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https://www.readbyqxmd.com/read/29054116/t-cell-epitope-content-comparison-epicc-of-swine-h1-influenza-a-virus-hemagglutinin
#1
Andres H Gutiérrez, Vicki Rapp-Gabrielson, Frances E Terry, Crystal Loving, Leonard Moise, William D Martin, Anne S De Groot
BACKGROUND: Predicting vaccine efficacy against emerging pathogen strains is a significant problem in human and animal vaccine design. T cell epitope cross-conservation may play an important role in cross-strain vaccine efficacy. While influenza A virus (IAV) hemagglutination inhibition (HI) antibody titers are widely used to predict protective efficacy of one IAV vaccine against new strains, no similar correlate of protection has been identified for T cell epitopes. OBJECTIVE: We developed a computational method (EpiCC) that facilitates pairwise comparison of protein sequences based on an immunological property - T cell epitope content - rather than sequence identity, and evaluated its ability to classify swine IAV strain relatedness to estimate cross-protective potential of a vaccine strain for circulating viruses...
October 20, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/29054092/protein-mimicking-nanoparticles-for-the-reproduction-of-transient-protein-receptor-interactions
#2
Jonghwan Lee
One of the major concerns in target identification has been the need for new methods to detect target molecules in the native cellular environment. In conventional target identification, affinity-based pull down has been conducted using cell lysates. However, interactions in cell lysate do not reflect real endogenous interactions in living cells, and can produce false-positive or false-negative results. This study aimed to develop a new method of target protein identification in living cells. Targeting probes were conjugated onto magnetic nanoparticles (MNPs)...
October 7, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29054075/evaluation-of-immunological-markers-of-ovine-vaginal-irritation-implications-for-preclinical-assessment-of-non-vaccine-hiv-preventive-agents
#3
Gregg N Milligan, Gracie Vargas, Kathleen L Vincent, Yong Zhu, Nigel Bourne, Massoud Motamedi
The presence of genital inflammatory responses and a compromised vaginal epithelial barrier have been linked to an increased risk of HIV acquisition. It is important to assure that application of candidate microbicides designed to limit HIV transmission will not cause these adverse events. We previously developed high resolution in vivo imaging methodologies in sheep to assess epithelial integrity following vaginal application of a model microbicide, however characterization of genital inflammation in sheep has not been previously possible...
October 13, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29054054/conformational-analysis-of-the-human-chemokine-receptor-cxcr3
#4
Raffaele Raucci, Andrea Polo, Alfredo Budillon, Giovanni Colonna, Susan Costantini
In the last years, some studies showed the patho-genetic role of CXCR3 bound to its ligands in many human inflammatory diseases and cancers. Thus, the blockage of the CXCR3 interaction site to its ligands is seen as a possible therapeutic target for the treatment of cancer. The presence of flexible regions in the chemokine receptors determines their capability to develop specific mechanisms of action. We have recently focused on the features of the N-terminal region of human CXCR3 free in solution, where we demonstrate the presence of numerous conformational ensembles, dynamically stabilized by H-bonds...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29054053/leptin-reduces-microrna-122-level-in-hepatic-stellate-cells-in-vitro-and-in-vivo
#5
Xuguang Zhai, Fangyun Cheng, Li Ji, Xiaofei Zhu, Qing Cao, Yali Zhang, Xin Jia, Qian Zhou, Wei Guan, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are more likely to develop liver fibrosis. Leptin, an adipocyte-derived hormone, augments inflammatory in liver and promotes hepatic stellate cell (HSC) activation (a key step for liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and can attenuate liver fibrosis. This study examined the effect of leptin on miR-122 level in HSCs in vivo and in vitro. Results demonstrated that leptin reduced the levels of both miR-122 (mature miR-122) and primary miR-122 (pri-miR-122)...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29053991/molecular-mechanisms-of-development-of-the-human-fetal-female-reproductive-tract
#6
Gerald R Cunha, Takeshi Kurita, Mei Cao, Joel Shen, Stanley Robboy, Laurence Baskin
Human female reproductive tract development rests mostly upon hematoxilyn and eosin stained sections despite recent advances on molecular mechanisms in mouse studies. We report application of immunohistochemical methods to explore the ontogeny of epithelial and mesenchymal differentiation markers (keratins, homobox proteins, steroid receptors), transcription factors and signaling molecules (TP63 and RUNX1) during human female reproductive tract development. Keratins 6, 7, 8, 10, 14 and 19 (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19) were expressed in a temporally and spatially dynamic fashion...
July 29, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29053971/a-gut-microbial-mimic-that-hijacks-diabetogenic-autoreactivity-to-suppress-colitis
#7
Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M Slattery, Madeleine Wyss, Catherine Mooser, Andrew J Macpherson, Laura K Sycuro, Pau Serra, Derek M McKay, Kathy D McCoy, Pere Santamaria
The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053925/mesenchymal-stem-cell-secretome-improves-tendon-cell-viability-in-vitro-and-tendon-bone-healing-in-vivo-when-a-tissue-engineering-strategy-is-used-in-a-rat-model-of-chronic-massive-rotator-cuff-tear
#8
Nuno Sevivas, Fábio Gabriel Teixeira, Raquel Portugal, Bruno Direito-Santos, João Espregueira-Mendes, Filipe J Oliveira, Rui F Silva, Nuno Sousa, Wan Ting Sow, Nguyen Luong, Kee Woei Ng, António J Salgado
BACKGROUND: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. PURPOSE: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model...
October 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29053845/substitution-of-yor1p-nbd1-residues-improves-the-thermal-stability-of-human-cystic-fibrosis-transmembrane-conductance-regulator
#9
B M Xavier, E Hildebrandt, F Jiang, H Ding, J C Kappes, I L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a plasma membrane chloride channel protein that regulates vertebrate fluid homeostasis. The inefficiency of wild type human CFTR protein folding/trafficking is exacerbated by genetic mutations that can cause protein misfolding in the endoplasmic reticulum (ER) and subsequent degradation. This project investigates small changes in protein sequence that can alter the thermal stability of the large multi-domain CFTR protein. We target a conserved 70-residue α-subdomain located in the first nucleotide-binding domain that hosts the common misfolding mutation ∆F508...
October 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#10
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer's disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies...
September 25, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053755/micrornas-expression-profile-in-solid-and-unicystic-ameloblastomas
#11
A Setién-Olarra, X Marichalar-Mendia, N G Bediaga, P Aguirre-Echebarria, J M Aguirre-Urizar, A Mosqueda-Taylor
OBJECTIVES: Odontogenic tumors (OT) represent a specific pathological category that includes some lesions with unpredictable biological behavior. Although most of these lesions are benign, some, such as the ameloblastoma, exhibit local aggressiveness and high recurrence rates. The most common types of ameloblastoma are the solid/multicystic (SA) and the unicystic ameloblastoma (UA); the latter considered a much less aggressive entity as compared to the SA. The microRNA system regulates the expression of many human genes while its deregulation has been associated with neoplastic development...
2017: PloS One
https://www.readbyqxmd.com/read/29053747/establishment-of-pten-knockout-medaka-with-transcription-activator-like-effector-nucleases-talens-as-a-model-of-pten-deficiency-disease
#12
Yuriko Matsuzaki, Tetsushi Sakuma, Takashi Yamamoto, Hideyuki Saya
Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. The PTEN gene is a major tumor suppressor, with mutations of this gene occurring frequently in tumors of humans and mice. We have now developed mutant medaka deficient in PTEN with the use of transcription activator-like effector nuclease (TALEN) technology. Medaka possesses two pten genes, ptena and ptenb, similar to zebrafish. We established 16 ptena mutant lines and two ptenb mutant lines...
2017: PloS One
https://www.readbyqxmd.com/read/29053735/characterization-of-the-first-knock-out-aldh7a1-zebrafish-model-for-pyridoxine-dependent-epilepsy-using-crispr-cas9-technology
#13
Nikita Zabinyakov, Garrett Bullivant, Feng Cao, Matilde Fernandez Ojeda, Zheng Ping Jia, Xiao-Yan Wen, James J Dowling, Gajja S Salomons, Saadet Mercimek-Andrews
Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites...
2017: PloS One
https://www.readbyqxmd.com/read/29053721/xx-disorder-of-sex-development-is-associated-with-an-insertion-on-chromosome-9-and-downregulation-of-rspo1-in-dogs-canis-lupus-familiaris
#14
Vicki N Meyers-Wallen, Adam R Boyko, Charles G Danko, Jennifer K Grenier, Jason G Mezey, Jessica J Hayward, Laura M Shannon, Chuan Gao, Afrah Shafquat, Edward J Rice, Shashikant Pujar, Stefanie Eggers, Thomas Ohnesorg, Andrew H Sinclair
Remarkable progress has been achieved in understanding the mechanisms controlling sex determination, yet the cause for many Disorders of Sex Development (DSD) remains unknown. Of particular interest is a rare XX DSD subtype in which individuals are negative for SRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family. This is a naturally occurring disorder in humans (Homo sapiens) and dogs (C. familiaris). Phenotypes in the canine XX DSD model are strikingly similar to those of the human XX DSD subtype...
2017: PloS One
https://www.readbyqxmd.com/read/29053679/measuring-the-effect-of-chemicals-on-the-growth-and-reproduction-of-caenorhabditis-elegans
#15
So Young Lee, Kyungsu Kang
Toxicological evaluation is crucial for understanding the effects of chemicals on living organisms in basic and applied biological science fields. A non-mammalian soil round worm, Caenorhabditis elegans, is a valuable model organism for toxicology studies due to its convenience and lack of animal ethics issues compared with mammalian animal systems. In this protocol, a detailed procedure of toxicological evaluation of chemicals in C. elegans is described. A clinical anticancer drug, etoposide, which targets human topoisomerase II and inhibits DNA replication of human cancer cells, was selected as a model testing chemical...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053678/assay-for-phosphorylation-and-microtubule-binding-along-with-localization-of-tau-protein-in-colorectal-cancer-cells
#16
Md Nazmul Huda, Erdenedolgor Erdene-Ochir, Cheol-Ho Pan
The microtubule-associated protein tau is a neuronal protein that localizes mostly in axons. Generally tau is essential for normal neuronal functioning because it is involved in microtubule assembly and stabilization. Besides neurons, tau is expressed in human breast, prostate, gastric, colorectal, and pancreatic cancers where it shows nearly similar structure and exerts similar functions as the neuronal tau. The amount of tau and its phosphorylation can change its function as a stabilizer of microtubules, and lead to the development of paired helical filaments in different neurodegenerative disorders, such as Alzheimer's disease...
October 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#17
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053671/cell-free-biochemical-fluorometric-enzymatic-assay-for-high-throughput-measurement-of-lipid-peroxidation-in-high-density-lipoprotein
#18
Shubhendu Sen Roy, Huy Cong Xuan Nguyen, Thomas A Angelovich, Anna C Hearps, Diana Huynh, Anthony Jaworowski, Theodoros Kelesidis
Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most powerful independent negative predictors of atherosclerotic cardiovascular disease (CVD). The structure and function of HDL rather than HDL-C may more accurately predict atherosclerosis. Several HDL protein and lipid compositional changes that impair HDL function occur in inflammatory states such as atherosclerosis. HDL function is usually determined by cell based assays such as cholesterol efflux assay but these assays have numerous drawbacks lack of standardization...
October 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053670/pattern-based-search-of-epigenomic-data-using-genemo
#19
Alvin Zheng, Xiaoyi Cao, Sheng Zhong
Compared with the robust text-based search tools for genomic or RNA sequencing data, current methodologies for pattern-based searches of epigenomic and other functional genomic data are very limited. GeNemo is the first online search tool that accomplishes this goal. Users input their functional genomic data in the Browser Extensible Data (BED), Peaks, and bigWig formats, and may search for data in any of the three formats. Users may specify which types of datasets to search against, choosing from a variety of online datasets, with the Encyclopedia of DNA Elements (ENCODE) representing different epigenomic marks, transcriptional factor binding sites, and chromatin hypersensitivities or accessibilities in specific cell types, and developmental stages or species (mouse or human)...
October 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053403/human-cytomegalovirus-vaccine-development-immune-responses-to-look-into-vaccine-strategy
#20
Lin Xia, Ruopeng Su, Zhiqiang An, Tong-Ming Fu, Wenxin Luo
Human cytomegalovirus (HCMV) causes considerable morbidity and disability in high risk, immunocompromised populations including recipients of solid organ transplants, and fetuses whose immune systems are not yet mature. Vaccines aimed at ameliorating the severity of disease and preventing HCMV infection can be categorized into two main approaches of vaccine design, with one focusing on virus modification and the other on individual antigens. However, no candidates in either class have been successful in achieving durable and protective immunity...
October 20, 2017: Human Vaccines & Immunotherapeutics
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