Characterization of ancient ceramic shreds: Insights into firing conditions and manufacturing technology

Four ancient ceramic shreds from the archaeological site Leletepe in the Fizuli region of the Republic of Azerbaijan and two local raw ceramic pastes were characterized by powder X-ray diffraction (PXRD) and thermal analysis (TG-DTG) techniques. XRD analysis of ceramic sherds reveals that all investigated samples contain similar minerals: quartz, feldspar, and clay. Three samples out of four contain calcite. Based on the traditional approach, it has been assumed that the firing process in these samples stopped before 700 °C. The mass loss ratios of samples of ancient ceramics also indicate that reversible dehydroxylation took place in all four samples, thus indicating the initial mild firing conditions. The summary of all the applied methods indicates that the ceramic samples were made using a similar manufacturing technology. According to XRD analysis, samples N1 and N4 contain diopside, and samples N2 and N3 contain maghemite, indicating the different origins of the ceramic shreds. Analysis of the raw ceramic mass also did not reveal the presence of these minerals, which may indicate a discrepancy between the origin of ancient ceramic sherds and modern ones

Lynch Syndrome - Cancer Pathways, Heterogeneity and Immune Escape

Recent work has provided evidence for genetic and molecular heterogeneity in colorectal cancers (CRCs) arising in patients with Lynch syndrome (LS), dividing these into two groups: G1 and G2. In terms of mutation and gene expression profile, G1 CRCs bear resemblance to sporadic CRCs with microsatellite instability (MSI), whereas G2 CRCs are more similar to microsatellite stable CRCs. Here we review the current state of knowledge on pathways of precursor progression to CRC in LS and how these might tie in with the new findings. Immunotherapies are an active field of research for MSI cancers and their potential use for cancer therapy for both sporadic and LS MSI cancers is discussed

The Thermoluminescence Parameters of Irradiated K-Feldspar

Isothermal decay of the TL glow curve has been studied at ambient temperature. Heating of feldspar at 600ºC leads to increased sensitivity of the samples upon irradiation for the whole range of glow curve. In general, we observe a sensitivity increase of about five times. Fading of the glow curve is observed at the low-temperature part of the glow curve while it has been kept in the dark at the ambient, constant temperature. After a certain period, approximately in 40 to 50 days, the low-temperature region of the glow curve fades down while the high-temperature part remains unchanged. Peaks at the low-temperature region of the TL glow curve were isolated by the curve subtraction method. Activation energy and frequency factor parameters of the isolated peaks were calculated, taking first and second-order kinetics into account. The values of the calculated activation energy vary between 0.7 to 1.1 eV, and frequency factor values of the isolated peaks change within the order of 109 to 1013s-1. The µ values clearly indicate that all isolated peaks are more likely to be second-order kinetics

Spectral Deconvolution of Fossil Tooth Enamel Electron Paramagnetic Resonance Spectrum

In this work the ESR method has been applied to determine the age of fossil tooth enamel found in Mingachevir archeological site (Azerbaijan, Mingachevir). The EPR spectrum of tooth enamel has been deconvoluted into four individual Gaussian lines. Equivalent dose (Absorbed dose in tooth enamel that was historically accumulated due to natural irradiation) calculated using dose-response curves of individual Gaussian lines shows significantly different values. Peak 1 (with g= 2.006848) gives a significantly lower, Peak 4 (with g=2.002942) a significantly higher value of absorbed dose. The use of integrated spectra gives lower absorption dose values than the use of differential spectra

The majority of β-catenin mutations in colorectal cancer is homozygous

Background: β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for Lynch syndrome (LS) associated cancers stabilizing mutations of β-catenin gene (CTNNB1) are rare in colorectal cancer (CRC). Previous animal studies provide an explanation for this observation. They showed that CTNNB1 mutations induced transformation in the colon only when CTNNB1 was homozygously mutated or when membranous β-catenin binding was hampered by E-cadherin haploinsufficiency. We were interested, if these mechanisms are also found in human CTNNB1 mutated CRCs. Results: Among 869 CRCs stabilizing CTNNB1 mutations were found in 27 cases. Homo- or hemizygous CTNNB1 mutations were detected in 74% of CTNNB1 mutated CRCs (13 microsatellite instabile (MSI-H), 7 microsatellite stabile (MSS)) but only in 3% (1/33) of extracolonic CTNNB1 mutated cancers. In contrast to MSS CRC, CTNNB1 mutations at codon 41 or 45 were highly selected in MSI-H CRC. Of the examined three CRC cell lines, β-catenin and E-cadherin expression was similar in cell lines without or with hetereozygous CTNNB1 mutations (DLD1 and HCT116), while a reduced E-cadherin expression combined with cytoplasmic accumulation of β-catenin was found in a cell line with homozygous CTNNB1 mutation (LS180). Reduced expression of E-cadherin in human MSI-H CRC tissue was identified in 60% of investigated cancers, but no association with the CTNNB1 mutational status was found. Conclusions: In conclusion, this study shows that in contrast to extracolonic cancers stabilizing CTNNB1 mutations in CRC are commonly homo- or hemizygous indicating a higher threshold of β-catenin stabilization to be required for transformation in the colon as compared to extracolonic sites. Moreover, we found different mutational hotspots in CTNNB1 for MSI-H and MSS CRCs suggesting a selection of different effects on β-catenin stabilization according to the molecular pathway of tumourigenesis. Reduced E-cadherin expression in CRC may further contribute to higher levels of transcriptionally active β-catenin, but it is not directly linked to the CTNNB1 mutational status

Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P <.001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.Peer reviewe

Thermo Luminescence Dating of Pottery Sample from Chukhur Gabala Archaeological Site in Gabala District of Azerbaijan

The age of fragments of the ancient pottery sample from Chukhur Gabala archeological site in Gabala district of Azerbaijan has been estimated by employing Thermoluminescence dating (TL) method. The annual dose rate was obtained using γ-spectrometer with a hyper-pure germanium detector and it was 2.741±0.121 mGy/year. The age of the sample was calculated by an additive dose method as 2230±510 years which are in line with the stratigraphically estimated age of this area

Beta-2-microglobulin Mutations Are Linked to a Distinct Metastatic Pattern and a Favorable Outcome in Microsatellite-Unstable Stage IV Gastrointestinal Cancers

Immune checkpoint blockade (ICB) shows remarkable clinical effects in patients with metastatic microsatellite-unstable (MSI) cancer. However, markers identifying potential non-responders are missing. We examined the prevalence of Beta-2-microglobulin (B2M) mutations, a common immune evasion mechanism, in stage IV MSI gastrointestinal cancer and its influence on metastatic pattern and patients’ survival under ICB. Twentyfive patients with metastatic, MSI gastrointestinal adenocarcinoma were included. Eighteen patients received ICB with pembrolizumab and one patient with nivolumab/ ipilimumab. Sequencing was performed to determine B2M mutation status. B2M mutations and loss of B2M expression were detected in 6 out of 25 stage IV MSI cancers. B2M mutations were strongly associated with exclusively peritoneal/peritoneal and lymph node metastases (p=0.0055). However, no significant differences in therapy response (25% vs. 46.6%, p>0.99) and survival (median PFS: 19.5 vs 33.0 months, p=0.74; median OS 39 months vs. not reached, p>0.99) were observed between B2Mmutant and B2M-wild type tumor patients. Among metastatic MSI GI cancers, B2Mmutant tumors represent a biologically distinct disease with distinct metastatic patterns. To assess ICB response in B2M-mutant MSI cancer patients, future studies need to account for the fact that baseline survival of patients with B2M-mutant MSI cancer may be longer than of patients with B2M-wild type MSI cancer