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https://www.readbyqxmd.com/read/28411375/development-of-tetramethylenedisulfotetramine-tets-hapten-library-synthesis-electrophysiological-studies-and-immune-response-in-rabbits
#1
Bogdan Barnych, Natalia Vasylieva, Tom Joseph, Susan Hulsizer, Hai Nguyen, Tomas Cajka, Isaac Pessah, Heike Wulff, Shirley Gee, Bruce Hammock
There is a need for fast detection methods for the banned rodenticide tetramethylenedisulfotetramine (TETS), a highly potent blocker of the γ-aminobutyric acid (GABAA) receptors. General synthetic approach toward two groups of analogues was developed. Screening of the resulting library of compounds by FLIPR or whole-cell voltage-clamp revealed that despite the structural differences some of the TETS analogues retained GABAA receptor inhibition, however their potency was an order of magnitude lower. Antibodies raised in rabbits against some of the TETS analogues conjugated to protein recognized free TETS and will be used for the development of an immunoassay for TETS...
April 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28409465/peroxisomal-membrane-and-matrix-protein-import-using-a-semi-intact-mammalian-cell-system
#2
Kanji Okumoto, Masanori Honsho, Yuqiong Liu, Yukio Fujiki
Peroxisomes are essential intracellular organelles that catalyze a number of essential metabolic pathways including β-oxidation of very long chain fatty acids, synthesis of plasmalogen, bile acids, and generation and degradation of hydrogen peroxide. These peroxisomal functions are accomplished by strictly and spatiotemporally regulated compartmentalization of the enzymes catalyzing these reactions. Defects in peroxisomal protein import result in inherited peroxisome biogenesis disorders in humans. Peroxisomal matrix and membrane proteins are synthesized on free ribosomes and transported to peroxisomes in a manner dependent on their specific targeting signals and their receptors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28399449/synthesis-and-biological-evaluation-of-neoglycosphingolipids
#3
Shuihong Cheng, Peixing Wu, Jing Han, Yiren Wang, Yuting Cui, Zhenxing Zhang, Tatsuya Yamagata, Xuebing Li
Various neoglycosphingolipids were efficiently synthesized in a one-step reaction by the coupling of free sugars with an N-alkylaminooxy-functionalized ceramide analogue. The bioactivity studies demonstrated that most of these compounds could upregulate the expression of matrix metalloproteinase-9 (MMP-9, extracellular matrix proteins associated with tumor migration) in murine melanoma B16 cells in a similar manner to the natural ganglioside monosialodihexosylganglioside (GM3), which highlights the potential use of these neoglycosphingolipids as inhibitors of tumor migration...
April 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28374993/removable-backbone-modification-method-for-the-chemical-synthesis-of-membrane-proteins
#4
Jia-Bin Li, Shan Tang, Ji-Shen Zheng, Chang-Lin Tian, Lei Liu
Chemical synthesis can produce water-soluble globular proteins bearing specifically designed modifications. These synthetic molecules have been used to study the biological functions of proteins and to improve the pharmacological properties of protein drugs. However, the above advances notwithstanding, membrane proteins (MPs), which comprise 20-30% of all proteins in the proteomes of most eukaryotic cells, remain elusive with regard to chemical synthesis. This difficulty stems from the strong hydrophobic character of MPs, which can cause considerable handling issues during ligation, purification, and characterization steps...
April 4, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28360896/comparative-genomics-of-four-isosphaeraceae-planctomycetes-a-common-pool-of-plasmids-and-glycoside-hydrolase-genes-shared-by-paludisphaera-borealis-px4-t-isosphaera-pallida-is1b-t-singulisphaera-acidiphila-dsm-18658-t-and-strain-sh-pl62
#5
Anastasia A Ivanova, Daniil G Naumoff, Kirill K Miroshnikov, Werner Liesack, Svetlana N Dedysh
The family Isosphaeraceae accommodates stalk-free planctomycetes with spherical cells, which can be assembled in short chains, long filaments, or aggregates. These bacteria inhabit a wide variety of terrestrial environments, among those the recently described Paludisphaera borealis PX4(T) that was isolated from acidic boreal wetlands. Here, we analyzed its finished genome in comparison to those of three other members of the Isosphaeraceae: Isosphaera pallida IS1B(T), Singulisphaera acidiphila DSM 18658(T), and the uncharacterized planctomycete strain SH-PL62...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28358123/molecular-therapy-for-degenerative-disc-disease-clues-from-secretome-analysis-of-the-notochordal-cell-rich-nucleus-pulposus
#6
Ajay Matta, M Zia Karim, David E Isenman, W Mark Erwin
Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM)...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357386/a-new-role-for-holliday-junction-resolvase-yen1-in-processing-dna-replication-intermediates-exposes-dna2-as-an-accessory-replicative-helicase
#7
COMMENT
Benoît Falquet, Ulrich Rass
DNA replication is mediated by a multi-protein complex known as the replisome. With the hexameric MCM (minichromosome maintenance) replicative helicase at its core, the replisome splits the parental DNA strands, forming replication forks (RFs), where it catalyses coupled leading and lagging strand DNA synthesis. While replication is a highly effective process, intrinsic and oncogene-induced replication stress impedes the progression of replisomes along chromosomes. As a consequence, RFs stall, arrest, and collapse, jeopardizing genome stability...
January 2, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28357359/chemical-proteomics-approach-reveals-the-direct-targets-and-the-heme-dependent-activation-mechanism-of-artemisinin-in-plasmodium-falciparum-using-an-artemisinin-based-activity-probe
#8
COMMENT
Jigang Wang, Qingsong Lin
Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA) of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for...
April 5, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28356734/therapeutic-effects-of-proteoliposomes-on-x-linked-chronic-granulomatous-disease-proof-of-concept-using-macrophages-differentiated-from-patient-specific-induced-pluripotent-stem-cells
#9
Julie Brault, Guillaume Vaganay, Aline Le Roy, Jean-Luc Lenormand, Sandra Cortes, Marie José Stasia
Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency due to dysfunction of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex leading to severe and recurrent infections in early childhood. The main genetic form is the X-linked CGD leading to the absence of cytochrome b558 composed of NOX2 and p22 (phox) , the membrane partners of the NADPH oxidase complex. The first cause of death of CGD patients is pulmonary infections. Recombinant proteoliposome-based therapy is an emerging and innovative approach for membrane protein delivery, which could be an alternative local, targeted treatment to fight lung infections in CGD patients...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28353640/bisarylureas-based-on-1h-pyrazolo-3-4-d-pyrimidine-scaffold-as-novel-pan-raf-inhibitors-with-potent-anti-proliferative-activities-structure-based-design-synthesis-biological-evaluation-and-molecular-modelling-studies
#10
Yu Fu, Yuanyuan Wang, Shanhe Wan, Zhonghuang Li, Guangfa Wang, Jiajie Zhang, Xiaoyun Wu
RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAF(V600E) kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK)...
March 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28350472/development-of-a-cho-based-cell-free-platform-for-synthesis-of-active-monoclonal-antibodies
#11
Rey W Martin, Natalia I Majewska, Cindy X Chen, Thomas E Albanetti, Rod Brian Jimenez, Albert E Schmelzer, Michael C Jewett, Varnika Roy
Chinese Hamster Ovary (CHO) cells are routinely optimized to stably express monoclonal antibodies (mAbs) at high titers. At the early stages of lead isolation and optimization, hundreds of sequences for the target protein of interest are screened. Typically, cell-based transient expression technology platforms are used for expression screening, but these can be time- and resource-intensive. Here, we have developed a cell-free protein synthesis (CFPS) platform utilizing a commercially available CHO extract for the rapid in vitro synthesis of active, aglycosylated mAbs...
March 28, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28345463/computational-and-mechanistic-studies-on-the-effect-of-galactoxyloglucan-imatinib-nanoconjugate-in-imatinib-resistant-k562-cells
#12
Alphy Rose James, B S Unnikrishnan, R Priya, Manu M Joseph, T K Manojkumar, K Raveendran Pillai, R Shiji, G U Preethi, P Kusumakumary, T T Sreelekha
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28341143/corrigendum-to-multiple-inhibitory-factor-removal-from-an-escherichia-coli-cell-extract-improves-cell-free-protein-synthesis-j-biosci-bioeng-108-2009-30-35
#13
Eiko Seki, Natsuko Matsuda, Takanori Kigawa
No abstract text is available yet for this article.
January 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28337140/antioxidant-and-anti-tyrosinase-activities-of-phenolic-extracts-from-rape-bee-pollen-and-inhibitory-melanogenesis-by-camp-mitf-tyr-pathway-in-b16-mouse-melanoma-cells
#14
Liping Sun, Yan Guo, Yanxin Zhang, Yongliang Zhuang
Rape bee pollen possesses many nutritional and therapeutic properties because of its abundant nutrimental and bioactive components. In this study, free (FPE) and bound (BPE) phenolic extracts of rape bee pollen were obtained, phenolic and flavonoid contents were determined, and composition of phenolic acids was analyzed. In vitro antioxidant and anti-tyrosinase (TYR) activities of FPE and BPE were compared, and inhibitory melanogenesis of FPE was further evaluated. Results showed FPE and BPE contain total phenolic contents of 11...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#15
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#16
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28302587/transcriptomic-changes-in-cho-cells-after-adaptation-to-suspension-growth-in-protein-free-medium-analysed-by-a-species-specific-microarray
#17
Smriti Shridhar, Gerald Klanert, Norbert Auer, Inmaculada Hernandez-Lopez, Maciej M Kańduła, Matthias Hackl, Johannes Grillari, Nancy Stralis-Pavese, David P Kreil, Nicole Borth
Chinese Hamster Ovary (CHO) cells are the preferred cell line for production of biopharmaceuticals. These cells are capable to grow without serum supplementation, but drastic changes in their phenotype occur during adaptation to protein-free growth, which typically include the change to a suspension phenotype with reduced growth rate. A possible approach to understand this transformation, with the intention to counteract the reduction in growth by targeted supplementation of protein-free media, is gene expression profiling...
March 14, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28301064/mitochondrial-biogenesis-in-neurodegeneration
#18
REVIEW
P Andy Li, Xiaolin Hou, Shaocai Hao
Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondrial dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria...
March 16, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28292742/fatty-acid-synthesis-intermediates-represent-novel-noninvasive-biomarkers-of-prostate-cancer-chemoprevention-by-phenethyl-isothiocyanate
#19
Krishna B Singh, Shivendra V Singh
Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model...
March 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28286305/yipf1-yipf2-and-yipf6-are-medial-trans-golgi-and-trans-golgi-network-localized-yip-domain-family-proteins-which-play-a-role-in-the-golgi-reassembly-and-glycan-synthesis
#20
Jeerawat Soonthornsit, Noriko Sakai, Yurika Sasaki, Ryota Watanabe, Shiho Osako, Nobuhiro Nakamura
In this study, we attempted to explore the function of three uncharacterized mammalian homologs of yeast Yip domain family proteins-YIPF6, a homolog of Yip1p, and YIPF1 and YIPF2, which are homologs of Yif1p. Immunofluorescence staining revealed that YIPF1, YIPF2, and YIPF6 mainly localize in the medial-/trans-Golgi and also partially in the trans-Golgi network (TGN). On treatment with brefeldin A (BFA), the homologs co-migrated partly with medial-/trans-Golgi markers and also with a TGN marker in earlier time point, but finally redistributed within cytoplasmic punctate structures that were distinct from medial-/trans-Golgi and the TGN markers...
March 9, 2017: Experimental Cell Research
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