The gradient of potential vorticity, quaternions and an orthonormal frame for fluid particles

The gradient of potential vorticity (PV) is an important quantity because of the way PV (denoted as $q$) tends to accumulate locally in the oceans and atmospheres. Recent analysis by the authors has shown that the vector quantity \bdB = \bnabla q\times \bnabla\theta for the three-dimensional incompressible rotating Euler equations evolves according to the same stretching equation as for \bom the vorticity and \bB, the magnetic field in magnetohydrodynamics (MHD). The \bdB-vector therefore acts like the vorticity \bom in Euler's equations and the \bB-field in MHD. For example, it allows various analogies, such as stretching dynamics, helicity, superhelicity and cross helicity. In addition, using quaternionic analysis, the dynamics of the \bdB-vector naturally allow the construction of an orthonormal frame attached to fluid particles\,; this is designated as a quaternion frame. The alignment dynamics of this frame are particularly relevant to the three-axis rotations that particles undergo as they traverse regions of a flow when the PV gradient \bnabla q is large.Comment: Dedicated to Raymond Hide on the occasion of his 80th birthda

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

Oligomeric Structure of the MALT1 Tandem Ig-Like Domains

Mucosa-associated lymphoid tissue 1 (MALT1) plays an important role in the adaptive immune program. During TCR- or BCR-induced NF-κB activation, MALT1 serves to mediate the activation of the IKK (IκB kinase) complex, which subsequently regulates the activation of NF-κB. Aggregation of MALT1 is important for E3 ligase activation and NF-κB signaling.Unlike the isolated CARD or paracaspase domains, which behave as monomers, the tandem Ig-like domains of MALT1 exists as a mixture of dimer and tetramer in solution. High-resolution structures reveals a protein-protein interface that is stabilized by a buried surface area of 1256 Å(2) and contains numerous hydrogen and salt bonds. In conjunction with a second interface, these interactions may represent the basis of MALT1 oligomerization.The crystal structure of the tandem Ig-like domains reveals the oligomerization potential of MALT1 and a potential intermediate in the activation of the adaptive inflammatory pathway.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Protective measures and H5N1-seroprevalence among personnel tasked with bird collection during an outbreak of avian influenza A/H5N1 in wild birds, Ruegen, Germany, 2006

Background: In Germany, the first outbreak of highly pathogenic avian influenza A/H5N1 occurred among wild birds on the island of Ruegen between February and April 2006. The aim of this study was to investigate the use of recommended protective measures and to measure H5N1- seroprevalence among personnel tasked with bird collection. Methods: Inclusion criteria of our study were participation in collecting wild birds on Ruegen between February and March 2006. Study participants were asked to complete a questionnaire, and to provide blood samples. For evaluation of the use of protective measures, we developed a personal protective equipment (PPE)-score ranging between 0 and 9, where 9 corresponds to a consistent and complete use of PPE. Sera were tested by plaque neutralization (PN) and microneutralization (MN) assays. Reactive sera were reanalysed in the World Health Organization- Collaborating Centre (WHO-CC) using MN assay. Results: Of the eligible personnel, consisting of firemen, government workers and veterinarians, 61% (97/154) participated in the study. Of those, 13% reported having always worn all PPE-devices during bird collection (PPE-score: 9). Adherence differed between firemen (mean PPE-score: 6.6) and government workers (mean PPE-score: 4.5; p = 0.006). The proportion of personnel always adherent to wearing PPE was lowest for masks (19%). Of the participants, 18% had received seasonal influenza vaccination prior to the outbreak. There were no reports of influenza-like illness. Five sera initially H5-reactive by PN assay were negative by WHO-CC confirmatory testing. Conclusion: Gaps and variability in adherence demonstrate the risk of exposure to avian influenza under conditions of wild bird collection, and justify serological testing and regular training of task personnel

Rye kernel breakfast increases satiety in the afternoon - an effect of food structure

<p>Abstract</p> <p>Background</p> <p>The structure of whole grain cereals is maintained to varying degrees during processing and preparation of foods. Food structure can influence metabolism, including perceived hunger and satiety. A diet that enhances satiety per calorie may help to prevent excessive calorie intake. The objective of this work was to compare subjective appetite ratings after consumption of intact and milled rye kernels.</p> <p>Methods</p> <p>Two studies were performed using a randomized, cross-over design. Ratings for appetite (hunger, satiety and desire to eat) were registered during an 8-h period after consumption of whole and milled rye kernels prepared as breads (study 1, n = 24) and porridges (study 2, n = 20). Sifted wheat bread was used as reference in both study parts and the products were eaten in iso-caloric portions with standardized additional breakfast foods. Breads and porridges were analyzed to determine whether structure (whole vs. milled kernels) effected dietary fibre content and composition after preparation of the products. Statistical evaluation of the appetite ratings after intake of the different breakfasts was done by paired t-tests for morning and afternoon ratings separately, with subjects as random effect and type of breakfast and time points as fixed effects.</p> <p>Results</p> <p>All rye breakfasts resulted in higher satiety ratings in the morning and afternoon compared with the iso-caloric reference breakfast with sifted wheat bread. Rye bread with milled or whole kernels affected appetite equally, so no effect of structure was observed. In contrast, after consumption of the rye kernel breakfast, satiety was increased and hunger suppressed in the afternoon compared with the milled rye kernel porridge breakfast. This effect could be related to structural differences alone, because the products were equal in nutritional content including dietary fibre content and composition.</p> <p>Conclusions</p> <p>The study demonstrates that small changes in diet composition such as cereal grain structure have the potential to effect feelings of hunger and satiety.</p> <p>Trial registration</p> <p>This trial was registered at clinicaltrials.gov as <a href="http://www.clinicaltrials.gov/ct2/show/NCT01042418">NCT01042418</a>.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Hippocampal Deletion of BDNF Gene Attenuates Gamma Oscillations in Area CA1 by Up-Regulating 5-HT3 Receptor

Background: Pyramidal neurons in the hippocampal area CA3 express high levels of BDNF, but how this BDNF contributes to oscillatory properties of hippocampus is unknown. Methodology/Principal Findings: Here we examined carbachol-induced gamma oscillations in hippocampal slices lacking BDNF gene in the area CA3. The power of oscillations was reduced in the hippocampal area CA1, which coincided with increases in the expression and activity of 5-HT3 receptor. Pharmacological block of this receptor partially restored power of gamma oscillations in slices from KO mice, but had no effect in slices from WT mice. Conclusion/Significance: These data suggest that BDNF facilitates gamma oscillations in the hippocampus by attenuating signaling through 5-HT3 receptor. Thus, BDNF modulates hippocampal oscillations through serotonergic system

Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

<p>Abstract</p> <p>Background</p> <p>Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α.</p> <p>Methods</p> <p>Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.</p> <p>Results</p> <p>CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α <it>in vitro</it>. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.</p> <p>Conclusions</p> <p>CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.</p