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https://www.readbyqxmd.com/read/28545128/common-variants-upstream-of-mlf1-at-3q25-and-within-cpz-at-4p16-associated-with-neuroblastoma
#1
Lee D McDaniel, Karina L Conkrite, Xiao Chang, Mario Capasso, Zalman Vaksman, Derek A Oldridge, Anna Zachariou, Millicent Horn, Maura Diamond, Cuiping Huo, Achille Iolascon, Hakon Hakonarson, Nazneen Rahman, Marcella Devoto, Sharon J Diskin
Neuroblastoma is a cancer of the developing sympathetic nervous system that most commonly presents in young children and accounts for approximately 12% of pediatric oncology deaths. Here, we report on a genome-wide association study (GWAS) in a discovery cohort or 2,101 cases and 4,202 controls of European ancestry. We identify two new association signals at 3q25 and 4p16 that replicated robustly in multiple independent cohorts comprising 1,163 cases and 4,396 controls (3q25: rs6441201 combined P = 1.2x10-11, Odds Ratio 1...
May 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28544379/a-widened-substrate-selectivity-filter-of-eukaryotic-formate-nitrite-transporters-enables-high-level-lactate-conductance
#2
Marie Wiechert, Holger Erler, André Golldack, Eric Beitz
Bacterial formate-nitrite transporters (FNT) regulate the metabolic flow of small weak mono-acids derived from anaerobic mixed-acid fermentation, such as formate, and further transport nitrite, and hydrosulfide. The eukaryotic Plasmodium falciparum FNT is vital for the malaria parasite by its ability to release the larger l-lactate substrate as the metabolic end product of anaerobic glycolysis in symport with protons preventing cytosolic acidification. However, the molecular basis for substrate discrimination by FNTs has remained unclear...
May 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28544195/long-and-branched-polyamines-are-required-for-maintenance-of-the-ribosome-trna-his-and-trna-tyr-in-thermus-thermophilus-cells-at-high-temperatures
#3
Misa Nakashima, Ryota Yamagami, Chie Tomikawa, Yuki Ochi, Toshiyuki Moriya, Haruichi Asahara, Dominique Fourmy, Satoko Yoshizawa, Tairo Oshima, Hiroyuki Hori
Thermus thermophilus is an extremely thermophilic eubacterium that produces various polyamines. Aminopropylagmatine ureohydrolase (SpeB) and SAM decarboxylase-like protein 1 (SpeD1) are involved in the biosynthesis of spermidine from arginine. Because long and branched polyamines in T. thermophilus are synthesized from spermidine, the speB and speD1 gene-deleted strains (ΔspeB and ΔspeD1, respectively) cannot synthesize long and branched polyamines. Although neither strain grew at high temperatures (>75°C) in minimal medium, both strains survived at 80°C when they were cultured at 70°C until the mid-log phase and then shifted to 80°C...
May 24, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28543930/further-analysis-of-acute-antinociceptive-and-anti-inflammatory-actions-of-4-phenylselenyl-7-chloroquinoline-in-mice
#4
Vanessa D G Silva, Angélica S Reis, Mikaela Pinz, Caren A R da Fonseca, Luis Fernando B Duarte, Juliano A Roehrs, Diego Alves, Cristiane Luchese, Ethel A Wilhelm
A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was to expand our previous findings by investigating the contribution of glutamatergic, serotonergic and nitrergic systems to the acute antinociceptive action of this compound. Pretreatment with 4-PSQ (0.01-25 mg/kg, p.o.) reduced the nociception induced by glutamate...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28543863/prmt8-controls-the-pluripotency-and-mesodermal-fate-of-human-embryonic-stem-cells-by-enhancing-the-pi3k-akt-sox2-axis
#5
Ho-Chang Jeong, Soon-Jung Park, Jong-Jin Choi, Young-Hyun Go, Soon-Ki Hong, Ok-Seon Kwon, Joong-Gon Shin, Rae-Kwon Kim, Mi-Ok Lee, Su-Jae Lee, Hyoung Doo Shin, Sung-Hwan Moon, Hyuk-Jin Cha
Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferases 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions...
May 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28542722/a-homozygous-potentially-pathogenic-variant-in-the-paxbp1-gene-in-a-large-family-with-global-developmental-delay-and-myopathic-hypotonia
#6
Essa Alharby, Alia M Albalawi, Abdul Nasir, Sabri A Alhijji, Amer Mahmood, Khushnooda Ramzan, Firoz Abdusamad, Abdulkarim Aljohani, Osama Abdelsalam, Amr Eldardear, Sulman Basit
PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...
May 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28542406/human-igg3-with-extended-half-life-does-not-improve-fc-gamma-receptor-mediated-cancer-antibody-therapies-in-mice
#7
Rens Braster, Simran Grewal, Remco Visser, Helga K Einarsdottir, Marjolein van Egmond, Gestur Vidarsson, Marijn Bögels
BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models...
2017: PloS One
https://www.readbyqxmd.com/read/28542332/non-canonical-binding-interactions-of-the-rna-recognition-motif-rrm-domains-of-p34-protein-modulate-binding-within-the-5s-ribonucleoprotein-particle-5s-rnp
#8
Anyango D Kamina, Noreen Williams
RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5...
2017: PloS One
https://www.readbyqxmd.com/read/28542086/corneal-endothelial-cells-have-an-absolute-requirement-for-cysteine-for-survival
#9
Naoki Okumura, Ryota Inoue, Kazuya Kakutani, Makiko Nakahara, Shigeru Kinoshita, Junji Hamuro, Noriko Koizumi
PURPOSE: The aim of this study was to evaluate which amino acid(s) among the 20 standard protein amino acids is indispensable for the survival of cultured human corneal endothelial cells (HCECs). METHODS: HCECs were cultured in amino acid screening media that were missing 1 specific amino acid, and cell growth was evaluated. After this first selection, we conducted a further evaluation of cell growth in response to the addition of 4 amino acids (cysteine, methionine, valine, and arginine) to amino acid-free culture media...
May 23, 2017: Cornea
https://www.readbyqxmd.com/read/28541755/epinephrine-but-not-vasopressin-attenuates-the-airway-response-to-anaphylactic-shock-in-rats
#10
Feng Zheng, Ruxandra Copotoiu, Charles Tacquard, Bruno Demoulin, Jean Marc Malinovsky, Bruno Levy, Dan Longrois, Grégoire Barthel, Paul Michel Mertes, François Marchal, Silvia Demoulin-Alexikova, Olivier Collange
PURPOSE: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. AIM OF THE STUDY: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS...
May 25, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#11
Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute towards a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) pathways...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28540509/short-term-supplementation-of-isocaloric-meals-with-l-tryptophan-affects-pig-growth
#12
H N Liu, C-A A Hu, M M Bai, Gang Liu, M C B Tossou, K Xu, F N Li, P Liao, X F Kong, X Wu, Y L Yin
L-Tryptophan (Trp) and some of its metabolites regulate the circadian rhythm in mammals. We aimed to investigate the effects of short-term supplementation of Trp in isocaloric meals on growth performance using the parameters of multiple blood biomarkers and free amino acids in growing pigs. A total of 32 Landrace × Yorkshire barrows with a mean body weight of 8.64 (±1.13) kg were randomly assigned to four groups and then fed with various concentrations of Trp diets daily. Our results showed that sequential supplementation of different concentrations of Trp in isocaloric meals decreased the feed:gain (F:G) ratio (P = 0...
May 24, 2017: Amino Acids
https://www.readbyqxmd.com/read/28539222/discovery-of-novel-cyclic-peptide-inhibitors-of-dengue-virus-ns2b-ns3-protease-with-antiviral-activity
#13
Youhei Takagi, Kouhei Matsui, Haruaki Nobori, Haruka Maeda, Akihiko Sato, Takeshi Kurosu, Yasuko Orba, Hirofumi Sawa, Kazunari Hattori, Kenichi Higashino, Yoshito Numata, Yutaka Yoshida
NS2B-NS3 protease is an essential enzyme for the replication of dengue virus (DENV), which continues to be a serious threat to worldwide public health. We designed and synthesized a series of cyclic peptides mimicking the substrates of this enzyme, and assayed their activity against the DENV-2 NS2B-NS3 protease. The introduction of aromatic residues at the appropriate positions and conformational restriction generated the most promising cyclic peptide with an IC50 of 0.95μM against NS2B-NS3 protease. Cyclic peptides with proper positioning of additional arginines and aromatic residues exhibited antiviral activity against DENV...
May 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28538366/preventing-necrotizing-enterocolitis-by-food-additives-in-neonates-a-network-meta-analysis-revealing-the-efficacy-and-safety
#14
Wentao Yu, Wu Sui, Linsong Mu, Wenying Yi, Haijuan Li, Liqin Wei, Weihong Yin
BACKGROUND: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. METHODS: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538181/malate-and-aspartate-increase-l-arginine-and-nitric-oxide-and-attenuate-hypertension
#15
Entai Hou, Na Sun, Fuchang Zhang, Chenyang Zhao, Kristie Usa, Mingyu Liang, Zhongmin Tian
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537329/efficacy-of-a-disease-specific-nutritional-support-for-pressure-ulcer-healing-a-systematic-review-and-meta-analysis
#16
E Cereda, J C L Neyens, R Caccialanza, M Rondanelli, J M G A Schols
OBJECTIVES: The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). METHODS: Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28537268/global-mapping-of-carm1-substrates-defines-enzyme-specificity-and-substrate-recognition
#17
Evgenia Shishkova, Hao Zeng, Fabao Liu, Nicholas W Kwiecien, Alexander S Hebert, Joshua J Coon, Wei Xu
Protein arginine methyltransferases (PRMTs) introduce arginine methylation, a post-translational modification with the increasingly eminent role in normal physiology and disease. PRMT4 or coactivator-associated arginine methyltransferase 1 (CARM1) is a propitious target for cancer therapy; however, few CARM1 substrates are known, and its mechanism of substrate recognition is poorly understood. Here we employed a quantitative mass spectrometry approach to globally profile CARM1 substrates in breast cancer cell lines...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536481/trpv4-dependent-induction-of-a-novel-mammalian-cold-inducible-protein-srsf5-as-well-as-cirp-and-rbm3
#18
Takanori Fujita, Hiroaki Higashitsuji, Hisako Higashitsuji, Yu Liu, Katsuhiko Itoh, Toshiharu Sakurai, Takahiro Kojima, Shuya Kandori, Hiroyuki Nishiyama, Motoi Fukumoto, Manabu Fukumoto, Koji Shibasaki, Jun Fujita
Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536288/cnot4-mediated-ubiquitination-of-influenza-a-virus-nucleoprotein-promotes-viral-rna-replication
#19
Yu-Chen Lin, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) RNA segments are individually packaged with viral nucleoprotein (NP) and RNA polymerases to form a viral ribonucleoprotein (vRNP) complex. We previously reported that NP is a monoubiquitinated protein which can be deubiquitinated by a cellular ubiquitin protease, USP11. In this study, we identified an E3 ubiquitin ligase, CNOT4 (Ccr4-Not transcription complex subunit 4), which can ubiquitinate NP. We found that the levels of viral RNA, protein, viral particles, and RNA polymerase activity in CNOT4 knockdown cells were lower than those in the control cells upon IAV infection...
May 23, 2017: MBio
https://www.readbyqxmd.com/read/28536076/polyarginine-and-its-analogues-inhibit-p53-mutant-aggregation-and-cancer-cell-proliferation-in-vitro
#20
Zhaolin Chen, Jun Chen, Venkateshwar G Keshamouni, Mathumai Kanapathipillai
Arginine, a cationic amino acid is known to stabilize proteins under harsh conditions. It is widely used to stabilize protein aggregation, and to correct protein folding during protein production. Hence it would be a good therapeutic candidate for treating protein aggregation related diseases. Recent reports suggest, that the aggregation of tumor suppressor protein p53 is one of the leading causes of tumor progression. When mutated, p53 protein aggregates, loses its function leading to unwanted cell growth and ultimately results in tumor...
May 20, 2017: Biochemical and Biophysical Research Communications
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