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https://www.readbyqxmd.com/read/28737770/tissue-specific-ctcf-cohesin-mediated-chromatin-architecture-delimits-enhancer-interactions-and-function-in-vivo
#1
Lars L P Hanssen, Mira T Kassouf, A Marieke Oudelaar, Daniel Biggs, Chris Preece, Damien J Downes, Matthew Gosden, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Jim R Hughes, Benjamin Davies, Douglas R Higgs
The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF-cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment...
July 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28737481/thermal-response-to-firefighting-activities-in-residential-structure-fires-impact-of-job-assignment-and-suppression-tactic
#2
Gavin P Horn, Richard M Kesler, Steve Kerber, Kenneth W Fent, Tad J Schroeder, William S Scott, Patricia C Fehling, Bo Fernhall, Denise L Smith
Firefighters' thermal burden is generally attributed to high heat loads from the fire and metabolic heat generation, which may vary between job assignments and suppression tactic employed. Utilizing a full-sized residential structure, firefighters were deployed in six job assignments utilizing two attack tactics (1. Water applied from the interior, or 2. Exterior water application before transitioning to the interior). Environmental temperatures decreased after water application, but more rapidly with transitional attack...
July 24, 2017: Ergonomics
https://www.readbyqxmd.com/read/28734164/cognitive-strategies-in-the-mental-rotation-task-revealed-by-eeg-spectral-power
#3
Aaron L Gardony, Marianna D Eddy, Tad T Brunyé, Holly A Taylor
The classic mental rotation task (MRT; Shepard & Metzler, 1971) is commonly thought to measure mental rotation, a cognitive process involving covert simulation of motor rotation. Yet much research suggests that the MRT recruits both motor simulation and other analytic cognitive strategies that depend on visuospatial representation and visual working memory (WM). In the present study, we investigated cognitive strategies in the MRT using time-frequency analysis of EEG and independent component analysis. We scrutinized sensorimotor mu (µ) power reduction, associated with motor simulation, parietal alpha (pα) power reduction, associated with visuospatial representation, and frontal midline theta (fmθ) power enhancement, associated with WM maintenance and manipulation...
July 19, 2017: Brain and Cognition
https://www.readbyqxmd.com/read/28732659/eye-tracking-measures-of-uncertainty-during-perceptual-decision-making
#4
Tad T Brunyé, Aaron L Gardony
Perceptual decision making involves gathering and interpreting sensory information to effectively categorize the world and inform behavior. For instance, a radiologist distinguishing the presence versus absence of a tumor, or a luggage screener categorizing objects as threatening or non-threatening. In many cases, sensory information is not sufficient to reliably disambiguate the nature of a stimulus, and resulting decisions are done under conditions of uncertainty. The present study asked whether several oculomotor metrics might prove sensitive to transient states of uncertainty during perceptual decision making...
July 18, 2017: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/28722729/a-healable-thermo-reversible-functional-polymer-prepared-via-raft-polymerization-and-ultrafast-click-chemistry-using-a-triazolinedione-derivative
#5
Prantik Mondal, Prasanta Kumar Behera, Nikhil K Singha
This communication reports the preparation and characterization of a functional polymer bearing a pendant indole group via a reversible-addition fragmentation and chain transfer (RAFT) process followed by its modification via an Alder-ene 'click' reaction using a 1,2,4-triazoline-3,5-dione (TAD) derivative. The resultant functional polymer showed thermo-reversible as well as healing characteristics.
July 19, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28712921/selective-regulation-of-biological-processes-by-vitamin-d-based-on-the-spatio-temporal-cistrome-of-its-receptor
#6
Antonio Neme, Sabine Seuter, Carsten Carlberg
The transcription factor vitamin D receptor (VDR) is the exclusive nuclear target of the biologically active form of vitamin D (1,25(OH)2D3). In THP-1 human monocytes we obtained a highly accurate VDR cistrome after 2 and 24 h ligand stimulation comprising more than 11,600 genomic loci, 78% of which were detected exclusively after 24 h. In contrast, a group of 510 persistent VDR sites occurred at all conditions and some 2,100 VDR loci were only transiently occupied. Machine learning and statistical analysis as well as a comparison with the re-analyzed B cell VDR cistrome indicated a subgroup of 339 highly conserved persistent VDR sites that were suited best for describing vitamin D-triggered gene regulatory scenarios...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28709003/3d-chromatin-structures-of-mature-gametes-and-structural-reprogramming-during-mammalian-embryogenesis
#7
Yuwen Ke, Yanan Xu, Xuepeng Chen, Songjie Feng, Zhenbo Liu, Yaoyu Sun, Xuelong Yao, Fangzhen Li, Wei Zhu, Lei Gao, Haojie Chen, Zhenhai Du, Wei Xie, Xiaocui Xu, Xingxu Huang, Jiang Liu
High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708583/circular-rna-expression-profile-and-potential-function-of-hsa_circrna_101238-in-human-thoracic-aortic-dissection
#8
Meisheng Zou, Chixiong Huang, Xinzhong Li, Xiang He, Yanmei Chen, Wangjun Liao, Yulin Liao, Jie Sun, Ze Liu, Lintao Zhong, Jianping Bin
OBJECTIVE: To assess the circular RNAs (circRNAs) expression profile and explore the potential functions in human thoracic aortic dissection (TAD). METHODS: The differentially expressed circRNAs profiles of the aortic segments between human type A TAD patients (n=3) and age-matched normal donors (NA; n=3) were analyzed using the Arraystar human circRNAs microarray. Quantitative real-time PCR was used to validate the expression pattern of circRNAs, parental genes, and hsa-miR-320a; Western blotting confirmed MMP9 expression with additional samples...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707474/native-hydrophobic-binding-interactions-at-the-transition-state-for-association-between-the-taz1-domain-of-cbp-and-the-disordered-tad-stat2-are-not-a-requirement
#9
Ida Lindström, Jakob Dogan
A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered in native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for the binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis), and found that the native protein-protein binding interface is not formed at the transition state for binding...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28703188/allelic-reprogramming-of-3d-chromatin-architecture-during-early-mammalian-development
#10
Zhenhai Du, Hui Zheng, Bo Huang, Rui Ma, Jingyi Wu, Xianglin Zhang, Jing He, Yunlong Xiang, Qiujun Wang, Yuanyuan Li, Jing Ma, Xu Zhang, Ke Zhang, Yang Wang, Michael Q Zhang, Juntao Gao, Jesse R Dixon, Xiaowo Wang, Jianyang Zeng, Wei Xie
In mammals, chromatin organization undergoes drastic reprogramming after fertilization. However, the three-dimensional structure of chromatin and its reprogramming in preimplantation development remain poorly understood. Here, by developing a low-input Hi-C (genome-wide chromosome conformation capture) approach, we examined the reprogramming of chromatin organization during early development in mice. We found that oocytes in metaphase II show homogeneous chromatin folding that lacks detectable topologically associating domains (TADs) and chromatin compartments...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28696098/enhanced-binding-affinity-via-destabilization-of-the-unbound-state-a-millisecond-hydrogen-deuterium-exchange-study-of-the-interaction-between-p53-and-a-pleckstrin-homology-domain
#11
Shaolong Zhu, Rahima Khatun, Cristina Lento, Yi Sheng, Derek J Wilson
The incorporation of intrinsically disordered domains enables proteins to engage a wide variety of targets, with phosphorylation often modulating target specificity and affinity. Although phosphorylation can clearly act as a chemical driver of complexation in structured proteins, e.g., by abrogating or permitting new charge-charge interactions, the basis for enhancement of the hydrophobically driven interactions that are typical of disordered protein-target complexation is less clear. To determine how phosphorylation can positively impact target recruitment in disordered domains, we have examined the interaction between the disordered N-terminal transactivation domain (TAD) of p53 and the pleckstrin homology (PH) domain of p62...
July 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28693562/activation-of-the-alpha-globin-gene-expression-correlates-with-dramatic-upregulation-of-nearby-non-globin-genes-and-changes-in-local-and-large-scale-chromatin-spatial-structure
#12
Sergey V Ulianov, Aleksandra A Galitsyna, Ilya M Flyamer, Arkadiy K Golov, Ekaterina E Khrameeva, Maxim V Imakaev, Nezar A Abdennur, Mikhail S Gelfand, Alexey A Gavrilov, Sergey V Razin
BACKGROUND: In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2...
July 11, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28691783/two-steps-towards-complex-and-artificial-medium-and-macrocycles
#13
Alexander Doemling, Rudrakshula Madhavachary, Eman M M Abdelraheem, Arianna Rossetti, Aleksandra Twarda-Clapa, Bogdan Musielak, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, Tad A Holak
The design and synthesis of head-to-tail linked artificial macrocycles using the Ugi-reaction has been developed. This synthetic approach in just two steps is unprecedented short, efficient and works over a wide range of medium and macrocyclic loop sizes. The substrate scope and functional group tolerance is exceptional. Using this approach, we have synthesized 39 novel macrocycles including for example tylosin and we incorporate glycosylated macrocycles as well by two or even one single synthetic operation...
July 10, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28682332/cell-cycle-dynamics-of-chromosomal-organization-at-single-cell-resolution
#14
Takashi Nagano, Yaniv Lubling, Csilla Várnai, Carmel Dudley, Wing Leung, Yael Baran, Netta Mendelson Cohen, Steven Wingett, Peter Fraser, Amos Tanay
Chromosomes in proliferating metazoan cells undergo marked structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures that facilitate chromosome segregation, and decondensed interphase structures that accommodate transcription, gene silencing and DNA replication. Here we use single-cell Hi-C (high-resolution chromosome conformation capture) analysis to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28681097/characterizing-diagnostic-search-patterns-in-digital-breast-pathology-scanners-and-drillers
#15
Ezgi Mercan, Linda G Shapiro, Tad T Brunyé, Donald L Weaver, Joann G Elmore
Following a baseline demographic survey, 87 pathologists interpreted 240 digital whole slide images of breast biopsy specimens representing a range of diagnostic categories from benign to atypia, ductal carcinoma in situ, and invasive cancer. A web-based viewer recorded pathologists' behaviors while interpreting a subset of 60 randomly selected and randomly ordered slides. To characterize diagnostic search patterns, we used the viewport location, time stamp, and zoom level data to calculate four variables: average zoom level, maximum zoom level, zoom level variance, and scanning percentage...
July 5, 2017: Journal of Digital Imaging: the Official Journal of the Society for Computer Applications in Radiology
https://www.readbyqxmd.com/read/28673418/sports-neurology
#16
EDITORIAL
Tad Seifert
No abstract text is available yet for this article.
August 2017: Neurologic Clinics
https://www.readbyqxmd.com/read/28673413/neurologic-health-in-combat-sports
#17
REVIEW
Tad Seifert
Neurologic injuries of both an acute and chronic nature have been reported in the literature for various combat sport styles; however, reports of the incidence and prevalence of these injury types vary greatly. Combat sports clinicians must continue to strive for the development, implementation, and enforcement of uniform minimum requirements for brain safety. These health care providers must also seize on the honor to provide this oft-underserved population with the health care advocacy they very much deserve, but often do not receive...
August 2017: Neurologic Clinics
https://www.readbyqxmd.com/read/28671686/the-methyltransferase-setdb1-regulates-a-large-neuron-specific-topological-chromatin-domain
#18
Yan Jiang, Yong-Hwee Eddie Loh, Prashanth Rajarajan, Teruyoshi Hirayama, Will Liao, Bibi S Kassim, Behnam Javidfar, Brigham J Hartley, Lisa Kleofas, Royce B Park, Benoit Labonte, Seok-Man Ho, Sandhya Chandrasekaran, Catherine Do, Brianna R Ramirez, Cyril J Peter, Julia T C W, Brian M Safaie, Hirofumi Morishita, Panos Roussos, Eric J Nestler, Anne Schaefer, Benjamin Tycko, Kristen J Brennand, Takeshi Yagi, Li Shen, Schahram Akbarian
We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TAD(cPcdh)) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression...
July 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28667354/dose-individualization-of-sunitinib-in-metastatic-renal-cell-cancer-toxicity-adjusted-dose-or-therapeutic-drug-monitoring
#19
Dhanusha Sabanathan, Alison Zhang, Peter Fox, Sally Coulter, Val Gebski, Bavanthi Balakrishnar, Mathew Chan, Christopher Liddle, Howard Gurney
PURPOSE: Dose individualization of sunitinib has been proposed using therapeutic drug monitoring (TDM) or toxicity-adjusted dose (TAD). We prospectively studied aspects of TDM and TAD to inform future trials, namely (1) intrapatient variability (CV) of sunitinib and (2) feasibility of a TAD protocol. METHODS: Sunitinib dose was adjusted to ensure grade 1 or 2 toxicity on 10-20 days of each 42-day cycle. Total trough levels (TTL) C min of sunitinib and its active metabolite were measured every 6 weeks...
June 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28662178/genetic-association-of-fto-irx-region-with-obesity-and-overweight-in-the-polish-population
#20
Marta Sobalska-Kwapis, Aleksandra Suchanecka, Marcin Słomka, Anna Siewierska-Górska, Ewa Kępka, Dominik Strapagiel
BACKGROUND/OBJECTIVES: Genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI) in many different populations. Variants in the FTO locus are reported to be one of the strongest genetic predictors of obesity. Recent publications pointed also to a topologically associated domain (TAD) which is identified as a novel region affecting BMI. The TAD area encompasses the IRXB cluster (IRX3, IRX5, IRX6), FTO and RPGRIP1L genes. SUBJECTS/METHODS: In this study, we investigated the relationship between variation of the FTO and IRX genes and obesity in Poles...
2017: PloS One
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