Refine
Year of publication
Document Type
- Article (260)
- Preprint (191)
- Part of Periodical (5)
- Doctoral Thesis (4)
- Part of a Book (1)
- Conference Proceeding (1)
- Working Paper (1)
Has Fulltext
- yes (463)
Is part of the Bibliography
- no (463)
Keywords
- BESIII (17)
- e +-e − Experiments (13)
- taxonomy (13)
- Branching fraction (9)
- Particle and Resonance Production (7)
- Fulgoroidea (6)
- Quarkonium (6)
- Spectroscopy (6)
- Hadronic decays (5)
- Oriental region (5)
- Branching fractions (4)
- Charm Physics (4)
- Exotics (4)
- Heavy-ion collisions (4)
- Lepton colliders (4)
- morphology (4)
- Borrelia (3)
- Charmed mesons (3)
- Charmonium (3)
- China (3)
- Diffraction (3)
- Electroweak interaction (3)
- Initial state radiation (3)
- e+-e− Experiments (3)
- Beam Energy Scan (2)
- Bhabha (2)
- Charm physics (2)
- Chiral Magnetic Effect (2)
- Collectivity (2)
- Correlation (2)
- Cross section (2)
- CspZ (2)
- Elastic scattering (2)
- Electroweak Interaction (2)
- Fulgoromorpha (2)
- Hadronic cross section (2)
- Leptonic, semileptonic & radiative decays (2)
- Muon anomaly (2)
- Particle decays (2)
- Pion form factor (2)
- QCD (2)
- Shear viscosity (2)
- bamboo pests (2)
- complement (2)
- distribution (2)
- factor H (2)
- faunal comparison (2)
- lyme disease (2)
- new species (2)
- new taxa (2)
- planthopper (2)
- (cardiac) surgery (1)
- ABC Transporter (1)
- ARA (1)
- Absolute branching fraction (1)
- Achilidae (1)
- Alleles (1)
- Angular distribution (1)
- Animal behavior (1)
- Anisozygoptera (1)
- Annihilation (1)
- Antigen Processing (1)
- Aortic valve (1)
- Apoptosis (1)
- Athena SWAN (1)
- Atherosclerosis (1)
- Augilini (1)
- Autophagic cell death (1)
- B-slope (1)
- BESIII detector (1)
- BPTI (1)
- Basidiomycota (1)
- Beam energy scan (1)
- Behavioral experiment (1)
- Biochemical simulations (1)
- Biological (1)
- Bipolar disorder (1)
- Blood (1)
- Born cross section measurement (1)
- Borrelia burgdorferi (1)
- Borrelia miyamotoi (1)
- Bromodomänen (1)
- CP violation (1)
- Call Market (1)
- Call for action (1)
- Canonical suppression (1)
- Cardiovascular diseases (1)
- Cell proliferation (1)
- Cellular Immune Response (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonium (-like) (1)
- Chemische Sonden (1)
- Chiral magnetic effect (1)
- Circadian (1)
- Closing Price (1)
- Closure (1)
- Coalescence (1)
- Cognitive behavioral therapy (1)
- Cold nuclear matter effects (1)
- Complement system (1)
- Covariance matrix (1)
- Critical point (1)
- Cross section measurements (1)
- CspA (1)
- D meson (1)
- D0 and D+ mesons (1)
- DAA (1)
- DNA barcoding (1)
- Dalitz decay (1)
- Danxia landform (1)
- Dark photon (1)
- Dark sector (1)
- Datong coalfield (1)
- Decision making (1)
- Delphacidae (1)
- Denosumab (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- Dicerapanorpa (1)
- Diseases (1)
- Dopamine (1)
- D⁰ meson (1)
- East Asia (1)
- Electromagnetic amplitude (1)
- Electromagnetic form factor (1)
- Electromagnetic form factors (1)
- Electronic properties and materials (1)
- Elliptic flow (1)
- Endothelial cells (1)
- Entomology (1)
- Eocene (1)
- Epigenetik (1)
- Epiophlebioptera (1)
- Epiproctophora (1)
- Equity Markets (1)
- Experimental nuclear physics (1)
- Experimental particle physics (1)
- Extension study (1)
- FOS: Physical sciences (1)
- FREEDOM (1)
- Factor H (1)
- Fish (1)
- Fistula (1)
- Flavor changing neutral currents (1)
- Flavor symmetries (1)
- Flavour Physics (1)
- Flow cytometry (1)
- Form factors (1)
- Forward physics (1)
- Free energy (1)
- G-protein coupled receptor (1)
- GABAergic interneurons (1)
- Gender (1)
- Germany (1)
- Get Pathway (1)
- Glomerulus (1)
- Groomed jet radius (1)
- Guidelines (1)
- Hadron-Hadron scattering (experiments) (1)
- Hadronization (1)
- Hadrons (1)
- Health research (1)
- Health risk analysis (1)
- Heart (1)
- Heavy Ion Experiments (1)
- Heavy Quark Production (1)
- Heavy ion collisions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- High Energy Physics - Experiment (hep-ex) (1)
- Higher moments (1)
- Homeostasis (1)
- Horses (1)
- Hyperons (1)
- IFN (1)
- Immunology (1)
- Immunostaining (1)
- Inclusive branching fraction (1)
- Interference fragmentation function (1)
- Intra-Day Volatility (1)
- Intra-abdominal infection (1)
- Intracellular Trafficking (1)
- Invisible decays (1)
- Italy (1)
- J/ψ suppression (1)
- Jet substructure (1)
- K0S (1)
- Kermesiinae (1)
- Kolonialstadt (1)
- Laparostomy (1)
- Lyme disease (1)
- Magnetic properties and materials (1)
- Main olfactory epithelium (1)
- Malaysia (1)
- Market Microstructure (1)
- Medizinische Chemie (1)
- Melanocortin (1)
- Membracidae (1)
- Membrane fusion (1)
- Membrane structures (1)
- Mesh (1)
- Microbiology (1)
- Molecular dynamics (1)
- Multiple parton interactions (1)
- Myocardial infarction (1)
- NACI (1)
- NDNF interneurons (1)
- NMR spectroscopy (1)
- NMR structure determination (1)
- Naja naja atra (1)
- Nasdaq (1)
- Neolithic (1)
- Net-charge correlations (1)
- Net-charge fluctuations (1)
- Neutrinos (1)
- Non-trauma (1)
- North Korea (1)
- Nutrition (1)
- Nymphs (1)
- Odorant receptor (1)
- Ommatidiotinae (1)
- Open abdomen (1)
- Opening Price (1)
- OspE (1)
- Osteoporosis (1)
- Otolith-based fish fauna (1)
- Outcome (1)
- Pancreatitis (1)
- Particle and resonance production (1)
- Particle phenomena (1)
- Particle production (1)
- Path dependency (1)
- Pathogenesis (1)
- Peritonitis (1)
- Personality (1)
- Personality differences (1)
- Personality traits (1)
- Phase (1)
- Phase transitions and critical phenomena (1)
- Phylogenomics (1)
- Physiological parameters (1)
- Polarization (1)
- Population genetics (1)
- Proton (1)
- Proton-proton collisions (1)
- Proton–proton collisions (1)
- Psychiatry (1)
- Quantum chromodynamics (1)
- Quark–gluon plasma (1)
- R value (1)
- RHIC (1)
- Radiative decay (1)
- Rare decays (1)
- Raumaufteilung (1)
- Re-exploration (1)
- Reintervention (1)
- Research impact assessment (1)
- Resonances (1)
- SAVI (1)
- STAR (1)
- STING (1)
- Science policy (1)
- Seasonal variation (1)
- Selection bias (1)
- Semi-leptonic decays (1)
- Social anxiety disorder (1)
- Social phobia (1)
- SoftDrop (1)
- Solar insolation (1)
- South China (1)
- Spirochetes (1)
- Splitting function (1)
- Strangeness enhancement (1)
- Stroke (1)
- Strong amplitude (1)
- Strukturbasiertes Design (1)
- Suicide (1)
- Sunlight (1)
- Sweden (1)
- Swimming (1)
- Synthetic (1)
- Südostasien (1)
- Tail-anchored Proteins (1)
- Taiwan (1)
- Technique (1)
- Techniques Electromagnetic calorimeters (1)
- Thermal model (1)
- Timing (1)
- Transversity (1)
- Trauma (1)
- Treatment (1)
- Triple quarkonia (1)
- Vascular emergencies (1)
- Vesicle fusion (1)
- Vesicles (1)
- Viral Immunology (1)
- W-exchange (1)
- Wohnhaus (1)
- Y (4260) (1)
- Y states (1)
- Zentraler Kontrahent (1)
- Zingiber (1)
- Zingiberaceae (1)
- achilid (1)
- acute kidney injury (1)
- anticoagulation (1)
- atrial fibrillation (1)
- bamboo (1)
- bamboo feeds (1)
- biogeography (1)
- borrelia (1)
- brachypterous Meconematini (1)
- branching fractions (1)
- bromodomains (1)
- cave (1)
- center-of-mass energy (1)
- charmed baryon (1)
- charmonium-like states (1)
- chemical probes (1)
- chymotrypsin inhibitor (1)
- clinical studies (1)
- combination (1)
- connectivity (1)
- cryptic species (1)
- decay (1)
- decays (1)
- dendritic inhibition (1)
- dimuon (1)
- diphoton (1)
- disulfide bond isomerization (1)
- domestication (1)
- drosophilid (1)
- drug interaction (1)
- e+e − annihilation (1)
- e+e⁻ − Experiments (1)
- e+e− Experiments (1)
- e+e− annihilation (1)
- electron-positron collision (1)
- endophytes (1)
- epigenetics (1)
- evolution (1)
- fear learning (1)
- felsic detrital (1)
- fibrinolysis (1)
- foliar pathogens (1)
- fossil record analysis (1)
- gene flow (1)
- genetic markers (1)
- genetic polymorphisms (1)
- hadron spectroscopy (1)
- hadronic events (1)
- heavy-ion collisions (1)
- helicity amplitude analysis (1)
- host-pathogen interaction (1)
- hostpathogen interaction (1)
- immune evasion (1)
- inclusive J/ψ decays (1)
- inflammatory cytokines (1)
- innate immunity (1)
- interneurons (1)
- layer 1 (1)
- lectotype (1)
- left atrial appendage occlusion (1)
- lithium (1)
- luminosity (1)
- medicinal chemistry (1)
- minerals (1)
- neocortical circuits (1)
- new combinations (1)
- new genera (1)
- new records (1)
- new taxon (1)
- nitro-fatty acids (1)
- number of J/ψ events (1)
- oriental region (1)
- p+p collisions (1)
- paleodiversity (1)
- paleoecology (1)
- palmitoylation (1)
- pathogenicity (1)
- phylogenetic analysis (1)
- plasminogen (1)
- price discovery (1)
- risk prediction (1)
- role labeling (1)
- scorpionfly (1)
- snake venom (1)
- somatostatin interneurons (1)
- southern China (1)
- species diversity (1)
- speech tagging (1)
- spirochete (1)
- spirochetes (1)
- stroke (1)
- structure-based design (1)
- systematics (1)
- tetraquark (1)
- tick (1)
- time annotation (1)
- top-down processing (1)
- trace elements (1)
- treebanking (1)
- treehopper (1)
- trigger efficiency (1)
- vaccine (1)
- virus-like particles (1)
- Λ+c baryon (1)
- Λc⁺ (1)
- Σ hyperon (1)
- Υ suppression (1)
- ψ(3686) (1)
Institute
- Physik (289)
- Frankfurt Institute for Advanced Studies (FIAS) (99)
- Medizin (25)
- Biowissenschaften (8)
- Biochemie und Chemie (4)
- Informatik (2)
- Institut für Ökologie, Evolution und Diversität (2)
- Kulturwissenschaften (2)
- Pharmazie (2)
- Psychologie (2)
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Background. Intervertebral disc degeneration (IDD) at the cervicothoracic junction of spine is clinically relevant, however, little attention had been paid. T2 mapping and magnetic transfer ratio (MTR) are useful magnetic resonance imaging (MRI) techniques to quantitatively evaluate IDD, revealing the biochemical changes within the intervertebral disc. To compare T2 mapping with MTR imaging regarding their accuracy to quantitatively diagnose intervertebral disc degeneration at the cervicothoracic junction, influences of anatomical level, gender, age, and Pfrrmann grade of T2 relaxation time values and MTR values were evaluated.
Methods. Sixty-seven patients with neck and upper back pain were included and examined with both T2 mapping andMTR imaging. Te Pfrrmann grade, T2 relaxation time values, and MTR value of each disc between C7 and T3 were measured. Diferences were investigated among diferent segmental levels, genders, age ranges, and Pfrrmann grades. Te diagnostic accuracy of both MRI techniques was compared using the receiver operating characteristic (ROC) curves.
Results. No signifcant diference was detected comparing T2 relaxation time values or MTR values among diferent anatomical levels, genders, and segmental levels. And we generally found that T2 relaxation time values decreased, while MTR value increased with increasing age. Importantly, we demonstrated the signifcant correlation between either T2 relaxation time values or MTR value and Pfrrmann grade.
Conclusion. We proved the better accuracy of T2 mapping over MTR imaging to quantitatively evaluate the intervertebral disc degeneration of the cervicothoracic junction.
Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10), and one in Frankfurt, Germany (n = 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90), negative affect (d = 1.98 and 0.92), and positive affect (d = 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.
Background: While the efficacy of cognitive therapy (CT) has been well established for social anxiety disorder (SAD) in several randomized controlled trials, there are still large differences between trials with respect to effect sizes. The present study investigates the question of whether enhanced training and the use of behavioral experiments (BEs) increases the efficacy of traditional CT, based on verbal methods of cognitive restructuring. Methods/design: A mixed within/between conditions design will be applied, with therapists and patients being randomly allocated to one of two conditions: (1) training of CT plus BEs, (2) training of CT “as usual”. Sixty patients with the primary diagnosis of SAD will be recruited and treated in the outpatient clinic of the Department of Psychology, University of Frankfurt. To ensure adherence to therapist protocols, all therapists will be trained and supervised by the project coordinators. In addition, videotaped treatment sessions will be independently evaluated to guarantee both adherence to protocols and the quality of the intervention. Treatment effects will be assessed by independent SAD symptom ratings using the Liebowitz Social Anxiety Scale as the primary outcome measure and self-report measures as secondary outcome measures. Discussion: The present cognitive behavioral therapy (CBT) trial will be the first to clarify the contribution of BEs to the efficacy of CT in a randomized controlled design. Study results are relevant to clinical training and implementation of evidence-based treatments. Trial registration: German Clinical Trials Register International Clinical Trials Registry Platform (ICTRP) identifier: DRKS00014349. Trial status: recruiting.
The planthopper genus Arcofaciella Fennah, 1956 (Hemiptera: Fulgoromorpha: Delphacidae) is reviewed. Four species are recognized, of which A. obflexa Guo & Liang, 2005 and A. verrucosa Fennah, 1956 are redescribed, and one new species, A. indiana sp. nov., is described. Habitus photos for adults and illustrations of male genitalia (excluding A. penangensis (Muir, 1919)) are given. A key for identifying the species of Arcofaciella is also provided.
The planthopper genus Augilina Melichar, 1914, is recorded in China for the first time. Two new species of the genus Augilina, A. tetraina Chen & Gong sp. nov. and A. triaina Chen & Gong sp. nov., are described and illustrated from South China. The genus now has a total of four described species. New generic characteristics are proposed and photographs of the new species are provided. A checklist and a key to the species of Augilina are also included.
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14–Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14–Cys38 disulfide bond.
Three new species of the bamboo-feeding genus Bambusiphaga Huang & Ding, 1979, B. parvula sp. nov., B. angulosa sp. nov., and B. nigrigena sp. nov., are described and illustrated from China. A key to species of the genus is provided. Habitus photos for adults and illustrations of male genitalia are also given.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Two new species, Russula pseudopunicea C.L.Hou, G.Q.Cheng & H.Zhou sp. nov. and R. wulingshanensis C.L.Hou, G.Q.Cheng & H.Zhou sp. nov., from Yanshan mountains in North China are described herein based on morphological and phylogenetic analyses of nrITS, and nrLSU-rpb2-mtSSU gene regions. Morphologically, R. pseudopunicea sp. nov. is characterised by a reddish brown, light brown to brownish orange pileus with a greyish yellow margin, subglobose to broadly ellipsoid basidiospores with warts forming a partial reticulum and pleurocystidia turning grey to purplish red in sulfovanillin. Russula wulingshanensis sp. nov. is characterised by a purple pinkish pileus with a grey-white to grey-purple margin, subglobose to broadly ellipsoid basidiospores with isolated warts, and pileocystidia turning black in sulfovanillin. Phylogenetic and morphological analyses resolved the two species in Russula subg. Heterophyllidia. Russula pseudopunicea sp. nov. and R. wulingshanensis sp. nov. were placed in the lineages of subsect. Virescentinae and subsect. Griseinae, respectively.
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.
This paper provides new geochemical data focusing on valuable elements in the coal, parting, and floor samples in the No. 5 coal seam of the Taiyuan Formation from the Wujiawan mine, Datong coalfield, northern China. The minerals mainly consist of kaolinite, calcite, and pyrite, as well as trace amounts of quartz and illite. The No. 5 coal is enriched in Li, Ga, high field strength elements (HFSEs), and rare earth elements and yttrium (REY) when compared with world hard coals. Of particular interest is the high average concentration of Li (67.66 μg/g), which is around seven times higher than the value for world hard coals. Lithium, Ga, and HFSEs have strong inorganic affinities, whereas REY have organic affinities. The main carrier of Li, Ga, and HFSEs is aluminosilicate minerals, while REY appear to occur with organophosphorus. These HFSEs are enriched, both in the parting and in the adjacent coal samples. This suggests that these elements are likely to leach out during the diagenetic process. The distribution patterns of REY, along with the ratio of Al2O3/TiO2 and the figure of Zr/TiO2 vs. Nb/Y are suggestive of their derivation from felsic parent material. In the northern and eastern part of the Datong coalfield, there are several regions where the Li content is higher than the mineable grade, in particular in the northern Datong coalfield where there is a mine with an Li content of 294.6 μg/g. This is significantly higher than the mineable grade. Therefore, there is a potential for financially viable recovery of Li in these coals of the Datong coalfield.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.