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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
#1
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/29454068/o-glcnacylation-of-rack1-promotes-hepatocellular-carcinogenesis
#2
Fangfang Duan, Hao Wu, Dongwei Jia, Weicheng Wu, Shifang Ren, Lan Wang, Shushu Song, Xinying Guo, Fenglin Liu, Yuanyuan Ruan, Jianxin Gu
BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal RACK1 promoted the chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis...
February 14, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29453960/synaptic-dysfunction-and-altered-excitability-in-c9orf72-als-ftd
#3
Alexander Starr, Rita Sattler
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29453938/barley-stripe-mosaic-virus-infection-requires-pka-mediated-phosphorylation-of-%C3%AE-b-for-suppression-of-both-rna-silencing-and-the-host-cell-death-response
#4
Xuan Zhang, Kai Dong, Kai Xu, Kun Zhang, Xuejiao Jin, Meng Yang, Yongliang Zhang, Xianbing Wang, Chenggui Han, Jialin Yu, Dawei Li
The Barley stripe mosaic virus (BSMV) γb protein is a viral suppressor of RNA silencing (VSR) and symptom determinant. However, it is unclear how post-translational modification affects the different functions of γb. Here, we demonstrate that γb is phosphorylated at Ser-96 by a PKA-like kinase in vivo and in vitro. Mutant viruses containing a nonphosphorylatable substitution (BSMV S 96A or BSMV S 96R ) exhibited reduced viral accumulation in Nicotiana benthamiana due to transient induction of the cell death response that constrained the virus to necrotic areas...
February 17, 2018: New Phytologist
https://www.readbyqxmd.com/read/29453454/a-microvascularized-tumor-mimetic-platform-for-assessing-anti-cancer-drug-efficacy
#5
Shantanu Pradhan, Ashley M Smith, Charles J Garson, Iman Hassani, Wen J Seeto, Kapil Pant, Robert D Arnold, Balabhaskar Prabhakarpandian, Elizabeth A Lipke
Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#6
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453282/eukaryotic-translation-elongation-factor-2-eef2-catalyzes-reverse-translocation-of-the-eukaryotic-ribosome
#7
Denis Susorov, Nikita Zakharov, Ekaterina Shuvalova, Alexander Ivanov, Tatiana Egorova, Alexey Shuvalov, Ivan N Shatsky, Elena Alkalaeva
During protein synthesis, a ribosome moves along the mRNA template and, using aminoacyl-tRNAs, decodes the template nucleotide triplets to assemble a protein amino acid sequence. This movement is accompanied by shifting of mRNA-tRNA complexes within the ribosome in a process called translocation. In living cells, this process proceeds in a unidirectional manner, bringing the ribosome to the 3'-end of mRNA, and is catalyzed by the GTPase translation elongation factor 2 (EF-G in prokaryotes, eEF2 in eukaryotes)...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29453199/simultaneous-assessment-of-clearance-metabolism-induction-and-drug-drug-interaction-potential-using-a-long-term-in-vitro-liver-model-for-a-novel-hepatitis-b-virus-inhibitor
#8
Nicole A Kratochwil, Miriam Triyatni, Martina B Mueller, Florian Klammers, Brian Leonard, Dan Turley, Josephine Schmaler, Aynur Ekiciler, Birgit Molitor, Isabelle Walter, Pierre-Alexis Gonsard, Charles A Tournillac, Alexandre Durrwell, Michaela Marschmann, Russell Jones, Mohammed Ullah, Franziska Boess, Giorgio Ottaviani, Yuyan Yin, Neil J Parrott, Stephen Fowler
Long-term in vitro liver models are now widely explored for human hepatic metabolic clearance prediction, enzyme phenotyping, cross species metabolism, comparison of low clearance drugs as well as induction studies. Here, we present studies using a long-term liver model which show how metabolism and active transport, drug-drug interactions and enzyme induction in healthy and diseased states, e.g. hepatitis B virus (HBV) infection, may be assessed in a single test system to enable effective data integration for PBPK modeling...
February 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29453154/unique-pharmacology-of-a-novel-allosteric-agonist-sensitizer-insulin-receptor-monoclonal-antibody
#9
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29451894/trade-off-between-synergy-and-efficacy-in-combinations-of-hiv-1-latency-reversing-agents
#10
Vipul Gupta, Narendra M Dixit
Eradicating HIV-1 infection is difficult because of the reservoir of latently infected cells that gets established soon after infection, remains hidden from antiretroviral drugs and host immune responses, and retains the capacity to reignite infection following the cessation of treatment. Drugs called latency-reversing agents (LRAs) are being developed to reactivate latently infected cells and render them susceptible to viral cytopathicity or immune killing. Whereas individual LRAs have failed to induce adequate reactivation, pairs of LRAs have been identified recently that act synergistically and hugely increase reactivation levels compared to individual LRAs...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29451124/copper-oxide-loaded-plga-nanospheres-towards-a-multifunctional-nanoscale-platform-for-ultrasound-based-imaging-and-therapy
#11
Or Perlman, Iris S Weitz, Sarit Sivan, Hiba Abu-Khalla, Madeleine Benguigui, Yuval Shaked, Haim Azhari
Copper oxide nanoparticles (CuO-NPs) are increasingly investigated for diagnostic and therapeutic purposes. Recent work have demonstrated their anticancer potential as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capabilities of CuO-NPS were demonstrated using conventional ultrasound systems, which, unlike the formers, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs were delayed from further clinical translation due to their inherent toxicity...
February 16, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29449530/the-type-2-diabetes-associated-hmg20a-gene-is-mandatory-for-islet-beta-cell-functional-maturity
#12
Jose M Mellado-Gil, Esther Fuente-Martín, Petra I Lorenzo, Nadia Cobo-Vuilleumier, Livia López-Noriega, Alejandro Martín-Montalvo, Irene de Gracia Herrera Gómez, Maria Ceballos-Chávez, Laura Gómez-Jaramillo, Antonio Campos-Caro, Silvana Y Romero-Zerbo, Júlia Rodríguez-Comas, Joan-Marc Servitja, Gemma Rojo-Martinez, Abdelkrim Hmadcha, Bernat Soria, Marco Bugliani, Piero Marchetti, Francisco J Bérmudez-Silva, Jose C Reyes, Manuel Aguilar-Diosdado, Benoit R Gauthier
HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449526/raised-serum-levels-of-syndecan-1-cd138-in-a-case-of-acute-idiopathic-systemic-capillary-leak-syndrome-scls-clarkson-s-disease
#13
Ole Wilhelm Bøe, Kjell Sveen, Magne Børset, Kirk M Druey
BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare disorder of unknown etiology, characterized by transient episodes of hypotension, and the microvascular leak of fluids into the peripheral tissues, resulting in edema. Between 80-90% of patients with SCLS have a concomitant monoclonal gammopathy. Although translational in vitro studies have implicated vascular endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease associations in clinical cases remain unknown...
February 16, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29448001/induced-pluripotent-stem-cells-ipsc-derived-retinal-cells-in-disease-modeling-and-regenerative-medicine
#14
REVIEW
Reena Rathod, Harshini Surendran, Rajani Battu, Jogin Desai, Rajarshi Pal
Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction.lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies...
February 12, 2018: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29447380/sirtuins-in-gamete-biology-and-reproductive-physiology-emerging-roles-and-therapeutic-potential-in-female-and-male-infertility
#15
Carla Tatone, Giovanna Di Emidio, Arcangelo Barbonetti, Gaspare Carta, Alberto M Luciano, Stefano Falone, Fernanda Amicarelli
BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking...
February 13, 2018: Human Reproduction Update
https://www.readbyqxmd.com/read/29447281/peptidic-inhibitors-of-insulin-degrading-enzyme-with-potential-for-dermatological-applications-discovered-via-phage-display
#16
Caitlin N Suire, Sarah Nainar, Michael Fazio, Adam G Kreutzer, Tara Paymozd-Yazdi, Caitlyn L Topper, Caroline R Thompson, Malcolm A Leissring
Insulin-degrading enzyme (IDE) is an atypical zinc-metalloendopeptidase that hydrolyzes insulin and other intermediate-sized peptide hormones, many of which are implicated in skin health and wound healing. Pharmacological inhibitors of IDE administered internally have been shown to slow the breakdown of insulin and thereby potentiate insulin action. Given the importance of insulin and other IDE substrates for a variety of dermatological processes, pharmacological inhibitors of IDE suitable for topical applications would be expected to hold significant therapeutic and cosmetic potential...
2018: PloS One
https://www.readbyqxmd.com/read/29447055/advanced-microengineered-lung-models-for-translational-drug-discovery
#17
Brian F Niemeyer, Peng Zhao, Rubin M Tuder, Kambez H Benam
Lung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike several other therapeutic areas, faces a disappointingly low number of new approved therapies. This is partly due to lack of reliable in vitro or in vivo models that can reproduce organ-level complexity and pathophysiological responses of human lung. Here, we examine new opportunities in application of recently emerged organ-on-chip technology to model human lung alveolus and small airway in preclinical drug development and biomarker discovery...
February 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29447021/release-of-pro-inflammatory-cytokines-from-muscle-and-bone-causes-tenocyte-death-in-a-novel-rotator-cuff-in-vitro-explant-culture-model
#18
Brianne K Connizzo, Alan J Grodzinsky
Tendinopathy is a significant clinical problem thought to be associated with altered mechanical loading. Explant culture models allow researchers to alter mechanical loading in a controlled in vitro environment while maintaining tenocytes in their native matrix. However, current models do not accurately represent commonly injured tendons, ignoring contributions of associated musculature and bone, as well as regional collagen structure. This study details the characterization of a mouse rotator cuff explant culture model, including bone, tendon, and muscle (BTM)...
February 15, 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29446774/proteome-wide-identification-of-ubiquitin-interactions-using-ubia-ms
#19
Xiaofei Zhang, Arne H Smits, Gabrielle Ba van Tilburg, Huib Ovaa, Wolfgang Huber, Michiel Vermeulen
Ubiquitin-binding proteins play an important role in eukaryotes by translating differently linked polyubiquitin chains into proper cellular responses. Current knowledge about ubiquitin-binding proteins and ubiquitin linkage-selective interactions is mostly based on case-by-case studies. We have recently reported a method called ubiquitin interactor affinity enrichment-mass spectrometry (UbIA-MS), which enables comprehensive identification of ubiquitin interactors for all ubiquitin linkages from crude cell lysates...
March 2018: Nature Protocols
https://www.readbyqxmd.com/read/29445920/phylogenetic-diversity-and-in-vitro-susceptibility-profiles-of-human-pathogenic-members-of-the-fusarium-fujikuroi-species-complex-isolated-from-south-india
#20
Ananya Tupaki-Sreepurna, Vijayakishore Thanneru, Sangeetha Natarajan, Savitri Sharma, Anjana Gopi, Murugan Sundaram, Anupma Jyoti Kindo
Availability of molecular methods, gene sequencing, and phylogenetic species recognition have led to rare fungi being recognized as opportunistic pathogens. Fungal keratitis and onychomycosis are fairly common mycoses in the tropics, especially among outdoor workers and enthusiasts. The frequently isolated etiological agents belong to genera Candida, Aspergillus, and Fusarium. Within the genus Fusarium, known to be recalcitrant to prolonged antifungal treatment and associated with poor outcome, members of the Fusarium solani species complex are reported to be most common, followed by members of the Fusarium oxysporum SC and the Fusarium fujikuroi SC (FFSC)...
February 14, 2018: Mycopathologia
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