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https://www.readbyqxmd.com/read/29677491/the-allergen-der-p3-from-house-dust-mite-stimulates-store-operated-ca-2-channels-and-mast-cell-migration-through-par4-receptors
#1
Yu-Ping Lin, Charmaine Nelson, Holger Kramer, Anant B Parekh
The house dust mite is the principal source of perennial aeroallergens in man. How these allergens activate innate and adaptive immunity is unclear, and therefore, there are no therapies targeting mite allergens. Here, we show that house dust mite extract activates store-operated Ca2+ channels, a common signaling module in numerous cell types in the lung. Activation of channel pore-forming Orai1 subunits by mite extract requires gating by STIM1 proteins. Although mite extract stimulates both protease-activated receptor type 2 (PAR2) and PAR4 receptors, Ca2+ influx is more tightly coupled to the PAR4 pathway...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29677472/translating-immunology-into-therapeutic-concepts-for-inflammatory-bowel-disease
#2
Holm H Uhlig, Fiona Powrie
Inflammatory bowel disease (IBD) defines a spectrum of complex disorders. Understanding how environmental risk factors, alterations of the intestinal microbiota, and polygenetic and epigenetic susceptibility impact on immune pathways is key for developing targeted therapies. Mechanistic understanding of polygenic IBD is complemented by Mendelian disorders that present with IBD, pharmacological interventions that cause colitis, autoimmunity, and multiple animal models. Collectively, this multifactorial pathogenesis supports a concept of immune checkpoints that control microbial-host interactions in the gut by modulating innate and adaptive immunity, as well as epithelial and mesenchymal cell responses...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677222/understanding-the-impact-of-the-cofactor-swapping-of-isocitrate-dehydrogenase-over-the-growth-phenotype-of-escherichia-coli-on-acetate-by-using-constraint-based-modeling
#3
Erick Armingol, Eduardo Tobar, Ricardo Cabrera
It has been proposed that NADP+-specificity of isocitrate dehydrogenase (ICDH) evolved as an adaptation of microorganisms to grow on acetate as the sole source of carbon and energy. In Escherichia coli, changing the cofactor specificity of ICDH from NADP+ to NAD+ (cofactor swapping) decreases the growth rate on acetate. However, the metabolic basis of this phenotype has not been analyzed. In this work, we used constraint-based modeling to investigate the effect of the cofactor swapping of ICDH in terms of energy production, response of alternative sources of NADPH, and partitioning of fluxes between ICDH and isocitrate lyase (ICL) -a crucial bifurcation when the bacterium grows on acetate-...
2018: PloS One
https://www.readbyqxmd.com/read/29676955/mitochondrial-genome-modulates-myocardial-akt-glut-hk-salvage-pathway-in-spontaneously-hypertensive-rats-adapted-to-chronic-hypoxia
#4
Iveta Nedvedova, David Kolar, Barbara Elsnicova, Daniela Hornikova, Jiri Novotny, Martin Kalous, Michal Pravenec, Jan Neckar, Frantisek Kolar, Jitka M Zurmanova
Recently we have shown that adaptation to continuous normobaric hypoxia (CNH) decreases myocardial ischemia/reperfusion injury in spontaneously hypertensive rats (SHR) and in conplastic strain (SHR-mtBN ). The protective effect was stronger in the latter group characterized by a selective replacement of SHR mitochondrial genome with that of a more ischemia-resistant Brown Norway strain. The aim of the present study was to examine the possible involvement of the hypoxia inducible factor (HIF)-dependent pathway of the protein kinase B/glucose transporters/hexokinase (Akt/GLUT/HK) in this mitochondrial genome-related difference of the cardioprotective phenotype...
April 20, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29676818/new-insights-into-the-phenotypes-of-atopic-dermatitis-linked-with-allergies-and-asthma-in-children-an-overview
#5
F Amat, A Soria, P Tallon, M Bourgoin-Heck, N Lambert, A Deschildre, J Just
Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy, and triggers. A group of difficult-to-manage patients characterized by early-onset AD and severe lifelong disease associated with allergic asthma and/or food allergy, has been identified. In this paper, we focus on these severe phenotypes, analyzing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta-analyses...
April 20, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29676246/enzymes-involved-in-posttranscriptional-rna-metabolism-in-gram-negative-bacteria
#6
Bijoy K Mohanty, Sidney R Kushner
Gene expression in Gram-negative bacteria is regulated at many levels, including transcription initiation, RNA processing, RNA/RNA interactions, mRNA decay, and translational controls involving enzymes that alter translational efficiency. In this review, we discuss the various enzymes that control transcription, translation, and RNA stability through RNA processing and degradation. RNA processing is essential to generate functional RNAs, while degradation helps control the steady-state level of each individual transcript...
April 2018: Microbiology Spectrum
https://www.readbyqxmd.com/read/29675583/do-alcohol-related-ampa-type-glutamate-receptor-adaptations-promote-intake
#7
F Woodward Hopf, Regina A Mangieri
Ionotropic glutamate receptors (AMPA, NMDA, and kainate receptors) play a central role in excitatory glutamatergic signaling throughout the brain. As a result, functional changes, especially long-lasting forms of plasticity, have the potential to profoundly alter neuronal function and the expression of adaptive and pathological behaviors. Thus, alcohol-related adaptations in ionotropic glutamate receptors are of great interest, since they could promote excessive alcohol consumption, even after long-term abstinence...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29674958/neuronal-calcium-signaling-in-metabolic-regulation-and-adaptation-to-nutrient-stress
#8
REVIEW
Siddharth Jayakumar, Gaiti Hasan
All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development...
2018: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29674714/mechanisms-of-physiological-and-pathological-cardiac-hypertrophy
#9
REVIEW
Michinari Nakamura, Junichi Sadoshima
Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure...
April 19, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29674704/mek-inhibitors-overcome-resistance-to-bet-inhibition-across-a-number-of-solid-and-hematologic-cancers
#10
Anastasia Wyce, Jeanne J Matteo, Shawn W Foley, Daniel J Felitsky, Satyajit R Rajapurkar, Xi-Ping Zhang, Melissa C Musso, Susan Korenchuk, Natalie O Karpinich, Kathryn M Keenan, Melissa Stern, Lijoy K Mathew, Charles F McHugh, Michael T McCabe, Peter J Tummino, Ryan G Kruger, Christopher Carpenter, Olena Barbash
BET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations...
April 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29674659/histone-demethylase-jmjd1a-coordinates-acute-and-chronic-adaptation-to-cold-stress-via-thermogenic-phospho-switch
#11
Yohei Abe, Yosuke Fujiwara, Hiroki Takahashi, Yoshihiro Matsumura, Tomonobu Sawada, Shuying Jiang, Ryo Nakaki, Aoi Uchida, Noriko Nagao, Makoto Naito, Shingo Kajimura, Hiroshi Kimura, Timothy F Osborne, Hiroyuki Aburatani, Tatsuhiko Kodama, Takeshi Inagaki, Juro Sakai
In acute cold stress in mammals, JMJD1A, a histone H3 lysine 9 (H3K9) demethylase, upregulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals have another mechanism to cope with long-term cold stress by inducing the browning of the subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic-dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29674613/risk-factors-and-disease-mechanisms-in-myositis
#12
REVIEW
Frederick W Miller, Janine A Lamb, Jens Schmidt, Kanneboyina Nagaraju
Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic processes in the various idiopathic inflammatory myopathy (IIM) phenotypes (known collectively as myositis) have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in some populations, and several genetic variants associated with other autoimmune diseases have been identified as IIM risk factors...
April 20, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29674598/online-monitoring-of-carbon-dioxide-and-oxygen-in-exhaled-mouse-breath-via-substrate-integrated-hollow-waveguide-fourier-transform-infrared-luminescence-spectroscopy
#13
Felicia Seichter, Erhan Tuetuencue, Tamina Hagemann, Josef Vogt, Ulrich Wachter, Michael Groeger, Sandra Kress, Peter Radermacher, Boris Mizaikoff
Exhaled breath offers monitoring bio markers, as well as diagnosing diseases and therapeutic interventions. In addition, vital functions may be non-invasively monitored on-line. Animal models are frequently used in research for determining novel therapeutic approaches and/or for investigating biological pathways. The exhaled carbon dioxide concentration, exhaled and inhaled oxygen concentration, and the subsequent respiratory quotient (RQ) offer insight into metabolic activity. One may adapt breath sampling systems and equipment designed for human applications to large animal studies, however, such adaptations are usually impossible for small animals due to their minuscule breath volume...
April 20, 2018: Journal of Breath Research
https://www.readbyqxmd.com/read/29673844/nongenomic-cortisol-signaling-in-fish
#14
REVIEW
Chinmayee Das, Marwa Thraya, Mathilakath M Vijayan
Glucocorticoids are critical regulators of the cellular processes that allow animals to cope with stressors. In teleosts, cortisol is the primary circulating glucocorticoid and this hormone mediates a suite of physiological responses, most importantly energy substrate mobilization that is essential for acute stress adaptation. Cortisol signaling has been extensively studied and the majority of work has been on the activation of the glucocorticoid receptor (GR), a ligand-bound transcription factor, and the associated downstream transcriptional and protein responses...
April 16, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29673567/electric-acoustic-forward-masking-in-cochlear-implant-users-with-ipsilateral-residual-hearing
#15
Marina Imsiecke, Benjamin Krüger, Andreas Büchner, Thomas Lenarz, Waldo Nogueira
In order to investigate the temporal mechanisms of the auditory system, psychophysical forward masking experiments were conducted in cochlear implant users who had preserved acoustic hearing in the ipsilateral ear. This unique electric-acoustic stimulation (EAS) population allowed the measurement of threshold recovery functions for acoustic or electric probes in the presence of electric or acoustic maskers, respectively. In the electric masking experiment, the forward masked threshold elevation of acoustic probes was measured as a function of the time interval after the offset of the electric masker, i...
April 9, 2018: Hearing Research
https://www.readbyqxmd.com/read/29672982/juvenile-divergence-in-adaptive-traits-among-seven-sympatric-fish-eco-morphs-arises-before-moving-to-different-lacustrine-habitats
#16
Evgeny V Esin, Grigorii N Markevich, Michail Yu Pichugin
Identifying the mechanisms initiating sympatric diversification in vertebrates has remained a conceptual challenge. Here we analyze an assemblage of sympatric charr (Salvelinus malma) morphs from landlocked Lake Kronotskoe basin as a model to uncover the divergence pathways in freshwater fishes during the early life history stages. All morphs have distinct developmental biology, but a similar developmental rate retardation compared to the ancestor. Our study reveals that adult morphological differences, which acquire functionality at maturation, originate in the early juvenile stages due to heterochrony in skeletogenesis and allometric changes triggered by variation in metabolic activity...
April 19, 2018: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/29672321/metabolic-plasticity-enables-circadian-adaptation-to-acute-hypoxia-in-zebrafish-cells
#17
Adolf M Sandbichler, Bianca Jansen, Bettina A Peer, Monika Paulitsch, Bernd Pelster, Margit Egg
BACKGROUND/AIMS: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. METHODS: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts...
April 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29671793/search-for-partner-proteins-of-a-thaliana-immunophilins-involved-in-the-control-of-plant-immunity
#18
Inna A Abdeeva, Gennady V Pogorelko, Liliya G Maloshenok, Maria V Mokrykova, Oksana V Fursova, Sergey A Bruskin
The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes ( AtCYP19-1/ROC3 , AtFKBP65/ROF2 , and AtCYP57 ) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins. As a result, candidate interactors have been determined and confirmed using a yeast 2-hybrid (Y2H) system for protein⁻protein interaction assays...
April 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29670683/nrf2-mediated-metabolic-reprogramming-in-cancer
#19
REVIEW
Yan-Yang Wang, Juan Chen, Xiao-Ming Liu, Ren Zhao, Hong Zhe
Metabolic reprogramming is one of the hallmarks of cancer. Nrf2 pathway is one of the critical signaling cascades involved in cell defense and survival against oxidative stress. The significance of Nrf2 in cancer metabolism begins to be recognized. In this minireview, we focus on the Nrf2-mediated cancer metabolic reprogramming and intend to highlight the role of Nrf2 in the regulation of malignant transformation, cancer proliferation, and the development of treatment resistance via metabolic adaptations. We hope for the development of noninvasive biomarkers and novel therapeutic approaches for cancer based on Nrf2-directed cancer metabolic reprogramming in the near future...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29670546/-in-utero-exposure-to-maternal-diabetes-is-associated-with-early-abnormal-vascular-structure-in-offspring
#20
Abdallah Dib, Cyrielle Payen, Jennifer Bourreau, Mathilde Munier, Linda Grimaud, Ziad Fajloun, Laurent Loufrani, Daniel Henrion, Céline Fassot
Aim/hypothesis: In utero exposure to maternal diabetes increases the risk of developing hypertension and cardiovascular disorders during adulthood. We have previously shown that this is associated with changes in vascular tone in favor of a vasoconstrictor profile, which is involved in the development of hypertension. This excessive constrictor tone has also a strong impact on vascular structure. Our objective was to study the impact of in utero exposure to maternal diabetes on vascular structure and remodeling induced by chronic changes in hemodynamic parameters...
2018: Frontiers in Physiology
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