Controlling Light Through Optical Disordered Media : Transmission Matrix Approach

We experimentally measure the monochromatic transmission matrix (TM) of an optical multiple scattering medium using a spatial light modulator together with a phase-shifting interferometry measurement method. The TM contains all information needed to shape the scattered output field at will or to detect an image through the medium. We confront theory and experiment for these applications and we study the effect of noise on the reconstruction method. We also extracted from the TM informations about the statistical properties of the medium and the light transport whitin it. In particular, we are able to isolate the contributions of the Memory Effect (ME) and measure its attenuation length

Structural insights into Clostridium perfringens delta toxin pore formation

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Translation correlations in anisotropically scattering media

Controlling light propagation across scattering media by wavefront shaping holds great promise for a wide range of communications and imaging applications. However, finding the right wavefront to shape is a challenge when the mapping between input and output scattered wavefronts (i.e. the transmission matrix) is not known. Correlations in transmission matrices, especially the so-called memory-effect, have been exploited to address this limitation. However, the traditional memory-effect applies to thin scattering layers at a distance from the target, which precludes its use within thick scattering media, such as fog and biological tissue. Here, we theoretically predict and experimentally verify new transmission matrix correlations within thick anisotropically scattering media, with important implications for biomedical imaging and adaptive optics.Comment: main article (18 pages) and appendices (6 pages

New Directions in the Development of Population Estimates in the United States?

The advent of a continuously updated Master Area File (MAF) following the 2000 census represents an information resource that can be tapped for purposes of developing timely, cost-effective, and precise population estimates for even the smallest of geographical units (e.g., census blocks). We argue that the MAF can be enhanced (EMAF) for these purposes. In support of our argument we describe a set of activities needed to develop EMAF, each of which is well within the current capabilities of the U.S. Census Bureau and discuss various costs and benefits of each. We also describe how EMAF would provide population estimates containing a wide range of demographic (e.g., age, race, and sex) and socio-economic characteristics (e.g., educational attainment, income, and employment). As such, it could largely negate and eliminate the need for many of the traditional demographic methods of population estimation and possibly reduce the number of sample surveys. We identify important challenges that must be surmounted in order to realize EMAF and make suggestions for doing so. We conclude by noting that the idea of the EMAF could be of interest to other countries with MAF files and strong administrative records systems that, like the United States, are facing the challenge of producing good population information in the face of increasing census costs

Wavefront shaping with disorder-engineered metasurfaces

Recently, wavefront shaping with disordered media has demonstrated optical manipulation capabilities beyond those of conventional optics, including extended volume, aberration-free focusing and subwavelength focusing. However, translating these capabilities to useful applications has remained challenging as the input–output characteristics of the disordered media (P variables) need to be exhaustively determined via O(P) measurements. Here, we propose a paradigm shift where the disorder is specifically designed so its exact input–output characteristics are known a priori and can be used with only a few alignment steps. We implement this concept with a disorder-engineered metasurface, which exhibits additional unique features for wavefront shaping such as a large optical memory effect range in combination with a wide angular scattering range, excellent stability, and a tailorable angular scattering profile. Using this designed metasurface with wavefront shaping, we demonstrate high numerical aperture (NA > 0.5) focusing and fluorescence imaging with an estimated ~2.2 × 10^8 addressable points in an ~8 mm field of view

FIP1/RCP Binding to Golgin-97 Regulates Retrograde Transport from Recycling Endosomes to the trans-Golgi Network

This study shows that Rab11 and its binding protein FIP1 are required for retrograde delivery of TGN38 and Shiga toxin from early/recycling endosomes to the TGN. We also demonstrate that Golgin-97 as a FIP1-binding protein and that this binding regulates the targeting of retrograde transport vesicles to the TGN

Tailored ß-Cyclodextrin Blocks the Translocation Pores of Binary Exotoxins from C. Botulinum and C. Perfringens and Protects Cells from Intoxication

International audienceBackgroundClostridium botulinum C2 toxin and Clostridium perfringens iota toxin are binary exotoxins, which ADP-ribosylate actin in the cytosol of mammalian cells and thereby destroy the cytoskeleton. C2 and iota toxin consists of two individual proteins, an enzymatic active (A-) component and a separate receptor binding and translocation (B-) component. The latter forms a complex with the A-component on the surface of target cells and after receptor-mediated endocytosis, it mediates the translocation of the A-component from acidified endosomal vesicles into the cytosol. To this end, the B-components form heptameric pores in endosomal membranes, which serve as translocation channels for the A-components.Here we demonstrate that a 7-fold symmetrical positively charged ß-cyclodextrin derivative, per-6-S-(3-aminomethyl)benzylthio-ß-cyclodextrin, protects cultured cells from intoxication with C2 and iota toxins in a concentration-dependent manner starting at low micromolar concentrations. We discovered that the compound inhibited the pH-dependent membrane translocation of the A-components of both toxins in intact cells. Consistently, the compound strongly blocked transmembrane channels formed by the B-components of C2 and iota toxin in planar lipid bilayers in vitro. With C2 toxin, we consecutively ruled out all other possible inhibitory mechanisms showing that the compound did not interfere with the binding of the toxin to the cells or with the enzyme activity of the A-component.Conclusions/SignificanceThe described ß-cyclodextrin derivative was previously identified as one of the most potent inhibitors of the binary lethal toxin of Bacillus anthracis both in vitro and in vivo, implying that it might represent a broad-spectrum inhibitor of binary pore-forming exotoxins from pathogenic bacteria

Diverse Temperate Bacteriophage Carriage in Clostridium difficile 027 Strains

The hypervirulent Clostridium difficile ribotype 027 can be classified into subtypes, but it unknown if these differ in terms of severity of C. difficile infection (CDI). Genomic studies of C. difficile 027 strains have established that they are rich in mobile genetic elements including prophages. This study combined physiological studies, electron microscopy analysis and molecular biology to determine the potential role of temperate bacteriophages in disease and diversity of C. difficile 027.We induced prophages from 91 clinical C. difficile 027 isolates and used transmission electron microscopy and pulsed-field gel electrophoresis to characterise the bacteriophages present. We established a correlation between phage morphology and subtype. Morphologically distinct tailed bacteriophages belonging to Myoviridae and Siphoviridae were identified in 63 and three isolates, respectively. Dual phage carriage was observed in four isolates. In addition, there were inducible phage tail-like particles (PT-LPs) in all isolates. The capacity of two antibiotics mitomycin C and norfloxacin to induce prophages was compared and it was shown that they induced specific prophages from C. difficile isolates. A PCR assay targeting the capsid gene of the myoviruses was designed to examine molecular diversity of C. difficile myoviruses. Phylogenetic analysis of the capsid gene sequences from eight ribotypes showed that all sequences found in the ribotype 027 isolates were identical and distinct from other C. difficile ribotypes and other bacteria species.A diverse set of temperate bacteriophages are associated with C. difficile 027. The observed correlation between phage carriage and the subtypes suggests that temperate bacteriophages contribute to the diversity of C. difficile 027 and may play a role in severity of disease associated with this ribotype. The capsid gene can be used as a tool to identify C. difficile myoviruses present within bacterial genomes