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https://www.readbyqxmd.com/read/28437843/a-bayesian-belief-network-model-assessing-the-risk-to-wastewater-workers-of-contracting-ebola-virus-disease-during-an-outbreak
#1
Joseph W Zabinski, Kelsey J Pieper, Jacqueline MacDonald Gibson
During an outbreak of Ebola virus disease (EVD), hospitals' connections to municipal wastewater systems may provide a path for patient waste bearing infectious viral particles to pass from the hospital into the wastewater treatment system, potentially posing risks to sewer and wastewater workers. To quantify these risks, we developed a Bayesian belief network model incorporating data on virus behavior and survival along with structural characteristics of hospitals and wastewater treatment systems. We applied the model to assess risks under several different scenarios of workers' exposure to wastewater for a wastewater system typical of a mid-sized U...
April 24, 2017: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/28437792/phase-plate-cryo-em-structure-of-a-class-b-gpcr-g-protein-complex
#2
Yi-Lynn Liang, Maryam Khoshouei, Mazdak Radjainia, Yan Zhang, Alisa Glukhova, Jeffrey Tarrasch, David M Thal, Sebastian G B Furness, George Christopoulos, Thomas Coudrat, Radostin Danev, Wolfgang Baumeister, Laurence J Miller, Arthur Christopoulos, Brian K Kobilka, Denise Wootten, Georgios Skiniotis, Patrick M Sexton
Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαsβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7...
April 24, 2017: Nature
https://www.readbyqxmd.com/read/28437083/dual-plug-and-display-synthetic-assembly-using-orthogonal-reactive-proteins-for-twin-antigen-immunization
#3
Karl Brune, Can Buldun, Yuanyuan Li, Iona Taylor, Florian Brod, Sumi Biswas, Mark Howarth
Engineering modular platforms to control biomolecular architecture can advance both the understanding and manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle, to induce broader immunity protective across strains or even against distinct diseases. Here we design a dually-addressable synthetic nanoparticle, by engineering the multimerizing coiled-coil IMX313 and two orthogonally-reactive split proteins...
April 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28436437/allele-selective-suppression-of-mutant-huntingtin-in-primary-human-blood-cells
#4
James R C Miller, Edith L Pfister, Wanzhao Liu, Ralph Andre, Ulrike Träger, Lori A Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary Ostroff, Neil Aronin, Sarah J Tabrizi
Post-transcriptional gene silencing is a promising therapy for the monogenic, autosomal dominant, Huntington's disease (HD). However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436274/depletion-of-hdl3-high-density-lipoprotein-and-altered-functionality-of-hdl2-in-blood-from-sickle-cell-patients
#5
Eric Soupene, Sandra K Larkin, Frans A Kuypers
In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL2 particle relative to the smaller higher density pre-β HDL (HDL3) particle was shifted toward HDL2. This lipoprotein imbalance is exacerbated during acute vaso-occlusive episodes (VOE) as the relative levels of HDL3 decrease...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28434655/apolipoprotein-e-receptors-and-modulation-of-alzheimer-s-disease
#6
REVIEW
Na Zhao, Chia-Chen Liu, Wenhui Qiao, Guojun Bu
Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and injury repair in the brain. Considering prevalence and relative risk magnitude, the ε4 allele of the APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways, including but not limited to the metabolism, aggregation, and toxicity of amyloid-β peptide, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, vascular integrity, and neuroinflammation...
March 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28432676/bifidobacterium-adolescentis-dsm-20083-and-lactobacillus-casei-lafti-l26-dsl-probiotics-able-to-block-the-in-vitro-adherence-of-rotavirus-in-ma104-cells
#7
Karem Prunella Fernandez-Duarte, Nury Nathalia Olaya-Galán, Sandra Patricia Salas-Cárdenas, Jazmin Lopez-Rozo, Maria Fernanda Gutierrez-Fernandez
Rotavirus is the leading worldwide cause of gastroenteritis in children under five years of age. Even though there are some available vaccines to prevent the disease, there are limited strategies for challenging diarrhea induced by rotavirus infection. For this reason, researchers are constantly searching for other approaches to control diarrhea by means of probiotics. In order to demonstrate the ability of some probiotic bacteria to interfere with the in vitro rotavirus infection in MA104 cells, strains of Lactobacillus sp...
April 21, 2017: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/28431813/evaluation-of-immune-responses-of-stabilised-sat2-antigens-of-foot-and-mouth-disease-in-cattle
#8
Katherine A Scott, N M Rathogwa, A V Capozzo, Francois F Maree
Foot-and-mouth disease (FMD) vaccines with improved stability and less reliant on a cold-chain are needed to improve the longevity of immune responses elicited in animals. This is especially so for serotypes O and SAT2 which are unstable in mildly acidic pH conditions or at elevated temperatures leading to dissociation of the capsid (146S particle) and loss of immunogenicity. Previously, stabilised SAT2 viruses were generated by reverse genetic approaches and assessed in vitro and in vivo with a guinea pig trial...
April 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28431523/the-utility-of-electron-microscopy-in-detecting-asbestos-fibers-and-particles-in-balf-in-diffuse-lung-diseases
#9
Takashi Kido, Yasuo Morimoto, Kazuhiro Yatera, Hiroshi Ishimoto, Takaaki Ogoshi, Keishi Oda, Kei Yamasaki, Toshinori Kawanami, Shohei Shimajiri, Hiroshi Mukae
BACKGROUND: In patients with diffuse lung diseases, differentiating occupational lung diseases from other diseases is clinically important. However, the value of assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated the utility of EM in detecting asbestos fibers and particles in patients with diffuse lung diseases. METHODS: The BALF specimens of 107 patients with diffuse lung diseases were evaluated...
April 21, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28429674/targeting-the-role-of-lipoprotein-a-in-stroke
#10
Mahdi Garelnabi, Zahra Mazhar, Andrew Hughes
Stroke is the third leading cause of death in the United States, behind only heart disease and cancer, with over 140,000 associated deaths per year. Considerable research is ongoing to examine the role of modifiable risk factors which may cause or contribute to a stroke occurring. Although age and family history are generally considered to be major risk factors, there are several modifiable and non-modifiable risk factors that are linked to the pathogenesis of a stroke. Lipoprotein (a), or Lp(a), is a type of low-density lipoprotein containing an integral apoB100 component with an attached ApoA1 isoform via a disulfide linkage...
April 21, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28429294/ocular-cubosome-drug-delivery-system-for-timolol-maleate-preparation-characterization-cytotoxicity-ex-vivo-and-in-vivo-evaluation
#11
Jiayuan Huang, Tingting Peng, Yanrong Li, Zhengwen Zhan, Youmei Zeng, Ying Huang, Xin Pan, Chuan-Yu Wu, Chuanbin Wu
Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization...
April 20, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28428482/triglyceride-rich-lipoprotein-lpl-vldl-receptor-and-lp-a-vldl-receptor-pathways-for-macrophage-foam-cell-formation
#12
Sadao Takahashi
Very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. It binds triglyceride rich lipoprotein (TGRL) but not LDL, because it recognizes apolipoprotein (apo)E only but not apoB. The VLDL receptor functions as a peripheral lipoprotein receptor in concert with lipoprotein lipase (LPL) in heart, muscle, adipose tissue and macrophages. In contrast to the LDL receptor, VLDL receptor binds apo E2/2 VLDL and apoE3/3 VLDL particles, and its expression is not down-regulated by intracellular lipoproteins...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#13
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mattew, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jun Song, Rose Ackermann, Yui Koike, Anna Schwendeman, Liangxue Lai, Subramaniam Pennathur, Minerva Garcia-Barrio, Jianglin Fan, Y Eugene Chen
OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427549/lung-diseases-associated-with-hydrocarbon-exposure
#14
REVIEW
Stephen J Connellan
The human race has been exposed to the potential toxicity of hydrocarbons, whether by the inhaled or ingested route, for thousands of years and the consequent inflammatory reaction in the lungs depends on the degree of exposure, volatility and viscosity of the particular hydrocarbon in question. Heating, lighting, transportation, industry and nature all provide the potential for both inhalation and/or ingestion of hydrocarbons. Some forms, such as those related to petroleum products, e.g. diesel exhaust particles (DEP) and polycyclic aromatic hydrocarbons (PAH) have been shown to cause both malignant and non-malignant respiratory diseases...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28427521/management-of-metastatic-castration-resistant-prostate-cancer-a-focus-on-radium-223-opinions-and-suggestions-from-an-expert-multidisciplinary-panel
#15
REVIEW
Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427491/identification-of-a-newly-isolated-getah-virus-in-the-china-laos-border-china
#16
Yuan Yuan Li, Shi Hong Fu, Xiao Fang Guo, Wen Wen Lei, Xiao Long Li, Jing Dong Song, Lei Cao, Xiao Yan Gao, Zhi Lyu, Ying He, Huan Yu Wang, Xiao Jie Ren, Hong Ning Zhou, Gui Qin Wang, Guo Dong Liang
In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus particles were spherical, 70 nm in diameter, and enveloped; they also featured surface fibers. Molecular genetic analysis revealed that YN12031 was closely related to alpha viruses such as Chikungunya virus and Sindbis virus, and located in the same clade as MM2021, the prototype of Getahvirus (GETV) isolated in Malaysia in 1955...
March 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28426042/antibodies-to-h2a-and-h2b-histones-from-the-sera-of-hiv-infected-patients-catalyze-site-specific-degradation-of-these-histones
#17
Svetlana V Baranova, Pavel S Dmitrienok, Nikita V Ivanisenko, Valentina N Buneva, Georgy A Nevinsky
Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Electrophoretically homogeneous IgGs containing no canonical enzymes were isolated from the sera of HIV-infected patients by chromatography on several affinity sorbents including anti-histone Sepharose...
April 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28424857/extraction-of-cell-free-dna-from-urine-using-polylysine-coated-silica-particles
#18
Sho Takano, Qingjiang Hu, Takaki Amamoto, Paulo Refinetti, Koshi Mimori, Takashi Funatsu, Masaru Kato
DNA analysis is used for a variety of purposes, including disease diagnosis and DNA profiling; this involves extracting DNA from living organisms. In this study, we prepared polycationic silica particles to extract DNA that has the negatively charged phosphate backbone from solution. The coated particles were prepared by mixing conventional silica gel particles and poly-Lys; these particles could efficiently extract 1.3 μg of cell-free DNA from 50 mL of (male) urine. It is expected that these easily prepared particles (just a mixture of two commercially available chemicals) can be used as a noninvasive diagnostic tool for genetic disorders such as cancer, diabetes, and hypertension...
April 19, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28423336/lung-homeostasis-influence-of-age-microbes-and-the-immune-system
#19
REVIEW
Clare M Lloyd, Benjamin J Marsland
Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28423226/rvx-208-a-novel-bet-protein-inhibitor-role-as-an-inducer-of-apo-a-i-hdl-and-beyond
#20
Gopal C Ghosh, Rajarshi Bhadra, Raktim K Ghosh, Kinjal Banerjee, Anjan Gupta
Low density cholesterol (LDL) has been the prime target of currently available lipid-lowering therapies although current research is expanding the focus beyond LDL lowering and has included high density cholesterol (HDL) also as the target. Bromo and extra-terminal (BET) proteins are implicated in the regulation of transcription of several regulatory genes and regulation of pro-inflammatory pathways. As atherosclerosis is an inflammatory pathway and studies showed that BET inhibition has a role in inhibiting inflammation, the concept of BET inhibition came in the field of atherosclerosis...
April 19, 2017: Cardiovascular Therapeutics
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