Dimensional crossover and cold-atom realization of topological Mott insulators

We propose a cold-atom setup which allows for a dimensional crossover from a two-dimensional quantum spin Hall insulating phase to a three-dimensional strong topological insulator by tuning the hopping between the layers. We further show that additional Hubbard onsite interactions can give rise to spin liquid-like phases: weak and strong topological Mott insulators. They represent the celebrated paradigm of a quantum state of matter which merely exists because of the interplay of the non-trivial topology of the band structure and strong interactions. While the theoretical understanding of this phase has remained elusive, our proposal shall help to shed some light on this exotic state of matter by paving the way for a controlled experimental investigation in optical lattices.Comment: 4+ pages, 3 figures; includes Supplemental Material (3 pages, 1 figure

Biologische und ökologische Beobachtungen an auf Pinus lebenden Cinarinen im Bereich der Dübener Heide (DDR) während der Jahre 1965-1967

kein Abstract vorhandenno abstract availabl

Materialien zur Verbreitung der auf Pinus silvestris L. lebenden Cinarinen im Gebiet der DDR

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Cinara curvipes (Patch) (Sternorrhyncha, Lachnidae) - eine invasive Rindenlaus in Mitteleuropa.

Seit dem Jahr 2000 wird die schwarz gefärbte und 4,5 bis 5,3 mm große Cinara curvipes (Patch) im Raum Eberswalde im Bundesland Brandenburg im Freiland ganzjährig an ihren Wirtspflanzen Abies grandis und A. concolor beobachtet, auch auf A. koreani und A. veitchii wurde diese Art gefunden. Diese Rindenlaus saugt vorzugsweise am Stamm, an den Astunterseiten und Astansatzstellen. In Deutschland fand man C. curvipes ebenfalls in den Bundesländern Bayern, Berlin, Mecklenburg-Vorpommern und Niedersachsen. Es gelang, die bisher unbekannten Fundatrices, oviparen Weibchen sowie die nur an einem Fundort in den USA festgestellten geflügelten Männchen und die nicht bekannten Wintereier nachzuweisen, auch wurde eine genaue Beschreibung der Alatae möglich. Der Jahresrhythmus dieser bisher nur aus den USA, Kanada und Mexiko bekannten Rindenlaus wurde ermittelt. Dabei zeigte sich, dass in Mitteleuropa die jährliche Generationenfolge dieser Species sowohl holozyklisch als auch anholozyklisch ablaufen kann. Im Holozyklus folgen auf die aus den Wintereiern schlüpfenden Fundatrices (Stammmütter) noch fünf Generationen, wobei allein die letzte Generation zweigeschlechtlich ist und mit der Ablage der Wintereier den Jahreszyklus abschließt. Im Anholozyklus entstehen weder ovipare Weibchen noch Männchen: es folgen während eines Jahres parthenogenetisch sechs Generationen aufeinander, wobei die letzte, von der V5 bis in den November hinein geborene Generation (V6) überwintern kann. Nach erfolgter Überwinterung dieser V6-Generation (Anholozyklus) und deren im März beginnender Vermehrung können sich bereits im Mai an Astunterseiten und Stämmen der Wirtspflanzen aus mehreren tausend Individuen bestehende Rindenlauskolonien entwickeln. Das ist ein bei einheimischen Cinara-Arten bislang nicht bekanntes Phänomen. – Die Angehörigen der V3-Generation beider Zyklen führen durch die Geburt sowohl von V4 als auch von Sexuparae zur gegenseitigen Überlappung von Anholozyklus und Holozyklus (sogar an einem Baum). - Bereits im März, während der Sommermonate und noch im November und Dezember, also vor der Überwinterung larvaler und adulter Morphen, scheidet C. curvipes große Mengen Honigtau aus. Dieser ist vom zeitigen Frühjahr bis in den November/Dezember eine wichtige Nahrungsgrundlage für Formiciden und Vespiden. - Die Ursachen für das weitgehende Fehlen von Insekten als Prädatoren und die mögliche lokal begrenzte imkerliche Bedeutung werden diskutiert.StichwörterCinara curvipes (Patch), Germany, morphs, biology.Since the year 2000 the black coloured 4.5 to 5.3 mm long Cinara curvipes (Patch) has been observed outdoors throughout the year in the area of Eberswalde, Brandenburg, on its hostplants Abies grandis and A. concolor. This insect was also found on A. koreana and A. veitchii. This bark aphid sucks preferentially on the trunk, on the undersides of branches and on the bases of branches. In Germany C. curvipes was also found in the federal states of Bavaria, Berlin, Mecklenburg-Western Pomerania and Lower Saxony. The previously unknown fundatrices, oviparous females, the winged male (previously known only from a single locality in the USA) and the unknown winter eggs were found. An exact description of the alatae was also possible. The annual cycle of this bark aphid, previously only known from the USA, Canada and Mexiko, was investigated. It became apparent that in Central Europe the yearly succession of generations may be holocyclic or anholocyclic. Where this is holocyclic, five generations follow from the fundatrices which emerge from the winter eggs, whilst only the last generation is bisexual and completes the annual cycle by laying the winter eggs. Under anholocyclism neither oviparous females nor males are produced: six generations follow upon each other during the year. The last of these, from the V5 to the V6 born into the beginning of November, can overwinter. After successful overwintering of this V6 generation (anholocyclism) and the onset of reproduction of these in March, bark louse colonies which already contain in May many thousands of individuals can develop on the undersides of branches and on the trunk of the hostplants. This phenomenon is hitherto unknown in native Cinara species of Central Europe. Members of the V3 generation of both cycles cause a reciprocal overlapping of anholocyclism and holocyclism by the birth of V4 and of sexuparae, which can occur even on the same tree. - As early as March, during the summer months and as late as November / December, thus before the overwintering of larval and adult morphs, C. curvipes secretes large quantities of honeydew. This is an important source of nutrition for Formicidae and Vespidae from early spring into November / December. - Reasons for the general absence of predatory insects and the possibly local significance for beekeeping are discussed.KeywordsCinara curvipes (Patch), Germany, morphs, biology

Ten-Year Minimum Follow-up Study of First Metatarsophalangeal Joint Fusion in Young vs Old Patients

BACKGROUND Painful degenerative joint disease (DJD) of the first metatarsophalangeal joint (MTP I), or hallux rigidus, mainly occurs in later stages of life. For end-stage hallux rigidus, MTP I arthrodesis is considered the gold standard. As young and active patients are affected considerably less frequently, it currently remains unclear, whether they benefit to the same extent. We hypothesized that MTP I arthrodesis in younger patients would lead to an inferior outcome with decreased rates of overall with lower rates of patient postoperative pain and function compared to an older cohort. METHODS All patients aged 60 years. Minimum follow-up was 10 years. Outcome measures were Tegner activity score (TAS), a "Virtual Tegner activity score" (VTAS), the visual analog scale (VAS), and the Foot Function index (FFI). RESULTS Sixty-one MTP I fusions (n = 28 young, n = 33 old) in 46 patients were included in our study at an average of 14 years after surgery. Younger patients experienced significantly more pain relief as reflected by changes in VAS and FFI Pain subscale scores. No difference in functional outcomes was found with change in the FFI function subscale or in the ability to have desired functional outcomes using the ratio of TAS to VTAS. Revision rate did not differ between the two groups apart from hardware removal, which was significantly more likely in the younger group. CONCLUSION In patients below the age of 50 years with end-stage DJD of the first metatarsal joint, MTP I arthrodesis not only yielded highly satisfactory postoperative results at least equal outcome compared to an older cohort of patients aged >60 years at an average 14 years' follow-up. Based on these findings, we consider first metatarsal joint fusion even for young patients is a valid option to treat end-stage hallux rigidus. LEVEL OF EVIDENCE Level III, a case-control study

CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis

Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.Fil: Blanco-Pérez, Frank. Paul-ehrlich-institut;Fil: Kato, Yoichiro. Tokyo Women's Medical University;Fil: Gonzalez-Menendez, Irene. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Laiño, Jonathan Emiliano. Paul-ehrlich-institut;Fil: Ohbayashi, Masaharu. Toyohashi Sozo University;Fil: Burggraf, Manja. Paul-ehrlich-institut;Fil: Krause, Maren. Paul-ehrlich-institut;Fil: Kirberg, Jörg. Paul-ehrlich-institut;Fil: Iwakura, Yoichiro. Tokyo University Of Science;Fil: Martella, Manuela. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Quintanilla-Martinez, Leticia. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Shibata, Noriyuki. Tokyo Women's Medical University;Fil: Vieths, Stefan. Paul-ehrlich-institut;Fil: Scheurer, Stephan. Paul-ehrlich-institut;Fil: Toda, Masako. Paul-ehrlich-institut; . Tohoku University

A flagellin-conjugate protein induces dual NLRC4- and NLRP3-inflammasome activation which modulates inflammatory cytokine secretion from macrophages

BackgroundA recombinant fusion protein combining the adjuvant and TLR5-ligand flagellin with the major birch pollen allergen Bet v 1 (rFlaA:Betv1) has been suggested to prevent the manifestation of birch allergy. Noteworthy, rFlaA:Betv1 induced both pro- and anti-inflammatory responses which were differentially regulated. However, the mechanism by which flagellin fusion proteins modulate allergen-specific immune responses, especially the mechanisms underlying IL-1β secretion and their contribution to the overall immune responses remains elusive.ObjectiveTo investigate the mechanisms underlying the production of IL-1β from rFlaA:Betv1 stimulated macrophages.MethodsMacrophages were derived from mouse peritoneal-, human buffy-coat-, and PMA-differentiated THP-1 (wild type or lacking either ASC, NLRP3, or NLRC4) cells. Macrophages were stimulated with non-modified rFlaA:Betv1, mutant variants lacking either the flagellin DC0 domain or a sequence motif formerly described to mediate TLR5-activation, and respective controls in the presence or absence of inhibitors interfering with MAPK- and NFκB-signaling. Cytokine secretion was analyzed by ELISA and intracellular signaling by Western Blot. To study the contribution of IL-1β to the overall immune responses, IL1R-deficient mouse peritoneal macrophages were used.ResultsrFlaA:Betv1 consistently activated all types of investigated macrophages, inducing higher IL-1β secretion compared with the equimolar mixture of both proteins. rFlaA:Betv1-induced activation of THP-1 macrophages was shown to be independent of either the TLR5-activating sequence motif or the flagellin DC0 domain but depended on both NLRP3- and NLRC4-inflammasomes. In addition, NFκB and SAP/JNK MAP kinases regulated rFlaA:Betv1-induced inflammasome activation and cytokine secretion by modulating pro-Caspase-1- and pro-IL-1β-expression in THP-1 macrophages. Finally, lack of IL-1β positive feedback via the IL1R strongly diminished the rFlaA:Betv1-induced secretion of IL-1β, IL-6, and TNF-α from peritoneal macrophages.ConclusionThe mechanisms contributing to rFlaA:Betv1-induced IL-1β secretion from macrophages were shown to be complex, involving both NLRC4- and NLRP3-inflammsomes, as well as NFκB- and SAP/JNK MAP kinase-signaling. Better understanding the mechanisms regulating the activation of immune cells by novel therapeutic candidates like the rFlaA:Betv1 fusion protein will allow us to further improve and develop new treatment strategies when using flagellin as an adjuvant

Mast cells partly contribute to allergic enteritis development: Findings in two different mast cell-deficient mice

Allergic enteritis (AE) is a gastrointestinal form of food allergy. The presence of mast cells and granulocytes has been detected in the inflamed tissues in AE. In this study, we aimed to elucidate the role of mast cells in AE development using two mast cell-deficient mouse strains: KIT(W-sh/W-sh) bearing the W-sash (W(sh)) inversion mutation and Cpa3Cre/+, which lack mast cells due to Cre-mediated mast cell eradication, were used in an AE experimental model. The development of clinical symptoms (e.g. drop in body temperature and weight loss) were abolished in both strains, whereas inflammatory levels of AE (e.g. villous atrophy, edema, and granulocyte accumulation) were reduced mainly in KITW-sh/W-sh mice. FACS analysis of the KITW-sh/W-sh intestinal lamina propria, showed a reduction in the eosinophil (CD45+CD11b+SiglecF+cells) and neutrophil (CD45+CD11b+SiglecF−Ly6G+ cells) accumulation. Cpa3Cre/+ mice showed reduced eosinophil (CD45+CD11b+SiglecF+cells) accumulation, but neutrophil (CD45+CD11b+SiglecF−Ly6G+ cells) accumulation was retained at AE sites. The concentrations of CC chemokine ligand 1 (CCL1), a known CC chemokine receptor 8 ligand leading to eosinophil recruitment, was reduced in intestinal homogenates of both mast cell-deficient mouse strains. These results suggest that mast cells play a role in AE development in part by expressing CCL1 and contributing to eosinophil accumulation at AE. This study offers implications for establishing AE treatments that target infiltrating leucocytes in AE tissues.Fil: Blanco Pérez, Frank. No especifíca;Fil: Gonzalez Menendez, Irene. No especifíca;Fil: Stassen, Michael. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Kato, Yoichiro. Tokyo Women's Medical University; JapónFil: Laiño, Jonathan Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kirberg, Jörg. No especifíca;Fil: Krause, Maren. No especifíca;Fil: Martella, Manuela. No especifíca;Fil: Shibata, Noriyuki. Tokyo Women's Medical University; JapónFil: Quintanilla-Martinez, Leticia. No especifíca;Fil: Feyerabend, Thorsten B.. No especifíca;Fil: Rodewald, Hans Reimer. No especifíca;Fil: Galli, Stephen J.. University of Stanford; Estados UnidosFil: Vieths, Stefan. No especifíca;Fil: Scheurer, Stephan. No especifíca;Fil: Toda, Masako. No especifíca

Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. METHOD AND FINDINGS: The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study