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N Moore, M Moreno Gonzales, K Bonner, B Smith, W Park, M Stegall
Plasma cells (PCs) are a major source of alloantibody in transplant patients and are resistant to current therapy. Since receptor/ligand interactions in stromal microenvironments play important roles in the localization, development and survival of normal PCs, we hypothesized that interfering with CXCR4/CXCL12 interactions with plerixafor might cause PC depletion and enhance the efficacy of the proteasome inhibitor, bortezomib. PCs in mouse spleen, bone marrow and peripheral blood demonstrated CXCR4 expression...
February 24, 2017: American Journal of Transplantation
Matthew E Welsch, Anna Kaplan, Jennifer M Chambers, Michael E Stokes, Pieter H Bos, Arie Zask, Yan Zhang, Marta Sanchez-Martin, Michael A Badgley, Christine S Huang, Timothy H Tran, Hemanth Akkiraju, Lewis M Brown, Renu Nandakumar, Serge Cremers, Wan Seok Yang, Liang Tong, Kenneth P Olive, Adolfo Ferrando, Brent R Stockwell
Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins...
February 23, 2017: Cell
Chia-Wei Cheng, Valentina Villani, Roberta Buono, Min Wei, Sanjeev Kumar, Omer H Yilmaz, Pinchas Cohen, Julie B Sneddon, Laura Perin, Valter D Longo
Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing β cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models...
February 23, 2017: Cell
Sofie V Hellsten, Mikaela M Eriksson, Emilia Lekholm, Vasiliki Arapi, Emelie Perland, Robert Fredriksson
SLC38A9 is characterized as a lysosomal component of the amino acid sensing Ragulator-RAG GTPase complex, controlling the mechanistic target of rapamycin complex 1 (mTORC1). Here, immunohistochemistry was used to map SLC38A9 in mouse brain and staining was detected throughout the brain, in cortex, hypothalamus, thalamus, hippocampus, brainstem and cerebellum. More specifically, immunostaining was found in areas known to be involved in amino acid sensing and signaling pathways e.g. piriform cortex and hypothalamus...
2017: PloS One
Elif Bozcal, Melih Dagdeviren, Atac Uzel, Mikael Skurnik
It is crucial to understand the in vitro and in vivo regulation of the virulence factor genes of bacterial pathogens. In this study, we describe the construction of a versatile reporter system for Yersinia enterocolitica serotype O:3 (YeO3) based on the luxCDABE operon. In strain YeO3-luxCDE we integrated the luciferase substrate biosynthetic genes, luxCDE, into the genome of the bacterium so that the substrate is constitutively produced. The luxAB genes that encode the luciferase enzyme were cloned into a suicide vector to allow cloning of any promoter-containing fragment upstream the genes...
2017: PloS One
Evilin Naname Komegae, Tais Aparecida Matozo Souza, Lidiane Zito Grund, Carla Lima, Monica Lopes-Ferreira
The pathological condition of multiple sclerosis (MS) relies on innate and adaptive immunity. New types of agents that beneficially modify the course of MS, stopping the progression and repairing the damage appear promising. Here, we studied TnP, a small stable synthetic peptide derived from fish venom in the control of inflammation and demyelination in experimental autoimmune encephalomyelitis as prophylactic treatment. TnP decreased the number of the perivascular infiltrates in spinal cord, and the activity of MMP-9 by F4/80+ macrophages were decreased after different regimen treatments...
2017: PloS One
Maria A Greenwood, Elizabeth A D Hammock
Oxytocin (OXT) is a pleiotropic regulator of physiology and behavior. An emerging body of evidence demonstrates a role for OXT in the transition to postnatal life of the infant. To identify potential sites of OXT action via the OXT receptor (OXTR) in the newborn mouse, we performed receptor autoradiography on 20 μm sagittal sections of whole postnatal day 0 male and female mice on a C57BL/6J background using the 125iodinated ornithine vasotocin analog ([125I]-OVTA) radioligand. A competitive binding assay on both wild-type (WT) and OXTR knockout (OXTR KO) tissue was used to assess the selectivity of [125I]-OVTA for neonatal OXTR...
2017: PloS One
Jo E Lewis, John M Brameld, Phil Hill, Cristina Cocco, Barbara Noli, Gian-Luca Ferri, Perry Barrett, Francis J P Ebling, Preeti H Jethwa
VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides...
2017: PloS One
Vanessa C McFadden, Rasha E Shalaby, Saira Iram, Claudia E Oropeza, Jennifer A Landolfi, Alexander V Lyubimov, Mark Maienschein-Cline, Stefan Green, Klaus H Kaestner, Alan McLachlan
The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV) transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development...
February 24, 2017: PLoS Pathogens
Manabu Tanaka, Yoshinori Sato, Hisao Haniu, Hiroki Nomura, Shinsuke Kobayashi, Seiji Takanashi, Masanori Okamoto, Takashi Takizawa, Kaoru Aoki, Yuki Usui, Ayumu Oishi, Hiroyuki Kato, Naoto Saito
Many recent studies have been conducted to assess the ability of composite materials containing carbon nanotubes (CNTs) with high bone affinity to serve as scaffolds in bone regenerative medicine. These studies have demonstrated that CNTs can effectively induce bone formation. However, no studies have investigated the usefulness of scaffolds consisting exclusively of CNTs in bone regenerative medicine. We built a three-dimensional block entity with maximized mechanical strength from multi-walled CNTs (MWCNT blocks) and evaluated their efficacy as scaffold material for bone repair...
2017: PloS One
Iris Haumann, Dirk Junghans, Max Anstötz, Michael Frotscher
Kainate receptors mediate glutamatergic signaling through both pre- and presynaptic receptors. Here, we studied the expression of the high affinity kainate receptor GluK5 in the mouse retina. Double-immunofluoresence labeling and electron microscopic analysis revealed a presynaptic localization of GluK5 in the outer plexiform layer. Unexpectedly, we found GluK5 almost exclusively localized to the presynaptic ribbon of photoreceptor terminals. Moreover, in GluK5-deficient mutant mice the structural integrity of synaptic ribbons was severely altered pointing to a novel function of GluK5 in organizing synaptic ribbons in the presynaptic terminals of rod photoreceptors...
2017: PloS One
Haruyo Nakajima-Adachi, Kyoko Shibahara, Yoko Fujimura, Jun Takeyama, Erika Hiraide, Akira Kikuchi, Hitoshi Murakami, Akira Hosono, Tomonori Nochi, Yoshio Wakatsuki, Naoki Shimojo, Shuichi Kaminogawa, Ryuichiro Sato, Hiroshi Kiyono, Satoshi Hachimura
BACKGROUND AND OBJECTIVE: The mechanism inducing either inflammation or tolerance to orally administered food allergens remains unclear. To investigate this we analyzed mouse models of food allergy (OVA23-3) and tolerance (DO11.10 [D10]), both of which express ovalbumin (OVA)-specific T-cell receptors. METHODS: OVA23-3, recombination activating gene (RAG)-2-deficient OVA23-3 (R23-3), D10, and RAG-2-deficient D10 (RD10) mice consumed a diet containing egg white (EW diet) for 2-28 days...
2017: PloS One
Lauren Carr, David B Parkinson, Xin-Peng Dun
The secreted glycoproteins, Slit1-3, are classic axon guidance molecules that act as repulsive cues through their well characterised receptors Robo1-2 to allow precise axon pathfinding and neuronal migration. The expression patterns of Slit1-3 and Robo1-2 have been most characterized in the rodent developing nervous system and the adult brain, but little is known about their expression patterns in the adult rodent peripheral nervous system. Here, we report a detailed expression analysis of Slit1-3 and Robo1-2 in the adult mouse sciatic nerve as well as their expression in the nerve cell bodies within the ventral spinal cord (motor neurons) and dorsal root ganglion (sensory neurons)...
2017: PloS One
Anna Curry, Ismat Khatri, Olha Kos, Fang Zhu, Reginald Gorczynski
Cell-surface CD200 expression by mouse EMT6 breast tumor cells increased primary tumor growth and metastasis to the draining lymph nodes (DLN) in normal (WT) BALB/c female recipients, while lack of CD200R1 expression in a CD200R1-/- host negated this effect. Silencing CD200 expression in EMT6siCD200 tumor cells also reduced their ability to grow and metastasize in WT animals. The cellular mechanisms responsible for these effects have not been studied in detail. We report characterization of tumor infiltrating (TILs) and draining lymph node (DLN) cells in WT and CD200-/- BALB/c mice, receiving WT tumor cells, or EMT6 lacking CD200 expression (EMT6siCD200 cells)...
2017: PloS One
Yuko Yamada, Masakatsu Takanashi, Katsuko Sudo, Shinobu Ueda, Shin-Ichiro Ohno, Masahiko Kuroda
MicroRNA 29b (miR-29b) replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments...
2017: PloS One
Melissa E Munroe, Nathan Pezant, Michael A Brown, Dustin A Fife, Joel M Guthridge, Jennifer A Kelly, Graham Wiley, Patrick M Gaffney, Judith A James, Courtney G Montgomery
Antiviral defenses are inappropriately activated in systemic lupus erythematosus (SLE) and association between SLE and the antiviral helicase gene, IFIH1, is well established. We sought to extend the previously reported association of pathogenic soluble mediators and autoantibodies with mouse Mda5 to its human ortholog, IFIH1. To better understand the role this gene plays in human lupus, we assessed association of IFIH1 variants with soluble mediators and autoantibodies in 357 European-American SLE patients, first-degree relatives, and unrelated, unaffected healthy controls...
2017: PloS One
Mahwish Siddiqui, Malik Shoaib Ahmad, Atia-Tul- Wahab, Sammer Yousuf, Narjis Fatima, Nimra Naveed Shaikh, Atta-Ur- Rahman, M Iqbal Choudhary
Seven metabolites were obtained from the microbial transformation of anabolic-androgenic steroid mibolerone (1) with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina. Their structures were determined as 10β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (2), 6β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (3), 6β,10β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (4), 11β,17β-dihydroxy-(20-hydroxymethyl)-7α,17α-dimethylestr-4-en-3-one (5), 1α,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (6), 1α,11β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (7), and 11β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (8), on the basis of spectroscopic studies...
2017: PloS One
Arnold Kuzniar, Charlie Laffeber, Berina Eppink, Karel Bezstarosti, Dick Dekkers, Henri Woelders, A Peter M Zwamborn, Jeroen Demmers, Joyce H G Lebbink, Roland Kanaar
The potential effects of non-ionizing electromagnetic fields (EMFs), such as those emitted by power-lines (in extremely low frequency range), mobile cellular systems and wireless networking devices (in radio frequency range) on human health have been intensively researched and debated. However, how exposure to these EMFs may lead to biological changes underlying possible health effects is still unclear. To reveal EMF-induced molecular changes, unbiased experiments (without a priori focusing on specific biological processes) with sensitive readouts are required...
2017: PloS One
Tatiana A Soboleva, Brian J Parker, Maxim Nekrasov, Gene Hart-Smith, Ying Jin Tay, Wei-Quan Tng, Marc Wilkins, Daniel Ryan, David J Tremethick
The replacement of histone H2A with its variant forms is critical for regulating all aspects of genome organisation and function. The histone variant H2A.B appeared late in evolution and is most highly expressed in the testis followed by the brain in mammals. This raises the question of what new function(s) H2A.B might impart to chromatin in these important tissues. We have immunopurified the mouse orthologue of H2A.B, H2A.B.3, from testis chromatin and found this variant to be associated with RNA processing factors and RNA Polymerase (Pol) II...
February 24, 2017: PLoS Genetics
Kenji Hayashida, Shuhei Yoshida, Hiroshi Yoshimoto, Masaki Fujioka, Hiroto Saijo, Kiyoshi Migita, Misato Kumaya, Sadanori Akita
BACKGROUND: Secondary lymphedema is often observed in postmalignancy treatment of the breast and the gynecologic organs, but effective therapies have not been established in chronic cases even with advanced physiologic operations. Currently, reconstructive surgery with novel approaches has been attempted. METHODS: The hindlimbs of 10-week-old male C57BL/6J mice, after 30-Gy x-irradiation, surgical lymph node dissection, and 5-mm gap creation, were divided into four groups, with vascularized lymph node transfer abdominal flap and 1...
March 2017: Plastic and Reconstructive Surgery
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