The comprehensive knowledge of karst surface, caves, waters and biodiversity were examined with special emphasis on planning for environmental management and land use in karst regions using examples ...of projects performed by the sta from the Karst Research Institute ZRC SAZU. Based on
the knowledge of karst, karst phenomena, karst waters and karst biodiversity, karstological monitoring was developed throughout the construction of expressways and planning for railways on karst terrain. Newly revealed karst phenomena were properly preserved. Regular climatic and biological
monitoring were developed and implemented, as well as karstology consultation with an emphasis on the impact of the use of caves as natural assets. To understand karst, its evolution dynamics and processes, models were developed with which the study of the risk posed by dam site construction
in karst areas was possible. Karst aquifers and their protection were studied using tracer tests and different methods of the transfer of contaminants through the vadose zone and underground flow connections. In assessing the vulnerability and contamination risk of groundwater, a comprehensive
method was elaborated. Microorganisms and fauna of dripping water in caves were used as monitors of cave ecosystem health. By applying high-quality karstological research results from individual spheres of karstology and interdisciplinary studies, a foundation for sustainable planning of life
in karst regions that will consider the natural and cultural characteristics and vulnerability of karst landscapes has been established.
Fotografija prikazuje traktor, narejen v domači delavnici, s katerim orjejo njivo na polju južno od vasi Hrašče (ledinsko ime Reberniki). Priprežen je plug znamke Martinelli. Traktor upravlja Vinko ...Sever, opazovalci na fotografiji so Peter Sever, Silvo Krma, Ivan Lumbar. Fotografijo je posnel in razvil v svoji temnici Vinko Krma, poštar iz Hrašč. Na sliki je za voznikom lepo vidna peč – generator plina.
Bacillus thuringiensis serovar israelensis is the most widely used biopesticide against insects, including vectors of animal and human diseases. Among several extrachromosomal elements, this ...endospore-forming entomopathogen harbors two bacteriophages: a linear DNA replicon named GIL01 that does not integrate into the chromosome during lysogeny and a circular-jumbo prophage known as pBtic235. Here, we show that GIL01 hinders the induction of cohabiting prophage pBtic235. The GIL01-encoded small protein, gp7, which interacts with the host LexA repressor, is a global transcription regulator and represses the induction of pBtic235 after DNA damage to presumably allow GIL01 to multiply first. In a complex with host LexA in stressed cells, gp7 down-regulates the expression of more than 250 host and pBtic235 genes, many of which are involved in the cellular functions of genome maintenance, cell-wall transport, and membrane and protein stability. We show that gp7 homologs that are found exclusively in bacteriophages act in a similar fashion to enhance LexA's binding to DNA, while likely also affecting host gene expression. Our results provide evidence that GIL01 influences both its host and its co-resident bacteriophage.
BackgroundMicrosatellite instability (MSI) has emerged as an important biomarker for guiding treatment decisions in immuno-oncology. The FDA recently approved the use of pembrolizumab in patients ...with metastatic MSI-high or mismatch repair-deficient (dMMR) solid tumors. Approved assays for MSI, such as Foundation One, typically rely on measuring variants by targeted DNA sequencing. While DNA-based assays are the state of the art today, the precision oncology field is beginning to see new types of biomarkers based on complex signatures like those measured by RNA sequencing, which aim to increase predictive accuracy by better describing disease subtypes. If MSI status could be determined from RNA-seq data, this would enable combining MSI with other biomarker signatures to provide a more comprehensive portrait of the disease state, all from a single sequencing assay. In this study, we developed a RNA-seq variant calling pipeline and used it to characterize MSI in different cancer indications from tumor samples without the need for matched normal samples.MethodsPublicly available data sets that included MSI status were selected for a range of cancer types—colorectal, ovarian, endometrial, and gastric cancer. A bioinformatics pipeline was developed following GATK best practices for calling and quantifying single nucleotide variants (SNVs) and insertion-deletion mutations (INDELs) from RNA-seq data. This pipeline was used to characterize an inventory of frequently altered MSI hotspots in the human transcriptome by filtering for microsatellites from MSI-high patients with high frequency of INDELs across multiple cancers. The RNA-seq variant calling pipeline is available under Apache 3.0 open source license.ResultsThe RNA-seq pipeline was validated by comparing its outputs to the 1000 Genomes Project. Next, the RNA-seq workflow was used to predict MSI status in hundreds of tumor samples representing four cancer types based on tumor INDEL alteration at the cataloged hotspots. We observed >90% deletions than insertions in the MSI-high hotspots, consistent with previously published observations. This method showed comparable performance to established commercially available tests.ConclusionsThis study demonstrated reliable prediction of MSI status using genomic variants called from RNA-seq data. Measuring variation at hundreds of hotspot loci present in different tissues and demographically distinct human cohorts may contribute to more robust and generalizable performance. Further, this method does not require a normal control to estimate the mutational load. Ongoing work aims to evaluate the potential as a pan-cancer diagnostic that can be combined readily with other gene signature biomarkers to maximize clinically actionable insights.
