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https://www.readbyqxmd.com/read/27933733/mannich-bases-of-1-2-4-triazole-3-thione-containing-adamantane-moiety-synthesis-preliminary-anticancer-evaluation-and-molecular-modeling-studies
#1
Milorad Z Milošev, Katarina Jakovljević, Milan D Joksović, Tatjana Stanojković, Ivana Z Matić, Milka Perović, Vesna Tešić, Selma Kanazir, Milan Mladenović, Marko V Rodić, Vukadin M Leovac, Snežana Trifunović, Violeta Marković
A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e and 5j on the cell cycle were investigated by flow cytometric analysis...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933730/reactivity-of-9-aminoacridine-drug-quinacrine-with-glutathione-limits-its-anti-prion-activity
#2
Martin Šafařík, Tibor Moško, Zbigniew Zawada, Eva Šafaříková, Martin Dračínský, Karel Holada, Jaroslav Šebestík
Quinacrine - the drug based on 9-aminoacridine - failed in clinical trials for prion diseases, whereas it was active in in-vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abundant glutathione. Here, we described the semi-large-scale synthesis of the acridinylated glutathione and the consequences of its formation on biological and biophysical activities. The acridinylated glutathione is one order of magnitude weaker prion protein binder than the parent quinacrine...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933725/cellular-engineering-for-therapeutic-protein-production-product-quality-host-modification-and-process-improvement
#3
REVIEW
Evan Wells, Anne Skaja Robinson
Recombinant proteins offer many therapeutic advantages unavailable in traditional small molecule drugs, but the need for cellular versus chemical synthesis complicates production. Avenues for producing therapeutic biologics are continuously expanding, and developments in biochemistry, cell biology, and bioengineering fuel new discoveries that promise safer, more efficient, and cheaper drugs for consumers. Numerous approaches to express recombinant proteins exist, but Escherichia coli, Saccharomyces cerevisiae, and mammalian systems (e...
December 9, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27933521/genenetwork-a-toolbox-for-systems-genetics
#4
Megan K Mulligan, Khyobeni Mozhui, Pjotr Prins, Robert W Williams
The goal of systems genetics is to understand the impact of genetic variation across all levels of biological organization, from mRNAs, proteins, and metabolites, to higher-order physiological and behavioral traits. This approach requires the accumulation and integration of many types of data, and also requires the use of many types of statistical tools to extract relevant patterns of covariation and causal relations as a function of genetics, environment, stage, and treatment. In this protocol we explain how to use the GeneNetwork web service, a powerful and free online resource for systems genetics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933189/insulin-resistance-of-protein-anabolism-accompanies-that-of-glucose-metabolism-in-lean-glucose-tolerant-offspring-of-persons-with-type-2-diabetes
#5
Sergio A Burgos, Vikram Chandurkar, Michael A Tsoukas, Stéphanie Chevalier, José A Morais, Marie Lamarche, Errol B Marliss
OBJECTIVE: To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Seven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m(2)/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp. Whole-body glucose and protein kinetics were measured with d-[3-(3)H]glucose and l-[l-(13)C]leucine, respectively...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27933082/rna-seq-transcriptome-response-of-flax-linum-usitatissimum-l-to-the-pathogenic-fungus-fusarium-oxysporum-f-sp-lini
#6
Leonardo Galindo-González, Michael K Deyholos
Fusarium oxysporum f. sp. lini is a hemibiotrophic fungus that causes wilt in flax. Along with rust, fusarium wilt has become an important factor in flax production worldwide. Resistant flax cultivars have been used to manage the disease, but the resistance varies, depending on the interactions between specific cultivars and isolates of the pathogen. This interaction has a strong molecular basis, but no genomic information is available on how the plant responds to attempted infection, to inform breeding programs on potential candidate genes to evaluate or improve resistance across cultivars...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27932990/regulation-of-connexins-expression-levels-by-micrornas-an-update
#7
REVIEW
Juan F Calderón, Mauricio A Retamal
Control of cell-cell coordination and communication is regulated by several factors, including paracrine and autocrine release of biomolecules, and direct exchange of soluble factors between cells through gap junction channels. Additionally, hemichannels also participate in cell-cell coordination through the release of signaling molecules, such as ATP and glutamate. A family of transmembrane proteins named connexins forms both gap junction channels and hemichannels. Because of their importance in cell and tissue coordination, connexins are controlled both by post-translational and post-transcriptional modifications...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27932980/tnf-%C3%AE-induced-cpla2-expression-via-nadph-oxidase-reactive-oxygen-species-dependent-nf-%C3%AE%C2%BAb-cascade-on-human-pulmonary-alveolar-epithelial-cells
#8
Chih-Chung Lin, Wei-Ning Lin, Rou-Ling Cho, Chen-Yu Wang, Li-Der Hsiao, Chuen-Mao Yang
Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that TNF-α-stimulated increases in cPLA2 mRNA (5.2 folds) and protein (3.9 folds) expression, promoter activity (4.3 folds), and PGE2 secretion (4.7 folds) in HPAEpiCs, determined by Western blot, real-time PCR, promoter activity assay and PGE2 ELISA kit...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932681/acute-intermittent-hypoxia-in-rats-activates-muscle-proteolytic-pathways-through-a-glucocorticoid-dependent-mechanism
#9
Franciele Przygodda, Leandro Henrique Manfredi, Juliano Machado, Dawit A P Gonçalves, Neusa Maria Zanon, Leni G H Bonagamba, Benedito H Machado, Isis do Carmo Kettelhut, Luiz C C Navegantes
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932679/tendon-collagen-synthesis-declines-with-immobilization-in-elderly-humans-no-effect-of-anti-inflammatory-medication
#10
Kasper Dideriksen, Anders Ploug Boesen, Søren Reitelseder, Christian Couppe, Rene Brüggebusch Svensson, Peter Schjerling, S Peter Magnusson, Lars Holm, Michael Kjaer
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are used as pain killers during periods of unloading caused by traumatic occurrences or diseases. However, it is unknown how the tendon protein turnover and mechanical properties responds to unloading and subsequent loading in elderly humans, and especially whether NSAIDs affect tendon adaptation during such periods. Thus, we studied the influence of NSAID upon the human patellar tendon protein synthesis and mechanical properties during immobilization and subsequent rehabilitating resistance training...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932585/structural-and-functional-characterization-of-the-tyw3-taw3-class-of-sam-dependent-methyltransferases
#11
Mark A Currie, Greg Brown, Andrew Wong, Takayuki Ohira, Kei Sugiyama, Tsutomu Suzuki, Alexander F Yakunin, Zongchao Jia
S-adenosylmethionine (SAM)-dependent methyltransferases regulate a wide range of biological processes through the modification of proteins, nucleic acids, polysaccharides, as well as various metabolites. TYW3/Taw3 is a SAM-dependent methyltransferase responsible for the formation of a tRNA modification known as wybutosine and its derivatives that are required for accurate decoding in protein synthesis. Here, we report the crystal structure of Taw3, a homolog of TYW3 from Sulfolobus solfataricus, which revealed a novel α/β fold...
December 8, 2016: RNA
https://www.readbyqxmd.com/read/27932574/ulk1-cycling-the-ups-and-downs-of-the-autophagy-response
#12
Yan G Zhao, Hong Zhang
The Ser/Thr kinase ULK1/Atg1 controls autophagy initiation under nutrient starvation conditions. In this issue, Nazio et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201605089) demonstrate that oscillatory modulation of NEDD4L-mediated proteasomal degradation and mTOR-dependent de novo protein synthesis of ULK1 ensures the proper amplitude and duration of the autophagy response during prolonged starvation, thus maintaining cellular homeostasis.
December 8, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27932573/fine-tuning-of-ulk1-mrna-and-protein-levels-is-required-for-autophagy-oscillation
#13
Francesca Nazio, Marianna Carinci, Cristina Valacca, Pamela Bielli, Flavie Strappazzon, Manuela Antonioli, Fabiola Ciccosanti, Carlo Rodolfo, Silvia Campello, Gian Maria Fimia, Claudio Sette, Paolo Bonaldo, Francesco Cecconi
Autophagy is an intracellular degradation pathway whose levels are tightly controlled to secure cell homeostasis. Unc-51-like kinase 1 (ULK1) is a conserved serine-threonine kinase that plays a central role in the initiation of autophagy. Here, we report that upon autophagy progression, ULK1 protein levels are specifically down-regulated by the E3 ligase NEDD4L, which ubiquitylates ULK1 for degradation by the proteasome. However, whereas ULK1 protein is degraded, ULK1 mRNA is actively transcribed. Upon reactivation of mTOR-dependent protein synthesis, basal levels of ULK1 are promptly restored, but the activity of newly synthesized ULK1 is inhibited by mTOR...
December 8, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27932527/mechanisms-of-in-vivo-ribosome-maintenance-change-in-response-to-nutrient-signals
#14
Andrew D Mathis, Bradley C Naylor, Richard H Carson, Eric Evans, Justin Harwell, Jared Knect, Eric Hexem, Fredrick Peelor, Benjamin F Miller, Karyn L Hamilton, Mark K Transtrum, Benjamin T Bikman, John C Price
Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging and disease, whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan...
December 8, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27932481/modeling-monogenic-human-nephrotic-syndrome-in-the-drosophila-garland-cell-nephrocyte
#15
Tobias Hermle, Daniela A Braun, Martin Helmstädter, Tobias B Huber, Friedhelm Hildebrandt
Steroid-resistant nephrotic syndrome is characterized by podocyte dysfunction. Drosophila garland cell nephrocytes are podocyte-like cells and thus provide a potential in vivo model in which to study the pathogenesis of nephrotic syndrome. However, relevant pathomechanisms of nephrotic syndrome have not been studied in nephrocytes. Here, we discovered that two Drosophila slit diaphragm proteins, orthologs of the human genes encoding nephrin and nephrin-like protein 1, colocalize within a fingerprint-like staining pattern that correlates with ultrastructural morphology...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932447/unloading-of-homologous-recombination-factors-is-required-for-restoring-double-stranded-dna-at-damage-repair-loci
#16
Yulia Vasianovich, Veronika Altmannova, Oleksii Kotenko, Matthew D Newton, Lumir Krejci, Svetlana Makovets
Cells use homology-dependent DNA repair to mend chromosome breaks and restore broken replication forks, thereby ensuring genome stability and cell survival. DNA break repair via homology-based mechanisms involves nuclease-dependent DNA end resection, which generates long tracts of single-stranded DNA required for checkpoint activation and loading of homologous recombination proteins Rad52/51/55/57. While recruitment of the homologous recombination machinery is well characterized, it is not known how its presence at repair loci is coordinated with downstream re-synthesis of resected DNA We show that Rad51 inhibits recruitment of proliferating cell nuclear antigen (PCNA), the platform for assembly of the DNA replication machinery, and that unloading of Rad51 by Srs2 helicase is required for efficient PCNA loading and restoration of resected DNA As a result, srs2Δ mutants are deficient in DNA repair correlating with extensive DNA processing, but this defect in srs2Δ mutants can be suppressed by inactivation of the resection nuclease Exo1...
December 8, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27932302/hippocampal-asymmetry-differences-in-the-left-and-right-hippocampus-proteome-in-the-rat-model-of-temporal-lobe-epilepsy
#17
Leila Sadeghi, Albert Anatolyevich Rizvanov, Ilnur Ildusovich Salafutdinov, Bahareh Dabirmanesh, Mohammad Sayyah, Yaghoub Fathollahi, Khosro Khajeh
: The hippocampus is a complex brain structure and undergoes severe sclerosis and gliosis in temporal lobe epilepsy (TLE) as the most common type of epilepsy. The key features of the TLE may be reported in chronic animal models of epilepsy, such as pilocarpine model. Therefore, the current study was conducted in a rat pilocarpine model of acquired epilepsy. Two-dimensional gel electrophoresis based proteomic technique was used to compare the proteome map of the left and right hippocampus in both control and epileptic rats...
December 5, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27931141/modulation-of-leukotriene-signaling-inhibiting-cell-growth-in-chronic-myeloid-leukemia
#18
Elham Yektaei-Karin, Ana Zovko, Anders Nilsson, Barbro Näsman-Glaser, Lena Kanter, Olof Rådmark, Jonas Wallvik, Marja Ekblom, Monika Dolinska, Hong Qian, Leif Stenke
Although tyrosine kinase inhibitors (TKIs) have dramatically improved clinical outcome in chronic myeloid leukemia (CML), cure rarely occurs. This may be due to BCR-ABL-independent, aberrant signaling pathways, one of which leads to leukotriene (LT) formation. Well-recognized as inflammatory mediators, LT can also affect oncogenic mechanisms of several tumors. We have previously discovered elevated LT-synthesis and up-regulated cysteinyl-LT-inducing enzyme in CML. Here we report on dose-dependent inhibition of CML cell growth exerted by specific blockers of LT-signaling...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27931028/sustained-effects-of-neonatal-systemic-lipopolysaccharide-on-il-1%C3%AE-and-nrf2-in-adult-rat-substantia-nigra-are-partly-normalized-by-a-spirulina-enriched-diet
#19
Jaspal Patil, Ashok Matte, Hans Nissbrandt, Carina Mallard, Mats Sandberg
BACKGROUND/AIM: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1β, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN...
December 9, 2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27930936/sunlight-exposure-increases-vitamin-d-sufficiency-in-growing-pigs-fed-a-diet-formulated-to-exceed-requirements
#20
B M Alexander, B C Ingold, J L Young, S R Fensterseifer, P J Wechsler, K J Austin, D E Larson-Meyer
Traditional confinement practices limit exposure to sunlight and vitamin D synthesis, and vitamin insufficiency occurs even with dietary supplementation. The aim of this study was to determine the effect of limited sun exposure on serum concentration of vitamin D and the expression of vitamin D synthesizing enzymes in the liver and kidney of pigs on a vitamin D sufficient diet. White-pigmented grower pigs (29.7 ± 2.3 kg) fed 15% CP diet ad libitum providing >1,200 IU vitamin D3/kg of feed were exposed to sunlight for 1 h each day at solar noon for 14 d at the spring equinox (March pigs, n = 10) or summer solstice (June pigs, n = 5) and again before slaughter in June (March pigs) and September (June pigs)...
November 11, 2016: Domestic Animal Endocrinology
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