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https://www.readbyqxmd.com/read/27932543/members-of-the-zinc-cluster-factor-family-alters-virulence-in-candida-albicans
#1
Luca Issi, Rhys A Farrer, Kelly Pastor, Benjamin Landry, Toni Delorey, George W Bell, Dawn A Thompson, Christina A Cuomo, Reeta P Rao
Virtually all humans are colonized with Candida albicans However, in immunocompromised individuals this benign commensal organism becomes a serious, life-threatening pathogen. Here, we describe and analyze the regulatory networks that modulate innate responses in the host niches. We identified Zcf15 and Zcf29, two Zinc Cluster transcription Factors (ZCF) that are required for C. albicans virulence. Previous sequence analysis of clinical C. albicans isolates from immunocompromised patients indicates that both ZCF genes diverged during clonal evolution...
December 7, 2016: Genetics
https://www.readbyqxmd.com/read/27932527/mechanisms-of-in-vivo-ribosome-maintenance-change-in-response-to-nutrient-signals
#2
Andrew D Mathis, Bradley C Naylor, Richard H Carson, Eric Evans, Justin Harwell, Jared Knect, Eric Hexem, Fredrick Peelor, Benjamin F Miller, Karyn L Hamilton, Mark K Transtrum, Benjamin T Bikman, John C Price
Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging and disease, whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan...
December 8, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27931811/the-pigret-assay-a-method-for-measuring-pig-a-gene-mutation-in-reticulocytes-is-reliable-as-a-short-term-in-vivo-genotoxicity-test-summary-of-the-mms-jems-collaborative-study-across-16-laboratories-using-24-chemicals
#3
Takafumi Kimoto, Katsuyoshi Horibata, Daishiro Miura, Satsuki Chikura, Yuki Okada, Akiko Ukai, Satoru Itoh, Shiho Nakayama, Hisakazu Sanada, Naomi Koyama, Shigeharu Muto, Yoshifumi Uno, Mika Yamamoto, Yuta Suzuki, Takayuki Fukuda, Ken Goto, Kunio Wada, Takahiro Kyoya, Miyuki Shigano, Hironao Takasawa, Shuichi Hamada, Hideki Adachi, Yasuaki Uematsu, Eri Tsutsumi, Hisako Hori, Ryuta Kikuzuki, Yosuke Ogiwara, Ikuma Yoshida, Akihisa Maeda, Kazunori Narumi, Yohei Fujiishi, Takeshi Morita, Masami Yamada, Masamitsu Honma
The in vivo mutation assay using the X-linked phosphatidylinositol glycan class A gene (Pig-a in rodents, PIG-A in humans) is a promising tool for evaluating the mutagenicity of chemicals. Approaches for measuring Pig-a mutant cells have focused on peripheral red blood cells (RBCs) and reticulocytes (RETs) from rodents. The recently developed PIGRET assay is capable of screening >1×10(6) RETs for Pig-a mutants by concentrating RETs in whole blood prior to flow cytometric analysis. Additionally, due to the characteristics of erythropoiesis, the PIGRET assay can potentially detect increases in Pig-a mutant frequency (MF) sooner after exposure compared with a Pig-a assay targeting total RBCs (RBC Pig-a assay)...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27929458/in-vivo-biosensor-tracks-non-apoptotic-caspase-activity-in-drosophila
#4
Ho Lam Tang, Ho Man Tang, Ming Chiu Fung, J Marie Hardwick
Caspases are the key mediators of apoptotic cell death via their proteolytic activity. When caspases are activated in cells to levels detectable by available technologies, apoptosis is generally assumed to occur shortly thereafter. Caspases can cleave many functional and structural components to cause rapid and complete cell destruction within a few minutes. However, accumulating evidence indicates that in normal healthy cells the same caspases have other functions, presumably at lower enzymatic levels. Studies of non-apoptotic caspase activity have been hampered by difficulties with detecting low levels of caspase activity and with tracking ultimate cell fate in vivo...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27924732/the-effect-of-a-hexanoic-acid-linker-insertion-on-the-pharmacokinetics-and-tumor-targeting-properties-of-the-melanoma-imaging-agent-99mtc-hynic-cycmsh
#5
Vania Teixeira, Marcelo Fernández, Natalia Oddone, Xiuli Zhang, Fabio Gallazzi, Hugo Cerecetto, Juan Pablo Gambini, Williams Porcal, Pablo Cabral, Thomas P Quinn
BACKGROUND: Lactam cyclized alpha-melanocyte stimulating hormone (α-MSH) analogues exhibit high stability and affinity for the MC1-R receptors over expressed in melanoma cells. Recently, we reported a novel <sup>99m</sup>Tc-HYNIC-cycMSH<sub>4-13</sub> analogue with the HYNIC chelator directly attached to the lactam cyclized ring. OBJECTIVE: In this study we proposed the introduction of a 6-aminohexanoic acid (Ahx) linker between the HYNIC chelator and lactam cyclized peptide cycMSH4-13 to reduce steric hindrance and improve the melanoma targeting and imaging proprieties of the radiolabeled peptide...
December 6, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#6
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We employed array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27922848/lung-regeneration-steps-toward-clinical-implementation-and-use
#7
Elizabeth A Calle, Katherine L Leiby, MichaSam B Raredon, Laura E Niklason
PURPOSE OF REVIEW: Whole lung tissue engineering is a relatively new area of investigation. In a short time, however, the field has advanced quickly beyond proof of concept studies in rodents and now stands on the cusp of wide-spread scale up to large animal studies. Therefore, this technology is ever closer to being directly clinically relevant. RECENT FINDINGS: The main themes in the literature include refinement of the fundamental components of whole lung engineering and increasing effort to direct induced pluripotent stem cells and lung progenitor cells toward use in lung regeneration...
December 5, 2016: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/27922334/ionizing-radiation-impairs-endogenous-regeneration-of-infarcted-heart-an-in-vivo-18-f-fdg-pet-ct-and-99m-tc-tetrofosmin-spect-ct-study-in-mice
#8
Lan Luo, Kodai Nishi, Yoshishige Urata, Chen Yan, Al Shaimaa Hasan, Shinji Goto, Takashi Kudo, Zhao-Lan Li, Tao-Sheng Li
Epidemiological studies have suggested that ionizing radiation increases cardiovascular disease risk, but the relevant mechanism is poorly understood. We recently demonstrated that adult mice exposed to whole-body irradiation with 3 Gy gamma rays significantly decreases the number and quality of cardiac stem cells. To further determine if radiation impairs myocardial regenerative potency, a myocardial infarction model was established in adult C57BL/6 mice by ligating the left anterior descending artery approximately 6 h after sham- or whole-body gamma irradiation (0 or 3 Gy)...
December 6, 2016: Radiation Research
https://www.readbyqxmd.com/read/27918471/polyphenols-and-dna-damage-a-mixed-blessing
#9
REVIEW
Amaya Azqueta, Andrew Collins
Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds...
December 3, 2016: Nutrients
https://www.readbyqxmd.com/read/27917891/modular-architecture-and-unique-teichoic-acid-recognition-features-of-choline-binding-protein-l-cbpl-contributing-to-pneumococcal-pathogenesis
#10
Javier Gutiérrez-Fernández, Malek Saleh, Martín Alcorlo, Alejandro Gómez-Mejía, David Pantoja-Uceda, Miguel A Treviño, Franziska Voß, Mohammed R Abdullah, Sergio Galán-Bartual, Jolien Seinen, Pedro A Sánchez-Murcia, Federico Gago, Marta Bruix, Sven Hammerschmidt, Juan A Hermoso
The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca(2+)-binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp_Lipoprotein domain...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#11
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27917175/nuclear-localization-of-suppressor-of-cytokine-signaling-1-regulates-local-immunity-in-the-lung
#12
Jana Zimmer, Michael Weitnauer, Sébastien Boutin, Günter Küblbeck, Sabrina Thiele, Patrick Walker, Felix Lasitschka, Lars Lunding, Zane Orinska, Christina Vock, Bernd Arnold, Michael Wegmann, Alexander Dalpke
Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGL(tg) mice). Whereas mice fully deficient for SOCS1 die within the first 3 weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1(-/-)MGL(tg) mice) were rescued from early lethality...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27917101/selective-enzymatic-transformation-to-aldehydes-in-vivo-by-fungal-carboxylate-reductase-from-neurospora-crassa
#13
Daniel Schwendenwein, Giuseppe Fiume, Hansjörg Weber, Florian Rudroff, Margit Winkler
The enzymatic reduction of carboxylic acids is in its infancy with only a handful of biocatalysts available to this end. We have increased the spectrum of carboxylate-reducing enzymes (CARs) with the sequence of a fungal CAR from Neurospora crassa OR74A (NcCAR). NcCAR was efficiently expressed in E. coli using an autoinduction protocol at low temperature. It was purified and characterized in vitro, revealing a broad substrate acceptance, a pH optimum at pH 5.5-6.0, a Tm of 45 °C and inhibition by the co-product pyrophosphate which can be alleviated by the addition of pyrophosphatase...
November 3, 2016: Advanced Synthesis & Catalysis
https://www.readbyqxmd.com/read/27915045/in-vivo-selection-of-heterotypically-interacting-transmembrane-helices-complementary-helix-surfaces-rather-than-conserved-interaction-motifs-drive-formation-of-transmembrane-hetero-dimers
#14
Dominik Steindorf, Dirk Schneider
Single pass transmembrane proteins make up almost half of the whole transmembrane proteome. Contacts between such bitopic transmembrane proteins are common, and oligomerization of their single transmembrane helix is involved in triggering and regulation of signal transduction across cell membranes. In several recent analyses the distribution of amino acids at helix-helix contact sides has been analyzed, and e.g. a preference of amino acids with small side chains has been identified. Here we select amino acids, amino acid pairings and amino acid motifs, which mediate strong interactions of single-span transmembrane α-helices...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913590/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#15
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an inhibitory postsynaptic potential (IPSP) at low stimulation frequency (0...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#16
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27910810/production-of-tnf-alpha-ex-vivo-is-predictive-of-an-immune-response-to-flu-vaccination-in-a-frail-elderly-population
#17
Frédéric Bloch, Bénédicte Charmeteau, Michael Tovey, Jean-François Meritet, Corinne Desaint, Odile Launay, Pierre Lebon
OBJECTIVE: To investigate the relationship between the response to influenza vaccination and the ability to produce proinflamatory cytokines in elderly subjects. METHODS: Whole blood samples from 25 elderly subjects collected before influenza vaccination were stimulated with the influenza vaccine in order to evaluate the secretion of five specific cytokines: TNFα, IFNα, IFNγ, IL2 and IL10. The results were correlated with the increased HAI antibody titres two weeks after vaccination...
September 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/27909721/protective-effect-of-vk2-on-glucocorticoid-treated-mc3t3-e1-cells
#18
Yue-Lei Zhang, Jun-Hui Yin, Hao Ding, Wei Zhang, Chang-Qing Zhang, You-Shui Gao
Glucocorticoids (GCs) contribute to the increased incidence of secondary osteoporosis and osteonecrosis, and medications for the prevention and treatment of these complications have been investigated for many years. Vitamin K2 (VK2) has been proven to promote bone formation both in vitro and in vivo. In this study, we examined the effects of VK2 on dexamethasone (DEX)-treated MC3T3-E1 osteoblastic cells. We observed that VK2 promoted the proliferation and enhanced the survival of dexamethasone-treated MC3T3-E1 cells...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#19
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
November 29, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27905300/intravital-imaging-of-mouse-urothelium-reveals-activation-of-extracellular-signal-regulated-kinase-by-stretch-induced-intravesical-release-of-atp
#20
Takeshi Sano, Takashi Kobayashi, Hiromitsu Negoro, Atsushi Sengiku, Takuya Hiratsuka, Yuji Kamioka, Louis S Liou, Osamu Ogawa, Michiyuki Matsuda
To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium...
November 2016: Physiological Reports
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