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https://www.readbyqxmd.com/read/29163920/harnessing-fungal-nonribosomal-cyclodepsipeptide-synthetases-for-mechanistic-insights-and-tailored-engineering
#1
Charlotte Steiniger, Sylvester Hoffmann, Andi Mainz, Marcel Kaiser, Kerstin Voigt, Vera Meyer, Roderich D Süssmuth
Nonribosomal peptide synthetases represent potential platforms for the design and engineering of structurally complex peptides. While previous focus has been centred mainly on bacterial systems, fungal synthetases assembling drugs like the antifungal echinocandins, the antibacterial cephalosporins or the anthelmintic cyclodepsipeptide (CDP) PF1022 await in-depth exploitation. As various mechanistic features of fungal CDP biosynthesis are only partly understood, effective engineering of NRPSs has been severely hampered...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29163479/discriminating-between-interstitial-and-circulating-leukocytes-in-tissues-of-the-murine-oral-mucosa-avoiding-nasal-associated-lymphoid-tissue-contamination
#2
Peter D Bittner-Eddy, Lori A Fischer, Andy A Tu, Daniel A Allman, Massimo Costalonga
Periodontitis is a chronic inflammatory response to a microbial biofilm that destroys bone and soft tissues supporting the teeth. Murine models of periodontitis based on Porphyromonas gingivalis (Pg) colonization have shown that extravasation of leukocytes into oral tissue is critical to driving alveolar bone destruction. Identifying interstitial leukocytes is key to understanding the immunopathogenesis of periodontitis. Here, we describe a robust flow cytometry assay based on intravenous FITC-conjugated anti-mouse CD45 mAb that distinguishes interstitial leukocytes in the oral mucosa of mice from those circulating within the vasculature or in post-dissection contaminating blood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158971/the-ultimate-legs-of-chilopoda-myriapoda-a-review-on-their-morphological-disparity-and-functional-variability
#3
Matthes Kenning, Carsten H G Müller, Andy Sombke
The arthropodium is the key innovation of arthropods. Its various modifications are the outcome of multiple evolutionary transformations, and the foundation of nearly endless functional possibilities. In contrast to hexapods, crustaceans, and even chelicerates, the spectrum of evolutionary transformations of myriapod arthropodia is insufficiently documented and rarely scrutinized. Among Myriapoda, Chilopoda (centipedes) are characterized by their venomous forcipules-evolutionarily transformed walking legs of the first trunk segment...
2017: PeerJ
https://www.readbyqxmd.com/read/29158603/realization-of-ground-state-in-artificial-kagome-spin-ice-via-topological-defect-driven-magnetic-writing
#4
Jack C Gartside, Daan M Arroo, David M Burn, Victoria L Bemmer, Andy Moskalenko, Lesley F Cohen, Will R Branford
Arrays of non-interacting nanomagnets are widespread in data storage and processing. As current technologies approach fundamental limits on size and thermal stability, enhancing functionality through embracing the strong interactions present at high array densities becomes attractive. In this respect, artificial spin ices are geometrically frustrated magnetic metamaterials that offer vast untapped potential due to their unique microstate landscapes, with intriguing prospects in applications from reconfigurable logic to magnonic devices or hardware neural networks...
November 20, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/29158514/large-magneto-seebeck-effect-in-magnetic-tunnel-junctions-with-half-metallic-heusler-electrodes
#5
Alexander Boehnke, Ulrike Martens, Christian Sterwerf, Alessia Niesen, Torsten Huebner, Marvin von der Ehe, Markus Meinert, Timo Kuschel, Andy Thomas, Christian Heiliger, Markus Münzenberg, Günter Reiss
Spin caloritronics studies the interplay between charge-, heat- and spin-currents, which are initiated by temperature gradients in magnetic nanostructures. A plethora of new phenomena has been discovered that promises, e.g., to make wasted heat in electronic devices useable or to provide new read-out mechanisms for information. However, only few materials have been studied so far with Seebeck voltages of only some microvolt, which hampers applications. Here, we demonstrate that half-metallic Heusler compounds are hot candidates for enhancing spin-dependent thermoelectric effects...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#6
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29156079/the-gard-platform-for-potency-assessment-of-skin-sensitizing-chemicals
#7
Kathrin S Zeller, Andy Forreryd, Tim Lindberg, Robin Gradin, Aakash Chawade, Malin Lindstedt
Contact allergy induced by certain chemicals is a common health concern, and several alternative methods have been developed to fulfill the requirements of European legislation with regard to hazard assessment of potential skin sensitizers. However, validated methods, which provide information about the potency of skin sensitizers, are still lacking. The cell-based assay Genomic Allergen Rapid Detection (GARD), targeting key event 3, dendritic cell activation, of the skin sensitization AOP, uses gene expression profiling and a machine learning approach for the prediction of chemicals as sensitizers or non-sensitizers...
2017: ALTEX
https://www.readbyqxmd.com/read/29155019/the-risk-of-hepatocellular-carcinoma-in-cirrhotic-patients-with-hepatitis-c-and-sustained-viral-response-role-of-the-treatment-regimen
#8
Hamish Innes, Stephen T Barclay, Peter C Hayes, Andrew Fraser, John F Dillon, Adrian Stanley, Andy Bathgate, Scott A McDonald, David Goldberg, Heather Valerio, Ray Fox, Nick Kennedy, Pete Bramley, Sharon J Hutchinson
BACKGROUND: Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon(IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV Clinical Database. METHODS: We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997-2016 resulting in a SVR...
November 15, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29154418/measuring-non-polyaminated-lipocalin-2-for-cardiometabolic-risk-assessment
#9
Kangmin Yang, Han-Bing Deng, Andy W C Man, Erfei Song, Jialiang Zhang, Cuiting Luo, Bernard M Y Cheung, Kwok-Yung Yuen, Pia Søndergaard Jensen, Akhmadjon Irmukhamedov, Atlanta G I M Elie, Paul M Vanhoutte, Aimin Xu, Jo G R De Mey, Yu Wang
AIMS: Lipocalin-2 is a pro-inflammatory molecule characterized by a highly diversified pattern of expression and structure-functional relationships. In vivo, this molecule exists as multiple variants due to post-translational modifications and/or protein-protein interactions. Lipocalin-2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non-polyaminated lipocalin-2 (npLcn2) plays a causal role in the pathogenesis of obesity-associated medical complications...
November 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/29152863/using-an-acculturation-stress-resilience-framework-to-explore-latent-profiles-of-latina-o-language-brokers
#10
Jennifer A Kam, Katerina M Marcoulides, Andy J Merolla
With survey data from 243 Latina/o early adolescent language brokers, latent profile analyses were conducted to identify different types (i.e., profiles) of brokers. Profiles were based on how often Latina/o early adolescents brokered for family members, as well as their levels of family-based acculturation stress, negative brokering beliefs, parentification, and positive brokering beliefs. Three brokering profiles emerged: (1) infrequent-ambivalents, (2) occasional-moderates, and (3) parentified-endorsers...
December 2017: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/29150909/genetic-analysis-of-osteogenesis-imperfecta-in-the-palestinian-population-molecular-screening-of-49-affected-families
#11
Osama Essawi, Sofie Symoens, Maha Fannana, Mohammad Darwish, Mohammad Farraj, Andy Willaert, Tamer Essawi, Bert Callewaert, Anne De Paepe, Fransiska Malfait, Paul J Coucke
BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous hereditary connective tissue disorder clinically hallmarked by increased susceptibility to bone fractures. METHODS: We analyzed a cohort of 77 diagnosed OI patients from 49 unrelated Palestinian families. Next-generation sequencing technology was used to screen a panel of known OI genes. RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes...
November 18, 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29150610/implications-of-improved-representations-of-plant-respiration-in-a-changing-climate
#12
Chris Huntingford, Owen K Atkin, Alberto Martinez-de la Torre, Lina M Mercado, Mary A Heskel, Anna B Harper, Keith J Bloomfield, Odhran S O'Sullivan, Peter B Reich, Kirk R Wythers, Ethan E Butler, Ming Chen, Kevin L Griffin, Patrick Meir, Mark G Tjoelker, Matthew H Turnbull, Stephen Sitch, Andy Wiltshire, Yadvinder Malhi
Land-atmosphere exchanges influence atmospheric CO2. Emphasis has been on describing photosynthetic CO2 uptake, but less on respiration losses. New global datasets describe upper canopy dark respiration (R d) and temperature dependencies. This allows characterisation of baseline R d, instantaneous temperature responses and longer-term thermal acclimation effects. Here we show the global implications of these parameterisations with a global gridded land model. This model aggregates R d to whole-plant respiration R p, driven with meteorological forcings spanning uncertainty across climate change models...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150472/are-food-and-drink-retailers-within-nhs-venues-adhering-to-nice-quality-standard-94-guidance-on-childhood-obesity-a-cross-sectional-study-of-two-large-secondary-care-nhs-hospitals-in-england
#13
Alice James, Laura Birch, Peter Fletcher, Sally Pearson, Catherine Boyce, Andy R Ness, Julian P Hamilton-Shield, Fiona E Lithander
OBJECTIVE: To assess whether the food and drink retail outlets in two major National Health Service (NHS) district general hospitals in England adhere to quality statements 1-3 of the UK National Institute for Health and Care Excellence (NICE) quality standard 94. DESIGN: Cross-sectional, descriptive study to assess the food and drink options available in vending machines, restaurants, cafes and shops in two secondary care hospitals. MAIN OUTCOME MEASURES: Adherence to quality statement 1 whereby the food and drink items available in the vending machines were classified as either healthy or less healthy using the Nutrient Profiling Model (NPM)...
November 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29149348/mechanistic-insight-into-the-assembly-of-the-hera-nura-helicase-nuclease-dna-end-resection-complex
#14
Zainab Ahdash, Andy M Lau, Robert Thomas Byrne, Katja Lammens, Alexandra Stüetzer, Henning Urlaub, Paula J Booth, Eamonn Reading, Karl-Peter Hopfner, Argyris Politis
The HerA-NurA helicase-nuclease complex cooperates with Mre11 and Rad50 to coordinate the repair of double-stranded DNA breaks. Little is known, however, about the assembly mechanism and activation of the HerA-NurA. By combining hybrid mass spectrometry with cryo-EM, computational and biochemical data, we investigate the oligomeric formation of HerA and detail the mechanism of nucleotide binding to the HerA-NurA complex from thermophilic archaea. We reveal that ATP-free HerA and HerA-DNA complexes predominantly exist in solution as a heptamer and act as a DNA loading intermediate...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29148976/small-molecule-photoregulin3-prevents-retinal-degeneration-in-the-rho-p23h-mouse-model-of-retinitis-pigmentosa
#15
Paul A Nakamura, Andy A Shimchuk, Shibing Tang, Zhizhi Wang, Kole DeGolier, Sheng Ding, Thomas A Reh
Regulation of rod gene expression has emerged as a potential therapeutic strategy to treat retinal degenerative diseases like retinitis pigmentosa (RP). We previously reported on a small molecule modulator of the rod transcription factor Nr2e3, Photoregulin1 (PR1), that regulates the expression of photoreceptor-specific genes. Although PR1 slows the progression of retinal degeneration in models of RP in vitro, in vivo analyses were not possible with PR1. We now report a structurally unrelated compound, Photoregulin3 (PR3) that also inhibits rod photoreceptor gene expression, potentially though Nr2e3 modulation...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29146990/how-gluttonous-cell-aggregates-clear-substrates-coated-with-microparticles
#16
Grégory Beaune, Andy Y W Lam, Sylvie Dufour, Françoise M Winnik, Françoise Brochard-Wyart
We study the spreading of cell aggregates deposited on adhesive substrates decorated with microparticles (MPs). A cell monolayer expands around the aggregate. The cells on the periphery of the monolayer take up the MPs, clearing the substrate as they progress and forming an aureole of cells filled with MPs. We study the dynamics of spreading and determine the width of the aureole and the level of MP internalization in cells as a function of MP size, composition, and density. From the radius and width of the aureole, we quantify the volume fraction of MPs within the cell, which leads to an easy, fast, and inexpensive measurement of the cell - particle internalization...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146920/andy-s-algorithms-new-automated-digital-image-analysis-pipelines-for-fiji
#17
Andrew M K Law, Julia X M Yin, Lesley Castillo, Adelaide I J Young, Catherine Piggin, Samuel Rogers, Catherine Elizabeth Caldon, Andrew Burgess, Ewan K A Millar, Sandra A O'Toole, David Gallego-Ortega, Christopher J Ormandy, Samantha R Oakes
Quantification of cellular antigens and their interactions via antibody-based detection methods are widely used in scientific research. Accurate high-throughput quantitation of these assays using general image analysis software can be time consuming and challenging, particularly when attempted by users with limited image processing and analysis knowledge. To overcome this, we have designed Andy's Algorithms, a series of automated image analysis pipelines for FIJI, that permits rapid, accurate and reproducible batch-processing of 3,3'-diaminobenzidine (DAB) immunohistochemistry, proximity ligation assays (PLAs) and other common assays...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29145650/loss-of-p300-and-cbp-disrupts-histone-acetylation-at-the-mouse-sry-promoter-and-causes-xy-gonadal-sex-reversal
#18
Gwenn-Aël Carré, Pam Siggers, Marilena Xipolita, Paul Brindle, Beat Lutz, Sara Wells, Andy Greenfield
CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex determination, the process by which the embryonic gonad develops into a testis or an ovary. By targeting gene ablation to embryonic gonadal somatic cells using an inducible Cre line, we show that gonads lacking either gene exhibit major abnormalities of XY gonad development at 14...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29145055/urban-stormwater-characterisation-and-nitrogen-composition-from-lot-scale-catchments-new-management-implications
#19
REVIEW
Terry Lucke, Darren Drapper, Andy Hornbuckle
Stormwater runoff from urban areas has been shown to contain a variety of pollutants which are often linked to the specific land use of the catchment. This research program investigated the pollutant concentrations in stormwater runoff from several sites in South-east Queensland (SEQ), in Australia. The study sites are predominantly single development lots, under 7.5hectares (Ha) in area, with a single land-use classification that have been developed with stormwater treatment measures to manage pollutant loads as required by local regulations...
November 13, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29143023/self-assembled-2-catenane-in-trapezoidal-metallacycles-with-cp-ir-corners
#20
Naifang Liu, Sheng-Li Huang, Xiaogang Liu, He-Kuan Luo, T S Andy Hor
A series of trapezoidal metallacycles were synthesized by the selective combination of a rigid with a flexible arm. [2]Catenane 3 was obtained by self-assembly when the cavity size of the trapezoidal rings was optimised.
November 16, 2017: Chemical Communications: Chem Comm
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