Phylogenetic trees in insects are frequently dated by applying a "standard" mitochondrial DNA (mtDNA) clock estimated at 2.3% My(-1), but despite its wide use reliable calibration points have been lacking. Here, we used a well-established biogeographic barrier, the mid-Aegean trench separating the western and eastern Aegean archipelago, to estimate substitution rates in tenebrionid beetles. Cytochrome oxidase I (cox1) for six codistributed genera across 28 islands (444 individuals) on both sides of the mid-Aegean trench revealed 60 independently coalescing entities delimited with a mixed Yule-coalescent model. One representative per entity was used for phylogenetic analysis of mitochondrial (cox1, 16S rRNA) and nuclear (Mp20, 28S rRNA) genes. Six nodes marked geographically congruent east-west splits whose separation was largely contemporaneous and likely to reflect the formation of the mid-Aegean trench at 9-12 Mya. Based on these "known" dates, a divergence rate of 3.54% My(-1) for the cox1 gene (2.69% when combined with the 16S rRNA gene) was obtained under the preferred partitioning scheme and substitution model selected using Bayes factors. An extensive survey suggests that discrepancies in mtDNA substitution rates in the entomological literature can be attributed to the use of different substitution models, the use of different mitochondrial gene regions, mixing of intraspecific with interspecific data, and not accounting for variance in coalescent times or postseparation gene flow. Different treatments of these factors in the literature confound estimates of mtDNA substitution rates in opposing directions and obscure lineage-specific differences in rates when comparing data from various sources.

Comparative phylogeographical studies in island archipelagos can reveal lineage-specific differential responses to the geological and climatic history. We analysed patterns of genetic diversity in six codistributed lineages of darkling beetles (Tenebrionidae) in the central Aegean archipelago which differ in wing development and habitat preferences. A total of 600 specimens from 30 islands and eight adjacent mainland regions were sequenced for mitochondrial cytochrome oxidase I and nuclear Muscular protein 20. Individual gene genealogies were assessed for the presence of groups that obey an independent coalescent process using a mixed Yule coalescent model. The six focal taxa differed greatly in the number of coalescent groups and depth of lineage subdivision, which was closely mirrored by the degree of geographical structuring. The most severe subdivision at both mitochondrial DNA and nuclear DNA level was found in flightless lineages associated with presumed stable compact-soil habitats (phrygana, maquis), in contrast to sand-obligate lineages inhabiting ephemeral coastal areas that displayed greater homogeneity across the archipelago. A winged lineage, although associated with stable habitats, showed no significant phylogenetic or geographical structuring. Patterns of nucleotide diversity and local genetic differentiation, as measured using PhiST and hierarchical AMOVA, were consistent with high levels of ongoing gene flow in the winged taxon; frequent local extinction and island recolonisation for flightless sand-obligate taxa; and very low gene flow and geographical structure largely defined by the palaeogeographical history of the region in flightless compact-soil taxa. These results show that differences in dispersal rate, mediated by habitat persistence, greatly influence the levels of phylogeographical subdivision in lineages that are otherwise subjected to the same geological events and palaeoclimatic changes.

A positive correlation between species diversity and genetic diversity has been proposed, consistent with neutral predictions in macroecology. We assessed the species--genetic diversity correlation in tenebrionid beetle communities of the Aegean archipelago on 15 islands of different sizes, distances to mainland, and ages of isolation. Alpha and beta diversity of species and haplotypes were assessed using sequences of > 1,000 individuals (mitochondrial cytochrome oxidase 1 and nuclear muscular protein 20). We show that (i) there is a strong species-area and haplotype-area relationship; (ii) species richness in island communities is correlated with intraspecific genetic diversity in the constituent species except when island size or distance to mainland is factored out in partial correlations; (iii) community similarity declines exponentially at an increasing rate when calculated on the basis of species, nuclear, and mtDNA haplotypes; and (iv) distance decay of community similarity is slower in dispersive sand-dwelling lineages compared with less dispersive lineages that are not sand obligate. Taken together, these correlated patterns at the species and haplotype level are consistent with individual-based stochastic dispersal proposed by neutral theories of biodiversity. The results also demonstrate the utility of haplotype data for exploring macroecological patterns in poorly known biota and predicting large-scale biodiversity patterns based on genetic inventories of local samples.

BackgroundAnastomosing hemangioma (AH) is a very rare vascular tumor mimicking angiosarcoma, predominately observed in kidney and less frequently in other organs. We present two new renal cases of AH at opposite ends of the clinical presentation spectrum, provide review of the literature and compare the epidemiological, clinical and pathological profiles of renal and non-renal cases.Case presentationThe first occurred in a 64-year-old woman presented with back pain and the second, a multifocal lesion, in a 47-year-old man with end stage renal disease (ESRD). Histology disclosed a vascular tumor with striking anastomosing pattern, minimal nuclear atypia and locally infiltrative pattern, mimicking superficially angiosarcoma. Extramedullary hematopoiesis, extensive perirenal fat entrapment and increased number of mast cells were additional features in the second lesion. Both patients are well, without disease, 25 and 14 months after diagnosis.ConclusionComprehensive review and analysis of the published literature show that the growing number of non-renal AHs exhibits similar epidemiologic, clinical, biologic and histologic characteristics with renal AHs and most mild differences vanish after exclusion of cases associated with ESRD. Better understanding of AH pathogenesis will contribute to optimal treatment choices.

Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to doublestrand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

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Electrical injury can affect any system and organ. Central nervous system (CNS) complications are especially well recognised, causing an increased risk of morbidity, while peripheral nervous system (PNS) complications, neurourological and cognitive and psychological abnormalities are less predictable after electrical injuries.

Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas.A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review.