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Summary: Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K2P potassium channel TREK-1 in a cAMP-dependent manner. POPDC1 and POPDC2 variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in Xenopus oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.5. POPDC proteins downregulate Nav1.5 currents in a cAMP-dependent manner by reducing the surface expression of the channel. POPDC2 and Nav1.5 are both expressed in different regions of the murine heart and consistently POPDC2 co-immunoprecipitates with Nav1.5 from native cardiac tissue. Strikingly, the knock-down of popdc2 in embryonic zebrafish caused an increased upstroke velocity and overshoot of cardiac action potentials. The POPDC modulation of Nav1.5 provides a new mechanism to regulate cardiac sodium channel densities under sympathetic stimulation, which is likely to have a functional impact on cardiac physiology and inherited arrhythmias.

Congenital heart disease (CHD) is the most prevalent hereditary disorder, affecting approximately 1% of all live births. A reduction in morbidity and mortality has been achieved with advancements in surgical intervention, yet challenges in managing complications, extracardiac abnormalities, and comorbidities still exist. To address these, a more comprehensive understanding of the genetic basis underlying CHD is required to establish how certain variants are associated with the clinical outcomes. This will enable clinicians to provide personalized treatments by predicting the risk and prognosis, which might improve the therapeutic results and the patient’s quality of life. We review how advancements in genome sequencing are changing our understanding of the genetic basis of CHD, discuss experimental approaches to determine the significance of novel variants, and identify barriers to use this knowledge in the clinics. Next-generation sequencing technologies are unravelling the role of oligogenic inheritance, epigenetic modification, genetic mosaicism, and noncoding variants in controlling the expression of candidate CHD-associated genes. However, clinical risk prediction based on these factors remains challenging. Therefore, studies involving human-induced pluripotent stem cells and single-cell sequencing help create preclinical frameworks for determining the significance of novel genetic variants. Clinicians should be aware of the benefits and implications of the responsible use of genomics. To facilitate and accelerate the clinical integration of these novel technologies, clinicians should actively engage in the latest scientific and technical developments to provide better, more personalized management plans for patients. Résumé: La cardiopathie congénitale (CC) est l’affection héréditaire la plus commune, soit environ 1 naissance vivante sur 100. Grâce aux progrès réalisés en chirurgie cardiaque, il a été possible de réduire la morbidité et la mortalité associées à la CC, mais les complications, les anomalies extracardiaques et les affections concomitantes demeurent préoccupantes. Dans ce contexte, il est nécessaire de mieux comprendre les fondements génétiques de la CC pour déterminer les variants qui sont à l’origine des complications cliniques. Les cliniciens pourront ainsi proposer des traitements personnalisés en tenant compte du risque et du pronostic dans l’espoir d’améliorer les résultats thérapeutiques et la qualité de vie des patients. Nous revenons ici sur les avancées réalisées dans le séquençage du génome et sur la façon dont elles ont changé notre compréhension des fondements génétiques de la CC. Nous décrivons les techniques expérimentales utilisées pour mettre au jour de nouveaux variants d’intérêt et présentons les obstacles qui empêchent d’utiliser ces connaissances en clinique. Les techniques de séquençage de nouvelle génération permettent de lever le voile sur le rôle de la transmission oligogénique, de la modification épigénétique, de la mosaïque génétique et des variants non codants dans la régulation de l’expression des gènes candidats associés à la CC. La prédiction du risque clinique en fonction de ces facteurs demeure toutefois hasardeuse. Les études sur les cellules souches pluripotentes induites et le séquençage unicellulaire aident à établir le cadre préclinique nécessaire pour déterminer l’importance des nouveaux variants génétiques. Les cliniciens doivent être conscients des bienfaits et de la portée que peut avoir la génomique lorsqu’elle est utilisée de façon responsable. Pour faciliter et accélérer l’intégration clinique de ces nouvelles technologies, les cliniciens doivent s’intéresser de près aux derniers développements scientifiques et techniques s’ils veulent un jour proposer à leurs patients un plan de traitement plus pertinent et plus personnalisé.

Abstract The Popeye domain containing (POPDC) genes encode sarcolemma-localized cAMP effector proteins. Mutations in blood vessel epicardial substance (BVES) also known as POPDC1 and POPDC2 have been associated with limb-girdle muscular dystrophy and cardiac arrhythmia. Muscle biopsies of affected patients display impaired membrane trafficking of both POPDC isoforms. Biopsy material of patients carrying mutations in BVES were immunostained with POPDC antibodies. The interaction of POPDC proteins was investigated by co-precipitation, proximity ligation, bioluminescence resonance energy transfer and bimolecular fluorescence complementation. Site-directed mutagenesis was utilised to map the domains involved in protein–protein interaction. Patients carrying a novel homozygous variant, BVES (c.547G > T, p.V183F) displayed only a skeletal muscle pathology and a mild impairment of membrane trafficking of both POPDC isoforms. In contrast, variants such as BVES p.Q153X or POPDC2 p.W188X were associated with a greater impairment of membrane trafficking. Co-transfection analysis in HEK293 cells revealed that POPDC proteins interact with each other through a helix-helix interface located at the C-terminus of the Popeye domain. Site-directed mutagenesis of an array of ultra-conserved hydrophobic residues demonstrated that some of them are required for membrane trafficking of the POPDC1–POPDC2 complex. Mutations in POPDC proteins that cause an impairment in membrane localization affect POPDC complex formation while mutations which leave protein–protein interaction intact likely affect some other essential function of POPDC proteins.

Abstract Background Popeye domain-containing proteins 1 and 2 (POPDC1 and POPDC2) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction. In order to identify novel protein interaction partners, POPDC1 and 2 proteins were attached to beads and compared by proteomic analysis with control beads in the pull-down of proteins from cultured human skeletal myotubes. Results There were highly-significant interactions of both POPDC1 and POPDC2 with XIRP1 (Xin actin binding repeat-containing protein 1), actin and, to a lesser degree, annexin A5. In adult human skeletal muscle, both XIRP1 and POPDC1/2 were present at the sarcolemma and in T-tubules. The interaction of POPDC1 with XIRP1 was confirmed in adult rat heart extracts. Using new monoclonal antibodies specific for POPDC1 and POPDC2, both proteins, together with XIRP1, were found mainly at intercalated discs but also at T-tubules in adult rat and human heart. Conclusions Mutations in human POPDC1, POPDC2 and in human XIRP1, all cause pathological cardiac arrhythmias, suggesting a possible role for POPDC1/2 and XIRP1 interaction in normal cardiac conduction.

Duckweed is a promising resource for future feed and food production as well as wastewater treatment. However, diseases and pests can critically limit the performance of the production systems. Patches of discolored and bleached duckweed (Lemna minor L.) appeared in hydroponic systems and spread rapidly through the crop. Pythium myriotylum was confirmed as the causing pathogen by microbiological and molecular biological analysis. This is the first report of P. myriotylum on duckweed in Germany. The result and possible countermeasures are discussed.

Der ursprüngliche Artikel wurde am 01.02.2021 im Journal für Kulturpflanzen 73 (1-2), 9-20, https://doi.org/10.5073/JfK.2021.01-02.01 publiziert. Der Artikel enthält eine fehlerhafte Abbildung (Abb. 7), deren rechte Teilabbildung versehentlich ein Duplikat der linken Teilabbildung ist. Die korrigierte Abb. 7 erscheint hier als Abb. . Die Schlussfolgerungen des Artikels bleiben unverändert. Wir entschuldigen uns für diesen Fehler.

Die Verteilung eines Pflanzenschutzmittels im Pflanzenbestand ist ganz wesentlich von der Verfügbarkeit und Verwendung einer geeigneten Applikationstechnik abhängig. Nur eine gute Verteilung gewährleistet den sicheren Kontakt der Zielorganismen mit dem Wirkstoff. Das gilt insbesondere für Schädlinge die sich auf der Blattunterseite aufhalten. Die Auswirkung des Düsentyps sowie die Verwendung eines Netzmittels auf die Wirkstoffanlagerung an die Blattober- und -unterseite und die resultierende Wirksamkeit sind Gegenstand dieser Untersuchungen. Für die Ermittlung der Wirkstoffanlagerung wurde ein künstliches Blatt eingesetzt, bei dem die daran befestigten Glasfaserfilter als Blattober- bzw. -unterseite getrennt analysiert werden konnten. Die Verwendung einer Hohlkegeldüse erhöhte im Vergleich zu einer Flachstrahldüse die Anlagerung auf der Oberseite der künstlichen Blätter in schmalblättrigen Brachyscome multifida. Die Doppelflachstrahldüse unterschied sich nicht von den anderen Düsentypen. In breitblättrigen Pelargonium-Zonale-Hybriden und Fuchsia-Hybriden wurden keine Unterschiede zwischen den Düsentypen festgestellt. Die Wirkstoffanlagerung auf der Blattunterseite der künstlichen Blätter an der Fuchsia-Hybride und die Wirksamkeit auf Trialeurodes vaporariorum war unabhängig vom Düsentyp gering.

Abstract Cardiac regeneration post-injury is a tantalizing feature of many lower vertebrates such as fishes and urodeles, but absent in adult humans. Restoration of pumping function is a key endpoint of cardiac regeneration, but very little is known about the biomechanical remodeling process. Here, we quantify and compare the evolution of cellular composition and mechanical stiffness of the zebrafish ventricular myocardium during maturation and following cryoinjury during regeneration to better understand the dynamics of biomechanical remodeling during these two processes. With increasing age, normal myocardial trabecular density and cardiomyocyte fraction increased, while non-myocyte cell fractions decreased. Cell density remained constant during maturation. Cardiomyocyte sarcomeres shortened to a minimum reached at 7.5 months of age, but lengthened with additional age. Concomitantly, ventricular wall stiffness increased up until 7.5 months before plateauing with additional age. Endothelial, myofibroblast/smooth muscle, and cardiomyocyte cell fractions were disrupted following cryoinjury, but were progressively restored to age-specific natural norms by 35 days post infarct (DPI). Infarcted myocardium stiffened immediately following cryoinjury and was a 100-fold greater than non-infarcted tissue by 3 DPI. By 14 DPI, stiffness of the infarcted myocardium had fallen below that of 0 DPI and had completely normalized by 35 DPI. Interestingly, cardiomyocyte sarcomere length increased until 14 DPI, but subsequently shortened to lengths below age-specific natural norms, indicating recovery from a volume overloaded condition. These observations are consistent with the view that regenerating myocardium requires biomechanical stimulation (e.g. strain) to rescue from a volume overloaded condition. Intriguingly, the biomechanical progression of the infarcted adult myocardial wall mirrors that of normal remodeling during aging. The biomechanical progression of the infarcted myocardium targets the values of age-specific norms despite a large divergence in initial conditions. These findings identify a novel biomechanical control of heart regeneration that may orchestrate cellular and tissue level remodeling responses.

The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described.

Speech comprehension requires effort in demanding listening situations. Selective attention may be required for focusing on a specific talker in a multi-talker environment, may enhance effort by requiring additional cognitive resources, and is known to enhance the neural representation of the attended talker in the listener’s neural response. The aim of the study was to investigate the relation of listening effort, as quantified by subjective effort ratings and pupil dilation, and neural speech tracking during sentence recognition. Task demands were varied using sentences with varying levels of linguistic complexity and using two different speech rates in a picture-matching paradigm with 20 normal-hearing listeners. The participants’ task was to match the acoustically presented sentence with a picture presented before the acoustic stimulus. Afterwards they rated their perceived effort on a categorical effort scale. During each trial, pupil dilation (as an indicator of listening effort) and electroencephalogram (as an indicator of neural speech tracking) were recorded. Neither measure was significantly affected by linguistic complexity. However, speech rate showed a strong influence on subjectively rated effort, pupil dilation, and neural tracking. The neural tracking analysis revealed a shorter latency for faster sentences, which may reflect a neural adaptation to the rate of the input. No relation was found between neural tracking and listening effort, even though both measures were clearly influenced by speech rate. This is probably due to factors that influence both measures differently. Consequently, the amount of listening effort is not clearly represented in the neural tracking.

The cardiac autonomic nervous system (CANS) plays a key role for the regulation of cardiac activity with its dysregulation being involved in various heart diseases, such as cardiac arrhythmias. The CANS comprises the extrinsic and intrinsic innervation of the heart. The intrinsic cardiac nervous system (ICNS) includes the network of the intracardiac ganglia and interconnecting neurons. The cardiac ganglia contribute to the tight modulation of cardiac electrophysiology, working as a local hub integrating the inputs of the extrinsic innervation and the ICNS. A better understanding of the role of the ICNS for the modulation of the cardiac conduction system will be crucial for targeted therapies of various arrhythmias. We describe the embryonic development, anatomy, and physiology of the ICNS. By correlating the topography of the intracardiac neurons with what is known regarding their biophysical and neurochemical properties, we outline their physiological role in the control of pacemaker activity of the sinoatrial and atrioventricular nodes. We conclude by highlighting cardiac disorders with a putative involvement of the ICNS and outline open questions that need to be addressed in order to better understand the physiology and pathophysiology of the ICNS.

An Achillea ptarmica wurde eine Infektion durch den Asco­mycet Schizothyrioma ptarmicae nachgewiesen. Kurze Beschreibungen der Symptome sowie des Pathogens werden gegeben.

In studies investigating binaural processing in human listeners, relatively long and task-dependent time constants of a binaural window ranging from 10 ms to 250 ms have been observed. Such time constants are often thought to reflect “binaural sluggishness.” In this study, the effect of binaural sluggishness on binaural unmasking of speech in stationary speech-shaped noise is investigated in 10 listeners with normal hearing. In order to design a masking signal with temporally varying binaural cues, the interaural phase difference of the noise was modulated sinusoidally with frequencies ranging from 0.25 Hz to 64 Hz. The lowest, that is the best, speech reception thresholds (SRTs) were observed for the lowest modulation frequency. SRTs increased with increasing modulation frequency up to 4 Hz. For higher modulation frequencies, SRTs remained constant in the range of 1 dB to 1.5 dB below the SRT determined in the diotic situation. The outcome of the experiment was simulated using a short-term binaural speech intelligibility model, which combines an equalization–cancellation (EC) model with the speech intelligibility index. This model segments the incoming signal into 23.2-ms time frames in order to predict release from masking in modulated noises. In order to predict the results from this study, the model required a further time constant applied to the EC mechanism representing binaural sluggishness. The best agreement with perceptual data was achieved using a temporal window of 200 ms in the EC mechanism.

3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.

The proepicardium (PE) is a cluster of cells that forms on the cardiac inflow tract and gives rise to the epicardium and connective tissue and largely contributes to the coronary vasculature. In many vertebrates, the PE undergoes left-right asymmetrical development. While PE cells and marker genes can be initially found on both sides, only the right-sided PE will fully develop and ultimately deliver cells to the heart. Several signalling inputs, like FGF and BMP signals, are involved in PE induction in the lateral plate mesoderm, as well as during inflow tract formation and, also, control asymmetric PE development. These signalling events will be put into the context of embryonic left-right asymmetry determination. Finally, it will be discussed whether PE development may serve as a readout for asymmetric inflow tract morphogenesis.

To characterize the individual patient’s hearing impairment as obtained with the matrix sentence recognition test, a simulation Framework for Auditory Discrimination Experiments (FADE) is extended here using the Attenuation and Distortion (A+D) approach by Plomp as a blueprint for setting the individual processing parameters. FADE has been shown to predict the outcome of both speech recognition tests and psychoacoustic experiments based on simulations using an automatic speech recognition system requiring only few assumptions. It builds on the closed-set matrix sentence recognition test which is advantageous for testing individual speech recognition in a way comparable across languages. Individual predictions of speech recognition thresholds in stationary and in fluctuating noise were derived using the audiogram and an estimate of the internal level uncertainty for modeling the individual Plomp curves fitted to the data with the Attenuation (A-) and Distortion (D-) parameters of the Plomp approach. The “typical” audiogram shapes from Bisgaard et al with or without a “typical” level uncertainty and the individual data were used for individual predictions. As a result, the individualization of the level uncertainty was found to be more important than the exact shape of the individual audiogram to accurately model the outcome of the German Matrix test in stationary or fluctuating noise for listeners with hearing impairment. The prediction accuracy of the individualized approach also outperforms the (modified) Speech Intelligibility Index approach which is based on the individual threshold data only.

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The Popeye domain containing (POPDC) genes encode transmembrane proteins, which are abundantly expressed in striated muscle cells. Hallmarks of the POPDC proteins are the presence of three transmembrane domains and the Popeye domain, which makes up a large part of the cytoplasmic portion of the protein and functions as a cAMP-binding domain. Interestingly, despite the prediction of structural similarity between the Popeye domain and other cAMP binding domains, at the protein sequence level they strongly differ from each other suggesting an independent evolutionary origin of POPDC proteins. Loss-of-function experiments in zebrafish and mouse established an important role of POPDC proteins for cardiac conduction and heart rate adaptation after stress. Loss-of function mutations in patients have been associated with limb-girdle muscular dystrophy and AV-block. These data suggest an important role of these proteins in the maintenance of structure and function of striated muscle cells.

The aim of this study was to validate a procedure for performing the audio-visual paradigm introduced by Wendt et al. (2015) with reduced practical challenges. The original paradigm records eye fixations using an eye tracker and calculates the duration of sentence comprehension based on a bootstrap procedure. In order to reduce practical challenges, we first reduced the measurement time by evaluating a smaller measurement set with fewer trials. The results of 16 listeners showed effects comparable to those obtained when testing the original full measurement set on a different collective of listeners. Secondly, we introduced electrooculography as an alternative technique for recording eye movements. The correlation between the results of the two recording techniques (eye tracker and electrooculography) was r = 0.97, indicating that both methods are suitable for estimating the processing duration of individual participants. Similar changes in processing duration arising from sentence complexity were found using the eye tracker and the electrooculography procedure. Thirdly, the time course of eye fixations was estimated with an alternative procedure, growth curve analysis, which is more commonly used in recent studies analyzing eye tracking data. The results of the growth curve analysis were compared with the results of the bootstrap procedure. Both analysis methods show similar processing durations.

Vowel identification in noise using consonant-vowel-consonant (CVC) logatomes was used to investigate a possible interplay of speech information from different frequency regions. It was hypothesized that the periodicity conveyed by the temporal envelope of a high frequency stimulus can enhance the use of the information carried by auditory channels in the low-frequency region that share the same periodicity. It was further hypothesized that this acts as a strobe-like mechanism and would increase the signal-to-noise ratio for the voiced parts of the CVCs. In a first experiment, different high-frequency cues were provided to test this hypothesis, whereas a second experiment examined more closely the role of amplitude modulations and intact phase information within the high-frequency region (4-8 kHz). CVCs were either natural or vocoded speech (both limited to a low-pass cutoff-frequency of 2.5 kHz) and were presented in stationary 3-kHz low-pass filtered masking noise. The experimental results did not support the hypothesized use of periodicity information for aiding low-frequency perception.

Im Sommer 2014 wurde an mehreren Orten nahe Oldenburg/Niedersachsen ein Triebsterben an älteren Bäumen von Cedrus atlantica beobachtet, charakterisiert durch hellbraune Verfärbung von Nadeln und Nadelbüscheln mit anschließendem Absterben der betroffenen Triebe. Auf Grund spezifischer, morphologischer Merkmale sowie vergleichender DNA-Sequenzanalysen konnte als Erreger der Pilz Sirococcus tsugae ermittelt werden. Bisher war der Coelomycet nur aus Nordamerika bekannt. Die phytosanitären Fragen, die sich aus dem Vorkommen eines neuen Krankheitserregers in Deutschland ergeben, werden diskutiert. DOI: 10.5073/JfK.2015.04.02, https://doi.org/10.5073/JfK.2015.04.02

The main objective of this study was to investigate the extent to which hearing impairment influences the duration of sentence processing. An eye-tracking paradigm is introduced that provides an online measure of how hearing impairment prolongs processing of linguistically complex sentences; this measure uses eye fixations recorded while the participant listens to a sentence. Eye fixations toward a target picture (which matches the aurally presented sentence) were measured in the presence of a competitor picture. Based on the recorded eye fixations, the single target detection amplitude, which reflects the tendency of the participant to fixate the target picture, was used as a metric to estimate the duration of sentence processing. The single target detection amplitude was calculated for sentence structures with different levels of linguistic complexity and for different listening conditions: in quiet and in two different noise conditions. Participants with hearing impairment spent more time processing sentences, even at high levels of speech intelligibility. In addition, the relationship between the proposed online measure and listener-specific factors, such as hearing aid use and cognitive abilities, was investigated. Longer processing durations were measured for participants with hearing impairment who were not accustomed to using a hearing aid. Moreover, significant correlations were found between sentence processing duration and individual cognitive abilities (such as working memory capacity or susceptibility to interference). These findings are discussed with respect to audiological applications.

Im Frühjahr 2014 wurde in einer Baumschule in Niedersachsen eine Nadelkrankheit an jüngeren Bäumen von Cedrus atlantica, C. deodara sowie C. libani beobachtet, charakterisiert durch gelb-braune Nadelfleckung mit anschließender Nadelschütte. Als Erreger wurde der zu den Hypodermataceen gehörige Ascomycet Lophodermium cedrinum Maire ermittelt. Es werden sowohl die Krankheitssymptome als auch die morphologischen Merkmale des Pilzes beschrieben, ergänzt durch entsprechende Abbildungen. Bisher liegen Beobachtungen über das Vorkommen des Nadelparasiten nur aus Nordafrika und Asien vor. Bei unserem Fund handelt es sich demnach um das Erstauftreten des Pilzes in Deutschland bzw. Europa. Die phytosanitären Fragen, die sich daraus ergeben, werden diskutiert. DOI: 10.5073/JfK.2014.09.03, https://doi.org/10.5073/JfK.2014.09.03

An eye-tracking paradigm was developed for use in audiology in order to enable online analysis of the speech comprehension process. This paradigm should be useful in assessing impediments in speech processing. In this paradigm, two scenes, a target picture and a competitor picture, were presented simultaneously with an aurally presented sentence that corresponded to the target picture. At the same time, eye fixations were recorded using an eye-tracking device. The effect of linguistic complexity on language processing time was assessed from eye fixation information by systematically varying linguistic complexity. This was achieved with a sentence corpus containing seven German sentence structures. A novel data analysis method computed the average tendency to fixate the target picture as a function of time during sentence processing. This allowed identification of the point in time at which the participant understood the sentence, referred to as the decision moment. Systematic differences in processing time were observed as a function of linguistic complexity. These differences in processing time may be used to assess the efficiency of cognitive processes involved in resolving linguistic complexity. Thus, the proposed method enables a temporal analysis of the speech comprehension process and has potential applications in speech audiology and psychoacoustics.

Im August 2011 traten an Euonymus fortunei Absterbe­erscheinungen unbekannter Ursache auf. Aus befallenen Trieben wurde ein Cylindrocladium-ähnlicher Pilz isoliert. Anhand seiner morphologischen Merkmale wurde der Pilz als Cylindrocladiella parva (P.J. Anderson) Boesewinkel identifiziert. Eine anschließende Sequenzanalyse der ITS-Region sowie des β-Tubulin-Gens bestätigte das Ergebnis. Die Pathogenität des Pilzes an E. fortunei 'Emerald’n Gold' wurde in mehreren Versuchsansätzen geprüft. Nach Inokulation an den Nodien nach leichter Verletzung entwickelten sich bei hoher Luftfeuchte innerhalb von sieben Wochen an zweijährigen Pflanzen deut­liche Krankheitssymptome. Cylindrocladiella parva ließ sich aus befallenen Trieben reisolieren. Die Pathogenität dieses Erregers an E. fortunei ist damit nachgewiesen. Es ist das erste bekannt gewordene Auftreten von Cylindro­cladiella parva an E. fortunei in Deutschland. DOI: 10.5073/JfK.2014.01.01, https://doi.org/10.5073/JfK.2014.01.01

Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveolae and play a role in myocardial ischemia tolerance. To address these issues, we analyzed hearts and cardiomyocytes of wild type and Popdc1-null mice. Immunoconfocal microscopy revealed co-localization of Popdc1 with caveolin3 in the sarcolemma, intercalated discs and T-tubules and with costameric vinculin. Popdc1 was co-immunoprecipitated with caveolin3 from cardiomyocytes and from transfected COS7 cells and was co-sedimented with caveolin3 in equilibrium density gradients. Caveolae disruption by methyl-β-cyclodextrin or by ischemia/reperfusion (I/R) abolished the cellular co-localization of Popdc1 with caveolin3 and modified their density co-sedimentation. The caveolin3-rich fractions of Popdc1-null hearts redistributed to fractions of lower buoyant density. Electron microscopy showed a statistically significant 70% reduction in caveolae number and a 12% increase in the average diameter of the remaining caveolae in the mutant hearts. In accordance with these changes, Popdc1-null cardiomyocytes displayed impaired [Ca(+2)]i transients, increased vulnerability to oxidative stress and no pharmacologic preconditioning. In addition, induction of I/R injury to Langendorff-perfused hearts indicated a significantly lower functional recovery in the mutant compared with wild type hearts while their infarct size was larger. No improvement in functional recovery was observed in Popdc1-null hearts following ischemic preconditioning. The results indicate that Popdc1 is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity and for heart protection.

The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the recent analysis of patients carrying a missense mutation in POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of interacting proteins. Furthermore, we will discuss the current catalogue of established protein-protein interactions. In recent years, the number of POPDC-interacting proteins has been rising and currently includes ion channels (TREK-1), sarcolemma-associated proteins serving functions in mechanical stability (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that POPDC proteins might also control the cellular level of the nuclear proto-oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins probably serves multiple roles in striated muscle.

The zebrafish Danio rerio, a tropical freshwater fish, belongs to the family of cyprinidae, which in the last 30 years has developed into a very popular model organism for studies of embryonic development and human diseases. Initially the zebrafish species has been selected on the basis of its small size of approximately 3-5 cm, its transparency during development and its high fertility, qualities first identified by George Stresinger, the founding father of zebrafish research [1]. The ability to house thousands of small fishes and the ease of screening mutations in the translucent embryos made it feasible to perform large-scale forward genetic screens in a vertebrate model organism. The abundance of eggs obtained, approximately 200 eggs per female per week, is ideal for genetic and statistical analysis. The mutagenesis screens performed in the early 1990s have led to the identification of genes important in vertebrate organogenesis in an unbiased fashion [2-3]. Many of the isolated mutants have now been fully characterized and the mutated genes mapped, as the zebrafish genome sequencing completes. The knowledge derived has led to a better understanding of the underlying genetic networks governing vertebrate development. More sophisticated phenotype-based screens have since been developed to screen for mutations in defined biological processes [4].

The embryonic heart initially consists of only two cell layers, the endocardium and the myocardium. The epicardium, which forms an epithelial layer on the surface of the heart, is derived from a cluster of mesothelial cells developing at the base of the venous inflow tract of the early embryonic heart. This cell cluster is termed the proepicardium and gives rise not only to the epicardium but also to epicardium-derived cells. These cells populate the myocardial wall and differentiate into smooth muscle cells and fibroblasts, while the contribution to the vascular endothelial lineage is uncertain. In this review we will discuss the signaling molecules involved in recruiting mesodermal cells to undergo proepicardium formation and guide these cells to the myocardial surface. Marker genes which are suitable to follow these cells during proepicardium formation and cell migration will be introduced. We will address whether the proepicardium consists of a homogenous cell population or whether different cell lineages are present. Finally the role of the epicardium as a source for cardiac stem cells and its importance in cardiac regeneration, in particular in the zebrafish and mouse model systems is discussed.

Cardiac malformations, most commonly valve defects, are some of the predominant causes of cardiovascular morbidity and mortality worldwide. Up to a third of all patients with complex congenital heart defects and numerous syndromic conditions, as well as a significant amount of the general population, exhibit valve defects. These observations have not only major implications in infancy; they also have a major impact on the adult population and the growing number of adults with congenital malformations. Over recent years, a large number of Mendelian inheritance patterns and syndromic causes have been identified, shedding light on the importance of genes encoding components of the extracelluar matrix in valve disease. Nevertheless, we still know little about the genetic origin of sporadic and more complex family traits. It is unclear to what extent genetic variations play a role in disease pathogenesis and influences phenotypes rooted in early development. Such knowledge would be greatly beneficial for counseling and treatment of patients. Therefore, this review summarizes the findings in human non-syndromic and syndromic valve disease with a special focus on extracellular matrix proteins, and discusses them in the context of vertebrate valve development.