Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Drosophila Evolution over Space and Time (DEST): A New Population Genomics Resource.

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.

Validity of the Health Personality Assessment among rectal cancer survivors in Serbia.

Understanding health personality traits in rectal cancer survivors could help to optimize recovery and coping mechanisms. The objective of this study was to evaluate psychometric properties of the Health Personality Assessment in Serbian language among rectal cancer survivors. A cross-sectional study was carried out from June to December 2022. The study sample consisted of 76 people who underwent the open lower anterior resection for rectal carcinoma at the Clinic for Digestive Surgery and the Clinic for Emergency Surgery, University of Clinical Center of Serbia (Belgrade, Serbia) and whose ileostomy was closed. Study participants were interviewed over the telephone using the Serbian version of the HPA which was translated according to the internationally accepted methodology for translation and adaptation of questionnaires. The confirmatory factor analysis suggested that the fit indices for 5-factor structure of the HPA were acceptable-to-good: Goodness of fit index = 0.939; Tucker Lewis fit index = 0.989; Comparative fit index = 0.992; Root Mean Square Error of Approximation = 0.019. Cronbach's alpha coefficients for Health Neuroticism, Health Extraversion and Health Agreeableness were>0.7 and for Health Openness and Health Conscientiousness were >0.4. Predictive validity testing suggested that not having complications with the ileostomy and a longer time since ileostomy closure were associated with stronger Health Agreeableness. Also, a longer time since ileostomy closure was associated with stronger Health Conscientiousness. The Serbian version of the HPA showed good construct validity and acceptable internal consistency. This is an important tool in further research of personality and health outcomes among rectal cancer survivors.

Population History Shapes Responses to Different Temperature Regimes in Drosophila subobscura.

Drosophila subobscura is considered a good model species for investigation of a population's ability to adapt and cope with climate changes. Decade long research has shown that inversion frequencies change in response to environmental factors indicating their role in adaptation to novel environments. The mechanisms behind organisms' responses to temperature are complex, involving changes in physiology, behavior, gene expression and regulation. On the other hand, a population's ability to respond to suboptimal conditions depends on standing genetic variation and population history. In order to elucidate the role of local adaptation in population response to the changing temperature, we investigated the response to temperature in D. subobscura individuals originating from two different altitudes by combining traditional cytogenetic techniques with assessing the levels of Hsp70 protein expression. Inversion polymorphism was assessed in the flies sampled from natural populations and in flies reared in laboratory conditions at three different temperatures after five and sixteen generations and Hsp70 protein expression profile in 12th generation flies at the basal level and after heat shock induction. Our results indicate that local adaptation and population history influence population response to the changing temperature.

Genetic analysis and allele-specific expression of SMAD7 3'UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance.

BACKGROUND: Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3' untranslated region ( 3'UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNA-mediated post-transcriptional regulation. PATIENTS AND METHODS: This study included 80 patients with different CRC stages and six human colon cancer cell lines of various histological origins. SMAD7 3'UTR was analyzed by direct sequencing, followed by the relative quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were employed for predictions of regulatory consequences of detected variants. RESULTS: A total of four different SNVs in one cell line and nine patients were found, among which were a novel somatic point variant and three already known germline variants (rs16950113, rs1050799536, and rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and creating new target sites for one or more miRNAs. CONCLUSION: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further studies should investigate.

Stress Resistance Traits under Different Thermal Conditions in Drosophila subobscura from Two Altitudes.

Global warming and climate change are affecting many insect species in numerous ways. These species can develop diverse mechanisms as a response to variable environmental conditions. The rise in mean and extreme temperatures due to global warming and the importance of the population's ability to adapt to temperature stress will further increase. In this study, we investigated thermal stress response, which is considered to be one of the crucial elements of population fitness and survival in fast-changing environments. The dynamics and variation of thermal stress resistance traits in D. subobscura flies originating from two natural populations sampled from different altitudes were analysed. Three different temperature regimes (25 °C, 19 °C, and 16 °C) were used for the F1 progeny from both localities to establish six experimental groups and investigate stress resistance traits: desiccation resistance, heat knock-down resistance, starvation resistance, and chill-coma recovery time. We detected that laboratory thermal conditions and population origin may have an effect on the analysed traits, and that sex also significantly influences stress resistance. Individuals from the lower altitude reared at higher temperatures show inferior resistance to thermal shock.

Urban ecosystem drives genetic diversity in feral honey bee.

Urbanization can change biodiversity in both directions, positive and negative, and despite the rising global trend of urban beekeeping, little is known about the impact of urbanization on the genetic diversity of honey bees. We investigate how urbanization affects the genetic variability of feral and managed honey bee colonies that are spread throughout the entire city, even in highly urban areas, through genetic analysis of 82 worker bees. We found convincing evidence of high genetic differentiation between these two groups. Additionally, by comparing city samples with 241 samples from 46 apiaries in rural parts of the country, variations in mitochondrial tRNAleu-cox2 intergenic region and microsatellite loci indicated that feral colonies have distinct patterns of genetic diversity. These results, with evidence that feral honey bees find niches within highly modified and human-dominated urban landscapes, lead us to conclude that urbanization is a driver of the genetic diversity of feral honey bees in the city.

Temperature-Specific and Sex-Specific Fitness Effects of Sympatric Mitochondrial and Mito-Nuclear Variation in Drosophila obscura.

The adaptive significance of sympatric mitochondrial (mtDNA) variation and the role of selective mechanisms that maintain it are debated to this day. Isofemale lines of Drosophila obscura collected from four populations were backcrossed within populations to construct experimental lines, with all combinations of mtDNA Cyt b haplotypes and nuclear genetic backgrounds (nuDNA). Individuals of both sexes from these lines were then subjected to four fitness assays (desiccation resistance, developmental time, egg-to-adult viability and sex ratio) on two experimental temperatures to examine the role of temperature fluctuations and sex-specific selection, as well as the part that interactions between the two genomes play in shaping mtDNA variation. The results varied across populations and fitness components. In the majority of comparisons, they show that sympatric mitochondrial variants affect fitness. However, their effect should be examined in light of interactions with nuDNA, as mito-nuclear genotype was even more influential on fitness across all components. We found both sex-specific and temperature-specific differences in mitochondrial and mito-nuclear genotype ranks in all fitness components. The effect of temperature-specific selection was found to be more prominent, especially in desiccation resistance. From the results of different components tested, we can also infer that temperature-specific mito-nuclear interactions rather than sex-specific selection on mito-nuclear genotypes have a more substantial role in preserving mtDNA variation in this model species.

Further Evidence of Population Admixture in the Serbian Honey Bee Population.

Socioeconomic interests and beekeeper preferences have often taken precedence over the conservation of locally native honey bee subspecies, leading to the predominance of admixture populations in human-dominated areas. To assess the genetic diversity of contemporary managed Serbian honey bee colonies, we used 14 microsatellite loci and analyzed 237 worker bees from 46 apiaries in eight localities of northern and southern Serbia. Furthermore, we compared data for nine microsatellite loci with 338 individuals from Italy, Hungary, Poland, and Spain. The standard parameters of genetic diversity in Serbian honey bee populations were in line with other analyses, although somewhat smaller. STRUCTURE analysis showed the existence of two equally distributed genetic clusters and Analysis of molecular variances could not confirm the presence of a geographically discrete population but showed local differences. Discriminant analysis of principal components showed overlapping of worker bees from different parts of Serbia. Clear genetic differentiation can be observed when comparing all populations between geographical regions and their corresponding subspecies. The absence of the A. m. macedonica subspecies from its historical distribution range in southern Serbia as well as the lack of distinctive geographical groups suggest that selective breeding, queen import, and migratory beekeeping practices strongly influence the genetic structure and diversity of honey bees, leading to the genetic uniformization and creation of the admixture population.

MtDNA Analysis Indicates Human-Induced Temporal Changes of Serbian Honey Bees Diversity.

Local populations of Apis mellifera are rapidly changing by modern beekeeping through the introduction of nonnative queens, selection and migratory beekeeping. To assess the genetic diversity of contemporary managed honey bees in Serbia, we sequenced mitochondrial tRNAleu-cox2 intergenic region of 241 worker bees from 46 apiaries at eight localities. Nine haplotypes were observed in our samples, with C2d being the most common and widespread. To evaluate genetic diversity patterns, we compared our data with 1696 sequences from the NCBI GenBank from neighbouring countries and Serbia. All 32 detected haplotypes belonged to the Southeast Europe lineage C, with two newly described haplotypes from our sample. The most frequent haplotype was C2d, followed by C2c and C1a. To distinguish A. m. carnica from A. m. macedonica, both previously reported in Serbia, PCR-RFLP analysis on the COI gene segment of mtDNA was used, and the result showed only the presence of A.m. carnica subspecies. An MDS plot constructed on pairwise FST values showed significant geographical stratification. Our samples are grouped together, but distant from the Serbian dataset from the GenBank. This, with the absence of A. m. macedonica subspecies from its historic range of distribution in southern Serbia, indicates that honey bee populations are changing rapidly due to the anthropogenic influence.

The discovery, distribution, and diversity of DNA viruses associated with Drosophila melanogaster in Europe.

Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here, we report fourteen DNA viruses detected in a metagenomic analysis of 6668 pool-sequenced Drosophila, sampled from forty-seven European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a double-stranded RNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to twelve segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2 per cent or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D.melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses.