Publications by authors named "F Horvat"

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths worldwide with limited treatment options due to extensive radiation and chemotherapy resistance. Monotherapy with immune checkpoint blockade showed no survival benefit. A combination of immunomodulation and radiotherapy may offer new treatment strategies, as demonstrated for non-small cell lung cancer.

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  • PIWI-interacting RNAs (piRNAs) are vital for maintaining genome integrity by silencing mobile genetic elements and are derived from long single-stranded precursors in various species.
  • The study explores how piRNA clusters form and adapt to genomic threats, presenting a roadmap of piRNA clusters in seven species, highlighting shared traits and differences.
  • Findings reveal transcriptional readthrough as a mechanism for piRNA production in mammals, especially in response to retroviral threats, and uncover dynamic piRNA clusters in human germ cells, enhancing understanding of piRNA biology across species.
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  • Canonical RNA interference (RNAi) is a process where small interfering RNAs (siRNAs) guide the breakdown of specific mRNAs, playing roles in gene regulation and defense mechanisms.
  • In mammals, RNAi is typically limited due to Dicer producing microRNAs instead, but a specific variant (ΔHEL1) allows for RNAi in mouse oocytes, and mutations to this variant can lead to severe developmental issues.
  • Research on Dicer mice shows they can exhibit increased siRNA levels without significant changes to their microRNA profiles, suggesting the possibility of using these mice to study the overall impacts and potential of RNAi in living organisms.
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  • Translation is essential for development, particularly during the silenced transcription phase of oocytes and early embryos.
  • A genome-wide translatome analysis revealed that while global protein synthesis decreases during M-phases, the initiation and elongation of translation are activated, showing a dynamic shift in how specific mRNAs are translated.
  • This study provides new insights into gene expression regulation during oocyte meiosis and the first two embryonic mitoses, marking a significant step towards understanding the molecular mechanisms of translation control in early development.
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  • Gene evolution is complex, with simpler genes like lncRNAs emerging de novo from non-genic sequences; however, protein-coding genes usually have ties to ancestral sequences.* -
  • The study focuses on the evolution of the D6Ertd527e gene in rodents, which likely started as an lncRNA due to a retrotransposon insertion, eventually acquiring protein-coding abilities in some species.* -
  • Although the D6Ertd527e gene shows limited function in lab mice, its evolutionary journey in rodents over the past ~40 million years illustrates key processes in gene formation and evolution.*
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