Ege University

Persistent organic pollutants (POPs) are lipophilic environmental contaminants with carcinogenic potential, yet data on their accumulation in human gastric tissue are limited. This study aimed to comprehensively quantify 32 POPs in malignant and non-malignant gastric tissues and to evaluate their distribution across blood and omental adipose tissue, together with metabolic enzyme activity, genetic polymorphisms, and oxidative damage markers. POP concentrations were measured in gastric tissue, blood, and omental adipose tissue from stomach cancer patients and controls undergoing stomach reduction surgery. Associations were evaluated using multivariable models adjusted for age, sex, and smoking. False discovery rate (FDR) correction was applied to account for multiple testing. Genotyping of CYP1A1, GSTP1, GSTM1, GSTT1, and OGG1 was performed, and CYP1A1 enzyme activity and urinary oxidative damage biomarkers were assessed. The most robust differences were observed in gastric tissue, where 13 individual POPs and selected chemical classes remained significantly different between cancer and control groups after FDR correction. In blood, five individual POPs remained significant after correction. Several cross-compartment correlations persisted following FDR adjustment, particularly for selected HCH isomers and 4,4'-DDE. CYP1A1 activity did not differ between groups. Among oxidative biomarkers, only urinary o,o'-dityrosine remained significantly lower in cancer patients after FDR correction. In adjusted genetic models, no polymorphism demonstrated a statistically robust association in the overall analysis; the GSTP1 estimate was elevated but imprecise. Direct quantification of POPs in gastric tissue revealed selective accumulation patterns associated with stomach cancer. While systemic distribution and genetic variability may influence susceptibility, tissue-level POP differences represented the most consistent findings. Larger prospective studies are warranted to clarify temporal and mechanistic relationships.

A new amphipod species, Niphargus hasansarii n. sp., is described based on a single female specimen collected from Homeros Valley in İzmir Province, Western Türkiye. The species is distinguished by a unique combination of characters, specifically the high setation (≥4) along the outer margin of dactyli on both gnathopods, a single spine on the inner margin of the dactyli of pereopods 3–7, three distal setae on the inner lobe of maxilla I, a subrounded third epimeral plate, a single robust seta at the base of uropod I, and distinct facial and lateral spines on the telson lobes. Detailed morphological examination and illustrations of the holotype’s appendages were performed. The new species is compared with morphologically similar congeners, and diagnostic differences are highlighted. Although molecular data could not be obtained due to the specimen’s preservation conditions and absence of additional material, the combination of unique morphological features strongly supports the species’ distinct taxonomic status.

The disruption of neural progenitor proliferation is a key mechanism underlying primary microcephaly, yet how cell cycle arrest leads to progenitor loss remains only partially understood. Cyclin-dependent kinases, CDK4 and CDK6, are central regulators of the G₁/S transition, but their role in cellular stress responses during neurodevelopment remains unclear. We studied fibroblasts from affected individuals in two families: siblings homozygous for a CDK4 frameshift (p.Glu94Argfs*65) presenting with microcephaly and pontine hypoplasiaand a child homozygous for a CDK6 missense variant (p.Thr154Ile) with microcephaly, brain atrophy, neutropenia and ovarian failure. Loss-of-function variants in CDK4 and CDK6, core G₁/S regulators, impaired proliferation and induced mitochondrial stress responses and apoptosis. Mutant fibroblasts exhibited significantly reduced DNA synthesis and cell cycle progression, along with increased mitochondrial activity, elevated reactive oxygen species and increased apoptosis. Mitochondrial responses differed by gene: CDK4 deficiency caused mitochondrial hyperpolarisation, while CDK6 deficiency resulted in depolarisation, suggesting differences in mitochondrial apoptotic dynamics. Both variants affected mTOR pathway signalling, linking cell cycle kinase loss to disrupted metabolic regulation. These findings uncover a previously unrecognised mitochondrial stress response accompanying proliferative failure, offering mechanistic insight into how cell cycle arrest could lead to neural progenitor depletion and brain growth disorders. More broadly, our results connect cyclin-dependent kinase dysfunction with mitochondrial homeostasis in neurodevelopment, highlighting shared pathways with neurodegeneration and cancer.