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https://www.readbyqxmd.com/read/29458175/maintenance-of-hematopoietic-stem-and-progenitor-cells-in-fetal-intra-aortic-hematopoietic-clusters-by-the-sox17-notch1-hes1-axis
#1
Kiyoka Saito, Ikuo Nobuhisa, Kaho Harada, Satomi Takahashi, Maha Anani, Heiko Lickert, Masami Kanai-Azuma, Yoshiakira Kanai, Tetsuya Taga
The aorta-gonad-mesonephros region, from which definitive hematopoiesis first arises in midgestation mouse embryos, has intra-aortic hematopoietic clusters (IAHCs) containing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We previously reported expression of the transcription factor Sox17 in IAHCs, and overexpression of Sox17 in CD45low c-KIThigh cells comprising IAHCs maintains the formation of cell clusters and their multipotency in vitro over multiple passages. Here, we demonstrate the importance of NOTCH1 in IAHC formation and maintenance of the HSC/HPC phenotype...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29455245/chronic-hyperinsulinemia-induced-mir-27b-is-linked-to-adipocyte-insulin-resistance-by-targeting-insulin-receptor
#2
Ankita Srivastava, Kripa Shankar, Muheeb Beg, Sujith Rajan, Abhishek Gupta, Salil Varshney, Durgesh Kumar, Sanchita Gupta, Raj Kumar Mishra, Anil Nilkanth Gaikwad
Defect in insulin signaling leads to the development of insulin resistance followed by type 2 diabetes. Exploiting our previously developed physiological chronic hyperinsulinemia (CI)-mediated insulin resistance (IR) model, we wanted to understand how miRNAs contribute to the development of IR. Amongst the identified and validate miRNAs, the expression of miR-27b was found to be highly upregulated during CI-induced IR in 3T3-L1 adipocytes. We also validated the expression of miR-27b in CI-induced IR in human mesenchymal stem cell (hMSC)-derived adipocytes and in vivo high fat diet (HFD)-induced IR mice model...
February 17, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29454215/effect-based-trigger-values-for-in-vitro-and-in-vivo-bioassays-performed-on-surface-water-extracts-supporting-the-environmental-quality-standards-eqs-of-the-european-water-framework-directive
#3
Beate I Escher, Selim Aїt-Aїssa, Peter A Behnisch, Werner Brack, François Brion, Abraham Brouwer, Sebastian Buchinger, Sarah E Crawford, David Du Pasquier, Timo Hamers, Karina Hettwer, Klára Hilscherová, Henner Hollert, Robert Kase, Cornelia Kienle, Andrew J Tindall, Jochen Tuerk, Ron van der Oost, Etienne Vermeirssen, Peta A Neale
Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures...
February 14, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29454148/-68-ga-galmydar-biodistribution-and-radiation-dosimetry-studies-in-rodents
#4
Jothilingam Sivapackiam, Richard Laforest, Vijay Sharma
INTRODUCTION: 68 Ga-Galmydar is an avid transport substrate of ABCB1 (P-Glycoprotein; 170kDa plasma membrane protein), breast cancer resistance protein (BCRP; ABCG2; 72kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and localizes within the mitochondria of tumor and myocardium cells. 68 Ga-Galmydar excretes from blood pool quickly, and shows stable retention within rat myocardium in vivo for extended periods, therefore, the agent shows potential to enable myocardial perfusion imaging...
December 1, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29453281/the-pi3k%C3%AE-selective-inhibitor-idelalisib-minimally-interferes-with-immune-effector-function-mediated-by-rituximab-or-obinutuzumab-and-significantly-augments-b-cell-depletion-in-vivo
#5
Adam Palazzo, Sylvia Herter, Laura Grosmaire, Randy Jones, Christian R Frey, Florian Limani, Marina Bacac, Pablo Umana, Robert J Oldham, Michael J E Marshall, Kerry L Cox, Anna H Turaj, Mark S Cragg, Christian Klein, Matthew J Carter, Stacey Tannheimer
Idelalisib is a highly selective oral inhibitor of PI3Kδ indicated for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab. Despite additive clinical effects, previous studies have paradoxically demonstrated that targeted therapies potentially negatively affect anti-CD20 mAb effector mechanisms. To address these potential effects, we investigated the impact of PI3Kδ inhibition by idelalisib on the effector mechanisms of rituximab and obinutuzumab. At clinically relevant concentrations, idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent cellular cytotoxicity and phagocytosis on human lymphoma cell lines, while maintaining the superiority of obinutuzumab-mediated Ab-dependent cellular cytotoxicity...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29451713/glucose-effectiveness-is-a-critical-pathogenic-factor-leading-to-the-emergence-of-glucose-intolerance-and-type-2-diabetes-mellitus-an-ignored-hypothesis
#6
F P Alford, J E Henriksen, C Rantzau, H Beck-Nielsen
BACKGROUND: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels, [glucose effectiveness (GE)], followed the introduction of the Minimal Model IVGTT technique. METHODS: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis...
February 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29447006/retinoic-acid-signaling-promotes-the-cytoskeletal-rearrangement-of-embryonic-epicardial-cells
#7
Suya Wang, Jianshi Yu, Jace W Jones, Keely Pierzchalski, Maureen A Kane, Paul A Trainor, José Xavier-Neto, Alexander R Moise
All- trans-retinoic acid (RA), a vitamin A metabolite, is an important signaling molecule required for the proper development of the heart. The epicardium is the main source of RA in the embryonic heart, yet the cardiogenic functions of epicardial-produced RA are not fully understood. Here, we investigated the roles of RA signaling in the embryonic epicardium using in vivo and in vitro models of excess or deficiency of RA. Our results suggested that RA signaling facilitates the cytoskeletal rearrangement required for the epicardial-to-mesenchymal transition of epicardial cells...
February 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29445990/time-dependent-lxr-rxr-pathway-modulation-characterizes-capillary-remodeling-in-inflammatory-corneal-neovascularization
#8
Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Pierfrancesco Mirabelli, Mieszko Lachota, Lasse Jensen, Beatrice Peebo, Neil Lagali
Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency...
February 14, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29445211/bronchoscopic-fibered-confocal-fluorescence-microscopy-for-longitudinal-in-vivo-assessment-of-pulmonary-fungal-infections-in-free-breathing-mice
#9
Liesbeth Vanherp, Jennifer Poelmans, Amy Hillen, Kristof Govaerts, Sarah Belderbos, Tinne Buelens, Katrien Lagrou, Uwe Himmelreich, Greetje Vande Velde
Respiratory diseases, such as pulmonary infections, are an important cause of morbidity and mortality worldwide. Preclinical studies often require invasive techniques to evaluate the extent of infection. Fibered confocal fluorescence microscopy (FCFM) is an emerging optical imaging technique that allows for real-time detection of fluorescently labeled cells within live animals, thereby bridging the gap between in vivo whole-body imaging methods and traditional histological examinations. Previously, the use of FCFM in preclinical lung research was limited to endpoint observations due to the invasive procedures required to access lungs...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444200/loss-of-sirt3-accelerates-arterial-thrombosis-by-increasing-formation-of-neutrophil-extracellular-traps-and-plasma-tissue-factor-activity
#10
Daniel S Gaul, Julien Weber, Lambertus J Van Tits, Susanna Sluka, Lisa Pasterk, Martin F Reiner, Natacha Calatayud, Christine Lohmann, Roland Klingenberg, Jürgen Pahla, Daria Vdovenko, Felix C Tanner, Giovanni G Camici, Urs Eriksson, Johan Auwerx, François Mach, Stephan Windecker, Nicolas Rodondi, Thomas F L Uuml Scher, Stephan Winnik, Christian M Matter
BACKGROUND: Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3-/- mice (n = 6) was reduced by half compared to Sirt3+/+ wildtype (WT, n = 8, p<0...
February 10, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29440725/development-of-a-primary-human-small-intestine-on-a-chip-using-biopsy-derived-organoids
#11
Magdalena Kasendra, Alessio Tovaglieri, Alexandra Sontheimer-Phelps, Sasan Jalili-Firoozinezhad, Amir Bein, Angeliki Chalkiadaki, William Scholl, Cheng Zhang, Hannah Rickner, Camilla A Richmond, Hu Li, David T Breault, Donald E Ingber
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440697/ectopic-expression-of-s28a-mutated-histone-h3-modulates-longevity-stress-resistance-and-cardiac-function-in-drosophila
#12
J P Joos, A R Saadatmand, C Schnabel, I Viktorinová, T Brand, M Kramer, S Nattel, D Dobrev, P Tomancak, J Backs, P Kleinbongard, G Heusch, K Lorenz, E Koch, S Weber, A El-Armouche
Histone H3 serine 28 (H3S28) phosphorylation and de-repression of polycomb repressive complex (PRC)-mediated gene regulation is linked to stress conditions in mitotic and post-mitotic cells. To better understand the role of H3S28 phosphorylation in vivo, we studied a Drosophila strain with ectopic expression of constitutively-activated H3S28A, which prevents PRC2 binding at H3S28, thus mimicking H3S28 phosphorylation. H3S28A mutants showed prolonged life span and improved resistance against starvation and paraquat-induced oxidative stress...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438534/both-in-vivo-fsh-depletion-and-follicular-exposure-to-gonadotrophin-releasing-hormone-analogues-in-vitro-are-not-effective-to-prevent-follicular-depletion-during-chemotherapy-in-mice
#13
F Horicks, G Van Den Steen, C Gervy, H J Clarke, I Demeestere
STUDY QUESTION: Does fertility preservation using gonadotrophin-releasing hormone (GnRH) analogues during chemotherapy act through a direct effect on the ovary or through inhibition of FSH secretion? SUMMARY ANSWER: The absence of FSH in vivo and the direct exposition of ovarian follicles to GnRH analogues in vitro did not prevent chemotherapy-induced ovarian damage. WHAT IS KNOWN ALREADY: The potential mechanisms of action of GnRH analogues in protecting ovaries against chemotherapy damage remain poorly understood...
February 9, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29436396/rapid-activation-of-tumor-associated-macrophages-boosts-preexisting-tumor-immunity
#14
Sabine Hoves, Chia-Huey Ooi, Carsten Wolter, Hadassah Sade, Stefan Bissinger, Martina Schmittnaegel, Oliver Ast, Anna M Giusti, Katharina Wartha, Valeria Runza, Wei Xu, Yvonne Kienast, Michael A Cannarile, Hyam Levitsky, Solange Romagnoli, Michele De Palma, Dominik Rüttinger, Carola H Ries
Depletion of immunosuppressive tumor-associated macrophages (TAMs) or reprogramming toward a proinflammatory activation state represent different strategies to therapeutically target this abundant myeloid population. In this study, we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAMs to profound and rapid reprogramming in the presence of a CD40 agonist before their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R+CD40 stimulation of macrophages is sufficient to create a proinflammatory tumor milieu that reinvigorates an effective T cell response in transplanted tumors that are either responsive or insensitive to immune checkpoint blockade...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29434189/ablation-of-protein-phosphatase-5-pp5-leads-to-enhanced-both-bone-and-cartilage-development-in-mice
#15
Jun Wang, Yong Cao, Bin Qiu, Jianyong Du, Tingting Wang, Chao Wang, Ran Deng, Xudong Shi, Kai Gao, Zhongwen Xie, Weidong Yong
This study aimed to investigate the role of protein phosphatase 5 (PP5) on bone and cartilage development using both in vivo and in vitro approaches. Six- to 8-week- old male PP5 knockout mice (KO) and their wild-type (WT) littermate controls were randomly selected for this study, and their body weights and bone (femur) lengths were measured. Micro-computed tomography scanning (Micro-CT) was performed to determine femoral bone density and micro-architecture. Mesenchymal stem cells (MSCs) isolated from bone marrow were used to examine the effects of PP5 on osteogenesis in vitro...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29431735/vhl-deletion-in-osteoblasts-boosts-cellular-glycolysis-and-improves-global-glucose-metabolism
#16
Naomi Dirckx, Robert J Tower, Evi M Mercken, Roman Vangoitsenhoven, Caroline Moreau-Triby, Tom Breugelmans, Elena Nefyodova, Ruben Cardoen, Chantal Mathieu, Bart Van der Schueren, Cyrille B Confavreux, Thomas L Clemens, Christa Maes
The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel-Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin...
February 12, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29431697/convergent-therapeutic-strategies-to-overcome-the-heterogeneity-of-acquired-resistance-in-brafv600e-colorectal-cancer
#17
Mehlika Hazar-Rethinam, Marianna Kleyman, G Celine Han, David Liu, Leanne G Ahronian, Heather A Shahzade, Lifeng Chen, Aparna R Parikh, Jill N Allen, Jeffrey W Clark, Eunice L Kwak, Jason E Faris, Janet E Murphy, Theodore S Hong, Emily E Van Seventer, Brandon Nadres, Catriona B Hong, Joseph M Gurski, Nicholas A Jessop, Dora Dias-Santagata, A John Iafrate, Eliezer M Van Allen, Ryan B Corcoran
Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from BRAFV600E colorectal cancer patients receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a novel pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivo...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29429092/use-of-cryo-em-to-study-the-structure-of-chemoreceptor-arrays-in-vivo
#18
Wen Yang, Ariane Briegel
Cryo-electron microscopy (cryo-EM) allows the imaging of intact macromolecular complexes in the context of whole cells. The biological samples for cryo-EM are kept in a near-native state by flash freezing, without the need for any additional sample preparation or fixation steps. Since transmission electron microscopy only generates 2D projections of the samples, the specimen has to be tilted in order to recover its 3D structural information. This is done by collecting images of the sample with various tilt angles in respect to the electron beam...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29429078/transmembrane-signal-transduction-in-bacterial-chemosensing
#19
Michael D Manson
Like all living organisms, bacteria must communicate with the world around them. As they typically live as single cells, the communication with their environment must occur at the cell membrane, both in moving molecules in and out and in transmitting information about their surroundings to response elements within the cell. This volume is devoted primarily to methods used to study either the behavior of bacteria in response to their environment or methods used to study events that involve signaling pathways that are initiated by events at the cell membrane...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29429012/er-stress-and-genomic-instability-induced-by-gamma-radiation-in-mice-primary-cultured-glial-cells
#20
Jit Chatterjee, Rajesha K Nairy, Jaldeep Langhnoja, Ashutosh Tripathi, Rajashekhar K Patil, Prakash P Pillai, Mohammed S Mustak
Ionizing radiation induces various pathophysiological conditions by altering central nervous system (CNS) homeostasis, leading to neurodegenerative diseases. However, the potential effect of ionizing radiation response on cellular physiology in glial cells is unclear. In the present study, micronucleus test, comet assay, and RT-PCR were performed to investigate the potential effect of gamma radiation in cultured oligodendrocytes and astrocytes with respect to genomic instability, Endoplasmic Reticulum (ER) stress, and inflammation...
February 10, 2018: Metabolic Brain Disease
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