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Amirav, I.

Publications and source records attributed to Amirav, I..

3 recordsLinked to original sources

Expanding Clinical Phage Microbiology:‎Simulating Phage Inhalation for Respiratory Tract Infections ‎

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target CF-common pathogens, were aerosolized and administered to a real-scale CT{square}derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success. Take-Home MessagePhage therapy can be used against infectious diseases if personally tailored. Using a 3D airways model, we show that phage delivery by inhalation to the respiratory tract is unpredictable and also requires a precise evaluation.

microbiology↗

A How-To guide to: Quantitative high-speed video profiling to discriminate between variants of primary ciliary dyskinesia

This document presents detailed steps to analysing the waveforms of beating cilia, measured in high speed video microscopy. We show that in the case of PCD caused by mutations in DNAH11 and HYDIN the classification by a handful of parameters describing ciliary dynamics allows to distinguish the genotype, as well as (much more easily) distinguishing healthy from PCD samples. This document is intended to complement the brief highlight (1) and presents the details of the datasets used in that letter.

cell biology↗

Mutations in C11ORF70 cause primary ciliary dyskinesia with randomization of left/right body asymmetry due to outer and inner dynein arm defects

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility and randomization of the left/right body axis caused by defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open reading frame C11ORF70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11ORF70 cause immotility of respiratory cilia and sperm flagella, respectively, due to loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11ORF70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11ORF70 showed that C11ORF70 is expressed in ciliated respiratory cells and that the expression of C11ORF70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein arm assembly factors. Furthermore, C11ORF70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11ORF70 is a novel preassembly factor involved in the pathogenesis of PCD. The identification of a novel genetic defect that causes PCD and male infertility is of great clinical importance as well as for genetic counselling.

molecular biology↗