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https://www.readbyqxmd.com/read/28345670/domain-dependent-effects-of-insulin-and-igf-1-receptors-on-signalling-and-gene-expression
#1
Weikang Cai, Masaji Sakaguchi, Andre Kleinridders, Gonzalo Gonzalez-Del Pino, Jonathan M Dreyfuss, Brian T O'Neill, Alfred K Ramirez, Hui Pan, Jonathon N Winnay, Jeremie Boucher, Michael J Eck, C Ronald Kahn
Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345344/unravelling-and-quantifying-the-nmr-invisible-metabolites-interacting-with-human-serum-albumin-by-binding-competition-and-t2-relaxation-based-decomposition-analysis
#2
Ruben Barrilero, Noelia Ramirez, Joan Carles Vallvé, Delia Taverner, Rocío Fuertes, Núria Amigó, Xavier Correig
Quantitative profiling of low-molecular-weight metabolites (LMWM) by 1H-NMR is routinely used in high-throughput serum metabolomics. First, the protein background is attenuated using a T2 filter, then the LMWM signals are resolved by line-shape fitting. However, protein binding modifies the motional properties of LMWM and their signal partially attenuates with the T2 filter, along with the protein background. Consequently, the quantified LMWM signal does not reflect the total concentration in serum but the non-binding part...
March 27, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28343576/the-metabolic-response-in-fish-to-mildly-elevated-water-temperature-relates-to-species-dependent-muscular-concentrations-of-imidazole-compounds-and-free-amino-acids
#3
Fikremariam Geda, Annelies M Declercq, Sofie C Remø, Rune Waagbø, Marta Lourenço, Geert P J Janssens
Fish species show distinct differences in their muscular concentrations of imidazoles and free amino acids (FAA). This study was conducted to investigate whether metabolic response to mildly elevated water temperature (MEWT) relates to species-dependent muscular concentrations of imidazoles and FAA. Thirteen carp and 17 Nile tilapia, housed one per aquarium, were randomly assigned to either acclimation (25°C) or MEWT (30°C) for 14 days. Main muscular concentrations were histidine (HIS; P<0.001) in carp versus N-α-acetylhistidine (NAH; P<0...
April 2017: Journal of Thermal Biology
https://www.readbyqxmd.com/read/28341273/branched-chain-amino-acids-enhance-cyst-development-in-autosomal-dominant-polycystic-kidney-disease
#4
Junya Yamamoto, Saori Nishio, Fumihiko Hattanda, Daigo Nakazawa, Toru Kimura, Michio Sata, Minoru Makita, Yasunobu Ishikawa, Tatsuya Atsumi
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1(flox/flox):Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age...
March 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28341051/whey-protein-derived-exosomes-increase-protein-synthesis-and-hypertrophy-in-c2-c12-myotubes
#5
C Brooks Mobley, Petey W Mumford, John J McCarthy, Michael E Miller, Kaelin C Young, Jeffrey S Martin, Darren T Beck, Christopher M Lockwood, Michael D Roberts
We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments...
January 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28341002/seroprevalence-survey-of-selective-anti-neuronal-autoantibodies-in-patients-with-first-episode-schizophrenia-and-chronic-schizophrenia
#6
Chia-Hsiang Chen, Min-Chih Cheng, Chih-Min Liu, Chen-Chung Liu, Ko-Huan Lin, Hai-Gwo Hwu
Autoimmune encephalopathy caused by autoantibodies against neuronal cell-surface proteins in the brain is a newly discovered disease category associated with psychiatric disorders. Correct diagnosis of this condition relies on the detection of specific autoantibodies in the blood or cerebral spinal fluid in addition to the clinical presentations. The study aimed to understand the seroprevalence of selective anti-neuronal autoantibodies in our patients with schizophrenia. First, we screened for six anti-neuronal autoantibodies in an archived blood sample collected from patients with the first-episode schizophrenia...
March 21, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28339214/muscle-protein-signaling-in-c2c12-cells-is-stimulated-to-a-similar-degree-by-diverse-commercial-food-protein-sources-and-experimental-soy-protein-hydrolysates
#7
David A Roeseler, Nancy J McGraw, Dustie N Butteiger, Naina Shah, Janine Hall-Porter, Ratna Mukherjea, Elaine Susan Krul
Dietary protein stimulates muscle protein synthesis and is essential for muscle health. We developed a screening assay using C2C12 mouse muscle cells to assess the relative abilities of diverse commercial proteins sources and experimental soy protein hydrolysates (ESH), after simulated gut digestion (SGD), to activate the mechanistic target of rapamycin complex I (mTORC1) muscle protein synthesis signaling pathway (p70S6K(Thr389) phosphorylation). Activation of mTORC1 was expressed as a percentage of a maximal insulin response...
March 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28339206/utilizing-electron-spin-echo-envelope-modulation-to-distinguish-between-the-local-secondary-structures-of-an-%C3%AE-helix-and-an-amphipathic-310-helical-peptide
#8
Lauren Bottorf, Sophia Rafferty, Indra Dev Sahu, Robert M McCarrick, Gary A Lorigan
Electron Spin Echo Envelope Modulation (ESEEM) spectroscopy was used to distinguish between the local secondary structures of an α-helix and a 310-helix. Previously, we have shown that ESEEM spectroscopy in combination with site-directed spin labeling (SDSL) and 2H-labeled amino acids (i) can probe the local secondary structure of α-helices, resulting in an obvious deuterium modulation pattern, where i+4 positions generally show larger 2H ESEEM peak intensities than i+3 positions. Here, we have hypothesized that due to the unique turn periodicities of an α-helix (3...
March 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28338918/integrated-mirna-and-mrna-expression-profiling-reveals-the-response-regulators-of-a-susceptible-tomato-cultivar-to-early-blight-disease
#9
Deepti Sarkar, Ranjan Kumar Maji, Sayani Dey, Arijita Sarkar, Zhumur Ghosh, Pallob Kundu
Early blight, caused by the fungus Alternaria solani, is a devastating foliar disease of tomatoes, causes massive yield loss each year worldwide. Molecular basis of the compatible host-pathogen interaction was elusive. We adopted next generation sequencing approach to decipher miRNAs and mRNAs that are differentially expressed during Alternaria-stress in tomato. Some of the interesting findings were also validated by alternative techniques. Our analysis revealed 181 known-miRNAs, belonging to 121 miRNA families, of which 67 miRNAs showed at least 2-fold change in expression level with the majority being downregulated...
March 3, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28338798/genetic-dissection-of-metabolite-variation-in-arabidopsis-seeds-evidence-for-mqtl-hotspots-and-a-master-regulatory-locus-of-seed-metabolism
#10
Dominic Knoch, David Riewe, Rhonda Christiane Meyer, Anastassia Boudichevskaia, Renate Schmidt, Thomas Altmann
To gain insight into genetic factors controlling seed metabolic composition and its relationship to major seed properties, an Arabidopsis recombinant inbred line (RIL) population, derived from accessions Col-0 and C24, was studied using an MS-based metabolic profiling approach. Relative intensities of 311 polar primary metabolites were used to identify associated genomic loci and to elucidate their interactions by quantitative trait locus (QTL) mapping. A total of 786 metabolic QTLs (mQTLs) were unequally distributed across the genome, forming several hotspots...
March 6, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28337968/crispr-cas9-mutagenesis-invalidates-a-putative-cancer-dependency-targeted-in-on-going-clinical-trials
#11
Ann Lin, Christopher J Giuliano, Nicole M Sayles, Jason M Sheltzer
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types...
March 24, 2017: ELife
https://www.readbyqxmd.com/read/28337836/plant-transcription-factors-from-the-homeodomain-leucine-zipper-family-i-role-in-development-and-stress-responses
#12
REVIEW
María Florencia Perotti, Pamela Anahí Ribone, Raquel Lía Chan
In front of stressful conditions plants display adaptation mechanisms leading to changes in their morphology, physiology, development and molecular composition. Transcription factors (TFs) play crucial roles in these complex adaptation processes. This work is focused in the homeodomain-leucine zipper I (HD-Zip I) family of TFs, unique to plants. First discovered in 1991, they were identified and isolated from monocotyledonous and dicotyledonous plants showing high structural similarity and diversified functions...
March 24, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#13
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28336771/dimerization-in-lbd16-and-lbd18-transcription-factors-is-critical-for-lateral-root-formation
#14
Han Woo Lee, Na Young Kang, Shashank Pandey, Chuloh Cho, Sung Haeng Lee, Jungmook Kim
LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD)/ASYMMETRIC LEAVES2-LIKE (ASL)s (hereafter referred to as LBD) are plant-specific transcription factors that play important roles in a plethora of plant growth and development. The leucine-zipper-like coiled-coil motif in the LOB domain of the class I LBD proteins has been proposed to mediate protein dimerization, but it has not been experimentally assessed yet. LBD16 and LBD18 have been well characterized to play important roles in lateral root development in Arabidopsis...
March 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28336464/new-insights-into-the-codon-usage-patterns-of-the-bactericidal-permeability-increasing-bpi-gene-across-nine-species
#15
Wei-Yun Qin, Li-Na Gan, Ri-Wei Xia, Shou-Yong Sun, Guo-Qiang Zhu, Sheng-Long Wu, Wen-Bin Bao
Bactericidal/permeability-increasing (BPI) protein is a member of a new generation of proteins known as super-antibiotics that are implicated as endotoxin neutralising agents. Non-uniform usage of synonymous codons for a specific amino acid during translation of a protein is known as codon usage bias (CUB). Analysis of CUB and compositional dynamics of coding sequences could contribute to a better understanding of the molecular mechanism and the evolution of a particular gene. In this study, we performed CUB analysis of the complete coding sequences of the BPI gene from nine different species...
March 20, 2017: Gene
https://www.readbyqxmd.com/read/28336113/effect-of-branched-chain-amino-acid-ratio-on-the-proliferation-differentiation-and-expression-levels-of-key-regulators-involved-in-protein-metabolism-of-myocytes
#16
Yehui Duan, Liming Zeng, Fengna Li, Wenlong Wang, Yinghui Li, Qiuping Guo, Yujiao Ji, Bi'e Tan, Yulong Yin
OBJECTIVES: Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are key regulators of protein synthesis in muscle. The aim of this study was to investigate the effect of different BCAA ratios (Leu:Ile:Val) on the proliferation, differentiation, and expression levels of the regulators related to protein metabolism of C2 C12 myocytes. METHODS: Studies were conducted in C2C12 myocytes exposed to different BCAA ratios (Leu: Ile: Val = 0, 1:0...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28335518/new-chiral-ebselen-analogues-with-antioxidant-and-cytotoxic-potential
#17
Agata J Pacuła, Katarzyna B Kaczor, Jędrzej Antosiewicz, Anna Janecka, Angelika Długosz, Tomasz Janecki, Andrzej Wojtczak, Jacek Ścianowski
New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid...
March 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#18
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334511/elongated-and-shortened-peptidomimetic-inhibitors-of-the-proprotein-convertase-furin
#19
Kornelia Hardes, Teodora Ivanova, Bastian Thaa, Gerald M McInerney, Tove Irene Klokk, Kirsten Sandvig, Sebastian Künzel, Iris Lindberg, Torsten Steinmetzer
Novel elongated and shortened derivatives of the peptidomimetic furin inhibitor phenylacteyl-Arg-Val-Arg-4-amidinobenzylamide were synthesized. The most potent compounds, e.g., Nα(carbamidoyl)Arg-Arg-Val-Arg-4-amidinobenzylamide (Ki = 6.2 pM), contain additional basic residues at the N-terminus and inhibit furin in the low picomolar range. Furthermore, to decrease the molecular weight of this inhibitor type, compounds lacking the P5-moiety were prepared. The best inhibitors of this series, 5-(guanidino)-valeroyl-Val-Arg-4-amidinobenzylamide and its P3 tert...
March 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28334275/identification-of-a-novel-bzip-transcription-factor-in-camellia-sinensis-as-a-negative-regulator-of-freezing-tolerance-in-transgenic-arabidopsis
#20
Lu Wang, Hongli Cao, Wenjun Qian, Lina Yao, Xinyuan Hao, Nana Li, Yajun Yang, Xinchao Wang
Background and Aims: Basic region/leucine zipper (bZIP) transcription factors play vital roles in the abiotic stress response of plants. However, little is known about the function of bZIP genes in Camellia sinensis . Methods: CsbZIP6 was overexpressed in Arabidopsis thaliana . Effects of CsbZIP6 overexpression on abscisic acid (ABA) sensitivity, freezing tolerance and the expression of cold-responsive genes in arabidopsis were studied. Key Results: CsbZIP6 was induced during cold acclimation in tea plant...
March 14, 2017: Annals of Botany
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