Background: Tick-borne diseases are of substantial concern worldwide in both humans and animals. Several hard tick species are of medical and veterinary interest in Europe, and changes in the range of tick species can affect the spread of zoonotic pathogens. The aim of the present study was to map the current prevalence and distribution pattern of ticks and related tick-borne pathogens in Latvia, a Baltic state in northern Europe. Methods: Nearly 4600 Ixodes ricinus, I. persulcatus and Dermacentor reticulatus tick samples were collected in all regions of Latvia during 2017–2019 and were screened by molecular methods to reveal the prevalence and distribution pattern of a wide spectrum of tick-borne pathogens. Results: New localities of D. reticulatus occurrence were found in western and central Latvia, including the Riga region, indicating that the northern border of D. reticulatus in Europe has moved farther to the north. Among the analyzed ticks, 33.42% carried at least one tick-borne pathogen, and 5.55% of tick samples were positive for two or three pathogens. A higher overall prevalence of tick-borne pathogens was observed in I. ricinus (34.92%) and I. persulcatus (31.65%) than in D. reticulatus (24.2%). The molecular analysis revealed the presence of tick-borne encephalitis virus, Babesia spp., Borrelia spp., Anaplasma phagocytophilum and Rickettsia spp. Overall, 15 and 7 tick-borne pathogen species were detected in Ixodes spp. and D. reticulatus ticks, respectively. This is the first report of Borrelia miyamotoi in Latvian field-collected ticks. Conclusions: This large-scale countrywide study provides a snapshot of the current distribution patterns of Ixodes and Dermacentor ticks in Latvia and gives us a reliable overview of tick-borne pathogens in Latvian field-collected ticks.

The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and cardiovascular disease. All of these sequelae are exacerbated by increased body weight, a major feature of PCOS. The protein encoded by the YAP1 gene plays a key role in one of the pivotal mechanisms that govern cellular/organismal metabolism and contributes to the pathogenesis of metabolic diseases. Aim: To compare the prevalence of single nucleotide variants (SNVs) in the YAP1 gene among adolescents with PCOS, adolescents at risk of PCOS development and healthy adolescents, and assess their association with the clinical characteristics of PCOS. Results: The frequencies of the five investigated YAP1 gene SNVs (rs11225161, rs11225166, rs3858420, rs11225138 and rs79981660) were not significantly different among adolescents with PCOS, risk group patients and healthy controls. Furthermore, none of the SNVs contributed to the clinical characteristics of adolescents with PCOS and adolescents at risk of PCOS development. Conclusions: No significant associations were found between PCOS in adolescents and the five investigated SNVs in the YAP1 gene.

(1) Background: Amplicon-based 16S rRNA profiling is widely used to study whole communities of prokaryotes in many niches. Here, we comparatively examined the microbial composition of three tick species, Ixodes ricinus, Ixodes persulcatus and Dermacentor reticulatus, which were field-collected in Latvia. (2) Methods: Tick DNA samples were used for microbiome analysis targeting bacterial 16S rDNA using next-generation sequencing (NGS). (3) Results: The results showed significant differences in microbial species diversity and composition by tick species and life stage. A close similarity between microbiomes of I. ricinus and I. persulcatus ticks was observed, while the D. reticulatus microbiome composition appeared to be more distinct. Significant differences in alpha and beta microbial diversity were observed between Ixodes tick life stages and sexes, with lower taxa richness indexes obtained for female ticks. The Francisella genus was closely associated with D. reticulatus ticks, while endosymbionts Candidatus Midichlorii and Candidatus Lariskella were associated with I. ricinus and I. persulcatus females, respectively. In I. ricinus females, the endosymbiont load negatively correlated with the presence of the Rickettsia genus. (4) Conclusions: The results of this study revealed important associations between ticks and their microbial community and highlighted the microbiome features of three tick species in Latvia.

Resistance to Vemurafenib (VEM), a targeted BRAFV600E inhibitor, was examined in the metastatic paratetraploid (XX, abnormal Y chromosome) melanoma cell line, SkMel28. During the first week of treatment, pERK suppression coincided with transcriptomic and phenotypic changes related to senescence, autophagy/mitophagy, neuro-melanogenesis, and cell co-alignment. By the second week, MAPK-ERK signalling was restored, coinciding with surmounting the G1/S checkpoint, G2M checkpoint delay, mitotic slippage (MS), and downregulation of senescence and melanogenesis. The dynamics of melanogenesis and MS were highly correlated. By days 12-15, ∼8% of cells with melanin remnants exhibited hyperploidy and multinucleation, some arranged as rosettes, encased by a Zona pellucida-positive structure reminiscent of oocytes, zygotes, or blastulae, occasionally yielding cellularised sub-cells or stalling in diapause. These parasexual processes eventually ceased; cells resumed proliferative clonogenic growth and their initial mito-meiotic, mesenchymal profile. Transcriptomic analysis confirmed the reversal of their cell fate direction: from senescence-induced neuro-melanogenesis to its suppression and activation of female meiosis-like and mitosis states. The transition point of this cell-fate reversal coincided with S-phase resumption, highlighted by replication delay and activation of the FOS-TEAD/Hippo axis of the "female pregnancy" (stress-response, embryonal placentation, vascularisation, stemness, anti-apoptosis) gene ontology module. We conclude that resistance to VEM in SkMel28 cells encompasses the transition between three possible cell fates: (1) senescence/differentiation, (2) reprogramming/blastulation, and (3) recovery of the proliferative mito-meiotic profile. The coexpression of senescence, reprogramming and gametogenetic genes in a dataset of late-stage melanoma patient samples supports these results.

The purpose of this study was to investigate the linkage of the association of azoospermia phenotype with genetic alterations, involved in genome instability. Male infertility is a multifactorial pathology, and genetic alterations might be the underlying factors in majority of cases of severe male infertility. The recent emergence of next‐generation sequencing offers an opportunity to analyze many genes and their interactions at once, and whole‐exome sequencing (WES) together with whole‐genome sequencing (WGS) was recently suggested for implementation of diagnosis workup in severe infertility cases. However, the reports on WES in conjunction with burden tests and gene network analysis are scarce or lacking in cases of severe male infertility. WES was performed on 21 nonobstructive azoospermia patients. DNA samples were sequenced using the Twist Comprehensive Exome Panel. Genetic burden test was performed with Testing Rare vAriants using Public Data. Protein interactions were investigated with ConsensusPathDB and Cytoscape. For single nucleotide variants and copy number variations (CNV) analysis, samples were analyzed with the Illumina’s BaseSpace Variant Interpreter. Genetic variant burden was found elevated in 1,473 genes out of 30,000 known testis expressed genes. Three hundred and two genes with increased loss‐of‐function (LoF) variant set were present in more than one sample. Overrepresentation analysis with pathway‐based set of genes with high variant burden demonstrated 26 pathways. Overrepresentation analysis with protein complex‐based gene sets obtained 14 sets, showing the involvement in cell proliferation and DNA repair. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) network analysis with Cytoscape identified two clusters: (1) genes, involved in DNA binding/condensation and repair processes and (2) genes with the role in ribosome biosynthesis and gene expression processes. Increased loss of function germline variant burden and sumoylation may have critical significance in spermatogenesis. These parameters may be used for focused diagnosis in nonobstructive azoospermia patients. This may have both general significance for the decreased organism functionality but in particular is critical in spermatogenesis.