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https://www.readbyqxmd.com/read/28941402/copper-ii-ions-interactions-in-the-systems-with-triamines-and-atp-potentiometric-and-spectroscopic-studies
#1
S K Hoffmann, J Goslar, R Bregier-Jarzebowska, A Gasowska, A Zalewska, L Lomozik
The mode of interaction and thermodynamic stability of complexes formed in binary and ternary Cu(II)/ATP/triamines systems were studied using potentiometric and spectroscopic (NMR, EPR, UV-Vis) methods. It was found that in binary metal-free systems ATP/HxPA species are formed (PA: Spd=spermidine or 3,3-tri=1,7-diamino-4-azaheptane) where the phosphate groups from nucleotides are preferred negative centers and protonated amine groups of amines are positive centers of reaction. In the ternary systems Cu/ATP/Hx(PA) as well as Cu/(ATP)(PA) species are formed...
September 9, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28941398/the-mechanisms-mediating-the-antiepileptic-effects-of-the-ketogenic-diet-and-potential-opportunities-for-improvement-with-metabolism-altering-drugs
#2
REVIEW
Neil A Youngson, Margaret J Morris, Bill Ballard
The ketogenic diet (KD) is increasingly being used to treat patients with intractable epilepsy. Despite decades of research, the reason for its success, when anticonvulsants have failed, is still not completely understood. There are, however, many candidate mechanisms which can be grouped into those that alter neuronal excitability at the synapse, and those that confer neuroprotection. The molecular underpinning of these mechanisms centres on the shift from glucose- to lipid-based energy generation that accompanies a high fat/low carbohydrate diet...
September 13, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28938766/dietary-effects-of-bacillus-subtilis-fmbj-on-the-antioxidant-capacity-of-broilers-at-an-early-age
#3
Lili Zhang, Kaiwen Bai, Jingfei Zhang, Wen Xu, Qiang Huang, Tian Wang
This study was designed to evaluate the usage of Bacillus subtilis fmbj (BS fmbj) in broiler diets, and its effects on the antioxidant capacity of broilers at an early age. A total of 240 day-old male Arbor Acres (AA) broilers were randomly assigned to 4 groups, namely the control (CON) group (fed basal diets with 0 cfu/kg BS fmbj), the BS-1 group (fed basal diet with 0.2 × 1011 cfu/kg BS fmbj), BS-2 group (fed basal diet with 0.3 × 1011 cfu/kg BS fmbj), and BS-3 group (fed basal diet with 0.4 × 1011 cfu/kg BS fmbj)...
October 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28938574/the-dual-pi3k-mtor-inhibitor-gsk2126458-is-effective-for-treating-solid-renal-tumours-in-tsc2-mice-through-suppression-of-cell-proliferation-and-induction-of-apoptosis
#4
Kalin Narov, Jian Yang, Paulina Samsel, Ashley Jones, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumour syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR. Tumour responses in TSC patients to rapamycin, an allosteric inhibitor of mTOR, or its analogs are partial and reversible probably due to feedback activation of Akt. In this study, we examined the efficacy of GSK2126458, an ATP-competitive dual inhibitor of PI3K/mTOR, in comparison to rapamycin for treatment of renal tumours in genetically engineered Tsc2(+/-) mice. We found that both GSK2126458 and rapamycin caused significant reduction in number and size of solid renal tumours...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#5
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938109/investigating-mutation-specific-biological-activities-of-small-molecules-using-quantitative-structure-activity-relationship-for-epidermal-growth-factor-receptor-in-cancer
#6
P Anoosha, R Sakthivel, M Michael Gromiha
Epidermal Growth Factor Receptor (EGFR) is a potential drug target in cancer therapy. Missense mutations play major roles in influencing the protein function, leading to abnormal cell proliferation and tumorigenesis. A number of EGFR inhibitor molecules targeting ATP binding domain were developed for the past two decades. Unfortunately, they become inactive due to resistance caused by new mutations in patients, and previous studies have also reported noticeable differences in inhibitor binding to distinct known driver mutants as well...
August 26, 2017: Mutation Research
https://www.readbyqxmd.com/read/28937704/a-high-concentration-of-fatty-acids-induces-tnf-%C3%AE-as-well-as-no-release-mediated-by-the-p2x4-receptor-and-the-protective-effects-of-puerarin-in-raw264-7-cells
#7
Yun-Ming Tu, Cheng-Xin Gong, Lu Ding, Xing-Zi Liu, Tao Li, Fang-Fang Hu, Shuo Wang, Chao-Peng Xiong, Shang-Dong Liang, Hong Xu
Circulating levels of free fatty acids (FFAs) are often found to be increased in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). High plasma FFA levels may give rise to maladaptive macrophage activation and promote inflammatory responses, which has been proposed as a potential mechanism for the development of DM and MS. P2X4 receptor (P2X4R), a ligand-gated cation channel activated by extracellular adenosine triphosphate (ATP), plays a primary role in the regulation of inflammatory responses...
September 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28937648/separation-and-enrichment-of-lectin-from-zihua-snap-bean-phaseolus-vulgaris-seeds-by-peg-600-ammonium-sulfate-aqueous-two-phase-system
#8
Bin Jiang, Yongqiang Yuan, Xiaoqing Zhang, Zhibiao Feng, Chunhong Liu
A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH₄)₂SO₄ aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box-Behnken design (BBD), involving four factors at three levels each subjected to analysis of variance (ANOVA) and response surface analysis, the protein recovery and the purification factor of lectin in the top phase were used as the response values of the variance analysis to acquire the multivariate quadratic regression model...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937645/bioelectrochemical-detection-of-mycobacterium-tuberculosis-esat-6-in-an-antibody-based-biomicrosystem
#9
Danna Sepulveda, Miguel A Aroca, Andres Varela, Patricia Del Portillo, Johann F Osma
Bioelectrochemical sensing of Mycobacterium tuberculosis through electro-immunosensors is a promising technique to detect relevant analytes. In general, immunosensors require the formation of organic assemblies by the adsorption of molecular constituents. Moreover, they depend on the correct immobilization of the bio-recognition element in the biosensor. These procedures cannot be easily monitored without the use of invasive methods. In this work, an impedance analysis technique was used, as a non-invasive method, to measure and differentiate the manufacturing stages of the sensors...
September 22, 2017: Sensors
https://www.readbyqxmd.com/read/28936802/significance-of-mitochondrial-protein-post-translational-modifications-in-pathophysiology-of-brain-injury
#10
Nina Klimova, Aaron Long, Tibor Kristian
Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage...
September 21, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28936218/atoma1-affects-the-oxphos-system-and-plant-growth-in-contrast-to-other-newly-identified-atp-independent-proteases-in-arabidopsis-mitochondria
#11
Iwona Migdal, Renata Skibior-Blaszczyk, Malgorzata Heidorn-Czarna, Marta Kolodziejczak, Arnold Garbiec, Hanna Janska
Compared with yeast, our knowledge on members of the ATP-independent plant mitochondrial proteolytic machinery is rather poor. In the present study, using confocal microscopy and immunoblotting, we proved that homologs of yeast Oma1, Atp23, Imp1, Imp2, and Oct1 proteases are localized in Arabidopsis mitochondria. We characterized these components of the ATP-independent proteolytic system as well as the earlier identified protease, AtICP55, with an emphasis on their significance in plant growth and functionality in the OXPHOS system...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28935700/mitochondrial-based-therapeutics-for-the-treatment-of-spinal-cord-injury-mitochondrial-biogenesis-as-a-potential-pharmacological-target
#12
Natalie E Scholpa, Rick G Schnellmann
Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, directly reducing the ability of mitochondria to maintain homeostasis, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury post-SCI represents a potentially effective therapeutic strategy...
September 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28935606/calcimycin-mediates-mycobacterial-killing-by-inducing-intracellular-calcium-regulated-autophagy-in-a-p2rx7-dependent-manner
#13
Shradha Mawatwal, Assirbad Behura, Abhirupa Ghosh, Saqib Kidwai, Abtar Mishra, Amar Deep, Sakshi Agarwal, Sudipto Saha, Ramandeep Singh, Rohan Dhiman
Phenotypic screening led to the identification of calcimycin as a potent inhibitor of Mycobacterium bovis BCG (M. bovis BCG) growth in vitro and in THP-1 cells. In the present study, we aim to decipher the mechanism of antimycobacterial activity of calcimycin. We noticed that treatment with calcimycin led to up-regulation of different autophagy markers like Beclin-1, autophagy-related gene (Atg) 7, Atg 3 and enhanced microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion in macrophages...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28935562/n-2-methoxyphenyl-benzenesulfonamide-a-novel-regulator-of-neuronal-g-protein-gated-inward-rectifier-k-channels
#14
Kenneth B Walsh, Elaine A Gay, Bruce E Blough, David W Geurkink
G protein-gated inward rectifier K(+) (GIRK) channels are members of the super-family of proteins known as inward rectifier K(+) (Kir) channels and are expressed throughout the peripheral and central nervous systems. Neuronal GIRK channels are the downstream targets of a number of neuromodulators including opioids, somatostatin, dopamine and cannabinoids. Previous studies have demonstrated that the ATP-sensitive K(+) channel, another member of the Kir channel family, is regulated by sulfonamide drugs. Therefore, to determine if sulfonamides also modulate GIRK channels, we screened a library of arylsulfonamide compounds using a GIRK channel fluorescent assay that utilized pituitary AtT20 cells expressing GIRK channels along with the somatostatin type-2 and -5 receptors...
September 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28935498/are-in-vivo-and-in-vitro-assessments-of-comparative-and-combined-toxicity-of-the-same-metallic-nanoparticles-compatible-or-contradictory-or-both-a-juxtaposition-of-data-obtained-in-respective-experiments-with-nio-and-mn3o4-nanoparticles
#15
Ilzira Minigalieva, Tatiana Bushueva, Eleonore Fröhlich, Claudia Meindl, Kristin Öhlinger, Vladimir Panov, Anatoly Varaksin, Vladimir Shur, Ekaterina Shishkina, Vladimir Gurvich, Boris Katsnelson
Comparative and combined damaging effects of NiO and Mn3O4 nanoparticles were estimated on cultures of several established human cell lines. The cytotoxicity indices used were: (a) reduction in cellular dehydrogenase activity, (b) decrease in the ATP-content, (c) for SH-SY5Y cells also decrease in the tyrosine hydroxylase content. The combined cytotoxicity was modeled using the Response Surface Methodology. When assessing the stability of metal oxide nanoparticles (MeO-NPs) in cultural media used by us, we found that the addition of the fetal bovine serum (FBS) to them renders NiO-NPs and, to even greater extent, Mn3O4-NPs exponentially slow soluble while without FBS their dissolution was virtually undetectable...
September 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28935446/mitochondrial-adaptation-in-steatotic-mice
#16
Claudia Einer, Simon Hohenester, Ralf Wimmer, Lena Wottke, Renate Artmann, Sabine Schulz, Christian Gosmann, Alisha Simmons, Christin Leitzinger, Carola Eberhagen, Sabine Borchard, Sabine Schmitt, Stefanie M Hauck, Christine von Toerne, Martin Jastroch, Ellen Walheim, Christian Rust, Alexander L Gerbes, Bastian Popper, Doris Mayr, Max Schnurr, Angelika M Vollmar, Gerald Denk, Hans Zischka
Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium...
September 18, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28934276/enhanced-pyruvate-dehydrogenase-activity-improves-cardiac-outcomes-in-a-murine-model-of-cardiac-arrest
#17
Lin Piao, Yong-Hu Fang, Manfred M Kubler, Michael W Donnino, Willard W Sharp
RATIONALE: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA) hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28934246/discovery-of-pf-06928215-as-a-high-affinity-inhibitor-of-cgas-enabled-by-a-novel-fluorescence-polarization-assay
#18
Justin Hall, Amy Brault, Fabien Vincent, Shawn Weng, Hong Wang, Darren Dumlao, Ann Aulabaugh, Dikran Aivazian, Dana Castro, Ming Chen, Jeffrey Culp, Ken Dower, Joseph Gardner, Steven Hawrylik, Douglas Golenbock, David Hepworth, Mark Horn, Lyn Jones, Peter Jones, Eicke Latz, Jing Li, Lih-Ling Lin, Wen Lin, David Lin, Frank Lovering, Nootaree Niljanskul, Ryan Nistler, Betsy Pierce, Olga Plotnikova, Daniel Schmitt, Suman Shanker, James Smith, William Snyder, Timothy Subashi, John Trujillo, Edyta Tyminski, Guoxing Wang, Jimson Wong, Bruce Lefker, Leslie Dakin, Karen Leach
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28934162/gas-chromatography-mass-spectrometry-for-metabolite-profiling-of-japanese-black-cattle-naturally-contaminated-with-zearalenone-and-sterigmatocystin
#19
Katsuki Toda, Emiko Kokushi, Seiichi Uno, Ayaka Shiiba, Hiroshi Hasunuma, Yasuo Fushimi, Missaka P B Wijayagunawardane, Chunhua Zhang, Osamu Yamato, Masayasu Taniguchi, Johanna Fink-Gremmels, Mitsuhiro Takagi
The objective of this study was to evaluate the metabolic profile of cattle fed with or without zearalenone (ZEN) and sterigmatocystin (STC)-contaminated diets using a gas chromatography-mass spectrometry metabolomics approach. Urinary samples were collected from individual animals (n = 6 per herd) from fattening female Japanese Black (JB) cattle herds (23 months old, 550-600 kg). Herd 1 had persistently high urinary ZEN and STC concentrations due to the presence of contaminated rice straw. Herd 2, the second female JB fattening herd (23 months old, 550-600 kg), received the same dietary feed as Herd 1, with non-contaminated rice straw...
September 21, 2017: Toxins
https://www.readbyqxmd.com/read/28934133/understanding-the-mechanism-of-translocation-of-adenylate-cyclase-toxin-across-biological-membranes
#20
REVIEW
Helena Ostolaza, César Martín, David González-Bullón, Kepa B Uribe, Asier Etxaniz
Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin...
September 21, 2017: Toxins
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