assembly has 2763 scaffolds, harboring 13,451 putative genes with an average length of 1626 bp. Gene prediction and annotation was performed by Funannotate pipeline, using a pattern for gene identification based on BUSCO.

Complete Genome Sequence of Xanthomonas citri pv. anacardii Strain IBSBF2579 from Brazil.

The bacterium Xanthomonas citri pv. anacardii is the agent of angular leaf spot of the cashew tree (Anacardium occidentale L.). The complete genome sequencing of the strain IBSBF2579 was done on an Illumina HiSeq 2500 platform. The de novo assembly of the X. citri pv. anacardii strain IBSBF2579 genome yielded 133 contigs, with a size of 5,329,247 bp and a G+C content of 64.03%. The prediction was performed by GeneMarkS and the automatic annotation by Rapid Annotations using Subsystems Technology (RAST), with 4,406 identified genes.