Intercellular communication is required for trap formation in the nematode-trapping fungus Duddingtonia flagrans

Nematode-trapping fungi (NTF) are a large and diverse group of fungi, which may switch from a saprotrophic to a predatory lifestyle if nematodes are present. Different fungi have developed different trapping devices, ranging from adhesive cells to constricting rings. After trapping, fungal hyphae penetrate the worm, secrete lytic enzymes and form a hyphal network inside the body. We sequenced the genome of Duddingtonia flagrans, a biotechnologically important NTF used to control nematode populations in fields. The 36.64 Mb genome encodes 9,927 putative proteins, among which are more than 638 predicted secreted proteins. Most secreted proteins are lytic enzymes, but more than 200 were classified as small secreted proteins (< 300 amino acids). 117 putative effector proteins were predicted, suggesting interkingdom communication during the colonization. As a first step to analyze the function of such proteins or other phenomena at the molecular level, we developed a transformation system, established the fluorescent proteins GFP and mCherry, adapted an assay to monitor protein secretion, and established gene-deletion protocols using homologous recombination or CRISPR/Cas9. One putative virulence effector protein, PefB, was transcriptionally induced during the interaction. We show that the mature protein is able to be imported into nuclei in Caenorhabditis elegans cells. In addition, we studied trap formation and show that cell-to-cell communication is required for ring closure. The availability of the genome sequence and the establishment of many molecular tools will open new avenues to studying this biotechnologically relevant nematode-trapping fungus

Vedolizumab use after failure of TNF- antagonists in children and adolescents with inflammatory bowel disease

BACKGROUND: Vedolizumab is safe and effective in adult patients with Crohn's disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD. METHODS: Twelve patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits. RESULTS: In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p=1,0), while median UC activity scores changed from 70 to 5 points (p<0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups. CONCLUSION: These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.(VLID)286504

Characterization of Turing diffusion-driven instability on evolving domains

In this paper we establish a general theoretical framework for Turing diffusion-driven instability for reaction-diffusion systems on time-dependent evolving domains. The main result is that Turing diffusion-driven instability for reaction-diffusion systems on evolving domains is characterised by Lyapunov exponents of the evolution family associated with the linearised system (obtained by linearising the original system along a spatially independent solution). This framework allows for the inclusion of the analysis of the long-time behavior of the solutions of reaction-diffusion systems. Applications to two special types of evolving domains are considered: (i) time-dependent domains which evolve to a final limiting fixed domain and (ii) time-dependent domains which are eventually time periodic. Reaction-diffusion systems have been widely proposed as plausible mechanisms for pattern formation in morphogenesis

Multipole approximations for local correlation methods

Eine neuartige Multipolnäherung für das linear skalierende lokale MP2-Verfahren wird vorgestellt. Nachdem die Wechselwirkung räumlich stark getrennter Elektronenpaare bereits in der dieser Doktorarbeit vorangegangenen Diplomarbeit durch eine einfache Multipolnäherung modelliert wurden, geht es hier um eine komplementäre Multipolnäherung für nahe, stark wechselwirkende Elektronenpaare. Für solche Paare konvergiert eine herkömmliche Multipolentwicklung aufgrund der Singularität der Coulombwechselwirkung beim Abstand null nicht mehr. Deshalb wurde ein Ansatz verfolgt, bei dem die Coulombwechselwirkung in zwei Summanden aufgespalten wird. Der eine enthält die Singularität und fällt mit steigendem Abstand rasch ab. Er wird auf herkömmliche Weise behandelt, wobei aufgrund des raschen Abklingens erhebliche Einsparungen erzielt werden. Der andere ist langreichweitig, aber nicht singulär und kann daher durch Multipolentwicklung approximiert werden. Den Schwerpunkt der Arbeit bildet die Ausarbeitung dieses Verfahrens. Konvergenzprobleme wurden angegangen, indem ein neuartiges Verfahren zur Gewinnung der Multipolreihe entwickelt wurde, das auf der Methode der kleinsten Fehlerquadrate anstelle der herkömmlichen Taylorentwicklung beruht. Die Effizienz wurde mit Hilfe eines kompakten Matrixformalismus und eines Prescreening-Algorithmus verbessert. Außerdem wurden Probleme mit der numerischen Genauigkeit gelöst. Die Implementierung der Methode erfolgte als Beitrag zum Programmpaket MOLPRO. Zuverlässigkeit, Genauigkeit und Effizienz werden im Rahmen einer umfangreichen Benchmarkstudie demonstriert. Es wird gezeigt, daß das Ziel erreicht wurde, die Computerkosten des bisherigen linear skalierenden LMP2-Algorithmus weiter zu verringern. Darüber hinaus bietet sich das Verfahren als vielversprechender Ausgangspunkt für weitere Entwicklungen an, etwa die Kopplung von LMP2 mit Dichtefunktionalmethoden.A novel multipole approximation for the linear scaling local MP2 method is presented. While the interaction of distant electron pairs has already been modeled by a simple multipole approximation in the past, the new approximation deals with the strong interaction of spacially close electron pairs. In this case, a conventional multipole expansion is divergent due to the singularity of the Coulomb operator at zero distance. As a solution, the Coulomb operator is expressed as a sum of two parts. The first one contains the singularity and is rapidly decaying with increasing distance. It is treated by conventional two-electron transformation, where the rapid decay leads to significant savings. The second addend is long-range, but non-singular and can therefore be approximated by multipole expansion. The main part of this work is the elaboration of this method. Convergence problems were tackled by a novel least-squares fit method for generating the multipole expansion, instead of the conventional Taylor expansion. Efficiency was improved by complete reformulation of the cartesian multipole expansion formalism using compact matrix algebra, and by introducing a prescreening algorithm for the multipole integrals. Numerical issues where solved by partitioning very large molecules in multipole domains and treating integrals separatly for each domain. The method has been implemented as contribution to the MOLPRO package of ab inito programs. Reliability, accuracy and efficiency are demonstrated by an extensive benchmark study. It is shown that the goal to further improve the efficiency of the existing linear scaling local MP2 algorithm has been achieved. Moreover, the new method is a promising starting-point for future developments, like coupling of MP2 with density functional theory

Global existence, uniqueness, and continuous dependence for a reaction-diffusion equation with memory

initial data are established for a quasilinear functional reaction-diffusion equation which arises from a two-dimensional energy balance climate model. Our approach relies heavily on the so-called stability estimates for linear evolution equations of parabolic type (cf. [6])