17 research outputs found

    Lectin staining and Western blot data showing differential sialylation of nutrient-deprived cancer cells to sialic acid supplementation

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    This report provides data that are specifically related to the differential sialylation of nutrient deprived breast cancer cells to sialic acid supplementation in support of the research article entitled, “Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation" [1]. Particularly, breast cancer cells, when supplemented with sialic acid under nutrient deprivation, display sialylated glycans at the cell surface, but non-malignant mammary cells show sialylated glycans intracellularly. The impact of sialic acid supplementation under nutrient deprivation was demonstrated by measuring levels of expression and sialylation of two markers, EGFR1 and MUC1. This Data in Brief article complements the main manuscript by providing detailed instructions and representative results for cell-level imaging and Western blot analyses of changes in sialylation during nutrient deprivation and sialic acid supplementation. These methods can be readily generalized for the study of many types of glycosylation and various glycoprotein markers through the appropriate selection of fluorescently-labeled lectins

    K-ras codon 12 and not TP53 mutations are predominant in advanced colorectal cancers

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    Background. Colorectal cancer (CRC) is one of the most common types of cancer, affecting 3 - 5% of the global population. K-ras protooncogene and TP53 tumour suppressor gene mutations are among the most common genetic alterations detected in advanced colorectal tumours. Objective. To investigate the role of K-ras codon 12 and TP53 exons 5 - 9 mutations in late-stage CRC patients. Methods. Blood samples were collected from 249 CRC patients, of whom 147 presented with advanced carcinoma. K-ras codon 12 mutations were analysed using polymerase chain reaction-restriction fragment length polymorphism, while direct sequencing was used in screening for TP53 exons 5 - 9 mutations. Results. No significant changes were observed in TP53 exons 5 - 9, except for two cases in which nucleotide replacements were observed in the non-coding regions in intron 4 (c.376-19C>T) and intron 9 (c.993+12T>C). Heterozygous mutations in K-ras codon 12 were observed in 79 individuals suffering from advanced CRC (53.7%). Colon and rectal tumours were equally distributed among the heterozygotes, but colon tumours were mostly present in wild-type homozygotes (84.6%). There was also a predominance of Caucasians among heterozygotes and a predominance of Asians among the wild-type homozygotes. Conclusion. Analysis of peripheral blood samples of CRC patients suffering from advanced carcinoma has prognostic value only for K-ras codon 12 mutations, and not for TP53 mutations

    Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

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    [Significance] The bacterium Yersinia pestis has caused numerous historically documented outbreaks of plague and research using ancient DNA could demonstrate that it already affected human populations during the Neolithic. However, the pathogen’s genetic diversity, geographic spread, and transmission dynamics during this early period of Y. pestis evolution are largely unexplored. Here, we describe a set of ancient plague genomes up to 5,000 y old from across Eurasia. Our data demonstrate that two genetically distinct forms of Y. pestis evolved in parallel and were both distributed across vast geographic distances, potentially occupying different ecological niches. Interpreted within the archeological context, our results suggest that the spread of plague during this period was linked to increased human mobility and intensification of animal husbandry.The bacterial pathogen Yersinia pestis gave rise to devastating outbreaks throughout human history, and ancient DNA evidence has shown it afflicted human populations as far back as the Neolithic. Y. pestis genomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to its emergence from a Yersinia pseudotuberculosis-like progenitor; however, the number of reconstructed LNBA genomes are too few to explore its diversity during this critical period of development. Here, we present 17 Y. pestis genomes dating to 5,000 to 2,500 y BP from a wide geographic expanse across Eurasia. This increased dataset enabled us to explore correlations between temporal, geographical, and genetic distance. Our results suggest a nonflea-adapted and potentially extinct single lineage that persisted over millennia without significant parallel diversification, accompanied by rapid dispersal across continents throughout this period, a trend not observed in other pathogens for which ancient genomes are available. A stepwise pattern of gene loss provides further clues on its early evolution and potential adaptation. We also discover the presence of the flea-adapted form of Y. pestis in Bronze Age Iberia, previously only identified in in the Caucasus and the Volga regions, suggesting a much wider geographic spread of this form of Y. pestis. Together, these data reveal the dynamic nature of plague’s formative years in terms of its early evolution and ecology.This study was funded by the Max Planck Society, Max Planck Harvard Research Center for the Archaeoscience of the Ancient Mediterranean and the European Research Council under the European Union’s Horizon 2020 research and innovation program under Grant Agreement 771234 – PALEoRIDER (to W.H.), 856453 – HistoGenes (to J.K.), and 834616 – ARCHCAUCASUS (to S.H.). The Heidelberg Academy of Science financed the genetic and archeological research on human individuals from the Augsburg region within the project WIN Kolleg: “Times of Upheaval: Changes of Society and Landscape at the Beginning of the Bronze Age. M.E. was supported by the award “Praemium Academiae” of the Czech Academy of Sciences. M.D. was supported by the project RVO 67985912 of the Institute of Archaeology of the Czech Academy of Sciences, Prague. I.O. was supported by the Ramón y Cajal grant from Ministerio de Ciencia e Innovación, Spanish Government (RYC2019-027909-I). A. H€ubner was supported by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy (EXC 2051 – Project-ID 390713860). J.F.-E. and J.A.M.-A. were supported by the Diputación Foral de Alava, IT 1223-19, Gobierno Vasco. A. Buzhilova was supported by the Center of Information Technologies and Systems (CITIS), Moscow, Russia 121041500329-0. L. M., L.B.D., and E. Khussainova were supported by the Grant AP08856654, Ministry of Education and Science of the Republic of Kazakhstan. A. Beisenov was supported by the Grant AP08857177, Ministry of Education and Science of the Republic of Kazakhstan.Peer reviewe

    Ten millennia of hepatitis B virus evolution

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    Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

    The Investigations of Nitric Oxide Influence on Lifespan of Fruit Fly D. melanogaster Transgenic Strain dNOS4

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    Introduction. Aging and longevity control are among the greatest problems in biology and medicine. The fruit fly Drosophila melanogaster is a nice model organism for longevity investigations because of its biological features. Many D. melanogaster genes have their orthologs, similar in other eukaryotes, including human. The role of nitric oxide (NO) in the D. melanogaster lifespan has been analyzed. Methods. Virgin flies of dNOS4 transgenic strain were used for the experiment. This strain contains non-functional additional copies of nitric oxide synthase (NOS) gene under heat shock promoter.  For promoter activation, transgenic flies on their second day of life were exposed to heat shock (37°C) for an hour. After heat shock, flies were maintained on standard medium temperatures at 25°C, with females separate from males. Two types of control were used: Oregon R wild-type strain and Oregon R strain exposed to heat shock. The average lifespan was evaluated. Results. It was revealed that the longevity of females was significantly higher than males in each series of experiments (p < 0.05). The survival rate of females and males was similar in the first month of their life, but in the second month the mortality among males was much higher than among females in all series of experiments. The average lifespan of dNOS4 imago was 31 days (34 days for females and 28 days for males), maximum lifespan was 63 days. In controls, the average lifespan of Oregon R flies was 54 days (58 days for females and 50 days for males), and the maximum lifespan was 94 days. The average lifespan of Oregon R flies exposed to heat shock was 45 days (48 days for females and 41 days for males), and the maximum lifespan was 72 days. The difference between average lifespan in all studied groups is statistically significant (p < 0.05). Conclusion. Thus, NOS-transgene activation results in formation of non-functional  dNOS4-transcripts and NO deficiency. In turn, NO deficiency decreases dNOS4 imago lifespan

    Phytoremediation of Soil Contaminated by Organochlorine Pesticides and Toxic Trace Elements: Prospects and Limitations of <i>Paulownia tomentosa</i>

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    Paulownia tomentosa (Thunb.) Steud is a drought-resistant, low-maintenance and fast-growing energy crop that can withstand a wide range of climatic conditions, provides a high biomass yield (approximately 50 t DM ha−1 yr−1), and develops successfully in contaminated sites. In Kazakhstan, there are many historically contaminated sites polluted by a mixture of xenobiotics of organic and inorganic origin that need to be revitalised. Pilot-scale research evaluated the potential of P. tomentosa for the phytoremediation of soils historically contaminated with organochlorine pesticides (OCPs) and toxic trace elements (TTEs) to minimise their impact on the environment. Targeted soils from the obsolete pesticide stockpiles located in three villages of Talgar district, Almaty region, Kazakhstan, i.e., Amangeldy (soil A), Beskainar (soil B), and Kyzylkairat (soil K), were subjected to research. Twenty OCPs and eight TTEs (As, Cr, Co, Ni, Cu, Zn, Cd, and Pb) were detected in the soils. The phytoremediation potential of P. tomentosa was investigated for OCPs whose concentrations in the soils were significantly different (aldrin, endosulfans, endrin aldehyde, HCB, heptachlor, hexabromobenzene, keltan, methoxychlor, and γ-HCH) and for TTEs (Cu, Zn, and Cd) whose concentrations exceeded maximum permissible concentrations. Bioconcentration (BCF) and translocation (TLF) factors were used as indicators of the phytoremediation process. It was ensured that the uptake and translocation of contaminants by P. tomentosa was highly variable and depended on their properties and concentrations in soil. Besides the ability to bioconcentrate Cr, Ni, and Cu, P. tomentosa demonstrated very encouraging results in the accumulation of endosulfans, keltan, and methoxychlor and the phytoextraction of γ-HCH (TLFs of 1.9–9.9) and HCB (BCFs of 197–571). The results of the pilot trials support the need to further investigate the potential of P. tomentosa for phytoremediation on a field scale

    Analysis of K-ras codon 12 and TP53 mutations in patients with advanced colorectal carcinoma

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    Background. Colorectal cancer (CRC) is one of the most common types of cancer, affecting 3 - 5% of the global population. K-ras protooncogene and TP53 tumour suppressor gene mutations are among the most common genetic alterations detected in advanced colorectal tumours.Objective. To investigate the role of K-ras codon 12 and TP53 exons 5 - 9 mutations in late-stage CRC patients.Methods. Blood samples were collected from 249 CRC patients, of whom 147 presented with advanced carcinoma. K-ras codon 12 mutations were analysed using polymerase chain reaction-restriction fragment length polymorphism, while direct sequencing was used in screening for TP53 exons 5 - 9 mutations.Results. No significant changes were observed in TP53 exons 5 - 9, except for two cases in which nucleotide replacements were observed in the non-coding regions in intron 4 (c.376-19C&gt;T) and intron 9 (c.993+12T&gt;C). Heterozygous mutations in K-ras codon 12 were observed in 79 individuals suffering from advanced CRC (53.7%). Colon and rectal tumours were equally distributed among the heterozygotes, but colon tumours were mostly present in wild-type homozygotes (84.6%). There was also a predominance of Caucasians among heterozygotes and a predominance of Asians among the wild-type homozygotes.Conclusion. Analysis of peripheral blood samples of CRC patients suffering from advanced carcinoma has prognostic value only for K-ras codon 12 mutations, and not for TP53 mutations

    Homozygosity mapping in the Kazakh national dog breed Tazy

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    Abstract The Tazy is a breed of sighthound common in Kazakhstan. The identification of runs of homozygosity (ROH) is an informative approach to assessing the history and possible patterns of directional selection pressure. To our knowledge, the present study is the first to provide an overview of the ROH pattern in the Tazy dogs from a genome-wide perspective. The ROH of the Tazy was found to be mainly composed of shorter segments (1–2 Mb), accounting for approximately 67% of the total ROH. The estimated ROH-based inbreeding coefficients (FROH) ranged from 0.028 to 0.058 with a mean of 0.057. Five genomic regions under positive selection were identified on chromosomes 18, 22, and 25. The regions on chromosomes 18 and 22 may be breed specific, while the region on chromosome 22 overlaps with regions of hunting traits in other hunting dog breeds. Among the 12 candidate genes located in these regions, the gene CAB39L may be a candidate that affects running speed and endurance of the Tazy dog. Eight genes could belong to an evolutionarily conserved complex as they were clustered in a large protein network with strong linkages. The results may enable effective interventions when incorporated into conservation planning and selection of the Tazy breed

    The source of the Black Death in fourteenth-century central Eurasia

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    The origin of the medieval Black Death pandemic (AD 1346–1353) has been a topic of continuous investigation because of the pandemic’s extensive demographic impact and long-lasting consequences1,2. Until now, the most debated archaeological evidence potentially associated with the pandemic’s initiation derives from cemeteries located near Lake Issyk-Kul of modern-day Kyrgyzstan1,3,4,5,6,7,8,9. These sites are thought to have housed victims of a fourteenth-century epidemic as tombstone inscriptions directly dated to 1338–1339 state ‘pestilence’ as the cause of death for the buried individuals9. Here we report ancient DNA data from seven individuals exhumed from two of these cemeteries, Kara-Djigach and Burana. Our synthesis of archaeological, historical and ancient genomic data shows a clear involvement of the plague bacterium Yersinia pestis in this epidemic event. Two reconstructed ancient Y. pestis genomes represent a single strain and are identified as the most recent common ancestor of a major diversification commonly associated with the pandemic’s emergence, here dated to the first half of the fourteenth century. Comparisons with present-day diversity from Y. pestis reservoirs in the extended Tian Shan region support a local emergence of the recovered ancient strain. Through multiple lines of evidence, our data support an early fourteenth-century source of the second plague pandemic in central Eurasia
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