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https://www.readbyqxmd.com/read/29351582/sco2-mutations-cause-early-onset-axonal-charcot-marie-tooth-disease-associated-with-cellular-copper-deficiency
#1
Adriana P Rebelo, Dimah Saade, Claudia P Pereira, Amjad Farooq, Tyler C Huff, Lisa Abreu, Carlos T Moraes, Diana Mnatsakanova, Kathy Mathews, Hua Yang, Eric A Schon, Stephan Zuchner, Michael E Shy
Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients...
January 16, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29351567/whole-thorax-irradiation-of-non-human-primates-induces-persistent-nuclear-damage-and-gene-expression-changes-in-peripheral-blood-cells
#2
Shanaz A Ghandhi, Helen C Turner, Igor Shuryak, Gregory O Dugan, J Daniel Bourland, John D Olson, Janet A Tooze, Shad R Morton, Ines Batinic-Haberle, J Mark Cline, Sally A Amundson
We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals...
2018: PloS One
https://www.readbyqxmd.com/read/29351497/screen-targeting-lung-and-prostate-cancer-oncogene-identifies-novel-inhibitors-of-rgs17-and-problematic-chemical-substructures
#3
Christopher R Bodle, Josephine H Schamp, Joseph B O'Brien, Michael P Hayes, Meng Wu, Jonathan A Doorn, David L Roman
Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein-coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29351433/%C3%AE-nitrostyrene-derivatives-attenuate-lps-mediated-acute-lung-injury-via-the-inhibition-of-neutrophil-platelet-interactions-and-net-release
#4
Yao-Wen Chang, Ching-Ping Tseng, Chih-Hsun Lee, Tsong-Long Hwang, Yu-Li Chen, Mei-Tzu Su, Kowit-Yu Chong, Ying-Wei Lan, Chin-Chung Wu, Kung-Ju Chen, Fen-Hua Lu, Hsiang-Ruei Liao, Chuen Hsueh, Pei-Wen Hsieh
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increases acute inflammation and contributes to the development of ALI. Even though numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies...
January 11, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351374/fast-dynamic-docking-guided-by-adaptive-electrostatic-bias-the-md-binding-approach
#5
Andrea Spitaleri, Sergio Decherchi, Andrea Cavalli, Walter Rocchia
Engineering chemical entities to modify how pharmaceutical targets function, as it is done in drug design, requires a good understanding of molecular recognition and binding. In this context, the limitations of statically describing bimolecular recognition, as done in docking/scoring, call for insightful and efficient dynamical investigations. On the experimental side, the characterization of dynamical binding processes is still in its infancy. Thus, computer simulations, particularly molecular dynamics (MD), are compelled to play a prominent role, allowing a deeper comprehension of the binding process and its causes and thus a more informed compound selection, making more significant the computational contribution to drug discovery1...
January 19, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29351292/allocation-of-distinct-organ-fates-from-a-precursor-field-requires-a-shift-in-expression-and-function-of-gene-regulatory-networks
#6
Sneha Palliyil, Jinjin Zhu, Luke R Baker, Sarah D Neuman, Arash Bashirullah, Justin P Kumar
A common occurrence in metazoan development is the rise of multiple tissues/organs from a single uniform precursor field. One example is the anterior forebrain of vertebrates, which produces the eyes, hypothalamus, diencephalon, and telencephalon. Another instance is the Drosophila wing disc, which generates the adult wing blade, the hinge, and the thorax. Gene regulatory networks (GRNs) that are comprised of signaling pathways and batteries of transcription factors parcel the undifferentiated field into discrete territories...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29351285/wine-yeast-phenomics-a-standardized-fermentation-method-for-assessing-quantitative-traits-of-saccharomyces-cerevisiae-strains-in-enological-conditions
#7
Emilien Peltier, Margaux Bernard, Marine Trujillo, Duyên Prodhomme, Jean-Christophe Barbe, Yves Gibon, Philippe Marullo
This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats...
2018: PloS One
https://www.readbyqxmd.com/read/29351264/identification-of-cyclic-dipeptides-from-escherichia-coli-as-new-antimicrobial-agents-against-ralstonia-solanacearum
#8
Shihao Song, Shuna Fu, Xiuyun Sun, Peng Li, Ji'en Wu, Tingyan Dong, Fei He, Yinyue Deng
Ralstonia solanacearum is a causative agent of bacterial wilt in many important crops throughout the world. How to control bacterial wilt caused by R. solanacearum is a major problem in agriculture. In this study, we aim to isolate the biocontrol agents that have high efficacy in the control of bacterial wilt. Three new bacterial strains with high antimicrobial activity against R. solanacearum GMI1000 were isolated and identified. Our results demonstrated that these bacteria could remarkably inhibit the disease index of host plant infected by R...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351263/twenty-nine-new-limonoids-with-skeletal-diversity-from-the-mangrove-plant-xylocarpus-moluccensis
#9
Jianzhi Zhang, Wanshan Li, Yiguo Dai, Li Shen, Jun Wu
Twenty-nine new limonoids-named xylomolins A₁-A₇, B₁-B₂, C₁-C₂, D-F, G₁-G₅, H-I, J₁-J₂, K₁-K₂, L₁-L₂, and M-N, were isolated from the seeds of the mangrove plant, Xylocarpus moluccensis. Compounds 1-13 are mexicanolides with one double bond or two conjugated double bonds, while 14 belongs to a small group of mexicanolides with an oxygen bridge between C1 and C8. Compounds 15-19 are khayanolides containing a Δ8,14 double bond, whereas 20 and 21 are rare khayanolides containing a Δ14,15 double bond and Δ8,9, Δ14,15 conjugated double bonds, respectively...
January 19, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29351247/b-type-and-complex-a-b-type-epicatechin-trimers-isolated-from-litchi-pericarp-aqueous-extract-show-high-antioxidant-and-anticancer-activity
#10
Yihui Gong, Fang Fang, Xin Zhang, Bin Liu, Honghui Luo, Zhen Li, Xuelian Zhang, Zhaoqi Zhang, Xuequn Pang
Litchi (Litchi chinensis Sonn.) fruit is known for its rich source of phenolics. Litchi pericarp contains high levels of epicatechin that may form oligomers of various lengths. Except for several A or B type epicatechin dimers, other soluble oligomers have rarely been identified in the pericarp. Here, bioassay-guided column fractionation was applied to isolate bioactive phenolics from aqueous pericarp extract. A fraction (S3) was obtained by two rounds of Sephadex LH-20 column chromatography, and showed higher antioxidant activity and inhibition on the proliferation of human lung cancer cells (A549) than Litchi anthocyanins...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351246/addition-of-berberine-to-preservation-solution-in-an-animal-model-of-ex-vivo-liver-transplant-preserves-mitochondrial-function-and-bioenergetics-from-the-damage-induced-by-ischemia-reperfusion
#11
Rui Miguel Martins, Anabela Pinto Rolo, João Soeiro Teodoro, Emanuel Furtado, Rui Caetano Oliveira, José Guilherme Tralhão, Carlos Marques Palmeira
Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351242/-vessels-in-the-storm-searching-for-prognostic-and-predictive-angiogenic-factors-in-colorectal-cancer
#12
REVIEW
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Ficorella Corrado
High expectations are placed upon anti-angiogenic compounds for metastatic colorectal cancer (mCRC), the first malignancy for which such type of treatment has been approved. Indeed, clinical trials have confirmed that targeting the formation of new vessels can improve in many cases clinical outcomes of mCRC patients. However, current anti-angiogenic drugs are far from obtaining the desirable or expected curative results. Many are the factors probably involved in such disappointing results, but particular attention is currently focused on the validation of biomarkers able to improve the direction of treatment protocols...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351216/in-silico-and-in-vitro-study-of-the-bromelain-phytochemical-complex-inhibition-of-phospholipase-a2-pla2
#13
Fatahiya Mohamed Tap, Fadzilah Adibah Abd Majid, Hassan Fahmi Ismail, Tet Soon Wong, Kamyar Shameli, Mikio Miyake, Nurul Bahiyah Ahmad Khairudin
Phospholipase A2 (Pla2) is an enzyme that induces inflammation, making Pla2 activity an effective approach to reduce inflammation. Therefore, investigating natural compounds for this Pla2 inhibitory activity has important therapeutic potential. The objective of this study was to investigate the potential in bromelain-phytochemical complex inhibitors via a combination of in silico and in vitro methods. Bromelain-amenthoflavone displays antagonistic effects on Pla2. Bromelian-asiaticoside and bromelain-diosgenin displayed synergistic effects at high concentrations of the combined compounds, with inhibition percentages of more than 70% and 90%, respectively, and antagonistic effects at low concentrations...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351214/synthesis-and-evaluation-of-the-antioxidant-activity-of-lipophilic-phenethyl-trifluoroacetate-esters-by-in-vitro-abts-dpph-and-in-cell-culture-dcf-assays
#14
Roberta Bernini, Maurizio Barontini, Valentina Cis, Isabella Carastro, Daniela Tofani, Rosa Anna Chiodo, Paolo Lupattelli, Sandra Incerpi
Polyphenols are natural compounds showing a variety of health-promoting effects. Unfortunately, due to low lipid solubility, their applications in the pharmaceutical, food, and cosmetic industries are limited. With the aim of obtaining novel lipophilic derivatives, the present study reports the synthesis of a series of phenethyl trifluoroacetate esters containing up to two hydroxyl groups in the aromatic ring. Experimental logP values confirmed a greater lipophilicity of the novel compounds compared to the parent compounds...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351078/asymmetric-peptidomimetics-containing-l-tartaric-acid-core-inhibit-the-aspartyl-peptidase-activity-and-growth-of-leishmania-amazonensis-promastigotes
#15
André L S Santos, Filipe P Matteoli, Leandro S Sangenito, Marta H Branquinha, Bruno A Cotrim, Gabriel O Resende
Aspartyl-type peptidases are promising chemotherapeutic targets in protozoan parasites. In the present work, we identified an aspartyl peptidase activity from the soluble extract of Leishmania amazonensis promastigotes, which cleaved the fluorogenic peptide 7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D-Arg-amide (cathepsin D substrate) under acidic pH conditions at 37°C, showing a KM of 0.58 μM and Vmax of 129.87 fluorescence arbitrary units/s mg protein. The leishmanial aspartyl peptidase activity was blocked by pepstatin A (IC50 = 6...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29351056/remediation-of-radiation-induced-cognitive-dysfunction-through-oral-administration-of-the-neuroprotective-compound-nsi-189
#16
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29351054/xyloglucans-fucosylation-defects-do-not-alter-plant-boundary-domain-definition
#17
Beatriz Gonçalves, Julien Sechet, Nicolas Arnaud
The CUP SHAPED COTYLEDON transcription factors play a fundamental role in plant morphogenesis by defining boundary domains throughout plant development. Despite their central roles in plant development, little is known about the CUC molecular network. In a recent work, we identified a role for MUR1, a protein involved in the production of GDP-L-Fucose, in this network and showed that fucose per se is required for proper boundary definition in various developmental contexts. Which pathway involving fucose is required to determine boundary is not known...
January 19, 2018: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29350927/synthesis-and-pharmacological-characterization-of-c4%C3%AE-amide-substituted-2-aminobicyclo-3-1-0-hexane-2-6-dicarboxylates-identification-of-1s-2s-4s-5r-6s-2-amino-4-3-methoxybenzoyl-amino-bicyclo-3-1-0-hexane-2-6-dicarboxylic-acid-ly2794193-a-highly-potent-and
#18
James A Monn, Steven S Henry, Steven M Massey, David K Clawson, Qi Chen, Benjamin A Diseroad, Rajni M Bhardwaj, Shane Atwell, Frances Lu, Jing Wang, Marijane Russell, Beverly A Heinz, Xu-Shan Wang, Joan H Carter, Brian G Getman, Kofi Adragni, Lisa M Broad, Helene E Sanger, Daniel Ursu, John T Catlow, Steven Swanson, Bryan G Johnson, David B Shaw, David L McKinzie, Junliang Hao
Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking. As part of our ongoing efforts to identify potent, selective and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1S,2S,5R,6S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350920/crystal-structures-and-human-leukemia-cell-apoptosis-inducible-activities-of-parthenolide-analogues-isolated-from-piptocoma-rufescens
#19
Yulin Ren, Judith C Gallucci, Xinxin Li, Lichao Chen, Jianhua Yu, A Douglas Kinghorn
The molecular structures of three parthenolide analogues, (-)-goyazensolide (1), (-)-15-deoxygoyazensolide (2), and (-)-ereglomerulide (3), isolated from the leaves of Piptocoma rufescens in a previous study were determined by X-ray analysis, and the absolute configuration of (-)-goyazensolide (1) was confirmed crystallographically using Cu Kα radiation at low temperature. Compounds 1-3, (+)-rufesolide A (4), and commercial parthenolide were found to be growth inhibitory toward MOLM-13 and EOL-1 human acute myeloid leukemia cells using PKC412 (midostaurin) as the positive control, with 1-3 being more active than parthenolide...
January 19, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29350916/rhombohedral-to-cubic-conversion-of-gete-via-mnte-alloying-leads-to-ultralow-thermal-conductivity-electronic-band-convergence-and-high-thermoelectric-performance
#20
Zheng Zheng, Xianli Su, Rigui Deng, Constantinos C Stoumpos, Hongyao Xie, Wei Liu, Yonggao Yan, Shiqiang Hao, Ctirad Uher, Chris Wolverton, Mercouri G Kanatzidis, Xinfeng Tang
In this study, a series of Ge1-xMnxTe (x=0-0.21) compounds were prepared by melting-quenching-annealing process combined with Spark Plasma Sintering (SPS). The effect of alloying MnTe into GeTe on the structure and thermoelectric properties of Ge1-xMnxTe is profound. With increasing content of MnTe, the structure of the Ge1-xMnxTe compounds gradually changes from rhombohedral to cubic, and the known R3m to Fm-3m phase transition temperature of GeTe moves from 700 K closer to room temperature. First-principles density functional theory calculations show that alloying MnTe into GeTe decreases the energy difference between the light and heavy valence bands in both the R3m and the Fm-3m structures, enhancing a multi-band character of the valence band edge that increases the hole carrier effective mass...
January 19, 2018: Journal of the American Chemical Society
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