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Theater-und Tanzfestivals sind bedeutende Orte, wenn es um die Dissemination von Theater und Tanz von und mit behinderten Künstler*innen geht. Die geforderte Mobilität der Künstler*innen mit Behinderungen, die an Festivals auftreten, bringt eine spezifische Ästhetik des Im/mobilen hervor und Festivals beeinflussen damit, welche Formen von Theater und Tanz mit behinderten Künstler*innen auf internationalen Bühnen repräsentiert und wahrgenommen wird. Gleichzeitig fungieren Festivals als Inkubatoren neuer Arbeitsweisen und Praktiken, die das Potenzial besitzen, ästhetische und strukturelle Rahmungen zu erweitern, zu hinterfragen und neu zu definieren, um Bühnen für Performer*innen und Zuschauer*innen mit verschiedenen Behinderungen zugänglich zu machen. Der Beitrag beleuchtet diese aktuelle Entwicklungen in der Festivalszene, auch vor dem Hintergrund einer Debatte um alternative Formen der Zirkulation und Dissemination von Theater-und Tanzperformances.

This submission by IFTR's Performance and Disability working group features responses by six participants – voices projected from Canada, New Zealand, Norway, Wales, England and Australia – to Per.Art's productionDis_Sylphide, which was presented on 7 July 2018 at the Cultural Institution Vuk Karadžić as part of IFTR's conference in Belgrade at the invitation of the Performance and Disability working group. Per.Art is an independent theatre company founded in 1999 in Novi Sad, Serbia, by the internationally recognized choreographer and performer Saša Asentić, the company's artistic director. The company brings together people with learning disabilities, artists (theatre, dance and visual arts), special educators, representatives of cultural institutions, philosophers, architects and students to make work. This co-authored submission examines how the production responds to three important dance works of the twentieth century – Mary Wigman'sHexentanz(1928), Pina Bausch'sKontakthof(1978) and Xavier Le Roy'sSelf Unfinished(1998) – to explore normalizing and normative body concepts in dance theatre and in society, and how they have been migrating over the course of dance histories. The shared experience of witnessing the performance provoked discussion on the migration of dance forms across time and cultures, as well issues of access and (im)mobility, which are especially pertinent to a disability studies context.

Immunohistochemical staining is widely used to identify opioid receptors in specific cell types throughout the nervous system. Opioid receptors are not restricted to the central nervous system, but are also present in peripheral sensory neurons, where their activation exerts analgesic effects without inducing centrally mediated side effects. Here, we describe immunohistochemical analysis of μ-opioid receptors in the peripheral sensory neuron cell bodies, along the axons and their peripheral endings in the hind paw skin, as well as in the spinal cord, under naive and sciatic nerve damage conditions in mice. Importantly, we consider the ongoing debate on the specificity of antibodies.

Immunohistochemical staining is widely used to identify opioid receptors in specific cell types or anatomical structures throughout the nervous system. Opioid receptors are not restricted to the central nervous system, but are also present in peripheral sensory neurons, where their activation exerts analgesic effects without inducing centrally mediated side effects. Here, we describe immunohistochemical analysis of opioid receptors in the peripheral sensory neuron cell bodies, along the axons and their peripheral endings in the hind paw skin, as well as in the spinal cord, under naïve and sciatic nerve damage conditions in mice. Moreover, we consider the current debate on the specificity of antibodies.

Endometriosis is a painful gynaecological condition characterized by ectopic growth of endometrial cells outside of the uterus. Little is known about the mechanisms by which endometrial fragments invade tissues. This is partially due to a lack of suitable experimental models. In this study, we show that a spheroid 3D model, but not single cells mimic the collective endometrial fragment-like invasion through the extracellular matrix. This model reveals that collagen I, the main constituent of surgical scars, significantly increases the rate of lesion formation by healthy endometrial stromal cells (St-T1b) in vitro compared to the basement membrane-like matrix Matrigel. Stromal cell invasion of collagen I requires MMPs, whereas collective migration of endometriotic epithelial 12Z cells involves Rac-signalling. We show that inhibiting ROCK signalling responsible for actomyosin contraction increases the lesion-size. Moreover, endometriotic epithelial 12Z cells, but not eutopic stromal cells St-T1b migrate on Matrigel. The rate of this migration is decreased by the microRNA miR-200b and increased by miR-145. Our 3D model offers a facile approach to dissect how endometrial fragments invade tissues and is an important step toward developing new personalized therapeutics for endometriosis. Moreover, our model is a suitable tool to screen small molecule drugs and microRNA-based therapeutics.

The article explores the interweaving of theater with and by disabled artists with so-called postdramatic theater practices. It elaborates points of connection between the postdramatic concept and ...

Zusammenfassung Einleitung In Studien zu überkronten Zähnen wird unter anderem wiederholt ein negativer Einfluss mangelhafter Restaurationen auf das umliegende parodontale Gewebe beschrieben. Daraus ergibt sich die Frage, welchen langfristigen Einfluss auf parodontale Parameter die Versorgung von Zähnen mit regelrecht ausgeführten Kronen- und Brückenkonstruktionen ausübt. Material und Methode Bei 3 Kohorten von Patienten, die mit festsitzendem Zahnersatz versorgt wurden, erfolgte eine Dokumentation der parodontalen Parameter „Sondierungstiefe“, „Attachment Level (AL)“, „Sondierungsblutung bzw. Bleeding on Probing (BOP)“ sowie „Plaquebefall“ an überkronten und nicht überkronten bzw. gesunden Kontrollzähnen. Die statistische Auswertung hatte eine Messwiederholungsanalyse bezüglich der Faktoren Zeit und Gruppe bzw. Zähne (gesund bzw. nicht überkront/überkront) zum Inhalt. Ergebnisse Die regelgerecht ausgeführten Konstruktionen zeigten im Vergleich zu nicht versorgten Kontrollzähnen kaum Unterschiede (p > 0,05) bei den untersuchten parodontalen Parametern. Lediglich beim Parameter „Sondierungstiefe“ konnten Unterschiede (p Schlussfolgerung Regelrecht ausgeführte Kronen- und Brückenkonstruktionen üben kaum einen Einfluss auf das umliegende parodontale Gewebe aus.

Background: The gold standard for the diagnosis of cow's milk allergy is the Double-Blind Placebo-Controlled Food Challenge (DBPCFC) test. However, disadvantages of the DBPCFC are the potential risk of anaphylactic reactions, the time-consuming procedure and high costs. Objective: The aim of this study was to determine the reliability of the Basophil Activation Test (BAT) both for the initial diagnosis of cow's milk allergy in children and for the determination of tolerance in children with cow's milk allergy. Methods: Ninety-seven BATs and cow's milk-specific IgE (sIgE) tests were performed in 86 infants/young children, suspected of (persistent) cow's milk allergy, who were qualified for an in-hospital DBPCFC. The BAT was performed with cow's milk extract and the purified major allergens casein, α-lactalbumin, β-lactoglubulin. Basophil activation was determined by CD63 upregulation measured by flow cytometry. The BAT results were compared to the DBPCFC outcomes. Results: Based on unequivocal DBPCFC and BAT result combinations (80%), the BAT had a sensitivity and specificity of 100% (CI: 86%-100% and 68%-100%, respectively) in IgE-sensitized children (41% of the tested children). All non-IgE-sensitized children (59%) had a negative DBPCFC and BAT, except for five patients. These latter showed delayed and relatively mild symptoms in the DBPCFC with a negative BAT, supporting a non-IgE-mediated allergy in these children. Conclusions and Clinical Relevance: The BAT seems reliable and cost-effective to diagnose patients with an IgE-mediated cow's milk allergy. In IgE-sensitized patients, a BAT might replace a DBPCFC. For non-IgE-sensitized patients presenting with mild symptoms, we propose to consider a (double-blind) extended (time) challenge test at home.

Ziel Uberprufung der These, dass offene Stationsturen Aggressivitat und Zwangsbehandlung reduzieren ohne Entweichungsraten zu erhohen. Methode Vergleich der genannten Zielparameter zwischen durchgehend geschlossenen (n gesamt = 409; n untergebracht = 64) und zu 90 % geoffneten (n gesamt = 571; n untergebracht = 99) Turen einer Akutstation. Ergebnisse Bei offenen Turen traten signifikant weniger aggressive Ubergriffe und Zwangsmedikationen auf, wahrend Entweichungsraten nicht zunahmen. Schlussfolgerung Offene Turen scheinen mit einer Reduktion von Zwangsmedikation und Aggressivitat einherzugehen, ohne dabei Entweichungsraten zu erhohen. Dies stutzt die Politik der offenen Tur zur Umsetzung der Menschenrechte in der Psychiatrie.

A Pd-catalyzed/N-heterocycle-directed C(sp(3) )-H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd-catalyzed C(sp(3) )-H olefination for the first time. Cu(OAc)2 instead of Ag(+) salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.

In this study, we show that cultivating of Saccharothrix espanaensis in the amino acid-rich SPY medium led to the detection of antibacterial and antifungal products. The cultivation in GYM-, HA- or NL111-medium did not lead to the production of these compounds. Four products were isolated from Saccharothrix espanaensis-SPY culture and determined as the known compounds anthranilic acid, indol-3-carboxylic acid, benzoic acid, and phenylacetic acid. In order to investigate the influence of SPY medium on gene transcription and to identify candidate genes involved in the biosynthesis of the purified compounds a comparative RNA sequencing analysis of Saccharothrix espanaensis cultivated in different media was performed. Total transcriptome analysis demonstrated that media composition has an influence on the expression of several genes. Among them are genes encoding enzymes belong to amino acid metabolism enzymes. Furthermore, based on the collected data genes involved in the biosynthesis of anthranilic acid, indol-3-carboxylic acid, benzoic acid, and phenylacetic acid could be predicted. Deletion of the genes BN6_01860 and BN6_67950 revealed their importance in the biosynthesis of indole-3-carboxylic acid and benzoic acid, respectively.

Vascularization is essential in bone tissue engineering and recent research has focused on interactions between osteoblasts (hOBs) and endothelial cells (ECs). It was shown that cocultivation increases the stability of osteoblastic alkaline phosphatase (ALP) mRNA. We investigated the mechanisms behind this observation, focusing on mRNA binding proteins. Using a luciferase reporter assay, we found that the 3′-untranslated region (UTR) of ALP mRNA is necessary for human umbilical vein endothelial cells (HUVEC)-mediated stabilization of osteoblastic ALP mRNA. Using pulldown experiments and nanoflow-HPLC mass spectrometry, vimentin was identified to bind to the 3′-UTR of ALP mRNA. Validation was performed by Western blotting. Functional experiments inhibiting intermediate filaments with iminodipropionitrile and specific inhibition of vimentin by siRNA transfection showed reduced levels of ALP mRNA and protein. Therefore, ALP mRNA binds to and is stabilized by vimentin. This data add to the understanding of intracellular trafficking of ALP mRNA, its function, and have possible implications in tissue engineering applications.

A sequential triple C–H activation reaction directed by a pyrazole and an amide group leads to the well-controlled construction of sterically congested dihydrobenzo[e]indazole derivatives. This cascade reaction demonstrates that the often problematic competing C–H activation pathways in the presence of multiple directing groups can be harvested by design to improve step economy in synthesis. Pyrazole as a relatively weak coordinating group is shown to direct C(sp3)–H activation for the first time.

Background: Inhibition assays are an useful tool to identify the allergen of primary sensitization of cross-reactive allergens. Classical ELISA-based inhibition assays are limited by both the availability of commercial standardized allergen extracts and the experience and knowledge needed for making home-made extracts. Moreover the direct comparison of the inhibition ELISAs outcomes between different laboratories is difficult because of different sources of used allergen extracts and a number of methodological variations. Therefore, we propose a novel ImmunoCap (Phadia, Thermofisher Scientific) based immunoinhibition method with the use of commercially available Caps as the allergen source. Methods: The novel ImmunoCap based immunoinhibition method was developed and tested with sera from patients with a well-known cross-reactive sensitization for fig (Ficus carica) and ficus (Ficus benjamina). Results were compared with a classically applied inhibition method, i.e. addition of homemade allergen extract to patient serum. Results: The amount of allergens (fig and ficus extracts) needed to reach a similar degree of inhibition was comparable for both inhibition methods. Conclusions: The ImmunoCap based inhibition assay, in addition to classical inhibition methods, is a valuable tool as the ImmunoCap analyzer and commercial allergens (Caps) are more widely available which makes the outcomes of inhibition tests comparable between different laboratories. Furthermore, in the ImmunoCap inhibition method the same protein source is used for both the inhibition of sIgE and sIgE measurement, which might be even more relevant when multiple cross-reactive allergens are tested.

Within the framework of our genome-based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A–C were isolated from plant-associated Pseudomonas sp. SH-C52. Brabantamides A–C displayed moderate to high in vitro activities against Gram-positive bacterial pathogens. Their shared structure is unique in that they contain a 5,5-bicyclic carbamate scaffold. Here, the biosynthesis of brabantamide A (SB-253514) was studied by a combination of bioinformatics, feeding experiments with isotopically labelled precursors and in vivo and in vitro functional analysis of enzymes encoded in the biosynthetic pathway. The studies resulted in the deduction of all biosynthetic building blocks of brabantamide A and revealed an unusual feature of this metabolite: its biosynthesis occurs via an initially formed linear di-lipopeptide that is subsequently rearranged by a novel FAD-dependent Baeyer–Villiger monooxygenase. [KEYWORDS: biosynthesis carbamates monooxygenases peptides Pseudomonas SB-253514]

A Pd-catalyzed/N-heterocycle-directed C(sp(3) )-H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd-catalyzed C(sp(3) )-H olefination for the first time. Cu(OAc)2 instead of Ag(+) salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.

Methods for the practical, intermolecular functionalization of aliphatic C-H bonds remain a paramount goal of organic synthesis. Free radical alkane chlorination is an important industrial process for the production of small molecule chloroalkanes from simple hydrocarbons, yet applications to fine chemical synthesis are rare. Herein, we report a site-selective chlorination of aliphatic C-H bonds using readily available N-chloroamides and apply this transformation to a synthesis of chlorolissoclimide, a potently cytotoxic labdane diterpenoid. These reactions deliver alkyl chlorides in useful chemical yields with substrate as the limiting reagent. Notably, this approach tolerates substrate unsaturation that normally poses major challenges in chemoselective, aliphatic C-H functionalization. The sterically and electronically dictated site selectivities of the C-H chlorination are among the most selective alkane functionalizations known, providing a unique tool for chemical synthesis. The short synthesis of chlorolissoclimide features a high yielding, gram-scale radical C-H chlorination of sclareolide and a three-step/two-pot process for the introduction of the β-hydroxysuccinimide that is salient to all the lissoclimides and haterumaimides. Preliminary assays indicate that chlorolissoclimide and analogues are moderately active against aggressive melanoma and prostate cancer cell lines.

Seit einigen Jahren ist eine spürbare Entgrenzung und Neuverhandlung der traditionellen Konzeption von Kunsttheater zu beobachten: vom Authentizitätsdiskurs, über die Debatten um »Experten des Alltags« und Partizipation bis hin zur jüngsten Diskussion um Theater mit und von behinderten Darstellern. Immer geht es darum, die Grenzen dessen, was wir als Kunsttheater kennen und anerkennen, produktiv zu verhandeln, sodass uns die historische Dimension unseres Denkens des Theaters vor Augen geführt wird. Unsere Beiträge gehen von der These aus, dass sich Kunsttheater seit der Moderne stets im Aushandlungsprozess zwischen einem ›professionellen‹ und einem ›dilettantischen Dispositiv‹ konstituiert und beleuchtet das Spannungsfeld zwischen dem Kunsttheater und seinem ›Anderen‹ auf gesellschaftlicher, institutioneller und ästhetischer Ebene, und zwar sowohl aus historischer Perspektive als auch am Beispiel der aktuellen Theaterpraxis mit und von Behinderten., + ID: 549457 + Reihentitel: Theater + PeerReviewed

Empedopeptin is a natural lipodepsipeptide antibiotic with potent antibacterial activity against multiresistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in vitro and in animal models of bacterial infection. Here, we describe its so far elusive mechanism of antibacterial action. Empedopeptin selectively interferes with late stages of cell wall biosynthesis in intact bacterial cells as demonstrated by inhibition of N-acetylglucosamine incorporation into polymeric cell wall and the accumulation of the ultimate soluble peptidoglycan precursor UDP-N-acetylmuramic acid-pentapeptide in the cytoplasm. Using membrane preparations and the complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes and their respective purified substrates, we show that empedopeptin forms complexes with undecaprenyl pyrophosphate containing peptidoglycan precursors. The primary physiological target of empedopeptin is undecaprenyl pyrophosphate-N-acetylmuramic acid(pentapeptide)-N-acetylglucosamine (lipid II), which is readily accessible at the outside of the cell and which forms a complex with the antibiotic in a 1:2 molar stoichiometry. Lipid II is bound in a region that involves at least the pyrophosphate group, the first sugar, and the proximal parts of stem peptide and undecaprenyl chain. Undecaprenyl pyrophosphate and also teichoic acid precursors are bound with lower affinity and constitute additional targets. Calcium ions are crucial for the antibacterial activity of empedopeptin as they promote stronger interaction with its targets and with negatively charged phospholipids in the membrane. Based on the high structural similarity of empedopeptin to the tripropeptins and plusbacins, we propose this mechanism of action for the whole compound class.

Lipopeptides (LPs) are a structurally diverse class of amphipathic natural products that were in the past mainly known for their surfactant properties. However, the recent discovery of their antimicrobial and cytotoxic bioactivities have fueled and renewed the interest in this compound class. Propelled by the antimicrobial potential of this compound class, in this study a range of six underinvestigated LPs from Pseudomonads were examined with respect to their antibiotic activities towards bacteria. The assays revealed that only the glycosylated lipodipeptide SB-253514, produced by Pseudomonas strain SH-C52, showed significant antibacterial activity. Since the bioactivity of LPs is commonly attributed to membrane interactions, we analyzed the molecular interactions between the LPs and bacteria-like lipid model membranes in more detail via complementary biophysical approaches. Application of the quartz crystal microbalance (QCM) showed that all LPs possess a high binding affinity towards the model membranes. Despite their similar membrane affinity, monolayer studies displayed different tendencies of LPs to incorporate into the membrane. The degree of membrane incorporation could be correlated with specific structural features of the investigated LPs, such as distance between the peptidic macrocycle and the fatty acid, but did not fully reflect their respective antibacterial activity. Cyclic voltammetry (CV) experiments further demonstrated that SB-253514 showed no membrane permeabilization effects at inhibitory concentrations. Collectively, these results suggests that the antibacterial activity of SB-253514 cannot be explained by an unspecific detergent-like mechanism generally proposed for amphiphilic molecules but instead appears to occur via a defined structural target.

Our current knowledge of the pathophysiological sequelae of ischemia or reperfusion (I/R) injury in free tissue transfer in reconstructive surgery is based on data obtained in animal experiments. In this study, we investigated the histologic and molecular changes after 11 free microsurgical muscle transfers in human muscle tissue.Biopsies of free muscle flap tissue were taken immediately before clipping of the pedicle and 5 days after ischemia and successful microanastomosis and restoration of the blood flow. Samples were analyzed histologically for edema formation and by immunohistochemistry for infiltration of inflammatory cells and angiogenesis. Expression levels of the inflammatory marker proteins interleukin-1β and tumor necrosis factor α and of complement component 3 as a major mediator of I/R injury were analyzed by real-time polymerase chain reaction. A TUNEL (terminal desoxynucleotidyl transferase-mediated-dUTP-nick-end-labeling) assay was used to assess apoptosis levels within the human muscle tissue.I/R injury leads to a significant up-regulation of inflammatory parameters, infiltration of inflammatory cells, and angiogenesis. Increased complement component 3 deposition and apoptosis of cells were accompanied by interstitial edema as indication for a pronounced postischemic inflammatory reaction within the muscle tissue after free tissue transfer.Our findings of molecular changes induced by I/R injury in human striated muscle tissue validate data obtained in animal models of I/R injury. The parameters and inflammatory patterns defined in this study will allow for the monitoring of the success of novel pharmaceutical strategies in the future and will help to transfer data obtained in animal work to the in vivo setting in human beings.

Background: Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results: Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO) significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions: Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.

Stereoselective and diversity-oriented synthesis of trisubstituted olefins was achieved by using ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing group for allylic substitution. The starting point of this methodology was a set of α-methylene aldehydes derived from Baylis-Hillman adducts. Subsequent addition of different organometallic reagents led to a variety of allylic alcohol substrates. After introduction of the reagent-directing o-DPPB group, copper-mediated allylic substitution with a wide range of Grignard reagents enabled the stereoselective construction of a large number of E-configured trisubstituted allylic alcohols and amines in excellent yields and stereoselectivities. Remarkable is the synthetic flexibility, which allows a wide range of permutations starting from an aldehyde followed by successive introduction of the substituents R(2) and R(3) from organometallic Grignard based reagents. Thus, starting from only a few precursors, a diversity-oriented synthesis of stereodefined trisubstituted allylic alcohols and amines becomes possible.

Introduction of vacuum-assisted closure (VAC) system into clinical practice has revolutionized wound care. Despite its multiple advantages, however, the VAC is only rarely used in the setting of microsurgical reconstruction. Concerns have been the inability to clinically monitor the flap as well the possibility of flap compression by the device. The authors put their postoperative treatment concept of applying the VAC to free flaps to the test by reviewing their experience with this concept in patients undergoing microsurgical reconstruction of posttraumatic lower-extremity soft tissue defects. Twenty-six patients (22 male, 4 female) were included in this study. Use of the implantable Doppler probe allowed for postoperative flap monitoring. Two flap failures were observed, both in patients with peripheral vascular disease. In conclusion, using the VAC device in the setting of microsurgical reconstruction is safe and allows for increased patient comfort.

Neuropathic pain is a debilitating consequence of nerve injuries and is frequently resistant to classical therapies. T lymphocytes mediate adaptive immune responses and have been suggested to generate neuropathic pain. In contrast, in this study we investigated T cells as a source of opioidergic analgesic β-endorphin for the control of augmented tactile sensitivity following neuropathy. We employed in vivo nociceptive (von Frey) testing, flow cytometry and immunofluorescence in wild-type and mice with severe combined immunodeficiency (SCID) subjected to a chronic constriction injury of the sciatic nerve. In wild-type mice, T lymphocytes constituted approximately 11% of all immune cells infiltrating the injury site, and they expressed β-endorphin and receptors for corticotropin-releasing factor (CRF), an agent releasing opioids from leukocytes. CRF applied at the nerve injury site fully reversed neuropathy-induced mechanical hypersensitivity in wild-type animals. In SCID mice, T cells expressing β-endorphin and CRF receptors were absent at the damaged nerve. Consequently, these animals had substantially reduced CRF-mediated antinociception. Importantly, the decreased antinociception was fully restored by transfer of wild-type mice-derived T lymphocytes in SCID mice. The re-established CRF antinociception could be reversed by co-injection of an antibody against β-endorphin or an opioid receptor antagonist with limited access to the central nervous system. We propose that, in response to CRF stimulation, T lymphocytes accumulating at the injured nerves utilize β-endorphin for activation of local neuronal opioid receptors to reduce neuropathy-induced mechanical hypersensitivity. Our findings reveal β-endorphin-containing T cells as a crucial component of beneficial adaptive immune responses associated with painful peripheral nerve injuries.

The striped cucumber beetle, Acalymma vittatum, is a cause of major damage to cucurbit crops in North America. To develop an environmentally benign plant protection strategy, recent research has focused on identifying sex pheromones of the cucumber beetle. In this context, we developed the asymmetric total synthesis of the aggregation pheromone of A. vittatum, Vittatalactone, to determine its absolute configuration and to further examine the pheromone response in field studies. The synthesis features an enzyme-catalyzed approach toward the deoxypropionate structural motif. A preformed organocopper reagent could then be coupled in an enantioselective o-DPPB-directed allylic substitution with a functionalized o-DPPB-ester. By means of this efficient transformation, Vittatalactone could be obtained following a highly convergent synthetic process.

An efficient and simple to perform large-scale synthesis of O- and M-diphenylphosphinobenzoicacids is presented. In a single step, both useful carboxylic acid-functionalizedphosphines can be accessed starting from the same inexpensive bulkchemicals O-chlorobenzoic acid, triphenylphosphine,and sodium. In both cases the formation of the desired product iscontrolled by the ratio of the starting materials only. Additionally,X-ray crystallographic data are reported for both products.

Theater fur alle, aber nicht von allen? Spannungsfelder und Perspektiven der Theatervermittlung

A radical mediated C–H functionalization of 3,6-dichloropyridazine using primary alcohols, t-BuOOH, and TiCl3 to access alkoxy pyridazines is described. This transformation is conducted open to air and on gram scale. A subsequent cyclization step can then be employed to efficiently access diversely substituted tetrahydropyridopyridazines with multiple functional handles.

SummaryThe sophisticated organization of eusocial insect societies is largely based on the regulation of complex behaviors by hydrocarbon pheromones present on the cuticle. We used electrophysiology to investigate the detection of cuticular hydrocarbons (CHCs) by female-specific olfactory sensilla basiconica on the antenna of Camponotus floridanus ants through the utilization of one of the largest family of odorant receptors characterized so far in insects. These sensilla, each of which contains multiple olfactory receptor neurons, are differentially sensitive to CHCs and allow them to be classified into three broad groups that collectively detect every hydrocarbon tested, including queen and worker-enriched CHCs. This broad-spectrum sensitivity is conserved in a related species, Camponotus laevigatus, allowing these ants to detect CHCs from both nestmates and non-nestmates. Behavioral assays demonstrate that these ants are excellent at discriminating CHCs detected by the antenna, including enantiomers of a candidate queen pheromone that regulates the reproductive division of labor.

Objectives The aim of our study was to analyse whether the κ/λ free light chain ratio reference range for screening for Bence Jones proteinuria should be dependent on the estimated glomerular filtration rate (eGFR). Methods The serum κ/λ free light chain ratio, eGFR, serum M-protein and Bence Jones protein were measured in 544 patients for whom Bence Jones protein analysis was ordered. Results In the population of patients without Bence Jones proteinuria or a M-protein (n = 402), there is no gradual increase in κ/λ free light chain ratio with diminishing eGFR. The κ/λ free light chain ratio in this group was 0.56–1.86 (95% interval). With this diagnostic reference range of the κ/λ ratio, 105 of the 110 patients with Bence Jones protein could be identified correctly. Only five patients with Bence Jones proteinuria (

A sequential triple C—H activation reaction directed by a pyrazole and an amide group leads to the well-controlled construction of sterically congested dihydrobenzo[e]indazole derivatives.

A radical mediated C–H functionalization of 3,6-dichloropyridazine using primary alcohols, t-BuOOH, and TiCl3 to access alkoxy pyridazines is described. This transformation is conducted open to air and on gram scale. A subsequent cyclization step can then be employed to efficiently access diversely substituted tetrahydropyridopyridazines with multiple functional handles.

BACKGROUND: The plant microbiome represents an enormous untapped resource for discovering novel genes and bioactive compounds. Previously, we isolated Pseudomonas sp. SH-C52 from the rhizosphere of sugar beet plants grown in a soil suppressive to the fungal pathogen Rhizoctonia solani and showed that its antifungal activity is, in part, attributed to the production of the chlorinated 9-amino-acid lipopeptide thanamycin (Mendes et al. 2011. Science). To get more insight into its biosynthetic repertoire, the genome of Pseudomonas sp. SH-C52 was sequenced and subjected to in silico, mutational and functional analyses. The sequencing revealed a genome size of 6.3 Mb and 5,579 predicted ORFs. Phylogenetic analysis placed strain SH-C52 within the Pseudomonas corrugata clade. In silico analysis for secondary metabolites revealed a total of six nonribosomal peptide synthetase (NRPS) gene clusters, including the two previously described NRPS clusters for thanamycin and the 2-amino acid antibacterial lipopeptide brabantamide. Here we show that thanamycin also has activity against an array of other fungi and that brabantamide A exhibits anti-oomycete activity and affects phospholipases of the late blight pathogen Phytophthora infestans. Most notably, mass spectrometry led to the discovery of a third LP, designated thanapeptin, with a 22-amino-acid peptide moiety. Seven structural variants of thanapeptin were found with varying degrees of activity against P. infestans. Of the remaining four NRPS clusters, one was predicted to encode for yet another and unknown lipopeptide with a predicted peptide moiety of 8-amino acids. Collectively, these results show an enormous metabolic potential for Pseudomonas sp. SH-C52, with at least three structurally diverse lipopeptides, each with a different antimicrobial activity spectrum.