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https://www.readbyqxmd.com/read/29775653/atomic-structure-of-a-rationally-engineered-gene-delivery-vector-aav2-5
#1
Matthew Burg, Claire Rosebrough, Lauren M Drouin, Antonette Bennett, Mario Mietzsch, Paul Chipman, Robert McKenna, Duncan Sousa, Mark Potter, Barry Byrne, R Jude Samulski, Mavis Agbandje-McKenna
AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Å using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2...
May 15, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29775511/optimized-fibril-network-morphology-by-precise-side-chain-engineering-to-achieve-high-performance-bulk-heterojunction-organic-solar-cells
#2
Tao Liu, Lijun Huo, Sreelakshmi Chandrabose, Kai Chen, Guangchao Han, Feng Qi, Xiangyi Meng, Dongjun Xie, Wei Ma, Yuanping Yi, Justin M Hodgkiss, Feng Liu, Jing Wang, Chuluo Yang, Yanming Sun
A polymer fibril assembly can dictate the morphology framework, in forming a network structure, which is highly advantageous in bulk heterojunction (BHJ) organic solar cells (OSCs). A fundamental understanding of how to manipulate such a fibril assembly and its influence on the BHJ morphology and device performance is crucially important. Here, a series of donor-acceptor polymers, PBT1-O, PBT1-S, and PBT1-C, is used to systematically investigate the relationship between molecular structure, morphology, and photovoltaic performance...
May 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29775130/taxonomy-of-clinical-encounters-during-the-first-90-days-post-delivery-of-an-initial-lower-limb-prosthesis
#3
Daniel Joseph Lee, Michael Wininger, David Mahler, Mark Parisi
BACKGROUND: The incidence and etiology of prosthetic services utilization is poorly understood during the first 90 days post-delivery of the initial lower limb prosthesis. This period is of critical importance, as prevailing policy dictates limits on the reimbursement for certain services provided during this time period. The first step in understanding the financial ramifications of such policy is to examine the taxonomy behind clinical encounters during this tenuous time period. OBJECTIVES: Quantify and categorize clinical encounters by incidence and etiology...
May 1, 2018: Prosthetics and Orthotics International
https://www.readbyqxmd.com/read/29774426/plant-physical-and-chemical-defence-variation-along-elevation-gradients-a-functional-trait-based-approach
#4
Alan Kergunteuil, Patrice Descombes, Gaetan Glauser, Loïc Pellissier, Sergio Rasmann
Predicting variation in plant functional traits related to anti-herbivore defences remains a major challenge in ecological research, considering that multiple traits have evolved in response to both abiotic and biotic conditions. Therefore, understanding variation in plant anti-herbivore defence traits requires studying their expression along steep environmental gradients, such as along elevation, where multiple biotic and abiotic factors co-vary. We expand on plant defence theory and propose a novel conceptual framework to address the sources of variations of plant resistance traits at the community level...
May 17, 2018: Oecologia
https://www.readbyqxmd.com/read/29773667/notch-ligand-dll1-mediates-cross-talk-between-mammary-stem-cells-and-the-macrophageal-niche
#5
Rumela Chakrabarti, Toni Celià-Terrassa, Sushil Kumar, Xiang Hang, Yong Wei, Abrar Choudhury, Julie Hwang, Jia Peng, Briana Nixon, John J Grady, Christina DeCoste, Jie Gao, Johan H van Es, Ming O Li, Iannis Aifantis, Hans Clevers, Yibin Kang
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, we show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feed back loop that promotes the function of Dll1+ MaSCs...
May 17, 2018: Science
https://www.readbyqxmd.com/read/29773557/a-length-dependent-evolutionarily-conserved-pathway-controls-nuclear-export-of-circular-rnas
#6
Chuan Huang, Dongming Liang, Deirdre C Tatomer, Jeremy E Wilusz
Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the Drosophila DExH/D-box helicase Hel25E results in nuclear accumulation of long (>800-nucleotide), but not short, circRNAs. The human homologs of Hel25E similarly regulate circRNA localization, as depletion of UAP56 (DDX39B) or URH49 (DDX39A) causes long and short circRNAs, respectively, to become enriched in the nucleus...
May 17, 2018: Genes & Development
https://www.readbyqxmd.com/read/29771336/fto-is-a-transcriptional-repressor-to-auto-regulate-its-own-gene-and-potentially-associated-with-homeostasis-of-body-weight
#7
Shu-Jing Liu, Hui-Ling Tang, Qian He, Ping Lu, Tao Fu, Xu-Ling Xu, Tao Su, Mei-Mei Gao, Shumin Duan, Yan Luo, Yue-Sheng Long
Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29770942/facile-preparation-of-nitrogen-and-sulfur-co-doped-graphene-based-aerogel-for-simultaneous-removal-of-cd-2-and-organic-dyes
#8
Qiaoping Kong, Chaohai Wei, Sergei Preis, Yun Hu, Feng Wang
The need in simultaneous removal of heavy metals and organic compounds dictates the development of synthetic adsorbents with tailor-made properties. A nitrogen (N) and sulfur (S) co-doped graphene-based aerogel (GBA) modified with 2,5-dithiobisurea was synthesized hydrothermally for simultaneous adsorption of Cd2+ and organic dyes-safranin-O (SO), crystal violet (CV), and methylene blue (MB). 2,5-Dithiobisurea was used as nitrogen and sulfur sources to introduce N and S-containing functional group onto graphene oxide...
May 17, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29770813/nanomaterial-based-devices-for-point-of-care-diagnostic-applications
#9
Daniel Quesada-González, Arben Merkoçi
In this review, we have discussed the capabilities of nanomaterials for point-of-care (PoC) diagnostics and explained how these materials can help to strengthen, miniaturize and improve the quality of diagnostic devices. Since the optical, electrochemical and other physical properties of nanomaterials are dictated by their composition, size and shape, these factors are critical in the design and function of nanomaterial-based PoC diagnostics.
May 17, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29769729/approaching-the-schottky-mott-limit-in-van-der-waals-metal-semiconductor-junctions
#10
Yuan Liu, Jian Guo, Enbo Zhu, Lei Liao, Sung-Joon Lee, Mengning Ding, Imran Shakir, Vincent Gambin, Yu Huang, Xiangfeng Duan
The junctions formed at the contact between metallic electrodes and semiconductor materials are crucial components of electronic and optoelectronic devices 1 . Metal-semiconductor junctions are characterized by an energy barrier known as the Schottky barrier, whose height can, in the ideal case, be predicted by the Schottky-Mott rule2-4 on the basis of the relative alignment of energy levels. Such ideal physics has rarely been experimentally realized, however, because of the inevitable chemical disorder and Fermi-level pinning at typical metal-semiconductor interfaces2,5-12 ...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769712/author-correction-szt2-dictates-gator-control-of-mtorc1-signalling
#11
Min Peng, Na Yin, Ming O Li
In the originally published version of this Letter, there was an error in Extended Data Fig. 7e and the corresponding uncropped blots in the Supplementary Information. The actin bands in the last blot of Extended Data Fig. 7e were duplicates  of the corresponding actin bands in the last blot of Extended Data Fig. 7 f. (In the uncropped blot for Extended Data Fig. 7e, the actin bands were mislabelled as 'WDR59' and this led to the error.) Extended Data Fig. 7 and the Supplementary Information of the original Letter have been corrected online...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769543/the-cytokine-secretion-profile-of-mesenchymal-stromal-cells-is-determined-by-surface-structure-of-the-microenvironment
#12
Daniëlle G Leuning, Nick R M Beijer, Nadia A du Fossé, Steven Vermeulen, Ellen Lievers, Cees van Kooten, Ton J Rabelink, Jan de Boer
Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769314/ablation-of-sirtuin5-in-the-postnatal-mouse-heart-results-in-protein-succinylation-and-normal-survival-in-response-to-chronic-pressure-overload
#13
Kathleen A Hershberger, Dennis M Abraham, Juan Liu, Jason W Locasale, Paul A Grimsrud, Matthew D Hirschey
Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function and metabolism under stress. Previously, we described a phenotype of increased mortality in whole-body SIRT5KO mice exposed to chronic pressure overload compared to their littermate WT controls. To determine if the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5, we developed a tamoxifen-inducible, heart-specific SIRT5KO mouse model...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768590/-construction-and-deconstruction-of-masculine-identities-among-metalworkers-with-rsi-wrmd
#14
Jorge Henrique Santos Saldanha, Mônica Angelim Gomes de Lima, Robson da Fonseca Neves, Jorge Alberto Bernstein Iriart
This study aimed to reveal how metalworkers experience prolonged incapacity for work due to repetitive strain injury/work-related musculoskeletal disorder (RSI/WRMD) and the impact of chronic illness on the construction/deconstruction of masculinity. A qualitative study was performed, based on narrative interviews with male metalworkers in an automotive factory in the State of Bahia, Brazil. The results showed how the conflict in the experience of illness, the maintenance of male identity, and expectations of meeting the rules dictated by hegemonic masculinity are experienced and signified in daily life...
May 10, 2018: Cadernos de Saúde Pública
https://www.readbyqxmd.com/read/29768242/antibacterial-anticancer-and-antioxidant-potential-of-silver-nanoparticles-engineered-using-trigonella-foenum-graecum-seed-extract
#15
Shivangi Goyal, Nidhi Gupta, Ajeet Kumar, Sreemoyee Chatterjee, Surendra Nimesh
In this study, the authors report a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using Trigonella foenum-graecum (TFG) seed extract. They explored several parameters dictating the biosynthesis of TFG-AgNPs such as reaction time, temperature, concentration of AgNO3 , and TFG extract amount. Physicochemical characterisation of TFG-AgNPs was done on dynamic light scattering (DLS), field emission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29764956/spotlight-on-the-transglutaminase-2-gene-a-focus-on-genomic-and-transcriptional-aspects
#16
REVIEW
Nicoletta Bianchi, Simone Beninati, Carlo M Bergamini
The type 2 isoenzyme is the most widely expressed transglutaminase in mammals displaying several intra- and extracellular activities depending on its location (protein modification, modulation of gene expression, membrane signalling and stabilization of cellular interactions with the extracellular matrix) in relation to cell death, survival and differentiation. In contrast with the appreciable knowledge about the regulation of the enzymatic activities, much less is known concerning its inducible expression, which is altered in inflammatory and neoplastic diseases...
May 15, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#17
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29760826/best-prophylactic-strategy-in-groups-at-risk-of-intraoperative-floppy-iris-syndrome-development-comparison-between-atropine-instillation-and-adrenaline-intracameral-injection
#18
Raffaele Nuzzi, Paolo Arnoffi, Federico Tridico
Background: Intraoperative Floppy Iris Syndrome (IFIS) is an important cause of surgical complications and iris defects in patients undergoing phacoemulsification that were treated with selective subtype α1A receptor antagonists for a long period of time. To date, no definitive preventive strategy has emerged, yet. The need of prophylaxis is dictated by the high prevalence of males affected by benign prostatic hyperplasia undergoing cataract surgery. Objective: To identify the best prophylactic strategy in groups at risk of IFIS development by comparing two mydriatic treatments in course of phacoemulsification surgery...
2018: Open Ophthalmology Journal
https://www.readbyqxmd.com/read/29760381/the-extent-of-liver-injury-determines-hepatocyte-fate-toward-senescence-or-cancer
#19
Chao Wang, Wen-Jian Chen, Ying-Fu Wu, Pu You, Shang-Yong Zheng, Chang-Cheng Liu, Dao Xiang, Min-Jun Wang, Yong-Chao Cai, Qing-Hui Zhao, Uyunbilig Borjigin, Wei Liu, Wu-Jun Xiong, Kirk J Wangensteen, Xin Wang, Zhong-Min Liu, Zhi-Ying He
It is well known that induction of hepatocyte senescence could inhibit the development of hepatocellular carcinoma (HCC). Until now, it is still unclear how the degree of liver injury dictates hepatocyte senescence and carcinogenesis. In this study, we investigated whether the severity of injury determines cell fate decisions between hepatocyte senescence and carcinogenesis. After testing of different degrees of liver injury, we found that hepatocyte senescence is strongly induced in the setting of severe acute liver injury...
May 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29760253/deprescribing-benzodiazepine-receptor-agonists-evidence-based-clinical-practice-guideline
#20
Kevin Pottie, Wade Thompson, Simon Davies, Jean Grenier, Cheryl A Sadowski, Vivian Welch, Anne Holbrook, Cynthia Boyd, Robert Swenson, Andy Ma, Barbara Farrell
OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest...
May 2018: Canadian Family Physician Médecin de Famille Canadien
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