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https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#1
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28821921/anti-nociceptive-effect-of-stigmasterol-in-mouse-models-of-acute-and-chronic-pain
#2
Cristiani Isabel Banderó Walker, Sara Marchesan Oliveira, Raquel Tonello, Mateus Fortes Rossato, Evelyne da Silva Brum, Juliano Ferreira, Gabriela Trevisan
Stigmasterol is a common sterol found in plants, but the anti-nociceptive effect of this compound and its mechanism of action are not fully explored. Thus, in the present study, the anti-nociceptive effect of stigmasterol was investigated in acute and chronic models of pain and its mechanism of action. We used adult male albino Swiss mice (25-35 g) to observe the anti-nociceptive effect of stigmasterol in acetic-acid writhing test or in complete Freund's adjuvant injection, surgical incision in hind paw, or partial sciatic nerve ligation...
August 18, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28821741/predicting-the-murine-enterocyte-metabolic-response-to-diets-that-differ-in-lipid-and-carbohydrate-composition
#3
Neeraj Sinha, Maria Suarez-Diez, Evert M van Schothorst, Jaap Keijer, Vitor A P Martins Dos Santos, Guido J E J Hooiveld
The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821731/stability-in-metabolic-phenotypes-and-inferred-metagenome-profiles-before-the-onset-of-colitis-induced-inflammation
#4
M Glymenaki, A Barnes, S O' Hagan, G Warhurst, A J McBain, I D Wilson, D B Kell, K J Else, S M Cruickshank
Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821730/infiltration-of-m1-but-not-m2-macrophages-is-impaired-after-unilateral-ureter-obstruction-in-nrf2-deficient-mice
#5
Yuji Sogawa, Hajime Nagasu, Shigeki Iwase, Chieko Ihoriya, Seiji Itano, Atsushi Uchida, Kengo Kidokoro, Shun'ichiro Taniguchi, Masafumi Takahashi, Minoru Satoh, Tamaki Sasaki, Takafumi Suzuki, Masayuki Yamamoto, Tiffany Horng, Naoki Kashihara
Chronic inflammation can be a major driver of the failure of a variety of organs, including chronic kidney disease (CKD). The NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been shown to play a pivotal role in inflammation in a mouse kidney disease model. Nuclear factor erythroid 2-related factor 2 (Nrf2), the master transcription factor for anti-oxidant responses, has also been implicated in inflammasome activation under physiological conditions. However, the mechanism underlying inflammasome activation in CKD remains elusive...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821675/synergistic-toxicity-of-polyglutamine-expanded-tbp-in-glia-and-neuronal-cells-therapeutic-implications-for-sca17
#6
Yang Yang, Su Yang, Jifeng Guo, Yiting Cui, Baisha Tang, Xiao-Jiang Li, Shihua Li
Spinocerebellar ataxia 17 (SCA17) is caused by polyglutamine (polyQ) repeat expansion in the TATA-binding protein (TBP) and is among a family of neurodegenerative diseases in which polyQ expansion leads to preferential neuronal loss in the brain. Although previous studies have demonstrated that expression of polyQ-expanded proteins in glial cells can cause neuronal injury via non-cell-autonomous mechanisms, these studies investigated animal models that overexpress transgenic mutant proteins. Since glial cells are particularly reactive to overexpressed mutant proteins, it is important to investigate the in vivo role of glial dysfunction in neurodegeneration when mutant polyQ proteins are endogenously expressed...
August 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821658/opposite-synaptic-alterations-at-the-neuromuscular-junction-in-an-als-mouse-model-when-motor-units-matter
#7
Tremblay Elsa, Martineau Éric, Robitaille Richard
Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU) dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast-fatigue resistant (FR) and slow (S) ones. However, changes of NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in a MU specific manner, prior to structural alterations of the NMJ...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821644/calpain-dependent-degradation-of-nucleoporins-contributes-to-motor-neuron-death-in-a-mouse-model-of-chronic-excitotoxicity
#8
Kaori Sugiyama, Tomomi Aida, Masatoshi Nomura, Ryoichi Takayanagi, Hanns U Zeilhofer, Kohichi Tanaka
Glutamate-mediated excitotoxicity induces neuronal death by altering various intracellular signaling pathways and is implicated as a common pathogenic pathway in many neurodegenerative diseases. In the case of motor neuron disease, there is significant evidence to suggest that overactivation of AMPA receptors due to deficiencies in the expression and function of glial glutamate transporter GLT1 and GLAST plays an important role in the mechanisms of neuronal death. However, a causal role for glial glutamate transporter dysfunction in motor neuron death remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821643/changes-in-the-excitability-of-neocortical-neurons-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-are-not-specific-to-corticospinal-neurons-and-are-modulated-by-advancing-disease
#9
Juhyun Kim, Ethan G Hughes, Ashwin S Shetty, Paola Arlotta, Loyal A Goff, Dwight E Bergles, Solange P Brown
Cell-type specific changes in neuronal excitability have been proposed to contribute to the selective degeneration of corticospinal neurons in amyotrophic lateral sclerosis (ALS) and to neocortical hyperexcitability, a prominent feature of both inherited and sporadic variants of the disease, but the mechanisms underlying selective loss of specific cell types in ALS are not known. We analyzed the physiological properties of distinct classes of cortical neurons in the motor cortex of hSOD1(G93A) mice of both sexes and found that they all exhibit increases in intrinsic excitability that depend on disease stage...
August 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821604/development-of-a-multiplexed-assay-for-oral-cancer-candidate-biomarkers-using-peptide-immunoaffinity-enrichment-and-targeted-mass-spectrometry
#10
Yung-Chin Hsiao, Lang-Ming Chi, Kun-Yi Chien, Wei-Fan Chiang, Szu-Fan Chen, Yao-Ning Chuang, Shih-Yu Lin, Chia-Chun Wu, Ya-Ting Chang, Lichieh Julie Chu, Yi-Ting Chen, Shu-Li Chia, Chih-Yen Chien, Kai-Ping Chang, Yu-Sun Chang, Jau-Song Yu
Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva...
August 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28821557/selected-alkylating-agents-can-overcome-drug-tolerance-of-g0-like-tumor-cells-and-eradicate-brca1-deficient-mammary-tumors-in-mice
#11
Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslı Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1(-/-);p53(-/-) mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821440/apelin-protects-against-liver-x-receptor-mediated-steatosis-through-ampk-and-ppar%C3%AE-in-human-and-mouse-hepatocytes
#12
Jin Huang, Saeromi Kang, Soo-Jin Park, Dong-Soon Im
Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G protein-coupled receptor named APJ, and has been established to play pivotal roles in various physiological conditions. However, the function of apelin in hepatocytes has not been fully investigated...
August 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28821136/discovery-of-enzymatically-depolymerized-heparins-capable-of-treating-bleomycin-induced-pulmonary-injury-and-fibrosis-in-mice
#13
Yishu Yan, Shanshan Du, Yang Ji, Nan Su, Yi Wang, Xiang Mei, Wenming Zhu, Dong He, Yuan Lu, Chong Zhang, Xin-Hui Xing
Heparin has recently been shown to slow down idiopathic pulmonary fibrosis (IPF) process and improve survival of patients in some cases. To improve the anti-IPF function while minimizing their side effects, we developed heparin libraries with different structures depolymerized by single or combined heparinases, and systematically screened the efficacy of the different heparins for treatment of Bleomycin-induced pulmonary injury and fibrosis using mice model. Then we characterized the structural properties of the components capable of treating pulmonary injury and fibrosis by use of chip-based amide hydrophilic interaction chromatography (HILIC)-fourier transform (FT)-ESI-MS, polyacrylamide gel electrophoresis (PAGE), and high performance liquid chromatography (HPLC)...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#14
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820994/relative-bioavailability-and-bioaccessibility-of-pcbs-in-soils-based-on-a-mouse-model-and-tenax-improved-physiologically-based-extraction-test
#15
Chao Li, Ruirui Zhang, Yunzi Li, Shujun Zhang, Peng Gao, Xinyi Cui, Lena Q Ma
In this study, bioavailability of polychlorinated biphenyls (PCBs) in soil samples aged for various time intervals (7 days, 1 and 5 months) was assessed by in vivo tests using mice. The in vivo bioavailability of PCBs in soil ranged from 45% (PCB180 in soil aging for 5 month) to 119% (PCB52 in soil aging for 1 month), indicating that not all PCBs was available for absorption after ingestion of soil samples. The bioaccessibility was assessed using both physiologically-based extraction test (PBET) and Tenax improved PBET (TI-PBET)...
August 8, 2017: Chemosphere
https://www.readbyqxmd.com/read/28820966/reactive-oxygen-species-responsive-polymeric-nanoparticles-for-alleviating-sepsis-induced-acute-liver-injury-in-mice
#16
Gan Chen, Hongzhang Deng, Xiang Song, Mingzi Lu, Lian Zhao, Sha Xia, Guoxing You, Jingxiang Zhao, Yulong Zhang, Anjie Dong, Hong Zhou
Sepsis-associated acute liver injury contributes to the pathogenesis of multiple organ dysfunction syndrome and is associated with increased mortality. Currently, no specific therapeutics for sepsis-associated liver injury are available. With excess levels of reactive oxygen species (ROS) being implicated as key players in sepsis-induced liver injury, we hypothesize that ROS-responsive nanoparticles (NPs) formed via the self-assembly of diblock copolymers of poly(ethylene glycol) (PEG) and poly(propylene sulfide) (PPS) may function as an effective drug delivery system for alleviating sepsis-induced liver injury by preferentially releasing drug molecules at the disease site...
August 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28820912/impact-of-novel-palmitoylated-prolactin-releasing-peptide-analogs-on-metabolic-changes-in-mice-with-diet-induced-obesity
#17
Veronika Pražienková, Martina Holubová, Helena Pelantová, Martina Bugáňová, Zdenko Pirník, Barbora Mikulášková, Andrea Popelová, Miroslava Blechová, Martin Haluzík, Blanka Železná, Marek Kuzma, Jaroslav Kuneš, Lenka Maletínská
Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus...
2017: PloS One
https://www.readbyqxmd.com/read/28820903/prominent-facilitation-at-beta-and-gamma-frequency-range-revealed-with-physiological-calcium-concentration-in-adult-mouse-piriform-cortex-in-vitro
#18
Marie Gleizes, Simon P Perrier, Caroline Fonta, Lionel G Nowak
Neuronal activity is characterized by a diversity of oscillatory phenomena that are associated with multiple behavioral and cognitive processes, yet the functional consequences of these oscillations are not fully understood. Our aim was to determine whether and how these different oscillatory activities affect short-term synaptic plasticity (STP), using the olfactory system as a model. In response to odorant stimuli, the olfactory bulb displays a slow breathing rhythm as well as beta and gamma oscillations...
2017: PloS One
https://www.readbyqxmd.com/read/28820892/maternal-autoimmune-antibodies-alter-the-dendritic-arbor-and-spine-numbers-in-the-infragranular-layers-of-the-cortex
#19
Jeanelle Ariza, Jesus Hurtado, Haille Rogers, Raymond Ikeda, Michael Dill, Craig Steward, Donnay Creary, Judy Van de Water, Verónica Martínez-Cerdeño
An association between maternal IgG antibodies reactive against proteins in fetal brain and an outcome of autism in the child has been identified. Using a mouse model of prenatal intraventricular administration of autism-specific maternal IgG, we demonstrated that these antibodies produce behavioral alterations similar to those in children with ASD. We previously demonstrated that these antibodies bind to radial glial stem cells (RG) and observed an increase in the number of divisions of translocating RG in the developing cortex...
2017: PloS One
https://www.readbyqxmd.com/read/28820694/differential-neurovirulence-of-african-and-asian-genotype-zika-virus-isolates-in-outbred-immunocompetent-mice
#20
Nisha K Duggal, Jana M Ritter, Erin M McDonald, Hannah Romo, Farshad Guirakhoo, Brent S Davis, Gwong-Jen J Chang, Aaron C Brault
Although first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain-Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
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