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https://www.readbyqxmd.com/read/29031033/an-arabidopsis-divergent-pumilio-protein-apum24-is-essential-for-embryogenesis-and-required-for-faithful-pre-rrna-processing
#1
Thiruvenkadam Shanmugam, Nazia Abbasi, Hyung-Sae Kim, Ho Bang Kim, Nam-Il Park, Guen Tae Park, Sung Aeong Oh, Soon Ki Park, Douglas G Muench, Yeonhee Choi, Youn-Il Park, Sang-Bong Choi
Pumilio RNA-binding proteins are largely involved in mRNA degradation and translation repression. However, a few evolutionarily divergent Pumilios are also responsible for proper pre-rRNA processing in human and yeast. Here, we describe an essential Arabidopsis nucleolar Pumilio, APUM24, that is expressed in tissues undergoing rapid proliferation and cell division. A T-DNA insertion for APUM24 did not affect the male and female gametogenesis, but instead resulted in a negative female gametophytic effect on zygotic cell division immediately after fertilization...
October 14, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29029246/the-epidermal-growth-factor-network-role-in-oocyte-growth-maturation-and-developmental-competence
#2
Dulama Richani, Robert B Gilchrist
BACKGROUND: The LH surge induces great physiological changes within the preovulatory follicle, which culminate in the ovulation of a mature oocyte that is capable of supporting embryo and foetal development. However, unlike mural granulosa cells, the oocyte and its surrounding cumulus cells are not directly responsive to LH, indicating that the LH signal is mediated by secondary factors produced by the granulosa cells. The mechanisms by which the oocyte senses the ovulatory LH signal and hence prepares for ovulation has been a subject of considerable controversy for the past four decades...
September 20, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29028357/folate-peg-nota-al18f-a-new-folate-based-radiotracer-for-pet-imaging-of-folate-receptor-positive-tumors
#3
Qingshou Chen, Xiangjun Meng, Paul McQuade, Daniel Rubins, Shu-An Lin, Zhizhen Zeng, Hyking Haley, Patricia Miller, Dinko Gonzalez Trotter, Philip S Low
The folate receptor (FR) has been established as a promising target for imaging and therapy of cancer (FR-α), inflammation, and autoimmune diseases (FR-β). Several folate-based PET radiotracers have been reported in the literature, but an 18F- labeled folate-PET imaging agent with optimal properties for clinical translation is still lacking. In the present study, we report the design and preclinical evaluation of folate-PEG12-NOTA-Al18F (1), a new folate-PET agent with improved potential for clinical applications...
October 13, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29027989/inhibition-of-neddylation-by-mln4924-improves-neointimal-hyperplasia-and-promotes-apoptosis-of-vascular-smooth-muscle-cells-through-p53-and-p62
#4
Tang-Jun Ai, Jian-Yong Sun, Lin-Juan Du, Chaoji Shi, Chao Li, Xue-Nan Sun, Yan Liu, Lihui Li, Zhixiong Xia, Lijun Jia, Jianmiao Liu, Sheng-Zhong Duan
Targeting apoptosis of vascular smooth muscle cells (VSMCs) represents an attractive approach to diminish the occurrence of restenosis. Neddylation is a highly conserved post-translational modification process and inhibition of neddylation has been shown to regulate apoptosis of other cells. However, the impacts of neddylation inhibition on VSMCs and neointimal hyperplasia have not been studied. In our present study, we have shown that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), markedly inhibited neointimal hyperplasia and accumulation of VSMCs, whereas increased apoptosis in the vascular wall...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29027937/abrin-toxicity-and-bioavailability-after-temperature-and-ph-treatment
#5
Christina C Tam, Thomas D Henderson, Larry H Stanker, Xiaohua He, Luisa W Cheng
Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation...
October 13, 2017: Toxins
https://www.readbyqxmd.com/read/29027792/multifunctional-cytochrome-c-learning-new-tricks-from-an-old-dog
#6
Damián Alvarez-Paggi, Luciana Hannibal, María A Castro, Santiago Oviedo-Rouco, Veronica Demicheli, Veronica Tórtora, Florencia Tomasina, Rafael Radi, Daniel H Murgida
Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells...
October 13, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/29026071/arginine-methylation-catalyzed-by-prmt1-is-required-for-b-cell-activation-and-differentiation
#7
Simona Infantino, Amanda Light, Kristy O'Donnell, Vanessa Bryant, Danielle T Avery, Michael Elliott, Stuart G Tangye, Gabrielle Belz, Fabienne Mackay, Stephane Richard, David Tarlinton
Arginine methylation catalyzed by protein arginine methyltransferases (PRMT) is a common post-translational modification in mammalian cells, regulating many important functions including cell signalling, proliferation and differentiation. Here we show the role of PRMT1 in B-cell activation and differentiation. PRMT1 expression and activity in human and mouse peripheral B cells increases in response to in vitro or in vivo activation. Deletion of the Prmt1 gene in mature B cells establishes that although the frequency and phenotype of peripheral B cell subsets seem unaffected, immune responses to T-cell-dependent and -independent antigens are substantially reduced...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29025768/action-potential-shortening-and-impairment-of-cardiac-function-by-ablation-of-slc26a6
#8
Padmini Sirish, Hannah A Ledford, Valeriy Timofeyev, Phung N Thai, Lu Ren, Hyo Jeong Kim, Seojin Park, Jeong Han Lee, Gu Dai, Maryam Moshref, Choong-Ryoul Sihn, Wei Chun Chen, Maria Valeryevna Timofeyeva, Zhong Jian, Rafael Shimkunas, Leighton T Izu, Nipavan Chiamvimonvat, Ye Chen-Izu, Ebenezer N Yamoah, Xiao-Dong Zhang
BACKGROUND: Intracellular pH (pHi) is critical to cardiac excitation and contraction; uncompensated changes in pHi impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pHi regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl(-)/HCO3(-) exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pHi, but also cardiac excitability...
October 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29024741/in-vivo-potency-revisited-keep-the-target-inl-sight
#9
REVIEW
Johan Gabrielsson, Lambertus A Peletier, Stephan Hjorth
Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure...
October 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024580/fos-promotes-early-stage-teno-lineage-differentiation-of-tendon-stem-progenitor-cells-in-tendon
#10
Jialin Chen, Erchen Zhang, Wei Zhang, Zeyu Liu, Ping Lu, Ting Zhu, Zi Yin, Ludvig J Backman, Huanhuan Liu, Xiao Chen, Hongwei Ouyang
Stem cells have been widely used in tendon tissue engineering. The lack of refined and controlled differentiation strategy hampers the tendon repair and regeneration. This study aims to find new effective differentiation factors for stepwise tenogenic differentiation. By microarray screening, the transcript factor Fos was found to be expressed in significantly higher amounts in postnatal Achilles tendon tissue derived from 1 day as compared with 7-days-old rats. It was further confirmed that expression of Fos decreased with time in postnatal rat Achilles tendon, which was accompanied with the decreased expression of multiply tendon markers...
October 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29024560/enhanced-stem-cell-differentiation-and-immunopurification-of-genome-engineered-human-retinal-ganglion-cells
#11
Valentin M Sluch, Xitiz Chamling, Melissa M Liu, Cynthia A Berlinicke, Jie Cheng, Katherine L Mitchell, Derek S Welsbie, Donald J Zack
Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1...
October 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29024485/placenta-derived-adherent-stromal-cells-improve-diabetes-mellitus-associated-left-ventricular-diastolic-performance
#12
Sophie Van Linthout, Nazha Hamdani, Kapka Miteva, Annika Koschel, Irene Müller, Lena Pinzur, Zami Aberman, Kathleen Pappritz, Wolfgang Albrecht Linke, Carsten Tschöpe
Left ventricular (LV) diastolic dysfunction is among others attributed to cardiomyocyte stiffness. Mesenchymal stromal cells (MSC) have cardiac-protective properties. We explored whether intravenous (i.v.) application of PLacenta-eXpanded (PLX) MSC-like cells (PLX) improves LV diastolic relaxation in streptozotocin (STZ)-induced diabetic mice and investigated underlying mechanisms. Diabetes mellitus was induced by STZ application (50 mg/kg body weight) during five subsequent days. One week after the first STZ injection, PLX or saline were i...
October 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29023674/reverse-translational-research-of-abcg2-bcrp-in-human-disease-and-drug-response
#13
Deanna J Brackman, Kathleen M Giacomini
Reverse translational research takes a bedside to bench approach, using sophisticated basic research to explain the biological mechanisms behind observed clinical data. For transporters, which play a role in human disease and drug response, this approach offers a distinct advantage over the typical translational research, which often falters due to inadequate in vitro and preclinical animal models. Research on ABCG2, which encodes the Breast Cancer Resistance Protein (BCRP), has benefited immensely from a reverse translational approach due to its broad implications to disease susceptibility and both therapeutic and adverse drug response...
October 12, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29023443/systematic-network-based-characterization-of-therapeutic-target-inhibitors
#14
Yao Shen, Mariano J Alvarez, Brygida Bisikirska, Alexander Lachmann, Ronald Realubit, Sergey Pampou, Jorida Coku, Charles Karan, Andrea Califano
A large fraction of the proteins that are being identified as key tumor dependencies represent poor pharmacological targets or lack clinically-relevant small-molecule inhibitors. Availability of fully generalizable approaches for the systematic and efficient prioritization of tumor-context specific protein activity inhibitors would thus have significant translational value. Unfortunately, inhibitor effects on protein activity cannot be directly measured in systematic and proteome-wide fashion by conventional biochemical assays...
October 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29020880/pulsed-electromagnetic-fields-and-tissue-engineering-of-the-joints
#15
Kenjiro Iwasa, Reddi A Hari
BACKGROUND: Bone and cartilage joint formation, maintenance and regeneration are regulated by both chemical and physical signals. Among the physical signals there is increasing realization of the role of Pulsed electromagnetic fields (PEMF) in the treatment of nonunions of bone fractures. The discovery of the piezoelectric properties of bone by Fukada and Yasuda in 1953 in Japan established the foundation of this field. Pioneering research by Bassett and Brighton and their teams resulted in the approval by Food and Drug Administration (FDA) the use of PEMF in treatment of fracture healing...
October 12, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29018134/neuronal-sirt1-silent-information-regulator-2-homologue-1-regulates-glycolysis-and-mediates-resveratrol-induced-ischemic-tolerance
#16
Kevin B Koronowski, Nathalie Khoury, Isabel Saul, Zachary B Loris, Charles H Cohan, Holly M Stradecki-Cohan, Kunjan R Dave, Juan I Young, Miguel A Perez-Pinzon
BACKGROUND AND PURPOSE: Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain...
October 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29017946/cloning-and-expression-of-malabar-grouper-epinephelus-malabaricus-adar1-gene-in-response-to-immune-stimulants-and-nervous-necrosis-virus
#17
Thirunavukkarasu Periyasamy, Joan Tang Xiao Joe, Ming-Wei Lu
ADARs are RNA editing catalysts that bind double-stranded RNA and convert adenosine to inosine, a process that can lead to destabilization of dsRNA structures and suppression of mRNA translation. In mammals, ADAR1 genes are involved in various cellular pathways, including interferon (IFN)-mediated response. However, the function of fish ADAR1 remains unclear. We report here the cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long, consisting of an open reading frame encoding a putative protein of 1381 amino acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29017848/suppression-of-cotton-leaf-curl-disease-symptoms-in-gossypium-hirsutum-through-overexpression-of-host-encoded-mirnas
#18
Mohd Akmal, Mirza S Baig, Jawaid A Khan
Cotton leaf curl disease (CLCuD), a major factor resulting in the enormous yield losses in cotton crop, is caused by a distinct monopartite begomovirus in association with Cotton leaf curl Multan betasatellite (CLCuMB). Micro(mi)RNAs are known to regulate gene expression in eukaryotes, including antiviral defense in plants. In a previous study, we had computationally identified a set of cotton miRNAs, which were shown to have potential targets in the genomes of Cotton leaf curl Multan virus (CLCuMuV) and CLCuMB at multiple loci...
October 7, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/29017547/reconstructing-cancer-drug-response-networks-using-multitask-learning
#19
Matthew Ruffalo, Petar Stojanov, Venkata Krishna Pillutla, Rohan Varma, Ziv Bar-Joseph
BACKGROUND: Translating in vitro results to clinical tests is a major challenge in systems biology. Here we present a new Multi-Task learning framework which integrates thousands of cell line expression experiments to reconstruct drug specific response networks in cancer. RESULTS: The reconstructed networks correctly identify several shared key proteins and pathways while simultaneously highlighting many cell type specific proteins. We used top proteins from each drug network to predict survival for patients prescribed the drug...
October 10, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29017520/the-nuclear-receptor-er%C3%AE-engages-ago2-in-regulation-of-gene-transcription-rna-splicing-and-risc-loading
#20
Roberta Tarallo, Giorgio Giurato, Giuseppina Bruno, Maria Ravo, Francesca Rizzo, Annamaria Salvati, Luca Ricciardi, Giovanna Marchese, Angela Cordella, Teresa Rocco, Valerio Gigantino, Biancamaria Pierri, Giovanni Cimmino, Luciano Milanesi, Concetta Ambrosino, Tuula A Nyman, Giovanni Nassa, Alessandro Weisz
BACKGROUND: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease...
October 6, 2017: Genome Biology
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