Late Little Ice Age palaeoenvironmental records from the Anzali and Amirkola Lagoons (south Caspian Sea): Vegetation and sea level changes

This is a postprint version of the article. The official published article can be found from the link below - Copyright @ 2011 Elsevier Ltd.Two internationally important Ramsar lagoons on the south coast of the Caspian Sea (CS) have been studied by palynology on short sediment cores for palaeoenvironmental and palaeoclimatic investigations. The sites lie within a small area of very high precipitation in a region that is otherwise dry. Vegetation surveys and geomorphological investigations have been used to provide a background to a multidisciplinary interpretation of the two sequences covering the last four centuries. In the small lagoon of Amirkola, the dense alder forested wetland has been briefly disturbed by fire, followed by the expansion of rice paddies from AD1720 to 1800. On the contrary, the terrestrial vegetation reflecting the diversity of the Hyrcanian vegetation around the lagoon of Anzali remained fairly complacent over time. The dinocyst and non-pollen palynomorph assemblages, revealing changes that have occurred in water salinity and water levels, indicate a high stand during the late Little Ice Age (LIA), from AD < 1620 to 1800–1830. In Amirkola, the lagoon spit remained intact over time, whereas in Anzali it broke into barrier islands during the late LIA, which merged into a spit during the subsequent sea level drop. A high population density and infrastructure prevented renewed breaking up of the spit when sea level reached its maximum (AD1995). Similar to other sites in the region around the southern CS, these two lagoonal investigations indicate that the LIA had a higher sea level as a result of more rainfall in the drainage basin of the CS.The coring and the sedimentological analyses were funded by the Iranian National Institute for Oceanography in the framework of a research project entitled “Investigation of the Holocene sediment along the Iranian coast of Caspian Sea: central Guilan”. The radiocarbon date of core HCGL02 was funded by V. Andrieu (Europôle Méditerranéen de l'Arbois, France) and that of core HCGA04 by Brunel University

BCL6 is critical for the development of a diverse primary B cell repertoire

BCL6 protects germinal center (GC) B cells against DNA damage–induced apoptosis during somatic hypermutation and class-switch recombination. Although expression of BCL6 was not found in early IL-7–dependent B cell precursors, we report that IL-7Rα–Stat5 signaling negatively regulates BCL6. Upon productive VH-DJH gene rearrangement and expression of a μ heavy chain, however, activation of pre–B cell receptor signaling strongly induces BCL6 expression, whereas IL-7Rα–Stat5 signaling is attenuated. At the transition from IL-7–dependent to –independent stages of B cell development, BCL6 is activated, reaches expression levels resembling those in GC B cells, and protects pre–B cells from DNA damage–induced apoptosis during immunoglobulin (Ig) light chain gene recombination. In the absence of BCL6, DNA breaks during Ig light chain gene rearrangement lead to excessive up-regulation of Arf and p53. As a consequence, the pool of new bone marrow immature B cells is markedly reduced in size and clonal diversity. We conclude that negative regulation of Arf by BCL6 is required for pre–B cell self-renewal and the formation of a diverse polyclonal B cell repertoire

BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is induced by the oncogenic BCR-ABL1 tyrosine kinase and can be effectively treated for many years with tyrosine kinase inhibitors (TKIs). However, unless CML patients receive life-long TKI treatment, leukemia will eventually recur; this is attributed to the failure of TKI treatment to eradicate leukemia-initiating cells (LICs). Recent work demonstrated that FoxO factors are critical for maintenance of CML-initiating cells; however, the mechanism of FoxO-dependent leukemia initiation remained elusive. Here, we identified the BCL6 protooncogene as a critical effector downstream of FoxO in self-renewal signaling of CML-initiating cells. BCL6 represses Arf and p53 in CML cells and is required for colony formation and initiation of leukemia. Importantly, peptide inhibition of BCL6 in human CML cells compromises colony formation and leukemia initiation in transplant recipients and selectively eradicates CD34+ CD38− LICs in patient-derived CML samples. These findings suggest that pharmacological inhibition of BCL6 may represent a novel strategy to eradicate LICs in CML. Clinical validation of this concept could limit the duration of TKI treatment in CML patients, which is currently life-long, and substantially decrease the risk of blast crisis transformation

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Extending the application of a magnetic PEG three-part drug release device on a graphene substrate for the removal of Gram-positive and Gram-negative bacteria and cancerous and pathologic cells

M Ramezani Farani,1 P Khadive Parsi,1 Gh Riazi,2 M Shafiee Ardestani,3 H Saligeh Rad4,5 1School of Chemical Engineering, University College of Engineering, University of Tehran, Tehran 4563-11155, Iran; 2Institute of Biophysics and Biochemistry, University of Tehran, Tehran 1417614411, Iran; 3Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Quantitative Medical Imaging Systems Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran; 5Medical Physics and Biomedical Engineering Department, Tehran University of Medical Sciences, Tehran, Iran Objective: In this study, novel graphene oxide (GO)-based nanocomposites are presented. In fact, we have tried to replace the carboxyl groups on the surface of GO with amine groups to allow the biocompatible poly(ethylene glycol) bis(carboxymethyl) ether (average Mn 600) polymer to bond through an amide bond. Materials and methods: The synthesis was conducted accurately according to final characterization experiments (Raman, X-ray diffraction [XRD], atomic force microscopy [AFM], X-ray photoelectron spectroscopy [XPS], thermogravimetric analysis [TGA], etc). The antimicrobial property of this nanocomposite was examined in Escherichia coli (ATCC 25922) as Gram-negative and Staphylococcus aureus (ATCC 25923) as Gram-positive bacterial species. Besides, curcumin (CUR) was added to the produced nanocomposite both as a promising anticancer drug and an antioxidant, the toxicity of which was then assessed on cellular-based HepG2 and pC12. Results: An intense increase in toxicity was detected by MTT assay. Conclusion: It can mainly be concluded that the nanocomposite synthesized in this study is capable of delivering drugs with antibacterial properties. Keywords: graphene oxide, magnetic nanocomposite, drug delivery, antimicrobial, curcumi

Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC

Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C') cells exit cell cycle to become resting, small pre-BII cells (Fraction D). The mechanism by which pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at the Fraction C'-D transition is critical for immunoglobulin light chain gene recombination and to prevent malignant transformation into acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor signaling induces cell-cycle exit through up-regulation of the transcriptional repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage