Significant scientific results


Conserved architectural elements of Alu RNA underlie Alu exon selection and point to a possible chaperone activity of SRP9/14 that represents a departure from its traditional function in regulating the process of translation

Ivana Borovská, Jana Královičová

Alu elments are retrotransposon sequences derived from 7SL RNA, which is part of the signal recognition particle (SRP) important in the process of translation. Alu sequences are present in the genome of all primates and contribute to variation in mRNA coding potential, but can also lead to the production of a non-functional protein with pathological consequences. Alu elements can be part of mRNA due to their localization in intronic regions of genes, and the minimal number of nucleotide changes required for their exonization.

To better understand the cellular mechanisms enabling Alu exonization, we used as a model the F8Alu exon, included in the primary transcript of the human F8 gene as a consequence of a hemophilia-associated mutation. We found that substitution-induced F8Alu exonization was better predicted by changes in Alu RNA conformation than by changes in the sequence of motifs regulating RNA editing. We also showed that the assembly of Alu-derived exons is regulated by the protein heterodimer SRP9/14, which is commonly part of SRP and helps stabilize the closed conformation of the Alu segment of 7SL RNA.

The exonization potential of Alu RNA is modulated by conformational changes of the RNA that are induced by its primary sequence. The SRP9/14 heterodimer is involved in the regulation of exonization and alternative assembly of Alu sequences.

BOROVSKÁ, Ivana – VOŘECHOVSKÝ, Igor – KRÁLOVIČOVÁ, Jana**. Alu RNA fold links splicing with signal recognition particle proteins. In Nucleic Acids Research, 2023, vol. 51, no. 15, p. 8199-8216. (2022: 14.9 – IF, Q1 – JCR, 8.234 – SJR, Q1 – SJR). ISSN 0305-1048.

Resistance of leukemia cells to 5-azacytidine: different responses to the same induction

Kristína Šimoničová, Ľuboš Janotka, Helena Kavcová, Zdena Sulová, Lucia Messingerová, Albert Breier

The development of resistance to oncological treatment is a serious problem in contemporary human medical practice. Our research group is working on hypomethylating agents used to treat predominantly elderly patients with acute myeloid leukemia who are not suitable for hematopoietic cell transplantation. Despite the best efforts of researchers around the world, no marker predicting patient sensitivity to hypomethylating agents is available today and, unfortunately, no other approved therapies are available following the failure of this treatment. Our group has observed the effect of combination therapy of the hypomethylating agent 5-azacytidine with the drug teriflunomide in a proportion of 5-azacytidine-resistant cells in vitro. The enzyme uridine-cytidine kinase 2 could be used as a marker of response to this combination therapy. We have observed novel mutations in the gene encoding this enzyme that are likely to play a role in the efficacy of such combination therapy in cell lines.

ŠIMONIČOVÁ, Kristína – JANOTKA, Ľuboš – KAVCOVÁ, Helena – SULOVÁ, Zdena – MESSINGEROVÁ, Lucia** – BREIER, Albert**. Resistance of Leukemia Cells to 5-Azacytidine: Different Responses to the Same Induction Protocol. In Cancers, 2023, vol. 15, no. 11, art. no. 3063. (2022: 5.2 – IF, Q2 – JCR, 1.312 – SJR, Q1 – SJR).

Therapeutic drugs and dietary supplements that activate GABA receptors can adversely affect early embryonal development

Veronika Kovaříková, Alexandra Špirková, Zuzana Šefčíková, Jozef Pisko, Laura Kalatová, Juraj Koppel, Dušan Fabian, Štefan Čikoš

Gamma aminobutyric acid (GABA) acts as a neurotransmitter in the brain through binding to its specific receptors. Molecules that activate GABA receptors (e.g. benzodiazepines and barbiturates) are widely used as drugs for a number of neurological and psychiatric conditions (such as depression, anxiety disorders, or epilepsy), and alcohol is also a positive modulator of GABA receptors. In addition, various “dietary supplements” containing GABA with claimed “relaxing effects” have recently become available. Our results (obtained in a mouse model) showed that GABA receptors are present not only in neurons but also in eggs and preimplantation embryos (i.e. embryos preparing for implantation in the uterus), and we detected subunits of both ionotropic (GABAA,C) and metabotropic (GABAB) receptors. Further results showed that activation of these receptors significantly increases the proportion of dead cells in the preimplantation embryo at the blastocyst stage, with this effect mediated by both types of GABA receptors. These results suggest that consumption of the above substances by women of reproductive age may harm the embryo at the earliest developmental stages and pose a significant risk to successful gestation.

KOVAŘÍKOVÁ, Veronika* – ŠPIRKOVÁ, Alexandra* – ŠEFČÍKOVÁ, Zuzana – PISKO, Jozef – KALATOVÁ, Laura – KOPPEL, Juraj – FABIAN, Dušan – ČIKOŠ, Štefan**. Gamma-aminobutyric acid (GABA) can affect physiological processes in preimplantation embryos via GABAA and GABAB receptors. In Reproductive Medicine and Biology, 2023, vol. 22, no. 1, art. no. e12528. (2022: 3.4 – IF, Q2 – JCR, 0.778 – SJR, Q2 – SJR, karentované – CCC).

Harnessing beneficial microbiota for health

Andrea Lauková, Monika Pogány Simonová, Valentína Focková, Eva Bino

Bacterial strains with beneficial properties, among which antimicrobial (postbiotic) activity dominates, were selected and characterized from sheep and goat milk as well as from sheep lump cheeses. The selected strains produce bacteriocins, natural bioactive substances of a protein nature with antimicrobial activity, i.e. postbiotics, with applications in human and animal nutrition for the maintenance of good health status. A strain isolated from sheep lump cheese (Lactiplantibacillus plantarum LP17L/1 producing plantaricin and the enzyme β-galactosidase) was used in a biotechnological process for the production of a goat milk-based milk drink with favourable sensory properties. This strain has the potential to enter the functional food market. The bacteriocin potential of Enterococcus moraviensis EM1-1Nik strain from the buccal mucosa of Slovak warm-blooded cowpea was also studied with the possibility of its application in horse breeding.

Patent: PP50021-2022 Strains of lactic acid bacteria Lactococcus lactis subsp. lactis MK1/3, Lactiplantibacillus plantarum LP17L/1, the use of said strains, a method of producing fermented goat milk, a product produced thereby. Patent application published in the Bulletin of the Industrial Property Office of the Slovak Republic on 8 November 2023.

LAUKOVÁ, Andrea – STYKOVÁ, Eva – FOCKOVÁ, Valentína – MAĎAR, Marián. Enterococcus moraviensis EMo 1-1Nik of horse origin:characteristics and potential bacteriocin-producing strain. In Veterinary Research Communications, 2023, vol. 47, no. 3, p. 1471-1478. (2022: 2.2 – IF, Q2 – JCR, 0.526 – SJR, Q1 – SJR, karentované – CCC). (2023 – Current Contents). ISSN 0165-7380.

Can touch stimulation induce positive emotions in hens?

Zuzana Skalná, Katarína Pichová, Ľubor Košťál

Human touch stimulation (tickling) leads to the induction of positive emotions in rats. Today, tickling is an accepted model for studying positive emotions in rats under laboratory conditions. This phenomenon was first pointed out by Jaak Panksepp, an American scientist of Estonian origin. Rat barking is based on a playful behaviour observed in this species – rough and tumble play. Tickled rats make 50 kHz sounds, which are considered to be the equivalent of human laughter. However, there are differences in this behaviour between individuals. Rats that made 50 k Hz sounds after touch stimulation (tickling) (laughter) were more optimistic on the cognitive bias test than those that did not make these sounds (no laughter). The design of our published experiment was inspired by this study by Rafal Rygula of the Polish Academy of Sciences. We tested whether tactile stimulation of the nostrils leads to the induction of positive emotions similarly to rats. We did not confirm this hypothesis, i.e. we failed to induce positive emotions in laying hens by tickling, measurable by the judgment bias test. Nevertheless, our study contributes to a better understanding of the human-animal relationship and to the expansion of knowledge about the possibilities of inducing positive welfar, which has recently been a topic attractive not only to the professional but also to the general public.

SKALNÁ, Zuzana** – PICHOVÁ, Katarína – KOŠŤÁL, Ľubor. Tickling and its effects on the affective states of laying hens. In Applied Animal Behaviour Science, 2023, vol. 265, art. no. 105984. (2022: 2.3 – IF, Q1 – JCR, 0.63 – SJR, Q1 – SJR). ISSN 0168-1591.

Production of biologically active unsaturated fatty acids using recombinant microorganisms

Roman Holič, Martina Garaiová, Daniela Krajčiová

Fatty acids with a conjugated double bond system are classified in the narrow subgroup of polyunsaturated fatty acids. They are characterised by a unique chemical structure, which gives them positive bioactive effects that have great potential in the treatment and prevention of a number of diseases. However, natural producers of these fatty acids are scarce in nature and alternative sources are being sought in the form of recombinant microorganisms. Representatives of this subgroup include calendulic acid (source – calendula seeds) and punicic acid (source – pomegranate seeds). Using metabolic engineering methods, we have succeeded in preparing yeast strains capable of synthesising the above-mentioned biologically active acids. In the model organism yeast Schizosaccharomyces pombe, we found that the accumulation of calidic acid was associated with reduced expression of the lcf1 gene encoding a long-chain acyl-CoA synthetase and the abundance of calidic acid in the free fatty acid fraction. By applying the findings to other yeast species that can utilize different types of industrial waste for growth while accumulating high levels of lipids, we can obtain production strains suitable for biotechnological applications. In collaboration with other laboratories, we have been able to establish punicic acid production in the lipid-forming yeast Yarrowia lipolytica with great potential in biotechnology. We are currently working intensively to optimize its accumulation in cells.

GARAIOVÁ, Martina – HUA, Qiang – HOLIČ, Roman. Heterologous Production of Calendic Acid Naturally Found in Calendula officinalis by Recombinant Fission Yeast. In Journal of Agricultural and Food Chemistry, 2023, vol. 71, no. 8, p. 3842-3851. (2022: 6.1 – IF, Q1 – JCR, 1.099 – SJR, Q1 – SJR). ISSN 0021-8561.

URBANÍKOVÁ, Veronika* – PARK, Young-Kyoung* – KRAJČIOVÁ, Daniela – TACHEKORT, Mehdi – ČERTÍK, Milan – GRIGORAS, Ioana – HOLIČ, Roman* – NICAUD, J.M.** – GAJDOŠ, P.**. Yarrowia lipolytica as a Platform for Punicic Acid Production. In International Journal of Molecular Sciences, 2023, vol. 24, no. 10, art. no. 8823. (2022: 5.6 – IF, Q1 – JCR, 1.154 – SJR, Q1 – SJR, karentované – CCC). (2023 – Current Contents). ISSN 1422-0067.

Potential treatment of alcoholism through targeted FGF2 receptor inhibition

Daniil Grinchii, Eliyahu Dremencov

In our research, we studied the effect of a protein called fibroblast growth factor 2 (FGF2) on alcohol consumption in rats. We found that this protein plays an important role in regulating the brain’s dopamine pathway system, which is associated with reward and feelings of pleasure. When we artificially increased FGF2 levels, the rats showed increased interest in alcohol and consumed more of it. Conversely, by blocking the receptor for FGF2, we achieved the opposite – the rats consumed less alcohol. An important finding is that blocking the FGF2 receptor did not affect the rats’ motivation to obtain alcohol, but it did substantially affect their ability to avoid returning to alcohol consumption after a period of abstinence. This observation, specific to male rats, opens the door for potential treatments for alcoholism, where targeted FGF2 receptor inhibition could be a promising strategy.

GRINCHII, Daniil* – LEVIN-GREENWALD, Matar* – LEZMY, Noa* – GORDON, Tamar – PALIOKHA, Ruslan – KHOURY, Talah – RAČICKÝ, Matej – HERBURG, Leonie – GROTHE, Claudia – DREMENCOV, Eliyahu** – BARAK, Segev**. FGF2 activity regulates operant alcohol self-administration and mesolimbic dopamine transmission. In Drug and Alcohol Dependence, 2023, vol. 248, art. no. 109920. (2022: 4.2 – IF, Q2 – JCR, 1.562 – SJR, Q1 – SJR). ISSN 0376-8716.