The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.

Multi-locus microsatellite analysis supports the hypothesis of an autochthonous focus of Echinococcus multilocularis in northern Italy

Echinococcus multilocularis is characterised by a wide geographical distribution, encompassing three continents (North America, Asia and Europe) yet very low genetic variability is documented. Recently, this parasite has been detected in red foxes (Vulpes vulpes) circulating in an Alpine region of Italy, close to Austria. This finding raised the question as to whether an autochthonous cycle exists in Italy or whether the infected foxes originated from the neighbouring regions of Austria. Studies have shown that multi-locus microsatellite analysis can identify genomic regions carrying mutations that result in a local adaptation. We used a tandem repeated multi-locus microsatellite (EmsB) to evaluate the genetic differences amongst adult worms of E. multilocularis collected in Italy, worms from neighbouring Austria and from other European and extra-European countries. Fluorescent PCR was performed on a panel of E. multilocularis samples to assess intra-specific polymorphism. The analysis revealed four closed genotypes for Italian samples of E. multilocularis which were unique compared with the other 25 genotypes from Europe and the five genotypes from Alaska. An analysis in the Alpine watershed, comparing Italian adult worms with those from neighbouring areas in Austria, showed a unique cluster for Italian samples. This result supports the hypothesis of the presence of an autochthonous cycle of E. multilocularis in Italy. EmsB can be useful for 'tracking' the source of infection of this zoonotic parasite and developing appropriate measures for preventing or reducing the risk of human alveolar echinococcosis.

Analyzing PL/1 Legacy Ecosystems: An Experience Report

This paper presents a case study of analyzing a legacy PL/1 ecosystem that has grown for 40 years to support the business needs of a large banking company. In order to support the stakeholders in analyzing it we developed St1-PL/1 — a tool that parses the code for association data and computes structural metrics which it then visualizes using top-down interactive exploration. Before building the tool and after demonstrating it to stakeholders we conducted several interviews to learn about legacy ecosystem analysis requirements. We briefly introduce the tool and then present results of analysing the case study. We show that although the vision for the future is to have an ecosystem architecture in which systems are as decoupled as possible the current state of the ecosystem is still removed from this. We also present some of the lessons learned during our experience discussions with stakeholders which include their interests in automatically assessing the quality of the legacy code.

Nuclear organization in the nematode C. elegans.

With its invariant cell lineage, easy genetics and small genome, the nematode Caenorhabditis elegans has emerged as one of the prime models in developmental biology over the last 50 years. Surprisingly however, until a decade ago very little was known about nuclear organization in worms, even though it is an ideal model system to explore the link between nuclear organization and cell fate determination. Here, we review the latest findings that exploit the repertoire of genetic tools developed in worms, leading to the identification of important sequences and signals governing the changes in chromatin tridimensional architecture. We also highlight parallels and differences to other model systems.

Type I hypersensitivity and its pharmacological modulation in {\it Trichinella\/}-induced intestinal fluid secretion and rapid rejection of the parasite in immunized rats

Studies were performed to test the hypothesis that type I hypersensitivity underlies worm induced intestinal fluid secretion and the rapid rejection of Trichinella spiralis from immunized rats, and the two events may be related in a cause-effect manner.^ Two approaches were taken. One was to determine whether inhibition of anaphylaxis-mediated Cl$\sp{-}$ and fluid secretion accompanying a secondary infection impedes worm rejection from immune hosts. The other was to determine whether induction of intestinal fluid secretion in nonimmune hosts interfered with worm establishment. In both studies, fluid secretion was measured volumetrically 30 min after a challenge infection and worms were counted.^ In immunized rats indomethacin did not affect the worm-induced fluid secretion when used alone, despite inhibiting mucosal prostaglandin synthesis. Fluid secretion was reduced by treatment with diphenhydramine and further reduced by the combination of diphenhydramine and indomethacin. The paradoxical effects of indomethacin when used alone compared with its coadministration with diphenhydramine is explained by the enhancing effect of indomethacin on histamine release. Abolishing net fluid secretion in these studies had no effect on rapid worm rejection in immune hosts.^ Worm establishment was reduced in recipients of immune serum containing IgE antibodies. Net intestinal fluid secretion induced in normal rats by PGE$\sb2$, cholera toxin, or hypertonic mannitol solution had no effect on worm establishment compared with untreated controls.^ In a related experiment, worm-induced intestinal fluid secretion and worm rejection in immune rats were partially blocked by concurrent injection with 5-HT$\sb2$ and 5-HT$\sb3$ blockers (Ketanserin and MDL-72222), suggesting that 5-HT is involved. This possible involvement was supported in that treatment of nonimmune rats with 5-HT significantly inhibited worm establishment in the intestine.^ Results indicate that anaphylaxis is the basis for both worm-induced intestinal fluid secretion and rapid rejection of T. spiralis in immune rats, but these events are independent of one another. 5-HT is a possible mediator of worm rejection, however, its mechanism of action is related to something other than fluid secretion. ^

Zur Geschichte der Wormser jüdischen Gemeinde, ihrer Friedhöfe und ihres Begräbniswesens : Gedenkschrift zur Eröffnung des neuen Friedhofs

[von Max Levy...]

... Lettre d'un Israélite français à ses coreligionnaires

[Tsarphati, d.i. Olry Terquem]

Dissertatio medica de cavsa immvnditiei spermatis hvmani apvd Ebraeos ...

Gießen, Univ., Diss., 1768

Die Abgaben und die Schuldenlast der Wormser jüd. Gemeinde : 1563 - 1854

ein Beitrag zur Geschichte der jüd. Gemeinde Worms mit zwei Briefen des A. Weckerling. Von S. Rothschild

Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan

Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.

Die Stammtafeln der Familie Geiger : zusammengest. im Auftr. von Alfred S. Geiger

Daniel August Worms

Die egyptischen grossen Offenbarungen, in sich begreifend die aufgefundenen Geheimnisbücher Mosis : ... sammt der Geister- und Wunder-Herrschaft ... alle Verborgenheiten der Kabbala umfassend ; aus einer hebräischen Pergament-Handschrift von 1387 im 17. Jahrhundert verteutscht und wortgetreu herausgegeben

[Anastat. Neudr. d. Ausg.1725] Köln a. Rh. : Hammer

A conserved role for p48 homologs in protecting dopaminergic neurons from oxidative stress.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Both environmental and genetic factors are thought to contribute to the pathogenesis of PD. Although several genes linked to rare familial PD have been identified, endogenous risk factors for sporadic PD, which account for the majority of PD cases, remain largely unknown. Genome-wide association studies have identified many single nucleotide polymorphisms associated with sporadic PD in neurodevelopmental genes including the transcription factor p48/ptf1a. Here we investigate whether p48 plays a role in the survival of DA neurons in Drosophila melanogaster and Caenorhabditis elegans. We show that a Drosophila p48 homolog, 48-related-2 (Fer2), is expressed in and required for the development and survival of DA neurons in the protocerebral anterior medial (PAM) cluster. Loss of Fer2 expression in adulthood causes progressive PAM neuron degeneration in aging flies along with mitochondrial dysfunction and elevated reactive oxygen species (ROS) production, leading to the progressive locomotor deficits. The oxidative stress challenge upregulates Fer2 expression and exacerbates the PAM neuron degeneration in Fer2 loss-of-function mutants. hlh-13, the worm homolog of p48, is also expressed in DA neurons. Unlike the fly counterpart, hlh-13 loss-of-function does not impair development or survival of DA neurons under normal growth conditions. Yet, similar to Fer2, hlh-13 expression is upregulated upon an acute oxidative challenge and is required for the survival of DA neurons under oxidative stress in adult worms. Taken together, our results indicate that p48 homologs share a role in protecting DA neurons from oxidative stress and degeneration, and suggest that loss-of-function of p48 homologs in flies and worms provides novel tools to study gene-environmental interactions affecting DA neuron survival.

Targûm aškenazzî ʿal ḥamiššā ḥûmšê Tôrā

min-... Mōše Desoi ... di iberzetzung oif der (toire) fon Mendel Zohn