Histidine Residue 94 Is Involved in pH Sensing by Histidine Kinase ArsS of Helicobacter pylori

The ArsRS two-component system is the master regulator of acid adaptation in the human gastric pathogen Helicobacter pylori. Low pH is supposed to trigger the autophosphorylation of the histidine kinase ArsS and the subsequent transfer of the phosphoryl group to its cognate response regulator ArsR which then acts as an activator or repressor of pH-responsive genes. Orthologs of the ArsRS two-component system are also present in H. pylori's close relatives H. hepaticus, Campylobacter jejuni and Wolinella succinogenes which are non-gastric colonizers.In order to investigate the mechanism of acid perception by ArsS, derivatives of H. pylori 26695 expressing ArsS proteins with substitutions of the histidine residues present in its periplasmic input domain were constructed. Analysis of pH-responsive transcription of selected ArsRS target genes in these mutants revealed that H94 is relevant for pH sensing, however, our data indicate that protonatable amino acids other than histidine contribute substantially to acid perception by ArsS. By the construction and analysis of H. pylori mutants carrying arsS allels from the related epsilon-proteobacteria we demonstrate that WS1818 of W. succinogenes efficiently responds to acidic pH.We show that H94 in the input domain of ArsS is crucial for acid perception in H. pylori 26695. In addition our data suggest that ArsS is able to adopt different conformations depending on the degree of protonation of acidic amino acids in the input domain. This might result in different activation states of the histidine kinase allowing a gradual transcriptional response to low pH conditions. Although retaining considerable similarity to ArsS the orthologous proteins of H. hepaticus and C. jejuni may have evolved to sensors of a different environmental stimulus in accordance with the non gastric habitat of these bacteria

Cultivation of Chamomile in Germany - Threat by unknown fungus

Seit 2007 wurde in den Kamillebeständen in Thüringen ein vermehrtes Auftreten von Krankheitssymptomen beobachtet, deren Ursache unklar war. Neben tierischen Schaderregern wurden verschiedene pilzliche Pathogene, vorrangig Septoria sp. und ein unbekannter Pilz (UBK), sowie weiter Pathogene wie Golovinomyces cichoracearum var. cichoracearum (Echter Mehltau), Paraperonospora leptosperma (Falscher Mehltau), Puccinia matricariae (Rost) und Colletotrichum sp. an Kamillebeständen in Thüringen aufgefunden. Die Bedeutung des unbekannten Pilzes für das Schadausmaß an Kamille war unklar und Hinweise aus der Literatur lagen nicht vor. In molekularbiologischen Untersuchungen konnte die Septoria-Art eindeutig als Septoria matricariae identifiziert werden. Der unbekannte Pilz UBK wird derAbteilung der Ascomyceten mit der Ordnung Helotiales zugeordnet.Since 2007, an increased incidence of disease symptoms had been observed in the chamomile stocks in Thuringia, the cause of which was unclear. In addition to animal pathogens, various fungal pathogens, primarily Septoria sp. and an unknown fungus (UBK), had been found on chamomile stocks in Thuringia as well as pathogens such as Golovinomyces cichoracearum var. cichoracearum (powdery mildew), Paraperonospora leptosperma (powdery mildew), Puccinia matricariae (rust) and Colletotrichum sp. The importance of the unknown fungus for the damage level of chamomile was unclear. References from the literature were not available. In molecular biological studies, the Septoria species was clearly identified as Septoria matricariae. The unknown fungus UBK is assigned to the division of the ascomycetes with the order helotiales

Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells

<p>Abstract</p> <p>Background</p> <p>While the diversity and spatio-temporal origin of olfactory bulb (OB) GABAergic interneurons has been studied in detail, much less is known about the subtypes of glutamatergic OB interneurons.</p> <p>Results</p> <p>We studied the temporal generation and diversity of Neurog2-positive precursor progeny using an inducible genetic fate mapping approach. We show that all subtypes of glutamatergic neurons derive from Neurog2 positive progenitors during development of the OB. Projection neurons, that is, mitral and tufted cells, are produced at early embryonic stages, while a heterogeneous population of glutamatergic juxtaglomerular neurons are generated at later embryonic as well as at perinatal stages. While most juxtaglomerular neurons express the T-Box protein Tbr2, those generated later also express Tbr1. Based on morphological features, these juxtaglomerular cells can be identified as tufted interneurons and short axon cells, respectively. Finally, targeted electroporation experiments provide evidence that while the majority of OB glutamatergic neurons are generated from intrabulbar progenitors, a small portion of them originate from extrabulbar regions at perinatal ages.</p> <p>Conclusions</p> <p>We provide the first comprehensive analysis of the temporal and spatial generation of OB glutamatergic neurons and identify distinct populations of juxtaglomerular interneurons that differ in their antigenic properties and time of origin.</p

A longitudinal, Bologna-compatible model curriculum "communicationand social competencies" : results of an interdisciplinary workshop of German-speaking medical schools

Zielsetzung: Ziel des Projekts ist es, ein longitudinales Modell-Curriculum "Kommunikative und soziale Kompetenzen" für die medizinische Ausbildung zur Diskussion zu stellen. Vorgehen und Ergebnisse: Auf einem 2-tägigen Workshop wurde interfakultär und interdisziplinär auf der Grundlage des "Basler Consensus Statements: Kommunikative und soziale Kompetenzen im Medizinstudium" ein Curriculum entwickelt, das deutschsprachigen Fakultäten bei der Planung und Implementierung als Vorlage dienen kann. Das Modell lässt sich als Gesamt-Curriculum oder in Teilmodulen implementieren. Es kann auch bei der Umstellung auf Bachelor- und Masterstudiengänge genutzt werden. Das longitudinale Modell-Curriculum weist neben 131 definierten Ausbildungszielen geeignete didaktische Konzepte und Prüfungsformate auf und gibt Vorschläge, zu welchem Zeitpunkt die verschiedenen Fächer die entsprechenden Lernziele vermitteln können. Fazit: Mit diesem longitudinalen "Modell-Curriculum Kommunikative und Soziale Kompetenzen" liegt für den deutschen Sprachraum erstmalig ein curriculares Instrument vor, das breite Anwendung an einer Vielzahl deutscher, österreichischer und schweizerischer Fakultäten finden und eine Umsetzung des Bologna-Prozesses auch fakultätsübergreifend vereinfachen kann. Schlüsselwörter: Modell-Curriculum, kommunikative/soziale Kompetenzen, Basler Consensus Statement, medizinische Ausbildung, Didaktik, Prüfung, Bologna-ProzessAim: The aim of the project is to present and discuss a longitudinal model curriculum "Communication and social competencies" for undergraduate medical education. Procedure and results: In a two-day workshop, a multidisciplinary, cross-faculty group of medical educators developed a curriculum model based on the "Basel Consensus Statement". It can now be used by German-speaking medical schools as a blueprint for curriculum planning and implementation processes. The modular structure enables it to be implemented either in whole or in part. The model can also be used to facilitate the conversion of medical education into Bachelor and Master degree programmes. The longitudinal model curriculum features 131 educational objectives and makes suggestions for didactic concepts and assessment tools. For various disciplines, it also recommends at what point in time specific topics should be taught. Conclusion: The longitudinal model curriculum "Communication and social competencies", based on the educational objectives of the "Basel Consensus Statement", is a new curricular instrument that can be used by German, Austrian and Swiss medical schools. It can help to simplify the realisation of the Bologna process, also across different faculties. Keywords: model curriculum, communication/social competencies, Basel Consensus Statement, undergraduate medical education, didactic, assessment, Bologna proces

Pseudohyperphosphorylation of tau is sufficient to induce aberrant sprouting and activation of ERK1/2 in transgenic mice

Poster presentation: Hyperphosphorylation of tau is a characteristic of Alzheimer's disease (AD). Our group has established a model for tau hyperphosphorylation by mutating 10 residues from Ser/Thr to Glu to simulate the negative charge of phosphorylated residues ("pseudohyperphosphorylated (PHP)-tau"). In order to analyze temporal and spatial effects of hyperphosphorylation of tau in a systemic context, we have established transgenic mouse lines that express human wild-type (wt)- or PHP-tau under the control of the CamKIIalpha-promoter that leads to a forebrain specific moderate expression in neurons, i.e. the region where also tau-pathology in AD is abundant. For the evaluation of tau-induced changes in the transgenic mice, we quantified spine densities in the neocortex and hippocampus of transgenic mice. The spine densitiy was significantly increased in PHP-tau compared to wt-tau expressing mice. It is known that AD is associated with aberrant pre- and postsynaptic sprouting. Axonal sprouting is also observed in transgenic mice expressing mutated amyloid precursor protein (APP), which suggests that Abeta plays a significant role in this process. We deduce from our results, that (pseudo)-hyperphosphorylation of tau is sufficient to induce aberrant sprouting in the absence of Abeta. Analyses whether this sprouting is induced by pre- or postsynaptic changes and if functionally active synapses are formed are in progress. It will be interesting to determine if stabilization of these newly formed synapses slows or – in contrary – accelerates the progression of the disease. Sprouting as observed in our PHP-tau expressing mice is part of neuronal differentiation. One family of enzymes that is involved in cell differentiation are mitogen-acitvated protein kinases (MAPK). Western blot analysis was performed with brain lysates from transgenic mice to check whether PHP-tau induced sprouting is associated with MAPK activation. In fact, we also observed an increased activation of the MAPK ERK1/2 evident by phosphorylation of the residues Thr202 and Tyr204. ERK1/2 is also known to phosphorylate tau at sites characteristic for AD. Our results suggest the presence of a vicious circle by which (pseudo)-hyperphosphorylated tau activates ERK1/2 which in turn phosphorylates tau

Sharpening emitter localization in front of a tuned mirror

Single-molecule localization microscopy (SMLM) aims for maximized precision and a high signal-to-noise ratio1. Both features can be provided by placing the emitter in front of a metal-dielectric nanocoating that acts as a tunedmirror2–4. Here, we demonstrate that a higher photon yield at a lower background on biocompatible metal-dielectric nanocoatings substantially improves SMLM performance and increases the localization precision by up to a factor oftwo. The resolution improvement relies solely on easy-to-fabricate nanocoatings on standard glass coverslips and is spectrally and spatially tunable by the layer design and wavelength, as experimentally demonstrated for dual-color SMLM in cells.Publisher PDFPeer reviewe

The impact of language co-activation on L1 and L2 speech fluency

Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production

Diagnosis of quarantine organisms at the JKI in the National Reference Laboratory for organisms harmful to plants

Dem JKI wurde im April 2019 durch das Bundesministerium für Ernährung und Landwirtschaft (BMEL) die Funktion des nationalen Referenzlaboratoriums (NRL) für Schadorganismen der Pflanzen zugewiesen. Mit dieser Funktion des NRL für Deutschland sind bestimmte Zuständigkeiten und Aufgaben verbunden, die in der EU-Verordnung 2017/625 (EU, 2017) geregelt sind. Dazu gehören auch Referenzuntersuchungen bzw. die Diag­nose von Quarantäneschadorganismen (QSO). Das NRL stellt eine übergeordnete Einheit innerhalb des JKI dar. Durch insgesamt 14 Prüflabore der JKI-Institute für Pflanzenschutz in Ackerbau und Grünland (A), nationale und internationale Angelegenheiten der Pflanzengesundheit (AG), Epidemiologie und Pathogendiagnostik (EP), Pflanzenschutz in Gartenbau und Forst (GF), Pflanzenschutz in Obst- und Weinbau (OW) wird die Referenzfunktion bei der Diagnose zu verschiedensten (Quarantäne)-Schadorganismen der Pathogengruppen Bakterien, Insekten, Nematoden, Pilze (einschließlich Oomyceten), Phytoplasmen und Viren wahrgenommen.In April 2019, the JKI was officially designated as the Natio­nal Reference Laboratory (NRL) for organisms harmful to plants by the Federal Ministry of Food and Agri­culture (BMEL). This function as NRL for Germany is associated with certain responsibilities and tasks, which are specified in the EU Regulation 2017/625 (EU, 2017). This also includes reference tests and the diagnosis of quarantine pests, respectively. The NRL represents a super­ordinate unit inside JKI. A total of 14 test laboratories from different JKI institutes, namely for Plant Protection in Field Crops and Grassland (A), for National and International Plant Health (AG), for Epidemiology and Pathogen Diagnostics (EP), Plant Protection in Horti­culture and Forests (GF), and for Plant Protection in Fruit Crops and Viticulture (OW) are in charge to carry out a reference function in the diagnosis of (quarantine) pests in the pathogen groups of bacteria, fungi (including oomycetes), insects, nematodes, phytoplasma und viruses