Erythematöse,ekzematöse,parenchymatöse Entzündungsprocesse

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Acute und chronische Infectionskrankheiten

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Efficient Method for Generating Point Mutations in the Vaccinia Virus Genome Using CRISPR/Cas9

The vaccinia virus (VACV) was previously used as a vaccine for smallpox eradication. Nowadays, recombinant VACVs are developed as vaccine platforms for infectious disease prevention and cancer treatment. The conventional method for genome editing of the VACV is based on homologous recombination, which is poorly efficient. Recently, the use of CRISPR/Cas9 technology was shown to greatly improve the speed and efficiency of the production of recombinant VACV expressing a heterologous gene. However, the ability to rapidly recover viruses bearing single nucleotide substitutions is still challenging. Notwithstanding, ongoing studies on the VACV and its interaction with the host cell could benefit from viral gene targeted mutagenesis. Here, we present a modified version of the CRISPR/Cas9 system for the rapid selection of mutant VACV carrying point mutations. For this purpose, we introduced a silent mutation into the donor gene (which will replace the wildtype gene) that serves a double function: it is located in the PAM (NGG) sequence, which is essential for Cas9 cleavage, and it alters a restriction site. This silent mutation, once introduced into the VACV genome, allows for rapid selection and screening of mutant viruses carrying a mutation of interest in the targeted gene. As a proof of concept, we produced several recombinant VACVs, with mutations in the E9L gene, upon which, phenotypic analysis was performed.     

The Coronavirus Might be Paradoxically Beneficial on the Risk of Autism

Journal of Autism and Developmental Disorders -     

Spastic paretic hemifacial contracture related to multiple sclerosis: a rare and under-recognized entity

We describe an additional case of spastic paretic hemifacial contracture, an uncommon condition characterized by sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis. This entity has only rarely been associated with multiple sclerosis (MS) and can be mistaken for hemifacial spasm. Early consideration of MS in the differential diagnosis of young patients admitted with these symptoms is essential.     

Atherosclerotic occlusive disease of the superior mesenteric artery: Late results of reconstructive surgery

Between 1975 and 1988, 103 patients underwent reconstruction of the superior mesenteric artery for atherosclerotic occlusive disease. Patients undergoing revascularization with associated mesenteric infarction were excluded. There were 89 men and 14 women whose mean age was 57.2 years. Six patients were operated on emergently for impending mesenteric infarction; six patients underwent revascularization after intestinal resection for ischemic lesions; 20 patients had typical abdominal angina; 39 patients had nonspecific abdominal symptoms, and 32 patients underwent revascularization of their superior mesenteric artery for asymptomatic lesions. Revascularization of the celiac axis and inferior mesenteric artery was associated in 36 and four cases, respectively. Four patients (4%) died postoperatively. Four early occlusions (4%) were observed. During the follow-up period (mean=69 months), 18 patients died; five patients had recurrent intestinal ischemic symptoms, four of whom died. All surviving patients underwent follow-up duplex scanning, examination, and arterial or venous digitalized angiograms in selected cases. Nine patients (9%) had anatomical abnormalities: two stenoses and seven occlusions. Failure of revascularization of the superior mesenteric artery was observed in patients with severe initial intestinal ischemia. Late complications were not statistically significantly related to the different techniques of revascularization used. Presented at the Annual Meeting of the Société de Chirurgie Vasculaire de Langue Française, June 23–24, 1989, Strasbourg, France.     

Reflections upon certain specific and current uses of the “unconscious” in clinical hypnosis

An attempt was made to confirm the previously reported finding of Hammer and Arkins (1964) of a significantly greater improvement in hypnotic performance as a result of 11 cps intermittent photic stimulation than with frequencies outside the range of EEG alpha activity. Using the Brain Wave Synchronizer, three groups of Ss were given stimulation at 5 cps, 11 cps, and 30 cps. Tests of hypnotic performance were made during stimulation, immediately after stimulation, and a week or more later. No evidence of frequency-specific effect was obtained, and the original finding was considered not confirmed.     

Deletion of the Uracil Permease Gene Confers Cross-Resistance to 5-Fluorouracil and Azoles in Candida lusitaniae and Highlights Antagonistic Interaction between Fluorinated Nucleotides and Fluconazole

We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast Candida lusitaniae. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport.