196,593 research outputs found
Physical methods to quantify small antibiotic molecules uptake into Gram-negative bacteria
No full textThe development of antibiotics against Gram-negative bacteria is a challenge: any active compound must cross the outer cell envelope composed of a hydrophilic highly charged lipopolysaccharide layer followed by a tight hydrophobic layer containing water filled gates called porins to reach the hydrophilic periplasmic space and depending on the target with the further need to cross the hydrophobic inner membrane. In addition to a possible rapid enzymatic deactivation efflux pumps shuffle compounds back outside. The resulting low permeability of cell envelope requires high dose and leads therefore to toxicity problems. Despite its relevance the permeability barrier in Gram-negative bacteria is not well understood partially caused by the lack of appropriate direct assays. Here we give a brief introduction on current available techniques to quantify passive diffusion of small hydrophilic molecules into Gram-negative bacteri
La moda. Dinamiche di innovazione e spinte conservatrici nel campo
No full textIn questo contributo la presunta innovatività della moda verrà messa “alla prova” attraverso l’analisi di tre diversi fenomeni in cui è possibile scorgere l’irruzione del nuovo all’interno del campo: 1) le prassi di ri- cerca (fashion forecasting prima e coolhunting poi) attraverso le quali il sistema moda, con largo anticipo rispetto ad altri settori dell’industria culturale, ha fatto dell’individuazione di novità e tendenze emergenti una propria caratteristica distintiva, nello sforzo continuo di immagi- nare l’innovazione; 2) l’affermazione del fashion blogging come forma di comunicazione dal basso capace di mettere in discussione il ruolo del tradizionale giornalismo di settore;1 3) le innovative soluzioni del fashion retail, che stanno spostando le attività di acquisto nel regno dello shoptainment.
La discussione di questi esempi porterà a riconoscere nel campo della moda la compresenza di elementi di innovazione e di conser- vatorismo, a dispetto di una retorica che celebra solo i primi dimen- ticando i secondi, secondo una logica di appropriazione e rimozione della tradizione, propria del capitalismo culturale
Antibiotic Permeation across the OmpF Channel: Modulation of the Affinity Site in the Presence of Magnesium
No full textWe characterize the rate-limiting interaction of the antibiotic
10 enrofloxacin with OmpF, a channel from the outer cell wall of Escherichia coli.
11 Reconstitution of a single OmpF trimer into planar lipid membranes allows
12 measurement of the ion current through the channel. Penetration of antibiotics causes
13 ion current blockages, and their frequency allows a conclusion on the kinetics of
14 channel entry and exit. In contrast to other antibiotics, enrofloxacin is able to block the
15 OmpF channel for several milliseconds, reflecting high affinities comparable to
16 substrate-specific channels such as the maltodextrin-specific maltoporin. Surprisingly,
17 the presence of a divalent ion such as Mg2+ leads to fast flickering with an increase in
18 the rates of association and dissociation. All-atom computer modeling provides the
19 most probable pathway able to identify the relevant rate-limiting interaction during antibiotic permeation. Mg2+ has a high affinity
20 for the aspartic acid at the 113 position (D113) in the center of the OmpF intracellular binding site. Therefore, the presence of Mg2+
21 reverses the charge and enrofloxacin may cross the constriction region in its favorable orientation with the carboxylic group first
Analysis of fast channel blockage: revealing substrate binding in the microsecond range
No full textFor an antibiotic to be effective, it needs to cross the outer membrane barrier and reach the target inside
the cell. Hydrophilic antibiotics, e.g. β-lactams, use porin channels to cross the outer membrane and
accumulate in the periplasm. Experimental determination of antibiotic interactions with porin is performed
by using electrophysiology on a single channel level by noise analysis or single event analysis methods.
We report a novel framework for analyzing the ion-current noise, taking into account the corrections
due to the analogous filter and the sampling procedure, with the goal of extending the time resolution
to a range previously inaccessible by event analysis or by conventional noise analysis. The new method
allows one to analyse fast binding events and/or the case when the single channel is not completely
blocked by the substrate. We demonstrate the power of this approach by using as an example the interactions
of meropenem, an antibiotic of the carbapenem family, with the OmpF porin that is considered
to be one of the main pathways for antibiotics to enter Escherichia coli. The presence of meropenem in
OmpF is detected by ion current blockages, and the on and off rates are estimated from the concentration
dependence of the average ion current and of its power spectral density. The obtained average
residence time of the antibiotic inside the channel is in the range of a few microseconds, i.e. more than
50 times smaller than the inverse cut-off frequency of the analogous filter
Spectral properties and reactivity towards azide of Dicrocoelium dendriticum met-hemoglobin
No full textFlight Data Entry, Descent, and Landing (EDL) Repository
No full textDr. Daniel Winterhalter, NASA Engineering and Safety Center Chief Engineer at the Jet Propulsion Laboratory, requested the NASA Engineering and Safety Center sponsor a 3-year effort to collect entry, descent, and landing material and to establish a NASA-wide archive to serve the material. The principle focus of this task was to identify entry, descent, and landing repository material that was at risk of being permanently lost due to damage, decay, and undocumented storage. To provide NASA-wide access to this material, a web-based digital archive was created. This document contains the outcome of the effort
Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane
No full textThe sophisticated envelope of Gram-negative bacteria modulates the uptake of small molecules in a side-chain-sensitive manner. Despite intensive theoretical and experimental investigations, a general set of pathways underpinning antibiotic uptake has not been identified. This manuscript discusses the passive influx versus active efflux of antibiotics, considering the responsible membrane proteins and the transported molecules. Recent methods have analyzed drug transport across the bacterial membrane in order to understand their activity. The combination of in vitro, in cellulo and in silico methods shed light on the key, mainly electrostatic, interactions between the molecule surface, porins and transporters during permeation. A key factor is the relationship between the dose of an active compound near its target and its antibacterial activity during the critical early window. Today, methodology breakthroughs provide fruitful tools to precisely dissect drug transport, identify key steps in drug resistance associated with membrane impermeability and efflux, and highlight key parameters to generate more effective drugs.Gram-negative bacteria envelope controls drug accumulation via passive influx and active efflux mechanisms. This article discusses recent in cellulo, in vitro, and in silico methods highlighting key "drug-transporters" dialogues and proposes new perspectives to overcome drug resistance
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
Insertion of membrane proteins in artificial polymer membranes
No full textThe last few decades have seen a huge growth in research on “soft materials”. A large part of the research in this field was dedicated to the preparation of new types of artificial membranes, which behave similar to lipid or cell membranes. A particular challenge is the preparation of stabilized, flexible, adaptable and responsive materials. Similar to nature such systems can only be realized using hierarchically self-assembled systems. In this context we have introduced a new way of stabilizing lipid-bilayers using hydrophobic polymer scaffold. In contrast to other approaches, presented by Ringsdorf et al., 1988, the hydrophobic polymer scaffold allowed us to insert membrane proteins into the polymer stabilized membranes. One representative example of the functional insertion of a membrane protein into such stabilized membranes will be described in the present work. In another approach we used the self assembling capacity of amphiphilic block copolymers to prepare stable biomimetic membranes. The last few years have seen considerable progress in the development of block copolymer chemistry. Particularly, a whole series of new amphiphilic block copolymers with low glass-transition temperatures have been introduced. The diversity of block copolymer chemistry allows to vary the chemical constitution, such as the nature and the sequence of the repeat unit (as mentioned in a later section), the length and the different structures of the different blocks and even the molecular architecture of the whole polymer, block, graft, star, etc. This may lead to the formation of new types of self-assembled superstructures that are not accessible to conventional low molar mass amphiphiles. Recently our group introduced a new type of amphiphilic block copolymer composed of two hydrophilic side blocks poly-methyloxazoline (PMOXA) and one hydrophobic middle block polydimethylsiloxane (PDMS), forming an ABA triblock copolymer. The physico-chemical characterization of the ABA block copolymer has been described by Nardin et al. Similar to conventional low molar mass amphiphiles (lipids, surfactants), this polymer selfassembles in aqueous media and forms well defined superstructures. Depending on its molecular composition and the experimental conditions various lyotropic mesophases, vesicles and nanotubes have been identified. Most interestingly it has been shown that membranes formed by such polymers could be used as a matrix for the incorporation of integral membrane proteins.
In the present work we developed new procedures for membrane proteins that are adapted and
optimized with respect to the artificial polymer membranes. For that purpose we performed a series of
experiments with different membrane proteins that have different structural properties and
functionality. In all systems investigated we could successfully proof the incorporation and the
functionality of the proteins.
For a first experiment we used well characterized and stable membrane proteins like bacterial
porins. Porins are well characterized integral membrane proteins possessing interesting structural and
physical properties, such as hydrophobic β-strands, which can interact and insert into the hydrophobic
part of the block copolymer. Additionally, the porins form β-stranded pores, which allow a passive and
selective transfer of small molecules across a membrane.
Then, more complex membrane proteins were used such as hemagglutinin or
NADH:oxydoreductase. Both proteins are composed of a large soluble part which contributes to their
structural and functional particularities. The globular part of hemagglutinin is involved in the fusion of
two membranes whereas the soluble part of NADH:oxydoreductase is responsible for proton and
electron transfer across the membrane.
The combination of natural proteins with artificial polymer membranes allows the formation of
a new type of hybrid material combining the mechanical, chemical, and biological stability of the
amphiphile block copolymer and the functional specificity of membrane proteins
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
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