Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication

Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.

Cytological features of crypt involvement by cervical intraepithelial neoplasia

Objective. To determine the cytological criteria of crypt lesion by cervical intraepithelial neoplasia (CIN). Patients and methods. The retrospective cohort study included 76 women who underwent a comprehensive medical evaluation after screening tests: cervical cytology test, colposcopy, biopsy and histological examination of the cervix, polymerase chain reaction (PCR) test for human papillomavirus (HPV). Cytological material was obtained using an endocervical brush (Cytobrush); it was stained by the Pappenheim method and examined by light microscopy; the Bethesda system was used. Results. Cytological examination of the cervical smears (cervical ectopy and endocervix) in 59 (78%) women revealed squamous epithelial cells with features typical for dysplasia of different severity: mild – LSIL (low-grade squamous intraepithelial lesions) and severe – HSIL (high-grade squamous intraepithelial lesion). Smears of 31 (53%) women also showed cylindrical (glandular) epithelial cells with signs of pronounced proliferation: 2 (9.5%) with LSIL and 29 (76.3%) with HSIL. Histological examination of the cervix in all 59 women revealed dysplasia of varying severity. Features of endocervical crypt involvement were detected in 28 women: 1 (4.8%) with LSIL and 27 (71.1%) with HSIL. The sensitivity and specificity of cytological diagnosis of cervical crypt involvement in LSIL were 100 and 95%, in HSIL – 87 and 67%, respectively. Conclusion. The cytological feature of crypt involvement by CIN is the presence in cervical mucus smears of clusters and papillary structures of proliferating, immature cylindrical epithelial cells, partially with cellular and nuclear polymorphism. Key words: crypts, cervical intraepithelial neoplasia, cytological examination

Micronuclei assay as biomarker for ethyl methane sulphonate (EMS) genotoxicity in Eclipta alba (L.) Hassk.

The eukaryotic cells are complemented with a single nucleus. However, several cells show abnormal small nuclei known as micronuclei, with addition to the main nucleus. These anomalous small nuclei along with main nucleus which may be the result of exposure of cell to cytotoxic agents (Chemicals/physical mutagens). These mutagens also cause structural or numerical chromosomal aberrations. The treatment of EMS, a chemical mutagen, induces micronuclei formation and nuclear as well as chromosomal peculiarities in Eclipta alba. The effect of micronuclei is discussed in terms of cytotoxicity of genotoxins and several evidences of nuclear polymorphism illustrated due to the mutagenic effect of EMS. Pollen viability was also examined through pollen fertility. Micronuclei causes the genomic instability and elimination of genome which is effectively put to use in breeding programmes for the creation of aneuploids and also for haploid lines.

Single nuclear polymorphism Val66Met (rs6265) of brain derived neurotrophic factor gene in prognostication of outcomes after ST segment elevation myocardial infarction

The aim – to investigate associations between single nucleotide polymorphism (SNP) Val66Met of the brain-derived neurotropic factor (BDNF) gene and conventional predictive biomarkers and combined 6-month clinical end points in post-ST segment elevation myocardial infarction (STEMI) patients. Materials and methods. Two hundred and fifty six acute STEMI patients after successful percutaneous coronary intervention with TIMI III blood flow restoring. Single nuclear polymorphism Val66Met of BDNF gene was determined by real-time polymerase chain reaction. Observation behind the patients has been performed during 6-month period. Results and discussion. The combined clinical end point (MACEs and hospitalization) after 6 month was determined in 61 (23.8 %) post-STEMI patients; 195 (7.2 %) patients did not meet the events. The frequency of Val66Met polymorphous genotypes of BDNF gene in STEMI patients was the following: Val66Val – 74.2 % (n=190), Val66Met + Met66Met – 25.8 % (n=66). Unadjusted multivariate linear regressions has shown that peak TnI levels, NT-proBNP, SYNTAX score, TIMI score, and Val66Met+Met66Met genotype of BDNF gene, remained independent predictors for combined clinical end point. After adjustment for SYNTAX score and TIMI score, genotype Val66Met+Met66Met of BDNF gene (OR 1.5476, 95 % CI 1.1277–4.1426, р=0.0246) and NT-proBNP (OR 1.7546, 95 % CI 1.0219–3.1002, р=0.046) were independent predictors for combined clinical end point. Kaplan – Meier curves demonstrated that post-STEMI patients having Val66Val genotype of BDNF gene had the lowest accumulation of combined end point when compared with those who had the combination of Va66lMet and Met66Met genotypes (Cox-criterion, p=0.019; log-rang criterion, p=0.03). Сonclusions. The Val66Met polymorphism of BDNF gene was found as an independent predictor for combined 6-month clinical end points amid post-STEMI patients treated with percutaneous coronary intervention.

Hyperketonemia GWAS and parity-dependent SNP associations in Holstein dairy cows intensively sampled for blood β-hydroxybutyrate concentration

Hyperketonemia (HYK) is a metabolic disorder that affects early postpartum dairy cows; however, there has been limited success in identifying genomic variants contributing to HYK susceptibility. We conducted a genome-wide association study (GWAS) using HYK phenotypes based on an intensive screening protocol, interrogated genotype interactions with parity group (GWIS), and evaluated the enrichment of annotated metabolic pathways. Holstein cows were enrolled into the experiment after parturition, and blood samples were collected at four timepoints between 5 and 18 days postpartum. Concentration of blood β-hydroxybutyrate (BHB) was quantified cow-side via a handheld BHB meter. Cows were labeled as a HYK case when at least one blood sample had BHB ≥ 1.2 mmol/L, and all other cows were considered non-HYK controls. After quality control procedures, 1,710 cows and 58,699 genotypes were available for further analysis. The GWAS and GWIS were performed using the forward feature select linear mixed model method. There was evidence for an association between ARS-BFGL-NGS-91238 and HYK susceptibility, as well as parity-dependent associations to HYK for BovineHD0600024247 and BovineHD1400023753. Candidate genes annotated to these single nuclear polymorphism associations have been previously associated with obesity, diabetes, insulin resistance, and fatty liver in humans and rodent models. Enrichment analysis revealed focal adhesion and axon guidance as metabolic pathways contributing to HYK etiology, while genetic variation in pathways related to insulin secretion and sensitivity may affect HYK susceptibility in a parity-dependent matter. In conclusion, the present work proposes several novel marker associations and metabolic pathways contributing to genetic risk for HYK susceptibility.

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication

Sheep was among the first domesticated animals, but its demographic history is little understood. Here we present combined analyses of mitochondrial and nuclear polymorphism data from ancient central and west Anatolian sheep dating to the Late Glacial and early Holocene. We observe loss of mitochondrial haplotype diversity around 7500 BCE during the early Neolithic, consistent with a domestication-related bottleneck. Post-7000 BCE, mitochondrial haplogroup diversity increases, compatible with admixture from other domestication centres and/or from wild populations. Analysing archaeogenomic data, we further find that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds, and especially those from central and north Europe. Our results indicate that Asian contribution to south European breeds in the post-Neolithic era, possibly during the Bronze Age, may explain this pattern.

CASE OF PHEOCHROMOCYTOMA WITH PERMANENT HYPERTENSION

Pheochromocytoma is a tumor of chromaffin tissue that produces a large amount of biologically active substances (adrenaline, noradrenaline, dopamine), clinically manifested by hypertension and various metabolic disorders. Quite often the diagnosis is made only after autopsy. One of the reasons for late diagnosis is a great number of different clinical masks of the disease. Usually pheochromocytoma is suspected in patients with paroxysmal hypertension. We present a 37-year-old pregnant female (week 8 of pregnancy) with pheochromocytoma and permanent hypertension and sustained elevation of blood pressure up to 220/150 mm Hg. Her only complaint was vision disorder that started 3 months ago. Also, she noted a weight loss of 4 kg over the last 6 months. Retinopathy, left ventricle hypertrophy, tumor of right adrenal gland and glucose level disorders were revealed. Pregnancy was terminated for medical reasons. The patient took combination of doxazosin 0.4 mg, metoprolol 100 mg and moxonidin 0.4 mg per day and blood pressure was normalized to 130/90 mm Hg. Due to hypertension and tumor of right adrenal gland that are accompanied by retinopathy and metabolic disorders, pheochromocytoma was suspected. Contrast-enhanced computed tomography confirmed the tumor (60×73×70 mm) of right adrenal gland. Urinary normetanephrine level was 5.5 times higher than the norm. Magnetic resonance angiography of cerebral vessels was done because of malignant hypertension and family history (the patient’s sister had died of cerebral hemorrhage). Fusiform aneurysm of right internal carotid artery was revealed. The patient underwent laparoscopic resection of right adrenal gland. Histologic examination: pronounced cellular and nuclear polymorphism, invasion of tumor cells into a fibrous capsule, which does not exclude the malignant nature of pheochromocytoma. Follow-up period lasted for 8 months and was characterized by normalization of blood pressure, glucose level and weight gain of 3.5 kg. Computed tomography of retroperitoneal space and normal urinary metanephrine tests revealed no recurrent pheochromocytoma.