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"François, M."
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Effect of Ocean Acidification on Iron Availability to Marine Phytoplankton
The acidification caused by the dissolution of anthropogenic carbon dioxide (CO₂) in the ocean changes the chemistry and hence the bioavailability of iron (Fe), a limiting nutrient in large oceanic regions. Here, we show that the bioavailability of dissolved Fe may decline because of ocean acidification. Acidification of media containing various Fe compounds decreases the Fe uptake rate of diatoms and coccolithophores to an extent predicted by the changes in Fe chemistry. A slower Fe uptake by a model diatom with decreasing pH is also seen in experiments with Atlantic surface water. The Fe requirement of model phytoplankton remains unchanged with increasing CO₂. The ongoing acidification of seawater is likely to increase the Fe stress of phytoplankton populations in some areas of the ocean.
Journal Article
Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress
Glioblastomas (GBM) are the most common primary brain tumor with a median survival of 15 months. A population of cells with stem cell properties (glioblastoma stem cells, GSCs) drives the initiation and progression of GBM and is localized in specialized microenvironments which support their behavior. GBM are characterized as extremely resistant to therapy, resulting in tumor recurrence. Reactive oxygen species (ROS) control the cellular stability by influencing different signaling pathways. Normally, redox systems prevent cell oxidative damage; however, in gliomagenesis, the cellular redoxmechanisms are highly impaired. Herein we review the dual nature of the redox status in drug resistance. ROS generation in tumor cells affects the cell cycle and is involved in tumor progression and drug resistance in GBM. However, excess ROS production has been found to induce cell death programs such as apoptosis and autophagy. Since GBM cells have a highmetabolic rate and produce high levels of ROS,metabolic adaptation in these cells plays an essential role in resistance to oxidative stress-induced cell death. Finally, the microenvironment with the stromal components participates in the enhancement of the oxidative stress to promote tumor progression and drug resistance.
Journal Article
دراسات جغرافية وعرقية للجزيرة العربية
الكتاب الذي بين أيدينا هو في جزءه الرئيسي دراسة قام بها الكاتب عن الجزيرة العربية، استند فيها إلى مجموعة كبيرة من المراجع الكلاسيكية والعربية وكتابات المستشرقين، والوثائق الخاصة، فخرج منها برؤية حول أصول العرق العربي، وتقييم موروثاته في هذا الخصوص، وعلاقته بالشعوب والحضارات المحيطة، وحول المد السكاني القادم من الجزيرة العربية لمصر عبر التاريخ، والذي يراه المكون الأساسي للشعب المصري، كما قام بدراسة تاريخ العرب في الجزيرة العربية والحضارات والدول التي قامت بها، وأحوالها، وقدم خلال ذلك سرداً لما تعرضت له الجزيرة العربية من غزوات متتالية من الرومان والفرس والمصريين وغيرهم.
Book
Three-dimensional in vitro culture models in oncology research
Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro. The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the limitations, and the fields of application of these models and their techniques of production are also discussed.
Journal Article
TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis
In this work, we have explored the subcellular localization of Bcl2, a major antiapoptotic protein. In U251 glioma cells, we found that Bcl2 is localized mainly in the ER and is translocated to MAM and mitochondria upon induction of apoptosis; this mitochondrial transfer was not restricted to the demonstrator cell line, even if cell-specific modulations exist. We found that the Bcl2/mitochondria interaction is controlled by TOM20, a protein that belongs to the protein import machinery of the mitochondrial outer membrane. The expression of a small domain of interaction of TOM20 with Bcl2 potentiates its anti-apoptotic properties, which suggests that the Bcl2–TOM20 interaction is proapoptotic. The role of MAM and TOM20 in Bcl2 apoptotic mitochondrial localization and function has been confirmed in a yeast model in which the ER–mitochondria encounter structure (ERMES) complex (required for MAM stability in yeast) has been disrupted. Bcl2–TOM20 interaction is thus an additional player in the control of apoptosis.
Journal Article
معضلة الأجناس الأدبية : نصوص ومقاربات
تعد نظرية الأجناس الأدبية من أقدم قضايا النظرية الأدبية المعاصرة، فقد أولاها المنظرون والنقاد والفلاسفة عناية كبيرة منذ فجر التاريخ، ولا غرابة في ذلك، فقد ظل البحث في الأدب وفي مفهومه معا يهيمن على الكثير من الدراسات القديمة والحديثة، سواء عند الغربيين الذين كان لهم قصب السبق، أو عند العرب الذين تأثروا بثقافة الحضارة الغربية. كانت الأبحاث التي تخصصت في نظرية الجنس الأدبي أو معضلته، تسعى إلى إستكشاف القوالب الفنية التي تمتلك ضوابط وحدودا فاصلة، نعمل على تكرس قواعد إنبناء الأجناس، وكان لليونانيين القدامى قصب السبق في ذلك، بل والجرأة على التفكير والتخييل والتقسيم والتنظير، كان لأفلاطون موقف من الأجناس الأدبية، موقف من الشعر والشعراء، ووضع أرسطو قواعد نظرية علمية في غاية الغنى والدقة والأهمية، ظهرت في كتابه \"فن الشعر\"، وبناء على وجهتي نظر هذين الفيلسوفين، تناسلت وتعددت أعمال الكثير من المنظرين، الذين كان ديدنهم هو البحث عن الفروق التي تفصل بين هذا الجنس الأدبي وذلك، مستغلين عدة أشكال من المقاربات مختلفة الأصول والأهداف.
Book
Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme
Background
Literature reports that mature microRNA (miRNA) can be methylated at adenosine, guanosine and cytosine. However, the molecular mechanisms involved in cytosine methylation of miRNAs have not yet been fully elucidated. Here we investigated the biological role and underlying mechanism of cytosine methylation in miRNAs in glioblastoma multiforme (GBM).
Methods
RNA immunoprecipitation with the anti-5methylcytosine (5mC) antibody followed by Array, ELISA, dot blot, incorporation of a radio-labelled methyl group in miRNA, and miRNA bisulfite sequencing were perfomred to detect the cytosine methylation in mature miRNA. Cross-Linking immunoprecipiation qPCR, transfection with methylation/unmethylated mimic miRNA, luciferase promoter reporter plasmid, Biotin-tagged 3’UTR/mRNA or miRNA experiments and in vivo assays were used to investigate the role of methylated miRNAs. Finally, the prognostic value of methylated miRNAs was analyzed in a cohorte of GBM pateints.
Results
Our study reveals that a significant fraction of miRNAs contains 5mC. Cellular experiments show that DNMT3A/AGO4 methylated miRNAs at cytosine residues inhibit the formation of miRNA/mRNA duplex and leading to the loss of their repressive function towards gene expression. In vivo experiments show that cytosine-methylation of miRNA abolishes the tumor suppressor function of miRNA-181a-5p miRNA for example. Our study also reveals that cytosine-methylation of miRNA-181a-5p results is associated a poor prognosis in GBM patients.
Conclusion
Together, our results indicate that the DNMT3A/AGO4-mediated cytosine methylation of miRNA negatively.
Graphical abstract
Journal Article