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https://www.readbyqxmd.com/read/28334916/mocap-large-scale-inference-of-transcription-factor-binding-sites-from-chromatin-accessibility
#1
Xi Chen, Bowen Yu, Nicholas Carriero, Claudio Silva, Richard Bonneau
Differential binding of transcription factors (TFs) at cis-regulatory loci drives the differentiation and function of diverse cellular lineages. Understanding the regulatory interactions that underlie cell fate decisions requires characterizing TF binding sites (TFBS) across multiple cell types and conditions. Techniques, e.g. ChIP-Seq can reveal genome-wide patterns of TF binding, but typically requires laborious and costly experiments for each TF-cell-type (TFCT) condition of interest. Chromosomal accessibility assays can connect accessible chromatin in one cell type to many TFs through sequence motif mapping...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28329690/tissue-myeloid-progenitors-differentiate-into-pericytes-through-tgf-%C3%AE-signaling-in-developing-skin-vasculature
#2
Tomoko Yamazaki, Ani Nalbandian, Yutaka Uchida, Wenling Li, Thomas D Arnold, Yoshiaki Kubota, Seiji Yamamoto, Masatsugu Ema, Yoh-Suke Mukouyama
Mural cells (pericytes and vascular smooth muscle cells) are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid progenitors contribute to pericyte development in embryonic skin vasculature. A series of in vivo fate-mapping experiments indicates that tissue myeloid progenitors differentiate into pericytes...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28325876/comprehensive-and-quantitative-mapping-of-rna-protein-interactions-across-a-transcribed-eukaryotic-genome
#3
Richard She, Anupam K Chakravarty, Curtis J Layton, Lauren M Chircus, Johan O L Andreasson, Nandita Damaraju, Peter L McMahon, Jason D Buenrostro, Daniel F Jarosz, William J Greenleaf
RNA-binding proteins (RBPs) control the fate of nearly every transcript in a cell. However, no existing approach for studying these posttranscriptional gene regulators combines transcriptome-wide throughput and biophysical precision. Here, we describe an assay that accomplishes this. Using commonly available hardware, we built a customizable, open-source platform that leverages the inherent throughput of Illumina technology for direct biophysical measurements. We used the platform to quantitatively measure the binding affinity of the prototypical RBP Vts1 for every transcript in the Saccharomyces cerevisiae genome...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28321204/a-comprehensive-view-of-the-%C3%AE-arrestinome
#4
Pascale Crépieux, Anne Poupon, Nathalie Langonné-Gallay, Eric Reiter, Javier Delgado, Martin H Schaefer, Thomas Bourquard, Luis Serrano, Christina Kiel
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28284818/distribution-and-importance-of-microplastics-in-the-marine-environment-a-review-of-the-sources-fate-effects-and-potential-solutions
#5
REVIEW
H S Auta, C U Emenike, S H Fauziah
The presence of microplastics in the marine environment poses a great threat to the entire ecosystem and has received much attention lately as the presence has greatly impacted oceans, lakes, seas, rivers, coastal areas and even the Polar Regions. Microplastics are found in most commonly utilized products (primary microplastics), or may originate from the fragmentation of larger plastic debris (secondary microplastics). The material enters the marine environment through terrestrial and land-based activities, especially via runoffs and is known to have great impact on marine organisms as studies have shown that large numbers of marine organisms have been affected by microplastics...
March 8, 2017: Environment International
https://www.readbyqxmd.com/read/28272836/mapping-carbon-fate-during-bleaching-in-a-model-cnidarian-symbiosis-the-application-of-13-c-metabolomics
#6
Katie E Hillyer, Daniel A Dias, Adrian Lutz, Ute Roessner, Simon K Davy
Coral bleaching is a major threat to the persistence of coral reefs. Yet we lack detailed knowledge of the metabolic interactions that determine symbiosis function and bleaching-induced change. We mapped autotrophic carbon fate within the free metabolite pools of both partners of a model cnidarian-dinoflagellate symbiosis (Aiptasia-Symbiodinium) during exposure to thermal stress via the stable isotope tracer ((13) C bicarbonate), coupled to GC-MS. Symbiont photodamage and pronounced bleaching coincided with substantial increases in the turnover of non(13) C-labelled pools in the dinoflagellate (lipid and starch store catabolism)...
March 8, 2017: New Phytologist
https://www.readbyqxmd.com/read/28271248/network-reconstruction-reveals-that-valproic-acid-activates-neurogenic-transcriptional-programs-in-adult-brain-following-traumatic-injury
#7
Gerald A Higgins, Patrick Georgoff, Vahagn Nikolian, Ari Allyn-Feuer, Brian Pauls, Richard Higgins, Brian D Athey, Hasan E Alam
OBJECTIVES: To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). METHODS: Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. RESULTS: The transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis...
March 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28263708/supporting-cells-remove-and-replace-sensory-receptor-hair-cells-in-a-balance-organ-of-adult-mice
#8
Stephanie A Bucks, Brandon C Cox, Brittany A Vlosich, James P Manning, Tot B Nguyen, Jennifer S Stone
Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreER(T2)-expressing supporting cells replace type II hair cells...
March 6, 2017: ELife
https://www.readbyqxmd.com/read/28260375/spatial-mapping-of-protein-adsorption-on-mesoporous-silica-nanoparticles-by-stochastic-optical-reconstruction-microscopy
#9
Alden M Clemments, Pablo Botella, Christopher C Landry
Exposure to biological fluid envelops a nanoparticle in layers of proteins and biomolecules, which has a profound impact on the nanoparticle's biological fate. Although the identities and amounts of the proteins in this "corona" have been thoroughly examined, the spatial arrangement of the proteins is unclear, a problem that is compounded on porous nanoparticles due to penetration of proteins within the porous network. To address this problem, we have developed a procedure based on information derived from stochastic optical reconstruction microscopy...
March 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28253481/a-lentiviral-fluorescent-genetic-barcoding-system-for-flow-cytometry-based-multiplex-tracking
#10
Tobias Maetzig, Jens Ruschmann, Courteney K Lai, Mor Ngom, Suzan Imren, Patricia Rosten, Gudmundur L Norddahl, Niklas von Krosigk, Lea Sanchez Milde, Christopher May, Anton Selich, Michael Rothe, Ishpreet Dhillon, Axel Schambach, R Keith Humphries
Retroviral integration site analysis and barcoding have been instrumental for multiplex clonal fate mapping, although their use imposes an inherent delay between sample acquisition and data analysis. Monitoring of multiple cell populations in real time would be advantageous, but multiplex assays compatible with flow cytometric tracking of competitive growth behavior are currently limited. We here describe the development and initial validation of three generations of lentiviral fluorescent genetic barcoding (FGB) systems that allow the creation of 26, 14, or 6 unique labels...
March 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28228010/selective-fusion-of-heterogeneous-classifiers-for-predicting-substrates-of-membrane-transporters
#11
Naeem Shaikh, Mahesh Sharma, Prabha Garg
Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic, and toxicological profiles. In the present study, predictive models for classifying small molecules into substrates and nonsubstrates of various pharmaceutically important membrane transporters were developed using quantitative structure-activity relationship (QSAR) and proteochemometric (PCM) approaches...
March 6, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28209809/macrophage-to-myofibroblast-transition-contributes-to-interstitial-fibrosis-in-chronic-renal-allograft-injury
#12
Ying-Ying Wang, Hong Jiang, Jun Pan, Xiao-Ru Huang, Yu-Cheng Wang, Hong-Feng Huang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan, Jiang-Hua Chen
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28209733/dual-function-of-tgf%C3%AE-in-lens-epithelial-cell-fate-implications-for-secondary-cataract
#13
Bruce A Boswell, Anna Korol, Judith A West-Mays, Linda S Musil
The most common vision-disrupting complication of cataract surgery is posterior capsule opacification (PCO; secondary cataract). PCO is caused by residual lens cells undergoing one of two very different cell fates: either transdifferentiating into myofibroblasts, or maturing into lens fiber cells. Although TGFβ has been strongly implicated in lens cell fibrosis, the factors responsible for the latter process have not been identified. We show here for the first time that TGFβ can induce purified primary lens epithelial cells within the same culture to undergo differentiation into either lens fiber cells or myofibroblasts...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28192080/evo-engineering-and-the-cellular-and-molecular-origins-of-the-vertebrate-spinal-cord
#14
REVIEW
Ben Steventon, Alfonso Martinez Arias
The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord...
February 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28177282/cilia-mediated-hedgehog-signaling-controls-form-and-function-in-the-mammalian-larynx
#15
Jacqueline M Tabler, Maggie M Rigney, Gordon J Berman, Swetha Gopalakrishnan, Eglantine Heude, Hadeel Adel Al-Lami, Basil Z Yannakoudiadkis, Rebecca D Fitch, Christopher Carter, Steven Vokes, Karen J Liu, Shahragim Tajbakhsh, Se Roian Egnor, John B Wallingford
Acoustic communication is fundamental to social interactions among animals, including humans. In fact, deficits in voice impair the quality of life for a large and diverse population of patients. Understanding the molecular genetic mechanisms of development and function in the vocal apparatus is thus an important challenge with relevance both to the basic biology of animal communication and to biomedicine. However, surprisingly little is known about the developmental biology of the mammalian larynx. Here, we used genetic fate mapping to chart the embryological origins of the tissues in the mouse larynx, and we describe the developmental etiology of laryngeal defects in mice with disruptions in cilia-mediated Hedgehog signaling...
February 13, 2017: ELife
https://www.readbyqxmd.com/read/28174244/a-novel-floor-plate-boundary-defined-by-adjacent-en1-and-dbx1-microdomains-distinguishes-midbrain-dopamine-and-hypothalamic-neurons
#16
Navid Nouri, Rajeshwar Awatramani
The mesodiencephalic floor plate (mdFP) is the source of diverse neuron types. Yet, how this structure is compartmentalized has not been clearly elucidated. Here, we identify a novel boundary subdividing the mdFP into two microdomains, defined by Engrailed 1 (En1) and developing brain homeobox 1 (Dbx1) Utilizing simultaneous dual and intersectional fate mapping, we demonstrate that this boundary is precisely formed with minimal overlap between En1 and Dbx1 microdomains, unlike many other boundaries. We show that the En1 microdomain gives rise to dopaminergic (DA) neurons, while the Dbx1 microdomain gives rise to subthalamic (STN), premammillary (PM), and posterior hypothalamic (PH) populations...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28143982/differential-binding-of-mitochondrial-transcripts-by-mrb8170-and-mrb4160-regulates-distinct-editing-fates-of-mitochondrial-mrna-in-trypanosomes
#17
Sameer Dixit, Michaela Müller-McNicoll, Vojtěch David, Kathi Zarnack, Jernej Ule, Hassan Hashimi, Julius Lukeš
A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28139650/corrigendum-clonal-fate-mapping-quantifies-the-number-of-haematopoietic-stem-cells-that-arise-during-development
#18
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
No abstract text is available yet for this article.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28135253/alternative-pathway-for-the-development-of-v%C3%AE-14-nkt-cells-directly-from-cd4-cd8-thymocytes-that-bypasses-the-cd4-cd8-stage
#19
Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi
Although invariant Vα14(+) natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28133805/evolution-of-b-cell-analysis-and-env-trimer-redesign
#20
REVIEW
Gunilla B Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T Wyatt
HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses...
January 2017: Immunological Reviews
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