Biology subjects

Hajek, R.

Publications and source records attributed to Hajek, R..

3 recordsLinked to original sources

bioRxiv2023

Brain map of aging-induced alterations in membrane ganglioside pattern

Recent efforts to develop comprehensive metabolome and proteome brain atlases for animal models have yielded significant progress. However, the ganglioside (GSs) profile of these models remains largely unexplored. As essential components of the brain, GSs play a crucial role in neuronal function. To address this gap in knowledge, we conducted an in-depth analysis of the young and adult rat brain, as well as its major brain regions, using ultra-high performance liquid chromatography and tandem mass spectrometry in positive and negative ion modes. We also analyzed GSs in cerebrospinal fluid (CSF) and serum from matched samples. Our findings indicate a shift in the ratio of a-series to b-series GSs with age, along with region-specific changes accompanied by aging. This could improve our understanding of brain aging and neurodegenerative diseases. Our study complements existing brain atlases of lipidome and protein expression and highlights the importance of further investigating the mechanisms underlying these GSs changes and the potential therapeutic implications of our findings.

neuroscience↗

bioRxiv2023

Cell competition for cancer treatment with Urine Progenitor Cells

Here, we provide evidence that urine progenitor cells (UPCs) might offer a novel therapeutic strategy for treating different types of cancer. We found that UPCs have inherent antitumor properties due to cell-cell competition, and we described their mechanism of action against different tumor cell lines. In vitro time-lapse analysis showed that the UPCs have tumor tropic properties, homing to various tumor-conditioned mediums. Besides, UPCs engineered for the expression of cytotoxic agents (the Tumor Necrosis Factor ligand superfamily member 10 and Herpesvirus-thymidine kinase) significantly increased their antitumor properties against several tumor cell lines and proved to serve as highly effective drug-delivery vehicles. Finally, using a mouse model of human triple-negative breast cancer, we observed a 150-fold decrease in tumor volumes in mice treated with engineered UPCs compared to controls. Collectively, our findings demonstrate for the first time the antitumor properties of the UPCs and form a foundation to continue exploring the new concept of cell-cell competition in progenitor cells to treat different types of cancer.

cancer biology↗

bioRxiv2023

Length-dependent translation efficiency of ER-destined proteins

Gene expression resulting in the generation of new proteins is a fundamental process critical for every living organism. Particularly in eukaryotic cells, complex organization of the cell body requires fine-tuning of every step prior to de novo protein synthesis. To ensure proper localization, certain mRNAs possess unique signal sequence, which destinies the translation apparatus to the specific organelle. Here we focus on the mechanisms governing the translation of signal sequence-bearing mRNAs, which encode proteins targeted to the endoplasmic reticulum (ER). The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches ER membrane. The commonly accepted model suggests that mRNA containing the ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with ER. In contrast with the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to a low ribosome occupancy, the short mRNAs continue the cycle always facing the translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.

molecular biology↗