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https://www.readbyqxmd.com/read/28231483/a-novel-redox-regulator-mntnbuoe-2-pyp-5-enhances-normal-hematopoietic-stem-progenitor-cell-function
#1
Y Zhao, D W Carroll, Y You, L Chaiswing, R Wen, I Batinic-Haberle, S Bondada, Y Liang, D K St Clair
The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP(5+)(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs...
February 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28231468/parkinson-sac-domain-mutation-in-synaptojanin-1-impairs-clathrin-uncoating-at-synapses-and-triggers-dystrophic-changes-in-dopaminergic-axons
#2
Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J McCartney, Heather Wheeler, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Timothy A Ryan, Pietro De Camilli
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1's 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#3
Lijuan Pang, Matthew S Macauley, Britni M Arlian, Corwin M Nycholat, James C Paulson
Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell Siglecs (sialic acid-binding immunoglobulin-like lectin) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#4
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28231300/detection-and-partial-discrimination-of-atypical-and-classical-bovine-spongiform-encephalopathies-in-cattle-and-primates-using-real-time-quaking-induced-conversion-assay
#5
Etienne Levavasseur, Anne-Gaëlle Biacabe, Emmanuel Comoy, Audrey Culeux, Katarina Grznarova, Nicolas Privat, Steve Simoneau, Benoit Flan, Véronique Sazdovitch, Danielle Seilhean, Thierry Baron, Stéphane Haïk
The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health...
2017: PloS One
https://www.readbyqxmd.com/read/28231293/photoacoustic-imaging-features-of-intraocular-tumors-retinoblastoma-and-uveal-melanoma
#6
Guan Xu, Yafang Xue, Zeynep Gürsel Özkurt, Naziha Slimani, Zizhong Hu, Xueding Wang, Kewen Xia, Teng Ma, Qifa Zhou, Hakan Demirci
The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images...
2017: PloS One
https://www.readbyqxmd.com/read/28231269/a-mouse-model-of-paralytic-myelitis-caused-by-enterovirus-d68
#7
Alison M Hixon, Guixia Yu, J Smith Leser, Shigeo Yagi, Penny Clarke, Charles Y Chiu, Kenneth L Tyler
In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM) cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68) respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF) from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28230931/spatially-assembled-bilayer-cell-sheets-of-stem-cells-and-endothelial-cells-using-thermosensitive-hydrogels-for-therapeutic-angiogenesis
#8
Indong Jun, Taufiq Ahmad, Seongwoo Bak, Joong-Yup Lee, Eun Mi Kim, Jinkyu Lee, Yu Bin Lee, Hongsoo Jeong, Hojeong Jeon, Heungsoo Shin
Although the coculture of multiple cell types has been widely employed in regenerative medicine, in vivo transplantation of cocultured cells while maintaining the hierarchical structure remains challenging. Here, a spatially assembled bilayer cell sheet of human mesenchymal stem cells and human umbilical vein endothelial cells on a thermally expandable hydrogel containing fibronectin is prepared and its effect on in vitro proangiogenic functions and in vivo ischemic injury is investigated. The expansion of hydrogels in response to a temperature change from 37 to 4 °C allows rapid harvest and delivery of the bilayer cell sheet to two different targets (an in vitro model glass surface and in vivo tissue)...
February 23, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28230865/erbb4-signaling-stimulates-pro-inflammatory-macrophage-apoptosis-and-limits-colonic-inflammation
#9
Michael A Schumacher, Matija Hedl, Clara Abraham, Jessica K Bernard, Patricia R Lozano, Jonathan J Hsieh, Dana Almohazey, Edie B Bucar, Shivesh Punit, Peter J Dempsey, Mark R Frey
Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230783/acute-toxicities-of-the-saxitoxin-congeners-gonyautoxin-5-gonyautoxin-6-decarbamoyl-gonyautoxin-2-3-decarbamoyl-neosaxitoxin-c-1-2-and-c-3-4-to-mice-by-various-routes-of-administration
#10
Andrew I Selwood, Craig Waugh, David T Harwood, Lesley L Rhodes, John Reeve, Jim Sim, Rex Munday
Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required...
February 21, 2017: Toxins
https://www.readbyqxmd.com/read/28230260/elevation-of-sharpin-protein-levels-in-prostate-adenocarcinomas-promotes-metastasis-and-impairs-patient-survivals
#11
Hai Huang, Tao Du, Yiming Zhang, Yiming Lai, Kaiwen Li, Xinxing Fan, Dingjun Zhu, Tianxin Lin, Kewei Xu, Jian Huang, Leyuan Liu, Zhenghui Guo
BACKGROUND: SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model...
February 23, 2017: Prostate
https://www.readbyqxmd.com/read/28230213/knock-in-human-fgfr3-achondroplasia-mutation-as-a-mouse-model-for-human-skeletal-dysplasia
#12
Yi-Ching Lee, I-Wen Song, Ya-Ju Pai, Sheng-De Chen, Yuan-Tsong Chen
Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3(G380R) (FGFR3(ACH)) cDNA, the most common mutation in human ACH...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230162/n-acetylated-proline-glycine-proline-accelerates-cutaneous-wound-healing-and-neovascularization-by-human-endothelial-progenitor-cells
#13
Yang Woo Kwon, Soon Chul Heo, Tae Wook Lee, Gyu Tae Park, Jung Won Yoon, Il Ho Jang, Seung-Chul Kim, Hyun-Chang Ko, Youngjae Ryu, Hyeona Kang, Chang Man Ha, Sang Chul Lee, Jae Ho Kim
Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230102/identification-of-a-new-virulent-clade-in-enterohemorrhagic-escherichia-coli-o26-h11-h-sequence-type-29
#14
Nozomi Ishijima, Ken-Ichi Lee, Tomomi Kuwahara, Haruyuki Nakayama-Imaohji, Saori Yoneda, Atsushi Iguchi, Yoshitoshi Ogura, Tetsuya Hayashi, Makoto Ohnishi, Sunao Iyoda
Enterohemorrhagic Escherichia coli (EHEC) O26 infections cause severe human diseases such as hemolytic uremic syndrome and encephalopathy, and is the predominant serogroup among non-O157 EHEC in many countries. Shiga toxin (Stx), which consists of two distinct types (Stx1 and Stx2), plays a central role in EHEC pathogenesis. The major stx gene type in EHEC O26 strains is stx1, although isolates with only stx2 have emerged in Japan since 2012 and have been reported in Europe. In this study, we selected 27 EHEC O26 strains isolated in Japan and identified a distinct genetic clade within sequence type (ST) 29, designated ST29C1, that carried only stx2 and had the plasmid gene profile ehxA+/katP-/espP+/etpD-...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230087/nardilysin-regulates-inflammation-metaplasia-and-tumors-in-murine-stomach
#15
Yuto Kimura, Kozo Ikuta, Takeshi Kimura, Tsutomu Chiba, Hiroko Oshima, Masanobu Oshima, Eiichiro Nishi, Hiroshi Seno
Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#16
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229935/mice-deficient-in-l-12-15-lipoxygenase-show-increased-vulnerability-to-3-nitropropionic-acid-neurotoxicity
#17
Yan He, Rita C Akumuo, Yuan Yang, Sandra J Hewett
Considerable evidence supports a contributory role for leukocyte-type 12/15 Lipoxygenase (L-12/15 LO) in mediating hippocampal and cortical neuronal injury in models of Alzheimer's disease and stroke. Whether L-12/15 LO contributes to neuronal injury in a model of Huntington's disease (HD) has yet to be determined. HD is characterized by marked striatal neuronal loss, which can be mimicked in humans and animals by inhibition of mitochondrial complex II using 3-Nitropropionic acid (3-NP). Herein, we compared histological and behavioral outcomes between mice that were wild-type or null for L-12/15 LO following systemic injection of 3NP...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229909/paradoxical-inhibition-of-glycolysis-by-pioglitazone-opposes-the-mitochondriopathy-caused-by-aif-deficiency
#18
Paule Bénit, Alice Pelhaître, Elise Saunier, Sylvie Bortoli, Assetou Coulibaly, Malgorzata Rak, Manuel Schiff, Guido Kroemer, Massimo Zeviani, Pierre Rustin
Mice with the hypomorphic AIF-Harlequin mutation exhibit a highly heterogeneous mitochondriopathy that mostly affects respiratory chain complex I, causing a cerebral pathology that resembles that found in patients with AIF loss-of-function mutations. Here we describe that the antidiabetic drug pioglitazone (PIO) can improve the phenotype of a mouse Harlequin (Hq) subgroup, presumably due to an inhibition of glycolysis that causes an increase in blood glucose levels. This glycolysis-inhibitory PIO effect was observed in cultured astrocytes from Hq mice, as well as in human skin fibroblasts from patients with AIF mutation...
February 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28229533/expansion-of-myeloid-derived-suppressor-cells-with-aging-in-the-bone-marrow-of-mice-through-a-nf-%C3%AE%C2%BAb-dependent-mechanism
#19
Rafael R Flores, Cheryl L Clauson, Joonseok Cho, Byeong-Chel Lee, Sara J McGowan, Darren J Baker, Laura J Niedernhofer, Paul D Robbins
With aging, there is progressive loss of tissue homeostasis and functional reserve, leading to an impaired response to stress and an increased risk of morbidity and mortality. A key mediator of the cellular response to damage and stress is the transcription factor NF-κB. We demonstrated previously that NF-κB transcriptional activity is upregulated in tissues from both natural aged mice and in a mouse model of a human progeroid syndrome caused by defective repair of DNA damage (ERCC1-deficient mice). We also demonstrated that genetic reduction in the level of the NF-κB subunit p65(RelA) in the Ercc1(-/∆) progeroid mouse model of accelerated aging delayed the onset of age-related pathology including muscle wasting, osteoporosis, and intervertebral disk degeneration...
February 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28229411/therapeutic-application-of-human-wharton-jelly-mesenchymal-stem-cells-in-skin-injury-of-scid
#20
Vikram Sabapathy, Balasubramanian Sundaram, Sanjay Kumar
Mesenchymal stem cells (MSCs) are blossoming as a credible source for regenerative medical applications. The use of fetal MSCs is gaining momentum for therapeutic use. The ease of isolation, enhanced characteristics, and immunomodulation properties renders the utilization of fetal MSCs for numerous clinical applications. In this article, we will demonstrate a step-by-step protocol for isolation of Wharton's jelly MSCs (WJMSCs) from the human umbilical cord matrix, preparation of human platelet lysate, fabricating amniotic membrane scaffold and mice model to study skin regeneration using a combination of MSCs and decellularized amniotic membrane scaffold...
2017: Methods in Molecular Biology
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