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https://www.readbyqxmd.com/read/29321194/polygenic-hazard-score-to-guide-screening-for-aggressive-prostate-cancer-development-and-validation-in-large-scale-cohorts
#1
Tyler M Seibert, Chun Chieh Fan, Yunpeng Wang, Verena Zuber, Roshan Karunamuni, J Kellogg Parsons, Rosalind A Eeles, Douglas F Easton, ZSofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch Garcia, Kenneth Muir, Henrik Grönberg, Fredrik Wiklund, Markus Aly, Johanna Schleutker, Csilla Sipeky, Teuvo Lj Tammela, Børge G Nordestgaard, Sune F Nielsen, Maren Weischer, Rasmus Bisbjerg, M Andreas Røder, Peter Iversen, Tim J Key, Ruth C Travis, David E Neal, Jenny L Donovan, Freddie C Hamdy, Paul Pharoah, Nora Pashayan, Kay-Tee Khaw, Christiane Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S Kibel, Cezary Cybulski, Dominika Wokolorczyk, Wojciech Kluzniak, Lisa Cannon-Albright, Hermann Brenner, Katarina Cuk, Kai-Uwe Saum, Jong Y Park, Thomas A Sellers, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Judith A Clements, Amanda Spurdle, Manuel R Teixeira, Paula Paulo, Sofia Maia, Hardev Pandha, Agnieszka Michael, Andrzej Kierzek, David S Karow, Ian G Mills, Ole A Andreassen, Anders M Dale
OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis)...
January 10, 2018: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29313684/interfering-with-hur-rna-interaction-design-synthesis-and-biological-characterization-of-tanshinone-mimics-as-novel-effective-hur-inhibitors
#2
Leonardo Manzoni, Chiara Zucal, Danilo Di Maio, Vito G D'Agostino, Natthakan Thongon, Isabelle Bonomo, Preet Lal, Marco Miceli, Vanessa Baj, Marta Brambilla, Linda Cerofolini, Saioa Elezgarai, Emiliano Biasini, Claudio Luchinat, Ettore Novellino, Marco Fragai, Luciana Marinelli, Alessandro Provenzani, Pierfausto Seneci
The human antigen R (HuR) is an RNA-binding protein known to modulate the expression of target mRNA coding for proteins involved in inflammation, tumorigenesis and stress responses and is a valuable drug target. We previously found that Dihydrotanshinone-I (DHTS, 1) prevents the association of HuR with its RNA substrate, thus imparing its function. Herein, inspired by DHTS structure, we designed and synthesized an array of ortho-quinones (tanshinone mimics) using a function-oriented synthetic approach. Among others, compound 6a and 6n turned out to be more effective than 1, showing a nanomolar Ki and disrupting HuR binding to RNA in cells...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29313657/spatial-resolved-photoelectrochemical-biosensing-array-based-on-cds-g-c3n4-heterojunction-a-universal-immunosensing-platform-for-accurate-detection
#3
Yu-Xiang Dong, Juntao Cao, Bing Wang, Shu-Hui Ma, Yan Ming Liu
The detection of biomarkers with high sensitivity and accuracy in real biosamples remains challenging. Herein, a universal spatial-resolved photoelectrochemical (PEC) ratiometry for biodetection of prostate specific antigen (PSA) as model biomarker was designed for the first time based on dual-electrodes array modified by CdS@g-C3N4 heterojunction coupled with CuS quantum dots (QDs) as signal amplification tags. Specifically, a new kind of photoactive material, CdS@g-C3N4 p-n heterojunction with highly photoelectric conversion efficiency and good chemical stability, was synthesized and immobilized on two spatial-resolved electrodes (WE1 and WE2)...
January 9, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29296782/whole-exome-sequencing-for-rh-genotyping-and-alloimmunization-risk-in-children-with-sickle-cell-anemia
#4
Stella T Chou, Jonathan M Flanagan, Sunitha Vege, Naomi L C Luban, R Clark Brown, Russell E Ware, Connie M Westhoff
RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)-based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289663/identification-of-the-antigenic-epitopes-of-maternal-autoantibodies-in-autism-spectrum-disorders
#5
Elizabeth Edmiston, Karen L Jones, Tam Vu, Paul Ashwood, Judy Van de Water
Several groups have described the presence of fetal brain-reactive maternal autoantibodies in the plasma of some mothers whose children have autism spectrum disorder (ASD). We previously identified seven autoantigens targeted by these maternal autoantibodies, each of which is expressed at significant levels in the developing brain and has demonstrated roles in typical neurodevelopment. To further understand the binding repertoire of the maternal autoantibodies, as well as the presence of any meaningful differences with respect to the recognition and binding of these ASD- specific autoantibodies to each of these neuronal autoantigens, we utilized overlapping peptide microarrays incubated with maternal plasma samples obtained from the Childhood Autism Risk from Genetics and Environment (CHARGE) Study...
December 28, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29285926/synthesis-of-oligosaccharide-components-of-the-outer-core-domain-of-p-aeruginosa-lipopolysaccharide-using-a-multifunctional-hydroquinone-derived-reducing-end-capping-group
#6
Abhishek Vartak, Fatma M Hefny, Steven J Sucheck
The synthesis of a trisaccharide (common to glycoform I and II) and a tetrasaccharide (common to glycoform I) from the outer core domain of Pseudomonas aeruginosa lipopolysaccharide (LPS) using a novel hydroquinone-based reducing-end capping group is reported. This multifunctional capping group was utilized as purification handle and was stable toward many common transformations in oligosaccharide synthesis. The access to outer-core LPS antigens with a TBDPS-protected hydroquinone (TPH) at the reducing end will be useful for glycan array and therapeutic glycoconjugate synthesis...
December 29, 2017: Organic Letters
https://www.readbyqxmd.com/read/29280974/harnessing-invariant-nkt-cells-to-improve-influenza-vaccines-a-pig-perspective
#7
REVIEW
Guan Yang, Jürgen A Richt, John P Driver
Invariant natural killer T (iNKT) cells are an "innate-like" T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell-CD1d system...
December 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29274250/an-exosome-based-vaccine-platform-imparts-cytotoxic-t-lymphocyte-immunity-against-viral-antigens
#8
Simona Anticoli, Francesco Manfredi, Chiara Chiozzini, Claudia Arenaccio, Eleonora Olivetta, Flavia Ferrantelli, Antonio Capocefalo, Emiliana Falcone, Anna Ruggieri, Maurizio Federico
Exosomes are 50-150 nm sized nanovesicles released by all eukaryotic cells. We very recently described a method to engineer exosomes in vivo with the E7 protein of Human Papilloma Virus (HPV). This technique consists in the intramuscular injection of a DNA vector expressing HPV-E7 fused at the C-terminus of an exosome-anchoring protein, i.e., Nefmut , we previously characterized for its high levels of incorporation in exosomes. In this configuration, the ∼11 kDa E7 protein elicited a both strong and effective antigen-specific cytotoxic T lymphocyte (CTL) immunity...
December 23, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29259314/lectin-activity-of-the-pneumococcal-pilin-proteins
#9
Christopher J Day, Adrienne W Paton, Richard M Harvey, Lauren E Hartley-Tassell, Kate L Seib, Joe Tiralongo, Nicolai Bovin, Silvana Savino, Vega Masignani, James C Paton, Michael P Jennings
Streptococcus pneumoniae is a leading cause of morbidity and mortality globally. The Pilus-1 proteins, RrgA, RrgB and RrgC of S. pneumoniae have been previously assessed for their role in infection, invasive disease and as possible vaccine candidates. In this study we have investigated the glycan binding repertoire of all three Pilus-1 proteins, identifying that the tip adhesin RrgA has the broadest glycan recognition of the three proteins, binding to maltose/cellobiose, α/β linked galactose and blood group A and H antigens...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29248716/visual-electrochemiluminescence-ratiometry-on-bipolar-electrode-for-bioanalysis
#10
Hai-Jie Lu, Wei Zhao, Jing-Juan Xu, Hong-Yuan Chen
In this work, we developed a visual ECL ratiometry on a closed bipolar electrode (BPE) for the detection of prostate specific antigen (PSA), prostate cancer biomarker. High efficient CdTe QDs was synthesized which emitted visualized red light at BPE cathode. Integrating with the anodic ECL emitters, luminol, visual emission of red-blue ratiometric ECL was achieved in BPE array chips. As a sensing probe, Au NRs nanocomposite was assembled on the surface of the cathode and acted as both the quencher of the CdTe QDs ECL and the promoter of the luminol ECL...
December 6, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29237129/zap-70-in-signaling-biology-and-disease
#11
Byron B Au-Yeung, Neel H Shah, Lin Shen, Arthur Weiss
T cells possess an array of functional capabilities important for host defense against pathogens and tumors. T cell effector functions require the T cell antigen receptor (TCR). The TCR has no intrinsic enzymatic activity, and thus signal transduction from the receptor relies on additional signaling molecules. One such molecule is the cytoplasmic tyrosine kinase ZAP-70, which associates with the TCR complex and is required for initiating the canonical biochemical signal pathways downstream of the TCR. In this article, we describe recent structure-based insights into the regulation and substrate specificity of ZAP-70, and then we review novel methods for determining the role of ZAP-70 catalytic activity-dependent and -independent signals in developing and mature T cells...
December 13, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29235974/processing-fixed-and-stored-adipose-derived-stem-cells-for-quantitative-protein-array-assays
#12
Jessica S Sadick, Eric M Darling
Accurately characterizing cellular subpopulations is essential for elucidating the mechanisms underlying normal and pathological biology. Isolation of specific cell types can be accomplished by labeling unique cell-associated proteins with fluorescent antibodies. Cell fixation is commonly used to prepare these samples and allow for long-term storage, but this poses challenges for subsequent protein analysis. We previously established the FITSAR (formaldehyde-fixed intracellular target-sorted antigen retrieval) method, in which protein can be isolated and characterized from fixed, enriched cell subpopulations...
December 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/29230367/a-novel-approach-for-human-whole-transcriptome-analysis-based-on-absolute-gene-expression-of-microarray-data
#13
Shirley Bikel, Leonor Jacobo-Albavera, Fausto Sánchez-Muñoz, Fernanda Cornejo-Granados, Samuel Canizales-Quinteros, Xavier Soberón, Rogerio R Sotelo-Mundo, Blanca E Del Río-Navarro, Alfredo Mendoza-Vargas, Filiberto Sánchez, Adrian Ochoa-Leyva
Background: In spite of the emergence of RNA sequencing (RNA-seq), microarrays remain in widespread use for gene expression analysis in the clinic. There are over 767,000 RNA microarrays from human samples in public repositories, which are an invaluable resource for biomedical research and personalized medicine. The absolute gene expression analysis allows the transcriptome profiling of all expressed genes under a specific biological condition without the need of a reference sample. However, the background fluorescence represents a challenge to determine the absolute gene expression in microarrays...
2017: PeerJ
https://www.readbyqxmd.com/read/29214121/towards-one-step-quantitation-of-prostate-specific-antigen-psa-in-microfluidic-devices-feasibility-of-optical-detection-with-nanoparticle-labels
#14
Ana I Barbosa, Jan H Wichers, Aart van Amerongen, Nuno M Reis
Rapid and quantitative prostate-specific antigen (PSA) biomarker detection would be beneficial to cancer diagnostics, improving early detection and therefore increasing chances of survival. Nanoparticle-based detection is routinely used in one-step nitrocellulose-based lateral flow (LF) immunoassays; however, it is well established within the scientific diagnostic community that LF technology lacks sensitivity for measuring biomarkers, such as prostate-specific antigen (PSA). A trend in point-of-care (POC) protein biomarker quantitation is the miniaturization of immunoassays in microfluidic devices...
2017: BioNanoScience
https://www.readbyqxmd.com/read/29213331/noninvasive-prenatal-diagnosis-of-fetal-aneuploidy-by-circulating-fetal-nucleated-red-blood-cells-and-extravillous-trophoblasts-using-silicon-based-nanostructured-microfluidics
#15
Chung-Er Huang, Gwo-Chin Ma, Hei-Jen Jou, Wen-Hsiang Lin, Dong-Jay Lee, Yi-Shing Lin, Norman A Ginsberg, Hsin-Fu Chen, Frank Mau-Chung Chang, Ming Chen
Background: Noninvasive prenatal testing (NIPT) based on cell-free DNA in maternal circulation has been accepted worldwide by the clinical community since 2011 but limitations, such as maternal malignancy and fetoplacental mosaicism, preclude its full replacement of invasive prenatal diagnosis. We present a novel silicon-based nanostructured microfluidics platform named as "Cell Reveal™" to demonstrate the feasibility of capturing circulating fetal nucleated red blood cells (fnRBC) and extravillous cytotrophoblasts (EVT) for cell-based noninvasive prenatal diagnosis (cbNIPD)...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29201383/an-autosomal-recessive-mutation-in-scl24a4-causing-enamel-hypoplasia-in-samoyed-and-its-relationship-to-breed-wide-genetic-diversity
#16
Niels C Pedersen, Bonnie Shope, Hongwei Liu
Background: Pure breeding of dogs has led to over 700 heritable disorders, of which almost 300 are Mendelian in nature. Seventy percent of the characterized mutations have an autosomal recessive mode of inheritance, indicative of positive selection during bouts of inbreeding primarily for new desired conformational traits. Samoyed suffer from several common complex genetic disorders, but up to this time only two X-linked and one autosomal dominant disorder have been identified. Previous studies based on pedigrees and SNP arrays have concluded that Samoyed breeders have done a good job in maintaining genetic diversity and avoiding excessive inbreeding...
2017: Canine Genetics and Epidemiology
https://www.readbyqxmd.com/read/29196495/comparative-transcriptome-profiling-reveals-coding-and-noncoding-rna-differences-in-nsclc-from-african-americans-and-european-americans
#17
Khadijah A Mitchell, Adriana Zingone, Leila Toulabi, Jacob Boeckelman, Bríd M Ryan
Purpose: To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs).Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and 19 EAs) and miRNA (n = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29194460/dynamical-system-modeling-to-simulate-donor-t-cell-response-to-whole-exome-sequencing-derived-recipient-peptides-understanding-randomness-in-alloreactivity-incidence-following-stem-cell-transplantation
#18
Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor
Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/29185390/modulation-of-antitumor-immunity-with-histone-deacetylase-inhibitors
#19
Tyler R McCaw, Troy D Randall, Andres Forero, Donald J Buchsbaum
Histone deacetylase inhibitors possess a broad array of antitumor activities; however, their net impact on the evolving antitumor immune response is highly dependent on the inhibitors used and the histone deacetylases they target. Herein, we sequentially focus on each stage of the antitumor immune response - from dendritic cell activation and migration, antigen uptake and presentation, T-cell activation and differentiation and the enactment of antitumor effector functions within the tumor microenvironment. In particular, we will discuss how various inhibitors have different effects depending on cellular activation, experimental design and specific histone deacetylases being targeted - and how these changes impact the outcome of an antitumor immune response...
December 2017: Immunotherapy
https://www.readbyqxmd.com/read/29184550/natural-killer-cell-interactions-with-classical-and-non-classical-human-leukocyte-antigen-class-i-in-hiv-1-infection
#20
REVIEW
Angelique Hölzemer, Wilfredo F Garcia-Beltran, Marcus Altfeld
Natural killer (NK) cells are effector lymphocytes of the innate immune system that are able to mount a multifaceted antiviral response within hours following infection. This is achieved through an array of cell surface receptors surveilling host cells for alterations in human leukocyte antigen class I (HLA-I) expression and other ligands as signs of viral infection, malignant transformation, and cellular stress. This interaction between HLA-I ligands and NK-cell receptor is not only important for recognition of diseased cells but also mediates tuning of NK-cell-effector functions...
2017: Frontiers in Immunology
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