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https://read.qxmd.com/read/30786239/high-resolution-regulatory-maps-connect-vascular-risk-variants-to-disease-related-pathways
#1
Örjan Åkerborg, Rapolas Spalinskas, Sailendra Pradhananga, Anandashankar Anil, Pontus Höjer, Flore-Anne Poujade, Lasse Folkersen, Per Eriksson, Pelin Sahlén
BACKGROUND: Genetic variant landscape of coronary artery disease (CAD) is dominated by non-coding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct genes both to gain insights into perturbed functions and better assess the risk of disease. METHODS: In this study, we generated high-resolution genomic interaction maps (~750 bases) in aortic endothelial, smooth muscle cells and THP-1 macrophages stimulated with lipopolysaccharide using Hi-C coupled with sequence capture targeting 25,429 features including variants associated with CAD...
February 20, 2019: Circulation. Genomic and precision medicine
https://read.qxmd.com/read/30780195/dynamics-of-transcriptional-enhancers-and-chromosome-topology-in-gene-regulation
#2
REVIEW
Moe Yokoshi, Takashi Fukaya
Transcriptional enhancers are regulatory DNAs that instruct when and where genes should be transcribed in response to a variety of intrinsic and external signals. They contain a cluster of binding sites for sequence-specific transcription factors and co-activators to determine the spatiotemporal specificity of gene activities during development. Enhancers are often positioned in distal locations from their target promoters. In some cases, they work over a million base pairs or more. In the traditional view, enhancers have been thought to stably interact with promoters in a targeted manner...
February 19, 2019: Development, Growth & Differentiation
https://read.qxmd.com/read/30778237/attenuated-chromatin-compartmentalization-in-meiosis-and-its-maturation-in-sperm-development
#3
Kris G Alavattam, So Maezawa, Akihiko Sakashita, Haia Khoury, Artem Barski, Noam Kaplan, Satoshi H Namekawa
Germ cells manifest a unique gene expression program and regain totipotency in the zygote. Here, we perform Hi-C analysis to examine 3D chromatin organization in male germ cells during spermatogenesis. We show that the highly compartmentalized 3D chromatin organization characteristic of interphase nuclei is attenuated in meiotic prophase. Meiotic prophase is predominated by short-range intrachromosomal interactions that represent a condensed form akin to that of mitotic chromosomes. However, unlike mitotic chromosomes, meiotic chromosomes display weak genomic compartmentalization, weak topologically associating domains, and localized point interactions in prophase...
February 18, 2019: Nature Structural & Molecular Biology
https://read.qxmd.com/read/30778236/dynamic-reorganization-of-the-genome-shapes-the-recombination-landscape-in-meiotic-prophase
#4
Lucas Patel, Rhea Kang, Scott C Rosenberg, Yunjiang Qiu, Ramya Raviram, Sora Chee, Rong Hu, Bing Ren, Francesca Cole, Kevin D Corbett
In meiotic prophase, chromosomes are organized into compacted loop arrays to promote homolog pairing and recombination. Here, we probe the architecture of the mouse spermatocyte genome in early and late meiotic prophase using chromosome conformation capture (Hi-C). Our data support the established loop array model of meiotic chromosomes, and infer loops averaging 0.8-1.0 megabase pairs (Mb) in early prophase and extending to 1.5-2.0 Mb in late prophase as chromosomes compact and homologs undergo synapsis...
February 18, 2019: Nature Structural & Molecular Biology
https://read.qxmd.com/read/30778195/multiplex-chromatin-interactions-with-single-molecule-precision
#5
Meizhen Zheng, Simon Zhongyuan Tian, Daniel Capurso, Minji Kim, Rahul Maurya, Byoungkoo Lee, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Zhihui Li, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan
The genomes of multicellular organisms are extensively folded into 3D chromosome territories within the nucleus1 . Advanced 3D genome-mapping methods that combine proximity ligation and high-throughput sequencing (such as chromosome conformation capture, Hi-C)2 , and chromatin immunoprecipitation techniques (such as chromatin interaction analysis by paired-end tag sequencing, ChIA-PET)3 , have revealed topologically associating domains4 with frequent chromatin contacts, and have identified chromatin loops mediated by specific protein factors for insulation and regulation of transcription5-7 ...
February 18, 2019: Nature
https://read.qxmd.com/read/30775004/addressing-the-information-deficit-in-global-health-lessons-from-a-digital-acute-care-platform-in-sri-lanka
#6
Abi Beane, Ambepitiyawaduge Pubudu De Silva, Priyantha Lakmini Athapattu, Saroj Jayasinghe, Anuja Unnathie Abayadeera, Mandika Wijerathne, Ishara Udayanga, Shriyananda Rathnayake, Arjen M Dondorp, Rashan Haniffa
Lack of investment in low-income and middle-income countries (LMICs) in systems capturing continuous information regarding care of the acutely unwell patient is hindering global efforts to address inequalities, both at facility and national level. Furthermore, this of lack of data is disempowering frontline staff and those seeking to support them, from progressing setting-relevant research and quality improvement. In contrast to high-income country (HIC) settings, where electronic surveillance has boosted the capability of governments, clinicians and researchers to engage in service-wide healthcare evaluation, healthcare information in resource-limited settings remains almost exclusively paper based...
2019: BMJ Global Health
https://read.qxmd.com/read/30774938/first-africa-non-communicable-disease-research-conference-2017-sharing-evidence-and-identifying-research-priorities
#7
Kenneth Juma, Pamela A Juma, Shukri F Mohamed, Jared Owuor, Ann Wanyoike, David Mulabi, George Odinya, Maureen Njeru, Gerald Yonga
Non-communicable diseases (NCDs) prevalence is rising fastest in lower income settings, and with more devastating outcomes compared to High Income Countries (HICs). While evidence is consistent on the growing health and economic consequences of NCDs in sub-Saharan Africa (SSA), specific efforts aimed at addressing NCD prevention and control remain less than optimum and country level progress of implementing evidence backed cost-effective NCD prevention approaches such as tobacco taxation and restrictions on marketing of unhealthy food and drinks is slow...
June 2019: Journal of Global Health
https://read.qxmd.com/read/30774289/factors-influencing-participation-in-daily-activities-by-persons-with-spinal-cord-injury-lessons-learned-from-an-international-scoping-review
#8
Yeasir Arafat Alve, Peter Bontje
Background: It is important to develop further understanding regarding the facilitating and constraining factors that influence participation in daily activities, including social and human rights issues faced by persons with spinal cord injury (SCI) that affect their opportunities to lead full social lives. Objectives: To identify, describe, and compare factors that influence participation in daily activities by persons with SCI living in high-income countries (HICs) and in low- and middle-income countries (LMICs)...
2019: Topics in Spinal Cord Injury Rehabilitation
https://read.qxmd.com/read/30767593/influence-of-hemolysis-on-clinical-chemistry-parameters-determined-with-beckman-coulter-tests-detection-of-clinically-significant-interference
#9
Antonija Perović, Maja Dolčić
The aim of this study was to examine the influence of hemolysis on 25 clinical chemistry parameters and to compare the resulting bias with clinically significant differences and the manufacturer's specifications. Using freeze-thawing of the treated blood aliquot of each subject (N = 17), four hemolysis levels were prepared with hemolysis index (HI) and hemoglobin concentration as follows: (+)=0.5-0.99 g/L, (2+)=1-1.99 g/L, (3+)=2-2.99 g/L and (4+)=3-4.99 g/L. All analytes were tested on the Beckman Coulter AU480 analyzer using proprietary reagents...
February 15, 2019: Scandinavian Journal of Clinical and Laboratory Investigation
https://read.qxmd.com/read/30761652/autoregressive-moving-average-modeling-for-hepatic-iron-quantification-in-the-presence-of-fat
#10
Aaryani Tipirneni-Sajja, Axel J Krafft, Ralf B Loeffler, Ruitian Song, Armita Bahrami, Jane S Hankins, Claudia M Hillenbrand
BACKGROUND: Measuring hepatic R2* by fitting a monoexponential model to the signal decay of a multigradient-echo (mGRE) sequence noninvasively determines hepatic iron content (HIC). Concurrent hepatic steatosis introduces signal oscillations and confounds R2* quantification with standard monoexponential models. PURPOSE: To evaluate an autoregressive moving average (ARMA) model for accurate quantification of HIC in the presence of fat using biopsy as the reference...
February 13, 2019: Journal of Magnetic Resonance Imaging: JMRI
https://read.qxmd.com/read/30759575/influence-of-select-bioenergy-by-products-on-soil-carbon-and-microbial-activity-a-laboratory-study
#11
T Bera, L Vardanyan, K S Inglett, K R Reddy, G A O'Connor, J E Erickson, A C Wilkie
Concerns about the negative impacts of crop biomass removal on soil ecological functions have led to questioning the long-term sustainability of bioenergy production. To offset this potential negative impact, use of organic C rich by-products from the bioenergy industries have been proposed as a means to replenish soil C in degraded soils. However, the impact of these by-products application on soil carbon dynamics is not fully understood. We measured biogeochemical changes in soil organic C following a three-year field application of two by-products, biochar (BC) and fermentation-by product (FBP), of bioenergy industry processes in an elephant grass [Pennisetum purpureum (L...
February 25, 2019: Science of the Total Environment
https://read.qxmd.com/read/30755246/integrated-epigenomic-analysis-stratifies-chromatin-remodellers-into-distinct-functional-groups
#12
Katherine A Giles, Cathryn M Gould, Qian Du, Ksenia Skvortsova, Jenny Z Song, Madhavi P Maddugoda, Joanna Achinger-Kawecka, Clare Stirzaker, Susan J Clark, Phillippa C Taberlay
BACKGROUND: ATP-dependent chromatin remodelling complexes are responsible for establishing and maintaining the positions of nucleosomes. Chromatin remodellers are targeted to chromatin by transcription factors and non-coding RNA to remodel the chromatin into functional states. However, the influence of chromatin remodelling on shaping the functional epigenome is not well understood. Moreover, chromatin remodellers have not been extensively explored as a collective group across two-dimensional and three-dimensional epigenomic layers...
February 12, 2019: Epigenetics & Chromatin
https://read.qxmd.com/read/30738526/image-quality-and-dose-evaluation-of-mvct-tomotherapy-acquisitions-a-phantom-study
#13
P De Marco, I Abdi Osman, F Castellini, R Ricotti, M C Leonardi, E Miglietta, R Cambria, D Origgi, B A Jereczek-Fossa, C Garibaldi, F Cattani
BACKGROUND: The aim of this study is to evaluate the dose delivered and the image quality of pre-treatment MVCT images with Hi-Art TomoTherapy system, varying acquisition and reconstruction parameters. MATERIALS AND METHODS: Catphan 500 MVCT images were acquired with all acquisition pitch and reconstruction intervals; image quality was evaluated in terms of noise, uniformity, contrast linearity, contrast-to-noise ratio (CNR) and spatial resolution with the Modulation Transfer Function (MTF)...
January 2019: Physica Medica: PM
https://read.qxmd.com/read/30738248/epilepsy-surgery-in-low-and-middle-income-countries-a-scoping-review
#14
REVIEW
Musa M Watila, Fenglai Xiao, Mark R Keezer, Anna Miserocchi, Andrea S Winkler, Andrew W McEvoy, Josemir W Sander
BACKGROUND: Epilepsy surgery is an important treatment option for people with drug-resistant epilepsy. Surgical procedures for epilepsy are underutilized worldwide, but it is far worse in low- and middle-income countries (LMIC), and it is less clear as to what extent people with drug-resistant epilepsy receive such treatment at all. Here, we review the existing evidence for the availability and outcome of epilepsy surgery in LMIC and discuss some challenges and priority. METHODS: We used an accepted six-stage methodological framework for scoping reviews as a guide...
February 6, 2019: Epilepsy & Behavior: E&B
https://read.qxmd.com/read/30736419/differential-efficacy-of-neurofeedback-in-children-with-adhd-presentations
#15
Marisol Cueli, Celestino Rodríguez, Paloma Cabaleiro, Trinidad García, Paloma González-Castro
Training in neurofeedback (NF) reduces the symptomatology associated with attention deficit with hyperactivity disorder (ADHD). However, ADHD differs in terms of the type of presentation, i.e., inattentive (ADHD-I), impulsive/hyperactive (ADHD-HI), or combined (ADHD-C). This study examines the efficacy of NF in ADHD presentations. Participants were 64 students (8⁻12 years old). Cortical activation, executive control, and observed symptomatology by parents were assessed. Results indicated that ADHD-C and ADHD-HI demonstrated greater improvements than ADHD-I...
February 7, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30735655/reprogramming-of-meiotic-chromatin-architecture-during-spermatogenesis
#16
Yao Wang, Hanben Wang, Yu Zhang, Zhenhai Du, Wei Si, Suixing Fan, Dongdong Qin, Mei Wang, Yanchao Duan, Lufan Li, Yuying Jiao, Yuanyuan Li, Qiujun Wang, Qinghua Shi, Xin Wu, Wei Xie
Chromatin organization undergoes drastic reconfiguration during gametogenesis. However, the molecular reprogramming of three-dimensional chromatin structure in this process remains poorly understood for mammals, including primates. Here, we examined three-dimensional chromatin architecture during spermatogenesis in rhesus monkey using low-input Hi-C. Interestingly, we found that topologically associating domains (TADs) undergo dissolution and reestablishment in spermatogenesis. Strikingly, pachytene spermatocytes, where synapsis occurs, are strongly depleted for TADs despite their active transcription state but uniquely show highly refined local compartments that alternate between transcribing and non-transcribing regions (refined-A/B)...
February 7, 2019: Molecular Cell
https://read.qxmd.com/read/30735652/pach-ing-it-in-the-peculiar-organization-of-mammalian-pachytene-chromosomes
#17
Yoon Hee Jung, Victor G Corces
In this issue of Molecular Cell, Wang et al. (2019) use Hi-C to visualize at high resolution the complex reprogramming of chromatin architecture during spermatogenesis in rhesus monkeys and mice. They find that pachytene spermatocytes have a unique chromosome organization that may result from the presence of the synaptonemal complex and transcription-associated proteins.
February 7, 2019: Molecular Cell
https://read.qxmd.com/read/30735446/study-of-the-possible-relationships-between-tramway-front-end-geometry-and-pedestrian-injury-risk
#18
Marie-Christine Chevalier, Denis Brizard, Philippe Beillas
OBJECTIVES: The aim of this article is to report on the possible relationships between tramway front-end geometry and pedestrian injury risk over a wide range of possible tramway shapes. METHODS: To study the effect of tramway front-end shape on pedestrian injury metrics, accidents were simulated using a custom parameterized model of tramway front-end and pedestrian models available with the MADYMO multibody solver. The approach was automated, allowing the systematic exploration of tramway shapes in conjunction with 4 pedestrian sizes (e...
February 8, 2019: Traffic Injury Prevention
https://read.qxmd.com/read/30734001/whole-ventricular-irradiation-for-intracranial-germ-cell-tumors-dosimetric-comparison-of-pencil-beam-scanned-protons-intensity-modulated-radiotherapy-and-volumetric-modulated-arc-therapy
#19
Dora Correia, Dario Terribilini, Stefan Zepter, Alessia Pica, Nicola Bizzocchi, Werner Volken, Sonja Stieb, Frank Ahlhelm, Evelyn Herrmann, Michael K Fix, Peter Manser, Daniel M Aebersold, Damien C Weber
Background: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1...
February 2019: Clinical and Translational Radiation Oncology
https://read.qxmd.com/read/30732559/chromosome-rearrangements-shape-the-diversification-of-secondary-metabolism-in-the-cyclosporin-producing-fungus-tolypocladium-inflatum
#20
Rodrigo A Olarte, Jon Menke, Ying Zhang, Shawn Sullivan, Jason C Slot, Yinyin Huang, Jonathan P Badalamenti, Alisha C Quandt, Joseph W Spatafora, Kathryn E Bushley
BACKGROUND: Genes involved in production of secondary metabolites (SMs) in fungi are exceptionally diverse. Even strains of the same species may exhibit differences in metabolite production, a finding that has important implications for drug discovery. Unlike in other eukaryotes, genes producing SMs are often clustered and co-expressed in fungal genomes, but the genetic mechanisms involved in the creation and maintenance of these secondary metabolite biosynthetic gene clusters (SMBGCs) remains poorly understood...
February 7, 2019: BMC Genomics
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