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Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp., (© 2023. The Author(s).)

Co-doped Ce 3+ , Cr 3+ and Pr 3+ yttrium-aluminium-gallium garnet powders of various sizes were obtained by co-precipitation method. The microstructure and morphology were investigated by XRPD, TEM and gas porosimetry. The luminescence properties were studied by excitation and emission spectra, quantum yield and decay times. Thermoluminescence measurements were performed to evaluate the activation energy, traps redistribution and frequency factor. Limitation in the energy transfer between dopant ions in the small particles, traps depth and surface defects were considered and investigated as responsible for the quenching of persistent luminescence. The phosphors annealed at 1100 °C show the optimal persistent luminescence and nano-particle size.

Sleep bruxism (SB) and obstructive sleep apnea (OSA) are co-occurring sleep conditions. The study aimed to evaluate the association of selected single-nucleotide polymorphisms (SNPs) occurring within the genes of the serotonin and dopamine pathways in SB and OSA and investigate the relationship between them. The study group included 100 Caucasian patients. SB and OSA were diagnosed in 74 and 28 patients, respectively. In addition, 125 unrelated Caucasian healthy blood donors served as randomly selected controls to enable comparison of polymorphisms. The following SNPs were analyzed: rs2770304 and rs6313 within the serotonin receptor encoding gene (HTR2A), rs4680 polymorphism of the catechol-O-methyltransferase (COMT) gene, and rs686 within the dopamine receptor (DRD1) encoding gene. The prevalence of the DRD1 rs686 G variant (GG homozygosity) was found to be high in the study group compared to the control group. Bruxism episode index (BEI) was found to be significantly increased in the HTR2A rs6313 TT homozygotes compared to the heterozygous patients. Moreover, within a group of the HTR2A rs2770304 TT homozygous cases, a statistically significant correlation was observed between BEI and apnea-hypopnea index. These results indicate that DRD1 rs686 may potentially affect predisposition to SB, that HTR2A rs6313 SNP may be involved in SB pathogenesis, and that HTR2A rs2770304 polymorphism might contribute to the association between SB and OSA. This suggests a possible genetic contribution to the etiology of primary SB.

Despite the efforts of a number of research groups worldwide, we still have a poor understanding of the chemical nature of the fish kairomones which induce defensive morphology, life history and behavior in their planktonic prey. Bile excreted by foraging fish play a crucial role in their signaling systems. Using high-performance liquid chromatography (HPLC), we revealed the presence of primary and secondary bile acids and bile salts in fish-conditioned water, similar as in carp bile. Upon exposure to either fish bile or commercially acquired bile salts, Daphnia demonstrated similar changes in life history and behavior as when exposed to fish kairomones. The synergic effect of the injured Daphnia alarm substance with fish bile on Daphnia life history is similar to the adaptive effect of the same alarm substance combined with fish kairomones. This strongly supports the view that fish bile or selected bile acids/salts may be responsible for the biological activity of kairomones.