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Emma Monte, Manuel Rosa Garrido, Thomas M Vondriska, Jessica Wang
The past two decades have witnessed a rapid evolution in our ability to measure RNA and protein from biological systems. As a result, new principles have arisen regarding how information is processed in cells, how decisions are made, and the role of networks in biology. This essay examines this technological evolution, reviewing (and critiquing) the conceptual framework that has emerged to explain how RNA and protein networks control cellular function. We identify how future investigations into transcriptomes, proteomes, and other cellular networks will enable development of more robust, quantitative models of cellular behavior whilst also providing new avenues to use knowledge of biological networks to improve human health...
September 15, 2016: Comprehensive Physiology
Y Zhang, F Zhang, D Chen, Q Lü, L Tang, C Yang, M Lei, N Tong
Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Ann-Sophie Schott, Jürgen Behr, Jennifer Quinn, Rudi F Vogel
Lactic acid bacteria (LAB) are widely used as starter cultures in the manufacture of foods. Upon preparation, these cultures undergo various stresses resulting in losses of survival and fitness. In order to find conditions for the subsequent identification of proteomic biomarkers and their exploitation for preconditioning of strains, we subjected Lactobacillus (Lb.) paracasei subsp. paracasei TMW 1.1434 (F19) to different stress qualities (osmotic stress, oxidative stress, temperature stress, pH stress and starvation stress)...
2016: PloS One
Anna Týčová, Vojtěch Ledvina, Karel Klepárník
This review focuses on the latest development of microseparation electromigration methods in capillaries and microfluidic devices coupled with MS for detection and identification of important analytes. It is a continuation of the review article on the same topic by Kleparnik (Electrophoresis 2015, 36, 159-178). A wide selection of 161 relevant articles covers the literature published from June 2014 till May 2016. New improvements in the instrumentation and methodology of MS interfaced with capillary or microfluidic versions of zone electrophoresis, isotachophoresis, and isoelectric focusing are described in detail...
October 26, 2016: Electrophoresis
V O Gunko, T N Pogorelova, V A Linde
Mass-spectrometric profiling of the serum in women at weeks 16-17 of gestation was carried out in order to detect proteomic predictors of preterm delivery. Changes in the production of 25 proteins (down-regulation for 13 proteins and up-regulation for 12 proteins) were detected in the sera of women whose pregnancies eventuated in premature deliveries. Among them, proteins with various regulatory functions were distinguished: antioxidant enzymes, chaperons, cytoskeleton proteins, cell adhesion molecules, and proteins involved in angiogenesis, proteolysis, transcription, inflammation processes, binding and transportation of various ligands...
October 26, 2016: Bulletin of Experimental Biology and Medicine
Daniel Goldenberger, Vladimira Hinić, Spasenija Savic Prince, Michael Tamm, Anna-Maria Balestra, Doris Hohler, Reno Frei
BACKGROUND: Trichosporon mycotoxinivorans is a recently described yeast-like fungal organism and its association as a pathogen for patients with cystic fibrosis (CF) was reported previously. We show the clinical course of a CF patient over 9 years as well as the applications of modern molecular and proteomic identification techniques of this rare fungus. CASE PRESENTATION: We present the case of a 32-year-old male CF patient with sputum cultures continuously positive with the anamorphic yeast T...
October 25, 2016: BMC Infectious Diseases
Andrea Schmitt, Daniel Martins-de-Souza, Schahram Akbarian, Juliana S Cassoli, Hannelore Ehrenreich, Andre Fischer, Alfred Fonteh, Wagner F Gattaz, Michael Gawlik, Manfred Gerlach, Edna Grünblatt, Tobias Halene, Alkomiet Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, Johannes Kornhuber, Theo F J Kraus, Berend Malchow, Juliana M Nascimento, Moritz Rossner, Markus Schwarz, Johann Steiner, Leda Talib, Florence Thibaut, Peter Riederer, Peter Falkai
OBJECTIVES: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. METHODS: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes...
October 26, 2016: World Journal of Biological Psychiatry
Franziska A Mandl, Volker C Kirsch, Ilke Ugur, Elena Kunold, Jan Vomacka, Christian Fetzer, Sabine Schneider, Klaus Richter, Thilo M Fuchs, Iris Antes, Stephan A Sieber
Gram-negative bacteria represent a challenging task for antibacterial drug discovery owing to their impermeable cell membrane and restricted uptake of small molecules. We herein describe the synthesis of natural-product-derived epoxycyclohexenones and explore their antibiotic activity against several pathogenic bacteria. A compound with activity against Salmonella Typhimurium was identified, and the target enzymes were unraveled by quantitative chemical proteomics. Importantly, two protein hits were linked to bacterial stress response, and corresponding assays revealed an elevated susceptibility to reactive oxygen species upon compound treatment...
October 26, 2016: Angewandte Chemie
G V Roshchupkin, H H H Adams, M W Vernooij, A Hofman, C M Van Duijn, M A Ikram, W J Niessen
High-throughput technology can now provide rich information on a person's biological makeup and environmental surroundings. Important discoveries have been made by relating these data to various health outcomes in fields such as genomics, proteomics, and medical imaging. However, cross-investigations between several high-throughput technologies remain impractical due to demanding computational requirements (hundreds of years of computing resources) and unsuitability for collaborative settings (terabytes of data to share)...
October 26, 2016: Scientific Reports
Ali Ebrahim, Elizabeth Brunk, Justin Tan, Edward J O'Brien, Donghyuk Kim, Richard Szubin, Joshua A Lerman, Anna Lechner, Anand Sastry, Aarash Bordbar, Adam M Feist, Bernhard O Palsson
Rapid growth in size and complexity of biological data sets has led to the 'Big Data to Knowledge' challenge. We develop advanced data integration methods for multi-level analysis of genomic, transcriptomic, ribosomal profiling, proteomic and fluxomic data. First, we show that pairwise integration of primary omics data reveals regularities that tie cellular processes together in Escherichia coli: the number of protein molecules made per mRNA transcript and the number of ribosomes required per translated protein molecule...
October 26, 2016: Nature Communications
José María Gutiérrez, Teresa Escalante, Alexandra Rucavado, Cristina Herrera, Jay W Fox
Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs...
October 22, 2016: Toxins
Robert Jin-Hong Chang, Dimitri T Azar, Kyu-Yeon Han
Vascular endothelial growth factor receptor 3 (VEGFR3) regulates the growth and differentiation of blood and lymphatic vessels. To determine whether matrix metalloproteinase 14 (MMP14) modulates VEGFR3 expression in the corneal epithelium to influence the avascularity of the cornea, VEGFR3 expression was compared between wild-type and MMP14-deficient (MMP14 Δexon4) corneal epithelial cells. Western blot analysis showed that VEGFR3 protein expression was higher on MMP14 Δexon4 corneal epithelial cells than on wild-type cells, and quantitative RT-PCR analysis showed that VEGFR3 gene expression was highly induced in MMP14 Δexon4 corneal epithelial cells but not in wild-type corneal epithelial cells or wild-type and MMP14 Δexon4 corneal keratocytes...
October 24, 2016: Protein and Peptide Letters
Dorothee Hartmann, Jan Fiedler, Kristina Sonnenschein, Annette Just, Angelika Pfanne, Karina Zimmer, Janet Remke, Ariana Foinquinos, Malte Butzlaff, Katharina Schimmel, Lars Maegdefessel, Denise Hilfiker-Kleiner, Nico Lachmann, Andreas Schober, Natali Froese, Joerg Heineke, Johann Bauersachs, Sandor Batkai, Thomas Thum
BACKGROUND: -The transcription factor GATA2 orchestrates the expression of many endothelial-specific genes illustrating its crucial importance for endothelial cell function. The capacity of this transcription factor in orchestrating endothelial important microRNAs (miRNAs/miR) is unknown. METHODS: -Endothelial GATA2 was functionally analyzed in human endothelial cells in vitro. Endogenous siRNA-mediated knockdown and lentiviral-based overexpression were applied to decipher capacity of GATA2 in regulating cell viability and capillary formation...
October 25, 2016: Circulation
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean Palecek, Jennifer Strande, Ramani Ramchandran
BACKGROUND: -Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our lab has previously shown that sucrose non-fermenting related kinase (SNRK) enzyme, which belongs to the AMP-activated kinase (AMPK) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure, and death by 8-10 months...
October 25, 2016: Circulation. Cardiovascular Genetics
Karina Zitta, Cacha Peeters-Scholte, Lena Sommer, Kerstin Parczany, Markus Steinfath, Martin Albrecht
Several animal models have been used to simulate cerebral hypoxia-ischemia and suggested neuroprotective effects of the biotin analogue 2-iminobiotin (2-IB). The aims of this study were to employ a human in-vitro hypoxia model to confirm protective effects of 2-IB on neuronal cells, determine the optimal neuroprotective concentrations of 2-IB and scrutinize underlying cellular effects of 2-IB. Neuronal IMR-32 cells were exposed to hypoxia employing an enzymatic hypoxia system and were thereafter incubated with various concentrations of 2-IB (10 to 300ng/ml)...
October 22, 2016: European Journal of Pharmacology
Ghazala Mustafa, Setsuko Komatsu
Rapid developments in nanotechnology have led to the increasing use of nanoparticles (NPs) in the agricultural sector. To investigate the possible interactions between NPs and crops under flooding stress, the molecular mechanisms in soybean affected by exposure to various sizes of Al2O3 NPs were analyzed using a proteomic technique. In plants exposed to 30-60 nm Al2O3 NPs, the length of root including hypocotyl was increased and proteins related to glycolysis were suppressed. Exposure to 30-60 nm Al2O3 NPs mediated the scavenging activity of cells by regulating the ascorbate/glutathione pathway...
October 26, 2016: Journal of Proteome Research
Núria Rovira-Graells, Sara Aguilera-Simón, Elisabet Tintó-Font, Alfred Cortés
The growth phenotype of asexual blood stage malaria parasites can influence their virulence and also their ability to survive and achieve transmission to the next host, but there are few methods available to characterise parasite growth parameters in detail. We developed a new assay to measure growth rates at different starting parasitaemias in a 96-well format and applied it to characterise the growth of Plasmodium falciparum lines 3D7-A and 3D7-B, previously shown to have different invasion rates and to use different invasion pathways...
2016: PloS One
Mindi Zhao, Jianqiang Wu, Youhe Gao
Urine, reflecting many changes in the body, is a better source than blood for biomarker discovery. However, even under physiological conditions, the urine proteome often varies. Understanding how various regulating factors affect urine proteome helps link changes to urine proteome with urinary biomarkers of physiological conditions as well as corresponding diseases. To evaluate the possible impact of α1-adrenergic receptor on urine proteome, this study investigated effects of the specific inhibitor prazosin on the urine proteome in a rat model by using tandem mass tagging and two-dimensional liquid chromatography-tandem mass spectrometry...
2016: PloS One
Richard H G Baxter
Both historically and at present, vector control is the most generally effective means of controlling malaria transmission. Insecticides are the predominant method of vector control, but the sterile insect technique (SIT) is a complementary strategy with a successful track record in both agricultural and public health sectors. Strategies of genetic and radiation-induced sterilization of Anopheles have to date been limited by logistical and/or regulatory hurdles. A safe and effective mosquito chemosterilant would therefore be of major utility to future deployment of SIT for malaria control...
October 2016: Chimia
Ursula R Rodgers, Thomas Lanyon-Hogg, Naoko Masumoto, Markus Ritzefeld, Rosemary Burke, Julian Blagg, Anthony I Magee, Edward W Tate
The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, raising interest in Hhat as a novel drug target. A recently identified series of dihydrothienopyridines has been proposed to function via this mode of action; however, the lead compound in this series (RUSKI-43) was subsequently shown to possess cytotoxic activity unrelated to canonical Shh signaling...
October 25, 2016: ACS Chemical Biology
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