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داروين ونظرية التطور للنشء
يشير المؤلف باسكال بيك، في مقدمته لكتابه \"داروين\" ونظرية التطور للنشء، إلي : لماذا أهدي هذا الكتاب إلى أحفادنا جميعا وليس إلى أحفادي القادمين فقط ؟ تتعلق الإجابة بالتطور، لأن التطور، كما سنري، ليس سلسلة طويلة من الكوارث، أو البقاء للأصلح، بل هو بكل بساطة \"التغيير في الصفات الوراثية\" أما كيف يحدث ؟ هذا هو موضوع الكتاب : فهم التطور، وما هية الحياة التي هي في الوقت نفسه قصة طويلة تعيد بناء تاريخها. ويضيف باسكال بيك : لقد ظهر الإنسان الحالي، وكل سلالات إنسان الحفريات في وقت متأخر جدا في تاريخ الحياة. وعليه فكل تنوع في الكائنات الحية التي تحيط بنا نابع من هذا التاريخ الطبيعي الهائل، الذي نسميه التطور. فإذا لم نعرف التطور، لن نتمكن من أن نفهم \"الانقراض السادس\" وعواقبه المحتملة على مستقبل الإنسانية ومن ثم مستقبلك ومستقبل كوكبنا الرائع.
Book
Sparse canonical methods for biological data integration: application to a cross-platform study
Background
In the context of systems biology, few sparse approaches have been proposed so far to integrate several data sets. It is however an important and fundamental issue that will be widely encountered in post genomic studies, when simultaneously analyzing transcriptomics, proteomics and metabolomics data using different platforms, so as to understand the mutual interactions between the different data sets. In this high dimensional setting, variable selection is crucial to give interpretable results. We focus on a sparse Partial Least Squares approach (sPLS) to handle two-block data sets, where the relationship between the two types of variables is known to be symmetric. Sparse PLS has been developed either for a regression or a canonical correlation framework and includes a built-in procedure to select variables while integrating data. To illustrate the canonical mode approach, we analyzed the NCI60 data sets, where two different platforms (cDNA and Affymetrix chips) were used to study the transcriptome of sixty cancer cell lines.
Results
We compare the results obtained with two other sparse or related canonical correlation approaches: CCA with Elastic Net penalization (CCA-EN) and Co-Inertia Analysis (CIA). The latter does not include a built-in procedure for variable selection and requires a two-step analysis. We stress the lack of statistical criteria to evaluate canonical correlation methods, which makes biological interpretation absolutely necessary to compare the different gene selections. We also propose comprehensive graphical representations of both samples and variables to facilitate the interpretation of the results.
Conclusion
sPLS and CCA-EN selected highly relevant genes and complementary findings from the two data sets, which enabled a detailed understanding of the molecular characteristics of several groups of cell lines. These two approaches were found to bring similar results, although they highlighted the same phenomenons with a different priority. They outperformed CIA that tended to select redundant information.
Journal Article
أجمل قصة عن اللغة
كل كائن بشري يبصر النور وهو يملك استعدادا للتكلم ولكن ينبغي، مع ذلك، تلقينه فعل هذا الأمر، فأي تكييف أنجزه التطور، أفضى ذات يوم من أيام العهود السحيقة إلى بروز اللغة ؟ وكيف كان أسلافنا يعبرون ؟ هل كان ثمة لغة وحيدة كونية في ما مضى ؟ ولم تنوعت اللغات، فيما بعد، على سطح المعمورة ؟ إن اللغز المحير هو في معرفة كيفية تعلم كل طفل بشري الكلام من جديد : كيف يتعرف إلى الكلمات وما الذي يحصل في دماغه ؟ إن الاكتشافات المذهلة التي أنجزها الأنثروبولوجيون والألسنيون وغيرهم تسمح لنا اليوم بتعقب مسارب اللغة، منذ الأحافير الأولى وهنا، في هذا الكتاب، يتعاون ثلاثة باحثين ليرووا لنا، بكلام بسيط، إحدى أجمل قصص البشرية وأكثرها فرادة، بلا أدنى شك.
Book
Towards general network architecture design criteria for negative gas adsorption transitions in ultraporous frameworks
Switchable metal-organic frameworks (MOFs) have been proposed for various energy-related storage and separation applications, but the mechanistic understanding of adsorption-induced switching transitions is still at an early stage. Here we report critical design criteria for negative gas adsorption (NGA), a counterintuitive feature of pressure amplifying materials, hitherto uniquely observed in a highly porous framework compound (DUT-49). These criteria are derived by analysing the physical effects of micromechanics, pore size, interpenetration, adsorption enthalpies, and the pore filling mechanism using advanced in situ X-ray and neutron diffraction, NMR spectroscopy, and calorimetric techniques parallelised to adsorption for a series of six isoreticular networks. Aided by computational modelling, we identify DUT-50 as a new pressure amplifying material featuring distinct NGA transitions upon methane and argon adsorption. In situ neutron diffraction analysis of the methane (CD
4
) adsorption sites at 111 K supported by grand canonical Monte Carlo simulations reveals a sudden population of the largest mesopore to be the critical filling step initiating structural contraction and NGA. In contrast, interpenetration leads to framework stiffening and specific pore volume reduction, both factors effectively suppressing NGA transitions.
Porous framework material DUT-49 was recently demonstrated to exhibit a unique counterintuitive negative gas adsorption (NGA) behaviour. Here the authors identify framework DUT-50 as an additional pressure amplifying material that features distinct NGA transitions, and suggest structural design criteria to access other such materials.
Journal Article
The colony : when the earth froze, the rules of survival changed forever
A savage and unrelenting thriller about mankind's greatest enemy: himself. As an endless winter engulfs Earth, humans struggle to survive in remote underground outposts. When Colony 7 receives a distress call from a nearby settlement, Sam and Briggs race through the snow on a dangerous rescue mission. What they find at the desolate base could mean mankind's salvation-or its total annihilation. Terrifying discoveries will unfold that will change the rules of survival forever.
DVD
Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma
Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.
Journal Article
HMGA2 as a Critical Regulator in Cancer Development
The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes.
Journal Article
A novel saliva-based miRNA profile to diagnose and predict oral cancer
Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n = 50), OPMD (n = 52), and controls (n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.
Journal Article
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response
Breast cancer (BCa) is a major global health challenge. The BCa genome often carries extensive somatic copy number alterations (CNAs), including gains/amplifications and losses/deletions. These CNAs significantly affect tumor development, drug response and patient survival. However, how individual CNAs contribute is mostly elusive. We identified loss of chromosome 13q14.2 as a key CNA in BCa, occurring in up to 63% of patients, depending on the subtype, and correlating with poor survival. Through multi-omics and in vitro analyses, we uncover a paradoxical role of 13q14.2 loss, promoting both cell cycle and pro-apoptotic pathways in cancer cells, while also associating with increased NK cell and macrophage populations in the tumor microenvironment. Notably, 13q14.2 loss increases BCa susceptibility to BCL2 inhibitors, both in vitro and in patient-derived xenografts. Thus, 13q14.2 loss could serve as a biomarker for BCa prognosis and treatment, potentially improving outcomes for BCa patients.
Graphical abstract
Journal Article
Chromosome arm aneuploidies shape tumour evolution and drug response
Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology.
Chromosome arm-level aneuploidies (CAAs) are frequently observed in cancer. Here, the authors analyse CAA landscapes across different tumour types, relating these chromosome arm gains and losses to tumour evolution, metastasis, patient survival and response to a range of anti-cancer therapies.
Journal Article