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https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#1
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544968/clinical-usefulness-of-videocapillaroscopy-and-selected-endothelial-cell-activation-markers-in-people-with-type-1-diabetes-mellitus-complicated-by-microangiopathy
#2
Anna Kuryliszyn-Moskal, Wieslaw Zarzycki, Artur Dubicki, Diana Moskal, Bozena Kosztyła-Hojna, Anna Hryniewicz
PURPOSE: Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of our study was to compare microvascular changes examined by nailfold videocapillaroscopy (NVC) examination with serum concentrations of vascular endothelial growth factor (VEGF), soluble thrombomodulin (sTM) and endothelin-1 (ET-1) in people with Type 1 diabetes with and without microangiopathy. MATERIAL/METHODS: The study included 106 people with Type 1 diabetes and 40 healthy controls...
May 22, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28544604/thymic-peripheral-crosstalk-in-lymphodepletion-therapy
#3
EDITORIAL
M E Snyder, D L Farber
T cell depletion is widely used as induction therapy in solid organ transplants and particularly in kidney transplantation, to reduce the episodes of acute cellular rejection. The resultant reduction in T cell numbers is usually temporary, as T cells are actively replenished due to thymic output and/or lymphopenia-induced proliferation of remaining, depletion-resistant T cells. However, the extent of T cell replenishment and the persistence of lymphopenia varies between individuals, with potential impacts on protective or pathogenic immune responses...
May 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544598/from-extended-nano-fluidics-to-an-autonomous-solar-light-driven-micro-fuel-cell-device
#4
Yuriy Pihosh, Jin Uemura, Ivan Turkevych, Kazuma Mawatari, Yutaka Kazoe, Adelina Smirnova, Takehiko Kitamori
Autonomous micro/nano mechanical, chemical and biomedical sensors require persistent power sources scaled to their size. Realization of autonomous micro-power sources is a challenging task, as it requires combination of wireless energy supply, conversion, storage and delivery to the sensor. In this work, we realized solar light driven power source that consists of a micro fuel cell (μFC) and a photocatalytic micro fuel generator (μFG) integrated on a single microfluidic chip. The μFG produces hydrogen by photocatalytic water splitting under solar light...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28544016/recent-advances-of-crispr-cas9-genome-editing-technologies-for-biological-and-biomedical-investigations
#5
Vijai Singh, Nisarg Gohil, Robert Ramírez García, Darren Braddick, Christian Kuete Fofié
The Type II CRISPR-Cas9 system is a simple, efficient, and versatile tool for targeted genome editing in a wide range of organisms and cell types. It continues to gain more scientific interest and has established itself as an extremely powerful technology within our synthetic biology toolkit. It works upon a targeted site and generates a double strand breaks that become repaired by either the NHEJ or HDR pathway, modifying or permanently replacing the genomic target sequences of interest. These can include viral targets, single-mutation genetic diseases, and multiple-site corrections for wide scale disease states, offering the potential to manage and cure some of mankind's most persistent biomedical menaces...
May 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543707/viable-bacteria-persist-on-antibiotic-spacers-following-two-stage-revision-for-periprosthetic-joint-infection
#6
Dongzhu Ma, Robert M Q Shanks, Charles M Davis, David W Craft, Thomas K Wood, Brian R Hamlin, Kenneth L Urish
Treatment in periprosthetic joint infection (PJI) remains challenging. The failure rate of two-stage revision and irrigation and debridement with component retention in PJI suggests that biofilm cells have a high tolerance to antibiotic chemotherapy. Previous work has demonstrated that biofilm cells have high antibiotic tolerance in vitro, but there is little clinical evidence to support these observations. The aim of this study was to determine if retrieved antibiotic spacers from two-stage revision total knee arthroplasty for PJI have evidence of remaining viable bacteria...
May 19, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28543541/human-schwann-cells-exhibit-long-term-cell-survival-are-not-tumorigenic-and-promote-repair-when-transplanted-into-the-contused-spinal-cord
#7
Johana Bastidas, Gagani Athauda, Gabriela De La Cruz, Wai-Man Chan, Roozbeh Golshani, Yerko Berrocal, Martha Henao, Anil Lalwani, Chikato Mannoji, Mazen Assi, P Anthony Otero, Aisha Khan, Alexander E Marcillo, Michael Norenberg, Allan D Levi, Patrick M Wood, James D Guest, W Dalton Dietrich, Mary Bartlett Bunge, Damien D Pearse
The transplantation of rodent Schwann cells (SCs) provides anatomical and functional restitution in a variety of spinal cord injury (SCI) models, supporting the recent translation of SCs to phase 1 clinical trials for human SCI. Whereas human (Hu)SCs have been examined experimentally in a complete SCI transection paradigm, to date the reported behavior of SCs when transplanted after a clinically relevant contusive SCI has been restricted to the use of rodent SCs. Here, in a xenotransplant, contusive SCI paradigm, the survival, biodistribution, proliferation and tumorgenicity as well as host responses to HuSCs, cultured according to a protocol analogous to that developed for clinical application, were investigated...
May 22, 2017: Glia
https://www.readbyqxmd.com/read/28542913/reduction-of-escherichia-coli-o157-h7-in-biofilms-using-bacteriophage-bpeco-19
#8
Mohammad Sadekuzzaman, Sungdae Yang, Md Furkanur Rahaman Mizan, Sang-Do Ha
Biofilm formation is a growing concern in the food industry. Escherichia coli O157:H7 is one of the most important foodborne pathogens that can persists in food and food-related environments and subsequently produce biofilms. The efficacy of bacteriophage BPECO 19 was evaluated against three E. coli O157:H7 strains in biofilms. Biofilms of the three E. coli O157:H7 strains were grown on abiotic (stainless steel, rubber, and minimum biofilm eradication concentration [MBEC(TM) ] device) and biotic (lettuce) surfaces at different temperatures...
May 19, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28542909/the-role-of-metabolic-reprogramming-in-%C3%AE-herpesvirus-associated-oncogenesis
#9
REVIEW
Angela Kwok-Fung Lo, Christopher W Dawson, Lawrence S Young, Kwok-Wai Lo
The γ-herpesviruses, EBV and KSHV, are closely associated with a number of human cancers. While the signal transduction pathways exploited by γ-herpesviruses to promote cell growth, survival and transformation have been reported, recent studies have uncovered the impact of γ-herpesvirus infection on host cell metabolism. Here, we review the mechanisms utilised by γ-herpesviruses to induce metabolic reprogramming in host cells, focusing on their ability to modulate the activity of metabolic regulators and manipulate metabolic pathways...
May 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#10
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#11
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542477/mycobacterium-tuberculosis-arrests-host-cycle-at-the-g1-s-transition-to-establish-long-term-infection
#12
Bridgette M Cumming, Md Aejazur Rahman, Dirk A Lamprecht, Kyle H Rohde, Vikram Saini, John H Adamson, David G Russell, Adrie J C Steyn
Signals modulating the production of Mycobacterium tuberculosis (Mtb) virulence factors essential for establishing long-term persistent infection are unknown. The WhiB3 redox regulator is known to regulate the production of Mtb virulence factors, however the mechanisms of this modulation are unknown. To advance our understanding of the mechanisms involved in WhiB3 regulation, we performed Mtb in vitro, intraphagosomal and infected host expression analyses. Our Mtb expression analyses in conjunction with extracellular flux analyses demonstrated that WhiB3 maintains bioenergetic homeostasis in response to available carbon sources found in vivo to establish Mtb infection...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542235/environmental-persistence-of-porcine-coronaviruses-in-feed-and-feed-ingredients
#13
Michaela P Trudeau, Harsha Verma, Fernando Sampedro, Pedro E Urriola, Gerald C Shurson, Sagar M Goyal
Porcine Epidemic Diarrhea Virus (PEDV), Porcine Delta Corona Virus (PDCoV), and Transmissible Gastroenteritis Virus (TGEV) are major threats to swine health and contaminated feed plays a role in virus transmission. The objective of our study was to characterize inactivation of PEDV, PDCoV, and TGEV in various feed ingredient matrices. Samples of complete feed, spray dried porcine plasma, meat meal, meat and bone meal, blood meal, corn, soybean meal, and corn dried distillers grains with solubles were weighed (5 g/sample) into scintillation vials and inoculated with 1 mL of PEDV, PDCoV, or TGEV...
2017: PloS One
https://www.readbyqxmd.com/read/28541545/kr%C3%A3-ppel-like-factors-compete-for-promoters-and-enhancers-to-fine-tune-transcription
#14
Melissa D Ilsley, Kevin R Gillinder, Graham W Magor, Stephen Huang, Timothy L Bailey, Merlin Crossley, Andrew C Perkins
Krüppel-like factors (KLFs) are a family of 17 transcription factors characterized by a conserved DNA-binding domain of three zinc fingers and a variable N-terminal domain responsible for recruiting cofactors. KLFs have diverse functions in stem cell biology, embryo patterning, and tissue homoeostasis. KLF1 and related family members function as transcriptional activators via recruitment of co-activators such as EP300, whereas KLF3 and related members act as transcriptional repressors via recruitment of C-terminal Binding Proteins...
May 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28541483/malaria-host-candidate-genes-validated-by-association-with-current-recent-and-historic-measures-of-transmission-intensity
#15
Nuno Sepúlveda, Alphaxard Manjurano, Susana G Campino, Martha Lemnge, John Lusingu, Raimos Olomi, Kirk A Rockett, Christina Hubbart, Anna Jeffreys, Kate Rowlands, Taane G Clark, Eleanor M Riley, Chris J Drakeley
Background: Human malaria susceptibility is determined by multiple genetic factors. It is however unclear which genetic variants remain important over time. Methods: Genetic associations of 175 high quality polymorphisms within several malaria candidate genes were examined in a sample of 8,096 individuals from northeast Tanzania using altitude, seroconversion rates and parasite rates as proxies of historical, recent and current malaria transmission intensity. A principal component (PC) analysis was used to derive two alternative measures of overall malaria propensity of a location across different time scales...
May 25, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28541273/nonlinear-mechanics-of-hybrid-polymer-networks-that-mimic-the-complex-mechanical-environment-of-cells
#16
Maarten Jaspers, Sarah L Vaessen, Pim van Schayik, Dion Voerman, Alan E Rowan, Paul H J Kouwer
The mechanical properties of cells and the extracellular environment they reside in are governed by a complex interplay of biopolymers. These biopolymers, which possess a wide range of stiffnesses, self-assemble into fibrous composite networks such as the cytoskeleton and extracellular matrix. They interact with each other both physically and chemically to create a highly responsive and adaptive mechanical environment that stiffens when stressed or strained. Here we show that hybrid networks of a synthetic mimic of biological networks and either stiff, flexible and semi-flexible components, even very low concentrations of these added components, strongly affect the network stiffness and/or its strain-responsive character...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540585/antibiofilm-activity-and-mode-of-action-of-dmso-alone-and-its-combination-with-afatinib-against-gram-negative-pathogens
#17
Mohd Fakharul Zaman Raja Yahya, Zazali Alias, Saiful Anuar Karsani
Biofilms are complex microbial communities that tend to attach to either biotic or abiotic surface. Enclosed in a self-produced extracellular polymeric substance (EPS) matrix, the biofilms often cause persistent infections. The objective of this study was to investigate the antibiofilm activity of dimethyl sulfoxide (DMSO) and afatinib against Gram-negative pathogens. Test microorganisms used in this study were Escherichia coli ATCC 1299, Pseudomonas aeruginosa ATCC 10145, and Salmonella typhimurium ATCC 14028...
May 24, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28540425/contribution-of-plasmid-encoded-peptidase-s8-prtp-to-adhesion-and-transit-in-the-gut-of-lactococcus-lactis-ibb477-strain
#18
Joanna Maria Radziwill-Bienkowska, Véronique Robert, Karolina Drabot, Florian Chain, Claire Cherbuy, Philippe Langella, Muriel Thomas, Jacek Karol Bardowski, Muriel Mercier-Bonin, Magdalena Kowalczyk
The ability of Lactococcus lactis to adhere to the intestinal mucosa can potentially prolong the contact with the host, and therefore favour its persistence in the gut. In the present study, the contribution of plasmid-encoded factors to the adhesive and transit properties of the L. lactis subsp. cremoris IBB477 strain was investigated. Plasmid-cured derivatives as well as deletion mutants were obtained and analysed. Adhesion tests were performed using non-coated polystyrene plates, plates coated with mucin or fibronectin and mucus-secreting HT29-MTX intestinal epithelial cells...
May 24, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28539455/functional-consequences-of-rna-5-terminal-deletions-on-coxsackievirus-b3-rna-replication-and-ribonucleoprotein-complex-formation
#19
Nicolas Lévêque, Magali Garcia, Alexis Bouin, Joseph H C Nguyen, Genevieve P Tran, Laurent Andreoletti, Bert L Semler
Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5' terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538401/atrial-fibrillation-was-changed-into-sinus-bradycardia-in-a-ros1-positive-advanced-lung-adenocarcinoma-patient-who-achieved-durable-response-to-crizotinib-a-case-report-and-literature-review
#20
Lan Liu, Jing Wu, Wei Zhao, Mei-Juan Huang
RATIONAL: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia...
May 2017: Medicine (Baltimore)
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