Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
99
result(s) for
"Chu, Ci"
Sort by:
عبارات \غامضة\ عن الصين : مقالات في الجغرافيا البشرية
هذا الكتاب هو الجزء الأول من سلسلة كتب \"الحكمة الصينية\" ويأتي تحت عنوان (عبارات \"غامضة\" عن الصين : مقالات في الجغرافيا البشرية)، وجمع بين دفتيه ما مجموعة أربعة عشر مصطلحا متعلقا بالجغرافيا البشرية، ومن بينها \"الأقاليم التسعة\"، \"العالم\"، \"النهر الأصفر\"، \"سور الصين العظيم\"، \"المدينة\"، \"و\"العاصمة\"، وغيرها، ويتمثل الغرض الرئيسي للكتاب في تعريف الأطفال بالجغرافيا الصينية التقليدية، وتعميم معارف الجغرافيا البشرية في نفس الوقت، وهو الأمر الذي يترك الأطفال يستكشفون المعنى الثقافي وراء المصطلحات والمفردات الشائعة.
Book
Technologies to probe functions and mechanisms of long noncoding RNAs
In this Perspective, Spitale, Chang and Chu discuss recent technological advances that will aid in the functional characterization of long noncoding RNAs, which up to now has posed a substantial challenge.
Thousands of long noncoding RNAs (lncRNAs) have been discovered, but their functional characterization has been slowed by a limited set of research tools. Here we review emerging RNA-centric methods to interrogate the intrinsic structure of lncRNAs as well as their genomic localization and biochemical partners. Understanding these technologies, including their advantages and caveats, and developing them in the future will be essential to progress from description to comprehension of the myriad roles of lncRNAs.
Journal Article
Control of somatic tissue differentiation by the long non-coding RNA TINCR
The human long non-coding RNA TINCR binds to STAU1 and controls epidermal differentiation by stabilizing key differentiation mRNAs, by means of a TINCR-binding motif found enriched in epidermal differentiation genes.
An lncRNA required for tissue differentiation
The human genome codes for thousands of long non-coding RNAs (lncRNAs), but their biological functions are mostly unknown. This study reports the identification and characterization of a 3.7-kilobase lncRNA, named TINCR (for terminal differentiation-induced ncRNA). TINCR controls epidermal differentiation by stabilizing the mRNA of an array of differentiation genes. A 25-nucleotide TINCR-binding motif is enriched in these epidermal differentiation genes. TINCR also combines with the RNA-binding protein staufen1 to form a complex that stabilizes differentiation transcripts via direct binding and other mechanisms yet to be identified.
Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized
1
,
2
,
3
,
4
; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including
FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14
and
ELOVL3
. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR–mRNA interaction occurs through a 25-nucleotide ‘TINCR box’ motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of
TINCR
RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of
UPF1
and
UPF2
, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR–STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as
KRT80
. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression.
Journal Article
Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification
Domain-specific chromatin isolation by RNA purification (dChIRP) identifies interacting partners of functional regions of long noncoding RNAs.
Little is known about the functional domain architecture of long noncoding RNAs (lncRNAs) because of a relative paucity of suitable methods to analyze RNA function at a domain level. Here we describe domain-specific chromatin isolation by RNA purification (dChIRP), a scalable technique to dissect pairwise RNA-RNA, RNA-protein and RNA-chromatin interactions at the level of individual RNA domains in living cells. dChIRP of roX1, a lncRNA essential for
Drosophila melanogaster
X-chromosome dosage compensation, reveals a 'three-fingered hand' ribonucleoprotein topology. Each RNA finger binds chromatin and the male-specific lethal (MSL) protein complex and can individually rescue male lethality in
roX
-null flies, thus defining a minimal RNA domain for chromosome-wide dosage compensation. dChIRP improves the RNA genomic localization signal by >20-fold relative to previous techniques, and these binding sites are correlated with chromosome conformation data, indicating that most roX-bound loci cluster in a nuclear territory. These results suggest dChIRP can reveal lncRNA architecture and function with high precision and sensitivity.
Journal Article
7SK-BAF axis controls pervasive transcription at enhancers
In addition to controlling Pol II pausing at promoters, the small nuclear RNA 7SK inhibits transcription at enhancers and super enhancers by recruiting the chromatin-remodeling complex BAF
RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA-damage signaling. 7SK physically interacts with the BAF chromatin-remodeling complex, recruits BAF to enhancers and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with that of Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK uses distinct mechanisms to counteract the diverse consequences of pervasive transcription that distinguish super enhancers, enhancers and promoters.
Journal Article
A pooled Cell Painting CRISPR screening platform enables de novo inference of gene function by self-supervised deep learning
Pooled CRISPR screening enables large-scale interrogation of gene functions but typically measures simple phenotypes such as fitness. High-content methods like Perturb-seq extend dimensionality to transcriptomics but are costly and limited in scope. Optical pooled screening (OPS) combines pooled CRISPR screening with imaging to yield scalable, information-rich readouts, yet existing implementations remain pathway-specific. Here we describe an OPS-compatible Cell Painting platform that enables hypothesis-free reverse genetic screening through multiplexed morphological profiling. We validate this technique using a well-defined morphological gene set, compare classical image analysis to self-supervised learning methods using a mechanism-of-action library, and perform discovery screening with a druggable genome library. By combining rich morphological data with deep learning, gene networks emerge without the need for target-specific biomarkers, leading to unbiased discovery of gene functions.
Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.
Journal Article
Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets
Background
Multiple sclerosis (MS) is an autoimmune condition of the central nervous system with a well-characterized genetic background. Prior analyses of MS genetics have identified broad enrichments across peripheral immune cells, yet the driver immune subsets are unclear.
Results
We utilize chromatin accessibility data across hematopoietic cells to identify cell type-specific enrichments of MS genetic signals. We find that CD4 T and B cells are independently enriched for MS genetics and further refine the driver subsets to T
h
17 and memory B cells, respectively. We replicate our findings in data from untreated and treated MS patients and find that immunomodulatory treatments suppress chromatin accessibility at driver cell types. Integration of statistical fine-mapping and chromatin interactions nominate numerous putative causal genes, illustrating complex interplay between shared and cell-specific genes.
Conclusions
Overall, our study finds that open chromatin regions in CD4 T cells and B cells independently drive MS genetic signals. Our study highlights how careful integration of genetics and epigenetics can provide fine-scale insights into causal cell types and nominate new genes and pathways for disease.
Journal Article
PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications
We develop PIRCh-seq, a method which enables a comprehensive survey of chromatin-associated RNAs in a histone modification-specific manner. We identify hundreds of chromatin-associated RNAs in several cell types with substantially less contamination by nascent transcripts. Non-coding RNAs are found enriched on chromatin and are classified into functional groups based on the patterns of their association with specific histone modifications. We find single-stranded RNA bases are more chromatin-associated, and we discover hundreds of allele-specific RNA-chromatin interactions. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interactions.
Journal Article
Performance Damage Characteristics of Asphalt Binder Suffered from the Action of Sulfate
Sulfate erosion is a threat to durability and sustainability of pavement structure. In this work, the performance degradation of asphalt binder under internal sulfate erosion was investigated. Different dosages of Na2SO4 (0 wt.%, 2.5 wt.%, 5 wt.%, and 10 wt.%) samples were prepared to investigate the effect of sulfate on the performance of the asphalt binder. The surface tension test and low-temperature rheological property test were carried out to evaluate the adhesion of sulfate-incorporated asphalt mastic. Rapid freezing and thawing test with different concentrations of sulfate solution was conducted to explore the effect of sulfate concentrations and freeze-thaw cycles on the softening point and force ductility of matrix asphalt. Phases of the asphalt binder were characterized by Fourier transform infrared (FTIR) spectroscopy. The results show that sulfate has a negative impact on the road performance of the asphalt binder. Internal sulfate erosion decreased the adhesion of the asphalt binder. Also, the low-temperature rheological property of asphalt binder was deteriorated. After the freeze-thaw cycles of external sulfate erosion, softening point and tensile force peak of matrix asphalt increased and the low-temperature ductility decreased. The main reason of performance deterioration of the asphalt binder is the “salt aging” effect causing by sulfate erosion. The research results can provide useful reference for the durability design of asphalt mixture in sulfate-enriched regions.
Journal Article