14 research outputs found

    Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

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    Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

    MicroRNAs Associated with Von Hippel–Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review

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    Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel–Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets

    Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells

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    MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle–arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies

    MiR-371a-3p serum levels are increased in recurrence of testicular germ cell tumor patients

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    Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (-subunit of human chorionic gonadotropin (-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials

    Data from: Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

    No full text
    Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

    Data from: Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

    No full text
    Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

    Shotgun sequences for bird remains from Swahili coast archaeological sites

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    Shotgun sequences for bird remains from Swahili coast archaeological sites. Files that are labeled "JK" correspond to specific archaeological bone samples, each 4-digit number representing a single library: JK2992, JK3005, JK2999, JK2989, JK3002, JK2995, JK2993, JK3004, JK3003, JK2994, JK2988, JK3001, JK2990, JK3008, JK2998, JK3007, JK1996, JK3006, JK3000, JK2991, JK2997 . The other files represent extraction blanks (EBB1, EBB2) and library blanks (LBB2, LBB1). Please see supplementary data in the Prendergast et al. paper to link JK numbers to archaeological contexts
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