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https://www.readbyqxmd.com/read/28645478/a-tspo-ligand-prevents-mitochondrial-sterol-accumulation-and-dysfunction-during-myocardial-ischemia-reperfusion-in-hypercholesterolemic-rats
#1
Julien Musman, Stéphanie Paradis, Mathieu Panel, Sandrine Pons, Caroline Barau, Claudio Caccia, Valerio Leoni, Bijan Ghaleh, Didier Morin
A major cause of cell death during myocardial ischemia-reperfusion is mitochondrial dysfunction. We previously showed that the reperfusion of an ischemic myocardium was associated with an accumulation of cholesterol into mitochondria and a concomitant strong generation of auto-oxidized oxysterols. The inhibition of mitochondrial accumulation of cholesterol abolished the formation of oxysterols and prevented mitochondrial injury at reperfusion. The aim of this study was to investigate the impact of hypercholesterolemia on sterol and oxysterol accumulation in rat cardiac cytosols and mitochondria and to analyse the effect of the translocator protein ligand 4'-chlorodiazepam on this accumulation and mitochondrial function...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28644741/ras-signaling-regulates-stem-cells-and-amelogenesis-in-the-mouse-incisor
#2
X Zheng, A F Goodwin, H Tian, A H Jheon, O D Klein
The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28641501/hematological-characterizations-and-molecular-diagnostic-aspects-of-hb-wiangpapao-%C3%AE-44-ce2-pro%C3%A2-ser-%C3%AE-1-ccg-tcg-hba1-c-133c-t-a-new-%C3%AE-globin-variant-found-in-a-pregnant-thai-woman
#3
Sitthichai Panyasai, Sakorn Pornprasert
We report the hematological parameters and provide a rapid molecular analysis method for detection of Hb Wiangpapao [α44(CE2)Pro→Ser, CCG>TCG; HBA1: c.133C>T], a new α-globin variant found in a pregnant Thai woman. Her red cell indices were measured by an automated blood counter. The results were: red blood cell (RBC) count 4.03 × 10(12)/L, Hb 13.1 (g/dL), packed cell volume (PCV) 0.39 L/L, mean corpuscular volume (MCV) 97.0 fL, mean corpuscular hemoglobin (Hb) (MCH) 32.5 pg, mean corpuscular Hb concentration (MCHC) 33...
June 23, 2017: Hemoglobin
https://www.readbyqxmd.com/read/28637904/ifn-%C3%AE-expressing-th17-cells-are-required-for-development-of-severe-ocular-surface-autoimmunity
#4
Yihe Chen, Sunil K Chauhan, Chunyi Shao, Masahiro Omoto, Takenori Inomata, Reza Dana
Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN-γ has also been implicated in DED; however, it remains unclear to what extent Th1 cells contribute to DED pathogenesis. In this study, we investigated the cellular source of IFN-γ and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A(+)IFN-γ(+) (Th17/1) population and determined that these cells are derived from Th17 precursors. Adoptive transfer of Th17/1, but not Th1, cells confers the disease to naive recipients as effectively as do Th17 cells alone...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28630448/progesterone-prevents-epithelial-mesenchymal-transition-of-ovine-amniotic-epithelial-cells-and-enhances-their-immunomodulatory-properties
#5
Angelo Canciello, Valentina Russo, Paolo Berardinelli, Nicola Bernabò, Aurelio Muttini, Mauro Mattioli, Barbara Barboni
The in vitro expansion is detrimental to therapeutic applications of amniotic epithelial cells (AEC), an emerging source of fetal stem cells. This study provides molecular evidences of progesterone (P4) role in preventing epithelial-mesenchymal transition (EMT) in ovine AEC (oAEC). oAEC amplified under standard conditions spontaneously acquired mesenchymal properties through the up-regulation of EMT-transcription factors. P4 supplementation prevented phenotype shift by inhibiting the EMT-inducing mechanism such as the autocrine production of TGF-β and the activation of intracellular-related signaling...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#6
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28626570/riboflavin-as-a-bioorthogonal-photocatalyst-for-the-activation-of-a-pt-iv-prodrug
#7
Silvia Alonso-de Castro, Emmanuel Ruggiero, Ane Ruiz-de-Angulo, Elixabete Rezabal, Juan C Mareque-Rivas, Xabier Lopez, Fernando López-Gallego, Luca Salassa
Encouraging developments demonstrate that few transition metal and organometallic catalysts can operate in a bioorthogonal fashion and promote non-natural chemistry in living systems by minimizing undesired side reactions with cellular components. These catalytic processes have potential for applications in medicinal chemistry and chemical biology. However, the stringent conditions of the cell environment severely limit the number of accessible metal catalysts and exogenous reactions. Herein, we report an unorthodox approach and a new type of bioorthogonal catalytic reaction, in which a metal complex is an unconventional substrate and an exogenous biological molecule acts as a catalyst...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28597843/dynamical-predictors-of-an-imminent-phenotypic-switch-in-bacteria
#8
Huijing Wang, Christian Ray
Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is "flickering" of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite and protein fluctuations in bacteria, we hypothesized that metabolic early warning indicators predict imminent transitions across a network threshold caused by enzyme saturation...
June 9, 2017: Physical Biology
https://www.readbyqxmd.com/read/28585693/influences-of-soaking-temperature-and-storage-conditions-on-hardening-of-soybeans-glycine-max-and-red-kidney-beans-phaseolus-vulgaris
#9
Takako Koriyama, Yoko Sato, Kumiko Iijima, Midori Kasai
The influences of soaking treatment and storage conditions on the softening of cooked beans, namely, soybeans and red kidney beans, were investigated. It was revealed that the softening of fresh soybeans and fresh red kidney beans was suppressed during subsequent boiling after soaking treatment at 50 and 60 °C. Furthermore, in treated aged soybeans and red kidney beans that were subjected to storage at 30 °C/75% relative humidity for 6 mo and soaking treatment at 50 to 60 °C, the hardness during cooking was further amplified...
June 6, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28580966/synergistic-cooperation-promotes-multicellular-performance-and-unicellular-free-rider-persistence
#10
William W Driscoll, Michael Travisano
The evolution of multicellular life requires cooperation among cells, which can be undermined by intra-group selection for selfishness. Theory predicts that selection to avoid non-cooperators limits social interactions among non-relatives, yet previous evolution experiments suggest that intra-group conflict is an outcome, rather than a driver, of incipient multicellular life cycles. Here we report the evolution of multicellularity via two distinct mechanisms of group formation in the unicellular budding yeast Kluyveromyces lactis...
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28570625/an-androgen-response-element-driven-reporter-assay-for-the-detection-of-androgen-receptor-activity-in-prostate-cells
#11
Waqas Azeem, Margrete Reime Hellem, Jan Roger Olsen, Yaping Hua, Kristo Marvyin, Yi Qu, Biaoyang Lin, Xisong Ke, Anne Margrete Øyan, Karl-Henning Kalland
The androgen receptor (AR) transcription factor plays a key role in the development and progression of prostate cancer, as is evident from the efficacy of androgen-deprivation therapy, AR is also the most frequently mutated gene, in castration resistant prostate cancer (CRPC). AR has therefore become an even more attractive therapeutic target in aggressive and disseminated prostate cancer. To investigate mechanisms of AR and AR target gene activation in different subpopulations of prostate cancer cells, a toolkit of AR expressor and androgen response element (ARE) reporter vectors were developed...
2017: PloS One
https://www.readbyqxmd.com/read/28560396/mitochondrial-ca2-removal-amplifies-trail-cytotoxicity-toward-apoptosis-resistant-tumor-cells-via-promotion-of-multiple-cell-death-modalities
#12
Natsuhiko Takata, Yohei Ohshima, Miki Suzuki-Karasaki, Yukihiro Yoshida, Yasuaki Tokuhashi, Yoshihiro Suzuki-Karasaki
Ca2+ has emerged as a new target for cancer treatment since tumor-specific traits in Ca2+ dynamics contributes to tumorigenesis, malignant phenotypes, drug resistance, and survival in different tumor types. However, Ca2+ has a dual (pro-death and pro-survival) function in tumor cells depending on the experimental conditions. Therefore, it is necessary to minimize the onset of the pro-survival Ca2+ signals caused by the therapy. For this purpose, a better understanding of pro-survival Ca2+ pathways in cancer cells is critical...
May 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28552952/asymmetric-regulation-of-quorum-sensing-receptors-drives-autoinducer-specific-gene-expression-programs-in-vibrio-cholerae
#13
Amanda Hurley, Bonnie L Bassler
Quorum sensing (QS) is a mechanism of chemical communication that bacteria use to monitor cell-population density and coordinate group behaviors. QS relies on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. Vibrio cholerae employs parallel QS circuits that converge into a shared signaling pathway. At high cell density, the CqsS and LuxPQ QS receptors detect the intra-genus and inter-species autoinducers CAI-1 and AI-2, respectively, to repress virulence factor production and biofilm formation...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#14
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28528511/met-overexpression-and-gene-amplification-prevalence-clinico-pathological-characteristics-and-prognostic-significance-in-a-large-cohort-of-patients-with-surgically-resected-nsclc
#15
William Sterlacci, Michael Fiegl, Mathias Gugger, Lukas Bubendorf, Spasenija Savic, Alexandar Tzankov
The prevalence of overexpression and amplification of the proto-oncogene mesenchymal epithelial transition (MET) in non-small cell lung cancer (NSCLC) varies greatly in the literature. Since MET is a potential treatment target, knowledge of its prevalence and prognostic importance is crucial. We investigated MET expression and gene status in 735 NSCLC cases using tissue microarrays. Prognostic significance as well as correlations with various clinico-pathological parameters were evaluated. The prevalence of MET overexpression was 17% and MET amplification was present in 2...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28498870/brg1-chromatin-remodeling-atpase-balances-germ-layer-patterning-by-amplifying-the-transcriptional-burst-at-midblastula-transition
#16
Gabriele Wagner, Nishant Singhal, Dario Nicetto, Tobias Straub, Elisabeth Kremmer, Ralph A W Rupp
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin remodeling complexes...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28498365/inhibition-of-twist1-mediated-invasion-by-chk2-promotes-premature-senescence-in-p53-defective-cancer-cells
#17
Debasis Nayak, Anmol Kumar, Souneek Chakraborty, Reyaz Ur Rasool, Hina Amin, Archana Katoch, Veena Gopinath, Vidushi Mahajan, Mahesh K Zilla, Bilal Rah, Sumit G Gandhi, Asif Ali, Lekha Dinesh Kumar, Anindya Goswami
Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28489848/a-coordinated-dna-damage-response-promotes-adult-quiescent-neural-stem-cell-activation
#18
Lara Barazzuol, Limei Ju, Penny A Jeggo
Stem and differentiated cells frequently differ in their response to DNA damage, which can determine tissue sensitivity. By exploiting insight into the spatial arrangement of subdomains within the adult neural subventricular zone (SVZ) in vivo, we show distinct responses to ionising radiation (IR) between neural stem and progenitor cells. Further, we reveal different DNA damage responses between neonatal and adult neural stem cells (NSCs). Neural progenitors (transit amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo apoptosis after 2 Gy IR...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28476157/microglia-amplify-inflammatory-activation-of-astrocytes-in-manganese-neurotoxicity
#19
Kelly S Kirkley, Katriana A Popichak, Maryam F Afzali, Marie E Legare, Ronald B Tjalkens
BACKGROUND: As the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses. In diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and human immunodeficiency virus-induced dementia, activation of microglia precedes astrogliosis and overt neuronal loss. Although microgliosis is implicated in manganese (Mn) neurotoxicity, the role of microglia and glial crosstalk in Mn-induced neurodegeneration is poorly understood...
May 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28476069/elac-3-12-di-o-acetyl-8-o-tigloilingol-a-plant-derived-lathyrane-diterpene-induces-subventricular-zone-neural-progenitor-cell-proliferation-through-pkc%C3%AE-activation
#20
Maribel Murillo-Carretero, Noelia Geribaldi-Doldán, Eugenia Flores-Giubi, Francisco García-Bernal, Elkin A Navarro-Quiroz, Manuel Carrasco, Antonio J Macías-Sánchez, Pilar Herrero-Foncubierta, Antonio Delgado-Ariza, Cristina Verástegui, Jesús Domínguez-Riscart, Mourad Daoubi, Rosario Hernández-Galán, Carmen Castro
BACKGROUND AND PURPOSE: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation...
May 5, 2017: British Journal of Pharmacology
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