Exceptional ancient DNA preservation and fibre remains of a Sasanian saltmine sheep mummy in Chehrābād, Iran

Funder: FP7 Ideas: European Research Council; Id: http://dx.doi.org/10.13039/100011199; Grant(s): 295729-CodeXMummified remains have long attracted interest as a potential source of ancient DNA. However, mummification is a rare process that requires an anhydrous environment to rapidly dehydrate and preserve tissue before complete decomposition occurs. We present the whole-genome sequences (3.94 X) of an approximately 1600-year-old naturally mummified sheep recovered from Chehrābād, a salt mine in northwestern Iran. Comparative analyses of published ancient sequences revealed the remarkable DNA integrity of this mummy. Hallmarks of postmortem damage, fragmentation and hydrolytic deamination are substantially reduced, likely owing to the high salinity of this taphonomic environment. Metagenomic analyses reflect the profound influence of high-salt content on decomposition; its microbial profile is predominated by halophilic archaea and bacteria, possibly contributing to the remarkable preservation of the sample. Applying population genomic analyses, we find clustering of this sheep with Southwest Asian modern breeds, suggesting ancestry continuity. Genotyping of a locus influencing the woolly phenotype showed the presence of an ancestral ‘hairy’ allele, consistent with hair fibre imaging. This, along with derived alleles associated with the fat-tail phenotype, provides genetic evidence that Sasanian-period Iranians maintained specialized sheep flocks for different uses, with the ‘hairy’, ‘fat-tailed’-genotyped sheep likely kept by the rural community of Chehrābād's miners

Monitoring of class1 integrons in diarrheagenic E. coli strains isolated from children in Yasouj

Introduction: Integrons are mobile genetic elements able to acquire and integrate the antibiotic resistance gene cassettes and play an important role in the development of the drug resistant. This study assessed the contribution of class 1 integron in drug resistant diarrheagenic Escherichia coli strains, in children under 5 years. Materials and methods: 164 diarrheagenic E. coli strains isolated from children under 5 were evaluated to investigate intI1 gene and gene cassette. Furthermore the antibiotic resistance was determined using CLSI critria. Results: The rate of intI1 gene and gene cassette in Escherichia coli isolates were 70.73 % and 64.63 %, respectively. In these samples, gene cassette sizes varied from 750 to 2000 bp. There was a significant correlation between the presence of class 1 integron and resistance to streptomycin, gentamicin, kanamycin, amikacin, chloramphenicol, tetracycline, nalidixic acid and cotrimoxazole. Discussion and conclusion: The present study elucidates that the rampancy of class 1 integron and the incorporated gene cassettes is quite high among diarrheagenic E. coli in our area of research. Hence, considering the prospect of widespread break out of the drug-resistant strains of E.coli, further molecular analysis in different regions of the country is essential

Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial-Dependent Apoptosis in GBM Cells, Which Is Regulated by Autophagy

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have had more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol-lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple-combination therapy of TMZ, Simvastatin (Simva), and acetylshikonin, and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species, mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that a TMZ/Simva/ASH combination therapy induced significantly more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to the partial inhibition of autophagy flux (accumulation of LC3β-II and a decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux, as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for a more effective treatment of GBM, but further investigations are required for a better identification of the mechanisms