Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles.

G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data.

The Role of Endoplasmic Reticulum Stress in Cell Injury Induced by Methimazole on Pancreatic Cells.

Purpose: Methimazole is an anti-thyroid agent, especially as main therapy option for Graves' disease in children and adults. Drug induced pancreatitis is one of the known adverse effect of methimazole mentioned in case reports. However, the detailed molecular mechanisms of methimazole-induced pancreatitis are still unclear. In this study, the aim is to investigate the adverse effect of methimazole on pancreas cell stress mechanism and apoptosis. Methods: Cytotoxicity was evaluated in human pancreas/duct (PANC-1) cell line. Total oxidant (TOS) and antioxidant status (TAS) for oxidative stress index, glutathione (GSH) level and endoplasmic reticulum (ER) stress biomarkers were evaluated by ELISA. Reactive oxygen species (ROS) levels and apoptosis were evaluated by flow-cytometer. Results: The 30% inhibition rate concentration (IC30) value was determined as 53 mM in PANC1 cells. The exposure concentrations were in the range of 0-40 mM for 48 hours. Methimazole might induce cellular stress conditions. ROS production increases depending on concentration, and this increase shows parallelism with the increase in ER stress biomarkers such as TOS, ERN1 and CASPASE12. Conversely, there was no significant difference between control and exposure groups in terms of apoptosis. Conclusion: In conclusion, methimazole might have triggered the mechanisms of inflammation or autophagy in the pancreatic cells. However, there is still a need for in vitro and in vivo studies including other cellular parameters related to apoptosis.

Is there a distinct harbor porpoise subpopulation in the Marmara Sea?

Genetic population structure of geographically isolated endangered Black Sea harbor porpoise (Phocoena phocoena relicta) is little known in Turkish waters, especially in the Turkish Straits System (TSS- Marmara Sea, Bosphorus and Dardanelles), which connects the Black Sea and the Aegean Sea. Mitochondrial DNA sequences of 70 new individuals sampled in the Turkish Black Sea, TSS and Aegean Sea, revealed five new haplotypes from the Black Sea. The findings support the idea that harbor porpoises from the Black Sea dispersed into the Aegean through the TSS. Considering signatures of population expansion, all subpopulations showed a signature of population expansion. The network data and the Фst calculations indicated that the Marmara Sea subpopulation was significantly differentiated from all of the other subpopulations, and supports the notion of its isolated. The finding of a potential management unit (MU) within an already heavily impacted subpopulation as a whole suggests that the individuals of P. p. relicta inhabiting the Marmara Sea require a very rigorous conservation strategy to ensure the survival of this subpopulation, represented by its unique haplotype.