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أرنوب لا يحب أذنية
تدور أحداث قصة \"أرنوب لا يجب أذنيه حول سوء فهم الأرنوب لولي لنفسه، لأنه أذنيه أصغر من آذان الأرانب الأخرى، فكان دائما يخاف من السخرية والاعتقاد بأنه فأر، لذلك قرر لولي ترك الأرانب، والتنكر في هيئة كلب ثم دب، وتتضمن القصة موضوعا مهما هو : الثقة بالنفس، وسواء أكنا أرانب أو طفلا أو بالغين فيجب أن نتعلم كيف نبني ثقتنا بأنفسنا، وأن ننظر إلأى أنفسنا نظرا صحيحا\"
BOOK
CRISPR-Sirius: RNA scaffolds for signal amplification in genome imaging
Clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA scaffolds have been adapted to carry multiple binding sites for fluorescent proteins to enhance brightness for live cell imaging of genomic loci. However, many of these modifications result in guide RNA instability and thus produce lower genome-labeling efficiency than anticipated. Here we introduce CRISPR-Sirius, based on octet arrays of aptamers conferring both enhanced guide RNA stability and brightness, and provide initial biological applications of this platform.
Journal Article
إدارة الأزمات في زمن الأوبئة : مقالات لـ 56 عالما في الإدارة
يضم هذا الكتاب خلاصة تجارب وعصارة أفكار 56 عالما، هم من أبرز علماء الإدارة في الصين، وقد حملوا على عاتقهم مسؤولية قيادة المؤسسات الصينية لسنوات عديدة، وهو كتاب مرجعي لكل المؤسسات على المستوى العالمي والتي إن حدث لها ضرر في فترات الأزمات أو الأوبئة، فلن يتوقف هذا الضرر عند ملاكها أو المنتفعين منها، بل سيمتد أثره إلى قطاعات عريضة من العمالة، وسيضرب القوة الإنتاجية ولا سيما الصادرات والواردات وغيرها من الموارد. ومن ثم فهم محاربون على الخطوط الأولى، مثلهم مثل الأطباء في أزمة انتشار فيروس كورونا المستجد، وإن كان مجال تخصص كل مختلفا منهم عن الآخر، ففريق منهم ينقذ حياة الناس، بينما الفريق الآخر ينقذ أقواتهم. ولغة الكتاب لغة سهلة وبسيطة، تنطلق أفكاره من مواقف عامة وليست من مواقف خاصة محددة، ومن هنا تعد أفكاره صالحة للتطبيق على المؤسسات الصغيرة والمتوسطة في كل مكان، والتي أصبح لزاما عليها أن تلجأ للابتكار والإبداع إن أرادت الاستمرار على قيد الحياة، وبات عليها أن تبحث وسط ركام الأزمة عن الإيجابيات التي يمكن أن تهب لها حياة جديدة وسبلا مبتكرة للخلاص.
Book
Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow
Multiple chromosomal sites are readily labeled using Cas9 and guide RNAs that bind fluorescent proteins, enabling visualization of chromatin dynamics.
A lack of techniques to image multiple genomic loci in living cells has limited our ability to investigate chromosome dynamics. Here we describe CRISPRainbow, a system for labeling DNA in living cells based on nuclease-dead (d) Cas9 combined with engineered single guide RNA (sgRNA) scaffolds that bind sets of fluorescent proteins. We demonstrate simultaneous imaging of up to six chromosomal loci in individual live cells and document large differences in the dynamic properties of different chromosomal loci.
Journal Article
حوكمة الصين في العلوم والتكنولوجيا والتعليم
دخلت الصين مرحلة جديدة من التطور خلال العقود الثلاثة، مع بدئها بتنفيذ سياسة الإصلاح والانفتاح، فاحتل اقتصادها في العام 2010 م، المرتبة الثانية لأكبر اقتصاد في العالم، نتيجة سنوات طويلة من العمل الشاق، لبناء دولة اشتراكية قوية، والترويج لحوكمة جديدة، إلى جانب التطور المتسارع لكل من العلوم والتكنولوجيا والتعليم، تحت قيادة الرئيس شي جين بينغ الحكيمة التي عكست وجهة نظره الثاقبة والمتمثلة في دمج النظرية بالممارسة لمواكبة الزمن. وبناء عليه، سيعالج هذا الكتاب أهم الخطوط العريضة التي قام عليها فكر شي جين بينغ في حوكمة الصين، وبناء دولة ابتكارية تعطي الأولوية لتطوير العلوم والتكنولوجيا والتعليم، وإغنائها بالمواهب الشابة، بهدف الحفاظ على استمرارية النهضة التي تشهدها الأمة الصينية حاليا، والشير أكثر فأكثر إلى الأمام.
Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1
Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC‐derived exosomes promote the migration and invasion of lung cancer cells, up‐regulate expression levels of N‐cadherin, vimentin, MMP‐9 and MMP‐1, and down‐regulate E‐cadherin expression. Moreover, we verified that these exosomes contribute to a pro‐metastatic phenotype in lung cancer cells via miR‐210‐3p transfer. The results of bioinformatics analysis and dual‐luciferase reporter assays further indicated that miR‐210‐3p may bind to fibroblast growth factor receptor‐like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC‐derived exosomal miR‐210‐3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.
Journal Article
MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31
hi
Emcn
hi
), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31
hi
Emcn
hi
vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31
hi
Emcn
hi
endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31
hi
Emcn
hi
vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31
hi
Emcn
hi
vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31
hi
Emcn
hi
vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.
H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yang
et al
. show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.
Journal Article
Large cargo transport by nuclear pores: implications for the spatial organization of FG-nucleoporins
Nuclear pore complexes (NPCs) mediate cargo traffic between the nucleus and the cytoplasm of eukaryotic cells. Nuclear transport receptors (NTRs) carry cargos through NPCs by transiently binding to phenylalanine‐glycine (FG) repeats on intrinsically disordered polypeptides decorating the NPCs. Major impediments to understand the transport mechanism are the thousands of FG binding sites on each NPC, whose spatial distribution is unknown, and multiple binding sites per NTR, which leads to multivalent interactions. Using single molecule fluorescence microscopy, we show that multiple NTR molecules are required for efficient transport of a large cargo, while a single NTR promotes binding to the NPC but not transport. Particle trajectories and theoretical modelling reveal a crucial role for multivalent NTR interactions with the FG network and indicate a non‐uniform FG repeat distribution. A quantitative model is developed wherein the cytoplasmic side of the pore is characterized by a low effective concentration of free FG repeats and a weak FG‐NTR affinity, and the centrally located dense permeability barrier is overcome by multivalent interactions, which provide the affinity necessary to permeate the barrier.
Nuclear transport receptors (NTRs) engage in multivalent interactions with nuclear pore complexes (NPCs). Single‐molecule fluorescence microscopy and quantitative modelling suggest that multiple NTRs are required for translocation of large cargo through the NPC.
Journal Article
Differential regulation of mesoscale chromosome conformations in osteoblasts and osteosarcoma
Background
Chromosome conformation within the nucleus is essential for genome function. These have primarily been studied at the scale of loops and compartments, or at lower spatial resolution using traditional in situ hybridization in chemically fixed samples. However, the mesoscale organization of single chromosomes in vivo, shaped by the interplay between chromatin architectural proteins and histone modifications, remains partially understood. In this study, we interrogated the mesoscale conformations of interphase chromosomes in live human osteoblasts and transformed osteosarcoma cells, focusing on chromosome 19.
Results
Chromosome conformations were quantified by the aspect ratio of the principal axes of gyration tensors. In osteoblasts, approximately 81% of chromosome 19 are observed to consist of regions characterized by highly extended organizations, with aspect ratios approximately four times greater than those of spheres. In contrast, in osteosarcoma cells, the chromosome displays an extensively collapsed conformation, with aspect ratios more closely approximately that of a sphere. In both cell types, the chromosome’s conformation is bimodal and the balance between these two modes differs very significantly between the two cell types. While the mesoscopic conformation is considerably stable, it is superimposed on dynamic, smaller scale regions. Additional results reveal that this significant conformational shift is independent of the cell cycle but co-regulated by CTCF, cohesion, and H3K27 modifications.
Conclusions
Our findings provide new insights into the coordinated complex regulatory mechanisms governing mesoscale chromosome organization in normal and transformed osteogenic tissues.
Journal Article
C-BERST: defining subnuclear proteomic landscapes at genomic elements with dCas9–APEX2
Mapping proteomic composition at distinct genomic loci in living cells has been a long-standing challenge. Here we report that dCas9–APEX2 biotinylation at genomic elements by restricted spatial tagging (C-BERST) allows the rapid, unbiased mapping of proteomes near defined genomic loci, as demonstrated for telomeres and centromeres. C-BERST enables the high-throughput identification of proteins associated with specific sequences, thereby facilitating annotation of these factors and their roles.
Journal Article