Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex

It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 201

Harmonization of RBSP and Arase Energetic Electron Measurements Utilizing ESA Radiation Monitor Data

Accurate measurements of trapped energetic electron fluxes are of major importance for the studies of the complex nature of radiation belts and the characterization of space radiation environment. The harmonization of measurements between different instruments increases the accuracy of scientific studies and the reliability of data-driven models that treat the specification of space radiation environment. An intercalibration analysis of the energetic electron flux measurements of the Magnetic Electron Ion Spectrometer (MagEIS) and the Relativistic Electron-Proton Telescope (REPT) instruments on-board the Van Allen Probes (VAP) Mission versus the measurements of the Extremely High Energy Electron Experiment (XEP) unit on-board Arase satellite is presented. The performed analysis demonstrates a remarkable agreement between the majority of MagEIS and XEP measurements and suggests the rescaling of MagEIS HIGH unit and of REPT measurements for the treatment of flux spectra discontinuities. The proposed adjustments were validated successfully using measurements from ESA Environmental Monitoring Unit (EMU) on-board GSAT0207 and the Standard Radiation Monitor (SREM) on-board INTEGRAL. The derived results lead to the harmonization of science-class experiments on-board VAP (2012–2019) and Arase (2017–) and propose the use of the data sets as reference in a series of space weather and space radiation environment developments

GAIA: a gram-based interaction analysis tool – an approach for identifying interacting domains in yeast

<p>Abstract</p> <p>Background</p> <p>Protein-Protein Interactions (PPIs) play important roles in many biological functions. Protein domains, which are defined as independently folding structural blocks of proteins, physically interact with each other to perform these biological functions. Therefore, the identification of Domain-Domain Interactions (DDIs) is of great biological interests because it is generally accepted that PPIs are mediated by DDIs. As a result, much effort has been put on the prediction of domain pair interactions based on computational methods. Many DDI prediction tools using PPIs network and domain evolution information have been reported. However, tools that combine the primary sequences, domain annotations, and structural annotations of proteins have not been evaluated before.</p> <p>Results</p> <p>In this study, we report a novel approach called Gram-bAsed Interaction Analysis (GAIA). GAIA extracts peptide segments that are composed of fixed length of continuous amino acids, called n-grams (where n is the number of amino acids), from the annotated domain and DDI data set in <it>Saccharomyces cerevisiae </it>(budding yeast) and identifies a list of n-grams that may contribute to DDIs and PPIs based on the frequencies of their appearance. GAIA also reports the coordinate position of gram pairs on each interacting domain pair. We demonstrate that our approach improves on other DDI prediction approaches when tested against a gold-standard data set and achieves a true positive rate of 82% and a false positive rate of 21%. We also identify a list of 4-gram pairs that are significantly over-represented in the DDI data set and may mediate PPIs.</p> <p>Conclusion</p> <p>GAIA represents a novel and reliable way to predict DDIs that mediate PPIs. Our results, which show the localizations of interacting grams/hotspots, provide testable hypotheses for experimental validation. Complemented with other prediction methods, this study will allow us to elucidate the interactome of cells.</p

Remote Detection of Drift Resonance Between Energetic Electrons and Ultralow Frequency Waves: Multisatellite Coordinated Observation by Arase and Van Allen Probes

We report the electron flux modulations without corresponding magnetic fluctuations from unique multipoint satellite observations of the Arase (Exploration of Energization and Radiation in Geospace) and the Van Allen Probe (Radiation Belt Storm Probe [RBSP])‐B satellites. On 30 March 2017, both Arase and RBSP‐B observed periodic fluctuations in the relativistic electron flux with energies ranging from 500 keV to 2 MeV when they were located near the magnetic equator in the morning and dusk local time sectors, respectively. Arase did not observe Pc5 pulsations, while they were observed by RBSP‐B. The clear dispersion signature of the relativistic electron fluctuations observed by Arase indicates that the source region is limited to the postnoon to the dusk sector. This is confirmed by RBSP‐B and ground‐magnetometer observations, where Pc5 pulsations are observed to drift‐resonate with relativistic electrons on the duskside. Thus, Arase observed the drift‐resonance signatures “remotely,” whereas RBSP‐B observed them “locally.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

C–H···p and C=O···p Intermolecular Interactions in Dibenzyl-3,6-dimethylpyrazine-2,5-dicarboxylate

Abstract A new pyrazine compound, has been synthesised and characterised by single-crystal X-ray diffraction: monoclinic, P21/c with a = 11.0707(3) Å, b = 5.23700(10) Å, c = 16.6997(5) Å, ß = 103.5385(16)°, Mr = 376.40, V = 941.30(4) Å3, Z = 2. Each molecule possesses C i symmetry with the two halves of the molecule related by an inversion centre. C–H···p and C=O···p interactions held the molecules together. Index Abstract C–H···p and C=O···p intermolecular interactions in dibenzyl-3,6-dimethylpyrazine-2,5-dicarboxylate Joana A. Silva, Ana C. Santos, Ana T. Marques, Manuela Ramos Silva, Ana Matos Beja, Abílio J. F. N. Sobrala In dibenzyl-3,6-dimethylpyrazine-2,5-dicarboxylate, each molecule possesses C i symmetry. The molecules are assembled in chains via carbonyl···p interactions

A CONTINUOUS CULTURE OF PLURIPOTENT FETAL HEPATOCYTES DERIVED FROM THE 8-DAY EPIBLAST OF THE PIG

Continuous cultures of pluripotent prenchymal hepatocytes were derived from the epiblasts of 8-day-old pig blastocytes. The cells were polygonal and had phase-contrast dark, granular cytoplasm with prominent nuclei and nucleoli. These feeder-dependent cell cultures differentiated into large, multicellular, secretory, duct-like structures or formed small canaliculi between individual cells. Alternatively, the cells accumulated droplets that stained intensely with Oil Red O, a lipid-specific stain. Alpha-fetoprotein (AFP), albumin, and β-fibrinogen mRNAs were expressed as the cells differentiated in culture. Serum-free medium that was conditioned by the cells contained transferrin, AFP, and albumin. The growth and viability of the cells were inhibited by transforming growth factor β1 (TGFβ1) at concentrations ≥ 1ng/ml. The cell cultures grew slowly with doubling times of 2 to 3 d. One of the cultures, pig inner cell mass-19 (PICM-19), was passaged continuously for over 2 yr [\u3e100 population doublings (PD)] and appears to be an infinitely self-renewing cell population. The stem cell characteristics of the epiblast-derived fetal hepatocytes indicate that the cells may be unique for investigations of liver differentiation and organogenesis

COLONY ISOLATION AND SECONDARY CULTURE OF FETAL PORCINE HEPATOCYTES ON STO FEEDER CELLS

The secondary culture of non-transformed parenchymal hepatocytes has not been possible. STO feeder cell-dependent secondary cultures of fetal pig hepatocytes were established by colony isolation from primary cultures of 26-d fetal livers. The liver cells had the typical polygonal morphology of parenchymal hepatocytes. They also spontaneously differentiated to form small biliary canaliculi between individual cells or progressed further to large multicellular duct-like structures or cells undergoing gross lipid accumulation and secretion. The secondary hepatocyte cultures expressed alpha-fetoprotein (AFP), albumin, and β-fibrinogen mRNA, and conditioned medium from the cells contained elevated levels of transferrin and albumin. STO feeder cell co-culture may be useful for the sustainable culture of hepatocytes from other species