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https://www.readbyqxmd.com/read/28227742/a-computational-model-of-orientation-dependent-activation-of-retinal-ganglion-cells
#1
Timothy Esler, Anthony N Burkitt, David B Grayden, Robert R Kerr, Bahman Tahayori, Hamish Meffin, Timothy Esler, Anthony N Burkitt, David B Grayden, Robert R Kerr, Bahman Tahayori, Hamish Meffin, Anthony N Burkitt, Timothy Esler, Hamish Meffin, David B Grayden, Robert R Kerr, Bahman Tahayori
Currently, a challenge in electrical stimulation for epiretinal prostheses is the avoidance of stimulation of axons of passage in the nerve fiber layer that originate from distant regions of the ganglion cell layer. A computational model of extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue is developed using a modified version of the standard volume conductor model, known as the cellular composite model, embedded in a four layer model of the retina. Simulations are conducted to investigate the interaction of neural tissue orientation, electrode placement, and stimulation pulse duration and amplitude...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28222195/autoantibodies-against-mono-and-tri-methylated-lysine-display-similar-but-also-distinctive-characteristics
#2
Zhiqiang Wang, Younan Ma, Fan Liu, Linjie Chen, Ruitong Gao, Wei Zhang
Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people's knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3)...
2017: PloS One
https://www.readbyqxmd.com/read/28222130/dengue-virus-antibody-database-systematically-linking-serotype-specificity-with-epitope-mapping-in-dengue-virus
#3
Sidhartha Chaudhury, Gregory D Gromowski, Daniel R Ripoll, Ilja V Khavrutskii, Valmik Desai, Anders Wallqvist
BACKGROUND: A majority infections caused by dengue virus (DENV) are asymptomatic, but a higher incidence of severe illness, such as dengue hemorrhagic fever, is associated with secondary infections, suggesting that pre-existing immunity plays a central role in dengue pathogenesis. Primary infections are typically associated with a largely serotype-specific antibody response, while secondary infections show a shift to a broadly cross-reactive antibody response. METHODS/PRINCIPAL FINDINGS: We hypothesized that the basis for the shift in serotype-specificity between primary and secondary infections can be found in a change in the antibody fine-specificity...
February 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28221346/synthesis-of-ent-be-43547a1-reveals-a-potent-hypoxia-selective-anticancer-agent-and-uncovers-the-biosynthetic-origin-of-the-apd-cld-natural-products
#4
Nikolaj L Villadsen, Kristian M Jacobsen, Ulrik B Keiding, Esben T Weibel, Bjørn Christiansen, Thomas Vosegaard, Morten Bjerring, Frank Jensen, Mogens Johannsen, Thomas Tørring, Thomas B Poulsen
Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28220783/an-integrative-approach-unveils-fosl1-as-an-oncogene-vulnerability-in-kras-driven-lung-and-pancreatic-cancer
#5
Adrian Vallejo, Naiara Perurena, Elisabet Guruceaga, Pawel K Mazur, Susana Martinez-Canarias, Carolina Zandueta, Karmele Valencia, Andrea Arricibita, Dana Gwinn, Leanne C Sayles, Chen-Hua Chuang, Laura Guembe, Peter Bailey, David K Chang, Andrew Biankin, Mariano Ponz-Sarvise, Jesper B Andersen, Purvesh Khatri, Aline Bozec, E Alejandro Sweet-Cordero, Julien Sage, Fernando Lecanda, Silve Vicent
KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220297/what-roles-do-colon-stem-cells-and-gap-junctions-play-in-the-left-and-right-location-of-origin-of-colorectal-cancers
#6
James E Trosko, Heinz-Josef Lenz
This "Commentary" examines an important clinical observation that right-sided colorectal cancers appear less treatable than the left-sided cancers. The concepts of (a) the "initiation/promotion/progression" process, (b) the stem cell hypothesis, (c) the role gap junctional intercellular communication, (d) cancer cells lacking GJIC either because of the non-expression of connexin genes or of non-functional gap junction proteins, and (e) the role of the microbiome in promoting initiated colon stem cells to divide symmetrically or asymmetrically are examined to find an explanation...
February 20, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28219207/-mutations-of-vitamin-d-receptor-gene-found-in-patients-with-multiple-myeloma
#7
Y Liu, H B Rui
Objective: To explore the mutations of vitamin D receptor (VDR) gene in patients with multiple myeloma (MM). Methods: Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the mutations of VDR gene(loci Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ, Taq Ⅰ) in forty MM cases and 84 healthy control subjects. Results: A synonymous mutation (ATC→ATA , both encode isoleucine) at cDNA codon1421 of VDR gene was found in one MM patients, which correlated to a better therapeutic response. Rare Bsm Ⅰ AA genotype and Taq Ⅰ CC genotype were detected in a MM patient, which might be related to the relapsing and refracfory disease...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218887/pathology-of-serially-sacrificed-female-b6c3f1-mice-chronically-exposed-to-very-low-dose-rate-gamma-rays
#8
I B Tanaka, J Komura, S Tanaka
We have previously reported on life span shortening as well as increased incidence rates in several neoplasms in B6C3F1 mice that were continuously exposed to 21 mGy/day of gamma rays for 400 days. To clarify whether the life shortening was due to early appearance of neoplasms (shortened latency) or increased promotion/progression, 8-week-old female specific-pathogen-free B6C3F1 mice were gamma-ray irradiated at a low dose rate of 20 mGy/day for 400 days. At 100 days postirradiation, 60-90 mice were sacrificed, and thereafter every 100 days alongside the age-matched nonirradiated controls, for 700 days...
February 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/28215840/cytidine-deaminase-apobec3a-induction-in-fallopian-epithelium-after-exposure-to-follicular-fluid
#9
Pavla Brachova, Nehemiah S Alvarez, Bradley J Van Voorhis, Lane K Christenson
OBJECTIVE: Ovarian carcinomas that originate from fallopian epithelial cells are suggested to arise due to repeated exposure to ovulatory follicular fluid (FF). Mechanistic explanation(s) for how this occurs are unknown. Here, we sought to understand if FF exposure to fallopian epithelial cells could induce DNA damage and expression of a known family of DNA mutators, apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) cytidine deaminases. METHODS: Follicular fluid and matched patient plasma samples were obtained from donors...
February 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28215293/neuronal-roles-of-the-bicaudal-d-family-of-motor-adaptors
#10
M Budzinska, K B Wicher, M Terenzio
All cell types rely on active intracellular cargo transport to shuttle essential cellular components such as proteins, lipids, RNA, and even organelles from the center to the periphery and vice versa. Additionally, several signaling pathways take advantage of intracellular transport to propagate their signals by moving activated receptors and protein effectors to specific locations inside the cell. Neurons particularly, being a very polarized cell type, are highly dependent on molecular motors for the anterograde and retrograde delivery of essential cellular components and signaling molecules...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28214127/functionalized-superparamagnetic-iron-oxide-nanoparticles-provide-highly-efficient-iron-labeling-in-macrophages-for-magnetic-resonance-based-detection-in-vivo
#11
Jack Sharkey, Philip J Starkey Lewis, Michael Barrow, Salamah M Alwahsh, June Noble, Eilidh Livingstone, Ross J Lennen, Maurits A Jansen, Jaime Garcia Carrion, Neill Liptrott, Shareen Forbes, Dave J Adams, Amy E Chadwick, Stuart J Forbes, Patricia Murray, Matthew J Rosseinsky, Christopher E Goldring, B Kevin Park
BACKGROUND AIMS: Tracking cells during regenerative cytotherapy is crucial for monitoring their safety and efficacy. Macrophages are an emerging cell-based regenerative therapy for liver disease and can be readily labeled for medical imaging. A reliable, clinically applicable cell-tracking agent would be a powerful tool to study cell biodistribution. METHODS: Using a recently described chemical design, we set out to functionalize, optimize and characterize a new set of superparamagnetic iron oxide nanoparticles (SPIONs) to efficiently label macrophages for magnetic resonance imaging-based cell tracking in vivo...
February 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#12
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212352/rta-occupancy-of-the-origin-of-lytic-replication-during-murine-gammaherpesvirus-68-reactivation-from-b-cell-latency
#13
Alexis L Santana, Darby G Oldenburg, Varvara Kirillov, Laraib Malik, Qiwen Dong, Roman Sinayev, Kenneth B Marcu, Douglas W White, Laurie T Krug
RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice...
February 16, 2017: Pathogens
https://www.readbyqxmd.com/read/28211887/germline-mutations-predisposing-to-diffuse-large-b-cell-lymphoma
#14
REVIEW
O C Leeksma, N F de Miranda, H Veelken
Genetic studies of diffuse large B-cell lymphomas (DLBCLs) in humans have revealed numerous targets of somatic mutations and an increasing number of potentially relevant germline alterations. The latter often affect genes involved in DNA repair and/or immune function. In general, defects in these genes also predispose to other conditions. Knowledge of these mutations can lead to disease-preventing measures in the patient and relatives thereof. Conceivably, these germline mutations will be taken into account in future therapy of the lymphoma...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211314/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#15
Christopher A Manuel Stacey M Bagby Julie A Reisinger Umarani Pugazhenthi Todd M Pitts Stephen B Keysar John J Arcaroli And Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as amodelfor cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retainmany of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strainsused to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At ourinstitution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infectedwith C...
February 16, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28202528/distinct-levels-of-radioresistance-in-lgr5-colonic-epithelial-stem-cells-versus-lgr5-small-intestinal-stem-cells
#16
Guoqiang Hua, Chu Wang, Yan Pan, Zhaoshi Zeng, Sang Gyu Lee, Maria Laura Martin, Adriana Haimovitz-Friedman, Zvi Fuks, Philip B Paty, Richard N Kolesnick
While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic epithelial stem cells (CESC) markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells (CBC) (D0 6.0±0.3 Gy vs. 1.3±0.1, respectively; p0...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28201964/plasmodium-falciparum-heat-shock-protein-70-lacks-immune-modulatory-activity
#17
Ofentse Jacob Pooe, Gabriele Köllisch, Holger Heine, Addmore Shonhai
Heat shock protein 70 (Hsp70) family are conserved molecules that constitute a major part of the cell's protein folding machinery. The role of Hsp70s of parasitic origin in host cell immune modulation has remained contentious. This is largely due to the fact that several studies implicating Hsp70 in immune modulation rely on the use of recombinant protein derived from bacteria which is often fraught contamination. Thus, in the current study, we expressed recombinant Plasmodium falciparum Hsp70 (PfHsp70) using in three bacterial expression hosts: E...
14, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28198528/the-expression-of-inhibitor-of-nuclear-factor-kappa-b-kinase-epsilon-ikk%C3%AE%C2%B5-in-human-aortic-aneurysm
#18
Leiyang Zhang, Lei Wang, Wen Chen, Yueyue Xu, Liming Wang, Reinard Iskandar, Yifei Wang, Xin Chen
BACKGROUND: Aortic aneurysm (AA) is one of the most common causes of sudden death among elderly people. Although AA can be detected by non-invasive imaging techniques, there are no pharmacological treatments currently available to prevent progression at any stage of the disease. In this study we will explore the expression of IKKε in AA and its potential underlying molecular mechanism in AA. Material s and methods: Human aortic tissue was taken from 14 patients who underwent surgical repair of AA for the AA group and another 11 patients with normal aorta who underwent aortic valve replacement surgery for the control group...
February 15, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28196764/nuclear-and-membrane-progestin-receptors-in-the-european-eel-characterization-and-expression-in-vivo-through-spermatogenesis
#19
Marina Morini, David S Peñaranda, María C Vílchez, Rasoul Nourizadeh-Lillabadi, Anne-Gaëlle Lafont, Sylvie Dufour, Juan F Asturiano, Finn-Arne Weltzien, Luz Pérez
Characterization of all the progestin receptor genes (PRs) found in the European eel has been performed. There were five membrane PRs (mPRs): mPRα (alpha), mPRAL1 (alpha-like1), mPRAL2 (alpha-like2), mPRγ (gamma), mPRδ (delta) and two nuclear PRs (nPRs or PGRs): pgr1 and pgr2. In silico studies showed that the C and E(F) domains of Pgr are well conserved among vertebrates whereas the A/B domain is not. Phylogeny and synteny analyses suggest that eel duplicated pgr (pgr1 and pgr2) originated from the teleost-specific third whole genome duplication (3R)...
February 11, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28196665/complement-s-hidden-arsenal-new-insights-and-novel-functions-inside-the-cell
#20
M Kathryn Liszewski, Michelle Elvington, Hrishikesh S Kulkarni, John P Atkinson
A key component of both innate and adaptive immunity, new understandings of the complement system are expanding its roles beyond that traditionally appreciated. Evidence is accumulating that complement has an intracellular arsenal of components that provide not only immune defense, but also assist in key interactions for host cell functions. Although early work has primarily centered on T cells, the intracellular complement system likely functions in many if not most cells of the body. Some of these functions may trace their origins to the primitive complement system that began as a primeval form of C3 likely tasked for protection from intracellular pathogen invasion...
February 10, 2017: Molecular Immunology
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