An opioid-like system regulating feeding behavior in C. elegans

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggestC. elegans may be the first genetically tractable invertebrate opioid model

Unilateral Breast Edema: Spectrum of Etiologies and Imaging Appearances

Breast edema is defined as a mammographic pattern of skin thickening, increased parenchymal density, and interstitial marking. It can be caused by benign or malignant diseases, as a result of a tumor in the dermal lymphatics of the breast, lymphatic congestion caused by breast, lymphatic drainage obstruction, or by congestive heart failure

Modified cardiovascular SOFA score in sepsis: development and internal and external validation

Background : The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. Methods : We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock. Results : We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%). Conclusions : Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1A2C3004508) to Kyuseok Kim. National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1F1A1052908) to Tae Gun Shin

UBR2 of the N-End Rule Pathway Is Required for Chromosome Stability via Histone Ubiquitylation in Spermatocytes and Somatic Cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe