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"Magee, Peter"
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The archaeology of prehistoric Arabia : adaptation and social formation from the neolithic to the iron age
\"Encompassing a landmass greater than the rest of the Near East and Eastern Mediterranean combined, the Arabian peninsula remains one of the last great unexplored regions of the ancient world. This book provides the first extensive coverage of the archaeology of this region from c. 9000 to 800 BC. Peter Magee argues that a unique social system, which relied on social cohesion and actively resisted the hierarchical structures of adjacent states, emerged during the Neolithic and continued to contour society for millennia later. The book also focuses on how the historical context in which Near Eastern archaeology was codified has led to a skewed understanding of the multiplicity of lifeways pursued by ancient peoples living throughout the Middle East\"-- Provided by publisher.
BOOK
Ancient and modern DNA reveal dynamics of domestication and cross-continental dispersal of the dromedary
Dromedaries have been fundamental to the development of human societies in arid landscapes and for long-distance trade across hostile hot terrains for 3,000 y. Today they continue to be an important livestock resource in marginal agro-ecological zones. However, the history of dromedary domestication and the influence of ancient trading networks on their genetic structure have remained elusive. We combined ancient DNA sequences of wild and early-domesticated dromedary samples from arid regions with nuclear microsatellite and mitochondrial genotype information from 1,083 extant animals collected across the species’ range. We observe little phylogeographic signal in the modern population, indicative of extensive gene flow and virtually affecting all regions except East Africa, where dromedary populations have remained relatively isolated. In agreement with archaeological findings, we identify wild dromedaries from the southeast Arabian Peninsula among the founders of the domestic dromedary gene pool. Approximate Bayesian computations further support the “restocking from the wild” hypothesis, with an initial domestication followed by introgression from individuals from wild, now-extinct populations. Compared with other livestock, which show a long history of gene flow with their wild ancestors, we find a high initial diversity relative to the native distribution of the wild ancestor on the Arabian Peninsula and to the brief coexistence of early-domesticated and wild individuals. This study also demonstrates the potential to retrieve ancient DNA sequences from osseous remains excavated in hot and dry desert environments.
Journal Article
The archaeology of prehistoric Arabia : adaptation and social formation from the neolithic to the iron age
\"Encompassing a landmass greater than the rest of the Near East and Eastern Mediterranean combined, the Arabian peninsula remains one of the last great unexplored regions of the ancient world. This book provides the first extensive coverage of the archaeology of this region from c. 9000 to 800 BC. Peter Magee argues that a unique social system, which relied on social cohesion and actively resisted the hierarchical structures of adjacent states, emerged during the Neolithic and continued to contour society for millennia later. The book also focuses on how the historical context in which Near Eastern archaeology was codified has led to a skewed understanding of the multiplicity of lifeways pursued by ancient peoples living throughout the Middle East\"-- Provided by publisher.
Book
A KRAS-responsive long non-coding RNA controls microRNA processing
Wild-type
KRAS
(
KRAS
WT
) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of
KRAS
WT
overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA,
KIMAT1
(ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically,
KIMAT1
is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex.
KIMAT1
knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for
KIMAT1
in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with
KIMAT1
could be a strategy to hamper KRAS-induced tumorigenesis.
Wild-type KRAS amplification is known to induce KRAS activation in cancer leading to poor prognostic outcomes. Here the authors identify a KRAS-responsive lncRNA, KIMAT1 that maintains KRAS signalling in lung cancer, suggesting that its targeting may prevent KRAS-driven tumourigenesis.
Journal Article
KRAS induces lung tumorigenesis through microRNAs modulation
Oncogenic
KRAS
induces tumor onset and development by modulating gene expression via different molecular mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs that have been established as main players in tumorigenesis. By overexpressing wild type or mutant KRAS (KRAS
G12D
) and using inducible human and mouse cell lines, we analyzed KRAS-regulated microRNAs in non-small-cell lung cancer (NSCLC). We show that miR-30c and miR-21 are significantly upregulated by both KRAS isoforms and induce drug resistance and enhance cell migration/invasion via inhibiting crucial tumor suppressor genes, such as NF1, RASA1, BID, and RASSF8. MiR-30c and miR-21 levels were significantly elevated in tumors from patients that underwent surgical resection of early stages NSCLC compared to normal lung and in plasma from the same patients. Systemic delivery of LNA-anti-miR-21 in combination with cisplatin in vivo completely suppressed the development of lung tumors in a mouse model of lung cancer. Mechanistically, we demonstrated that ELK1 is responsible for miR-30c and miR-21 transcriptional activation by direct binding to the miRNA proximal promoter regions. In summary, our study defines that miR-30c and miR-21 may be valid biomarkers for early NSCLC detection and their silencing could be beneficial for therapeutic applications.
Journal Article
Vulnerability of drug‐resistant EML4‐ALK rearranged lung cancer to transcriptional inhibition
A subset of lung adenocarcinomas is driven by the EML4‐ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on‐target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4‐ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti‐apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first‐, second‐ and third‐generation ALK inhibitors.
Synopsis
Acquired drug resistance to ALK inhibitors prevents the effective management of lung cancer. This study shows that treatment with CDK inhibitors may be tested as an alternative upon development of resistance.
EML4‐ALK‐mutant cells were sensitive to CDK inhibition, which resulted in apoptosis induction.
CDK treatment reduced tumour growth in crizotinib‐ and alectinib‐resistant mouse models.
Transcriptional perturbation was the main outcome of treatment with alvocidib or THZ1.
Graphical Abstract
Acquired drug resistance to ALK inhibitors prevents the effective management of lung cancer. This study shows that treatment with CDK inhibitors may be tested as an alternative upon development of resistance.
Journal Article
MiRNA-based therapeutic intervention of cancer
MicroRNAs (miRNAs) are important modulators of eukaryotic gene expression. By targeting protein coding transcripts, miRNAs influence the cellular transcriptome and proteome, thus helping to determine cell fate. MiRNAs have emerged as crucial molecules in cancer research, in which recent studies have linked erratic expression of miRNAs to carcinogenesis and have provided solid evidence for their potential in cancer therapy. This review briefly summarises the recent knowledge on the involvement of miRNAs in tumourigenesis and reviews current studies on the therapeutic strategies and advances in the delivery of miRNAs.
Journal Article
Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer
Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS is the main oncogenic driver in lung cancer that can be activated by gene mutation or amplification, but whether long non-coding RNAs (lncRNAs) regulate its activation remains unknown. Through gain and loss of function approaches, we identified that lncRNA HIF1A-As2, a KRAS-induced lncRNA, is required for cell proliferation, epithelial-mesenchymal transition (EMT) and tumor propagation in non-small cell lung cancer (NSCLC) in vitro and in vivo. Integrative analysis of HIF1A-As2 transcriptomic profiling reveals that HIF1A-As2 modulates gene expression in trans, particularly regulating transcriptional factor genes including MYC. Mechanistically, HIF1A-As2 epigenetically activates MYC by recruiting DHX9 on MYC promoter, consequently stimulating the transcription of MYC and its target genes. In addition, KRAS promotes HIF1A-As2 expression via the induction of MYC, suggesting HIF1A-As2 and MYC form a double-regulatory loop to strengthen cell proliferation and tumor metastasis in lung cancer. Inhibition of HIF1A-As2 by LNA GapmeR antisense oligonucleotides (ASO) significantly improves sensitization to 10058-F4 (a MYC-specific inhibitor) and cisplatin treatment in PDX and KRASLSLG12D-driven lung tumors, respectively.
Journal Article
Reservoir Effects from Shells of Tell Abraq, Sharjah Emirate, UAE
We present reservoir effects on shells of species Terebralia palustris and Marcia spp. that were recovered during archaeological excavations at the multi-period site of Tell Abraq, Sharjah Emirate, UAE (This paper was presented at the combined 24th Radiocarbon and 10th Radiocarbon & Archaeology International Conference, Zurich, Switzerland, Sept. 2022.). The site was inhabited during the mid to late Holocene. It is situated in a lagoonal environment with former mangrove forests at the Arabian Gulf coast of southeast Arabia. Due to availability in the immediate proximity, shellfish played an important role for the local subsistence throughout the site’s occupation. Tell Abraq provides a well-defined and stratigraphically controlled archaeological context for investigations on the reservoir effect of the two species chosen. Crucial for the determination of the marine reservoir effect is comparison with contemporaneous terrestrial carbon samples. We discuss the data in a wider context with respect to results obtained at other sites.
Journal Article
Revisiting Indian Rouletted Ware and the impact of Indian Ocean trade in Early Historic south Asia
Indian Rouletted Ware pottery is the iconic marker of the overseas reach of the subcontinent at the turn of the first millennium AD. In the mid twentieth century this was naturally seen as prompted by the contemporary Roman Empire, while the later post-colonial discourse has emphasised the independence and long life of Indian initiatives. In this new analysis the author demonstrates a more complex socio-economic situation. While Greyware is distributed long term over south India, Rouletted ware is made in at least two regional centres for coastal communities using a new ceramic language, one appropriate to an emerging international merchant class.
Journal Article