By linking actin dynamics to extracellular components, integrins are involved in a wide range of cellular processes that are associated with or require cytoskeletal remodelling and cell-shape ...changes. One such function is integrin-dependent phagocytosis, a process that several integrins are capable of mediating and that allows the binding and clearance of particles. Integrin-dependent phagocytosis is involved in a wide range of physiological processes, from the clearance of microorganisms and apoptotic-cell removal to extracellular-matrix remodelling. Integrin signalling is also exploited by microbial pathogens for entry into host cells. Far from being a particular property of specific integrins and specialised cells, integrin-dependent uptake is emerging as a general, intrinsic ability of most integrins that is associated with their capacity to signal to the actin cytoskeleton. Integrin-mediated phagocytosis can therefore be used as a robust model in which to study integrin regulation and signalling.
This paper studies gratings engraved in multilayer dielectric stacks for ultra high intensity laser compressors application. We design various grating profiles with high reflected efficiencies for ...1780 l/mm multilayer dielectric gratings (MLD). Each grating is defined to exhibit a different electric field maximum value in the pillars of the grating. A damage testing facility operating at 1.053 mum, 500 fs pulse duration is used to damage test the parts manufactured from these designs. It is evidenced that for fixed incident angle and materials the damage of the grating is directly related to the electric field intensity maximum in the material, which depends on the groove profile. Laser induced damage thresholds of 5 J/ cm(2) are experimentally reached with very high and uniform efficiencies.
The main scope of the present study was to analyze the membrane interaction of members of different classes of polyphenols, i.e. resveratrol, naringenin, epigallocatechin gallate and enterodiol, in ...model systems of different compositions and phase states. In addition, the possible association between membrane affinity and membrane protection against both lipid oxidation and bilayer-disruptive compounds was studied.
Gibbs monolayer experiments indicated that even though polyphenols showed poor surface activity, it readily interacted with lipid films. Actually, a preferential interaction with expanded monolayers was observed, while condensed and cholesterol-containing monolayers decreased the affinity of these phenolic compounds. On the other hand, fluorescence anisotropy studies showed that polyphenols were able to modulate membrane order degree, but again this effect was dependent on the cholesterol concentration and membrane phase state. In fact, cholesterol induced a surface rather than deep into the hydrophobic core localization of phenolic compounds in the membranes.
In general, the polyphenolic molecules tested had a better antioxidant activity when they were allowed to get inserted into the bilayers, i.e. in cholesterol-free membranes. On the other hand, a membrane-protective effect against bilayer permeabilizing activity of lysozyme, particularly in the presence of cholesterol, could be assessed. It can be hypothesized that phenolic compounds may protect membrane integrity by loosely covering the surface of lipid vesicles, once cholesterol push them off from the membrane hydrophobic core. However, this cholesterol-driven distribution may lead to a reduced antioxidant activity of linoleic acid double bonds.
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•The four polyphenols in study favorably interacted with lipid mono and bilayers.•Cholesterol prevented a deep penetration of phenolic compounds into membranes.•Polyphenol proximity to reactive bis-allylic groups improved antioxidant efficiency.•Surface localization enhanced protection against lysozyme-induced membrane leakage.•Scavenging activity: Nar>Resv~Ed>EGCG; bilayer stabilization: EGCG>Nar~Ed>Resv.
We report on manufacturing and testing results of high efficiency mixed metal dielectric gratings (MMLD) for high power pulse compression applications. The gratings with 1780 l/mm are etched in the ...top low index layer of a Au-(SiO2/HfO2)4-SiO2 mirror stack. Various grating profiles manufactured in order to modify the near electric field distribution are damage tested on a facility operating at 1.053 µm, 500 fs pulse duration. We evidence that damage threshold is governed by the value of the maximum electric field intensity inside the grating pillar. Moreover thresholds close to 3 J/cm
beam normal are obtained with this new MMLD grating being thus an interesting alternative to gold and pure dielectric gratings for pulse compression applications.
Elhers-Danlos syndrome (EDS) is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which ...result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS) is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability. Therefore, the purpose of this study was twofold: (i) to assess the impact of somatosensory deficit on subjective visual vertical (SVV) and postural stability; and (ii) to quantify the effect of wearing somatosensory orthoses (i.e., compressive garments and insoles) on postural stability. Six hEDS patients and six age- and gender-matched controls underwent a SVV (sitting, standing, lying on the right side) evaluation and a postural control evaluation on a force platform (Synapsys), with or without visual information (eyes open (EO)/eyes closed (EC)). These two latter conditions performed either without orthoses, or with compression garments (CG), or insoles, or both. Results showed that patients did not exhibit a substantial perceived tilt of the visual vertical in the direction of the body tilt (Aubert effect) as did the control subjects. Interestingly, such differential effects were only apparent when the rod was initially positioned to the left of the vertical axis (opposite the longitudinal body axis). In addition, patients showed greater postural instability (sway area) than the controls. The removal of vision exacerbated this instability, especially in the mediolateral (ML) direction. The wearing of orthoses improved postural stability, especially in the eyes-closed condition, with a particularly marked effect in the anteroposterior (AP) direction. Hence, this study suggests that hEDS is associated with changes in the relative contributions of somatosensory and vestibular inputs to verticality perception. Moreover, postural control impairment was offset, at least partially, by wearing somatosensory orthoses.
We report an experimental investigation of high reflection mirrors used to fabricate gratings for pulse compression application at the wavelength of 1.053microm. Two kinds of mirrors are studied: the ...mixed Metal MultiLayer Dielectric (MMLD) mirrors which combine a gold metal layer with some e-beam evaporated dielectric bilayers on the top and the standard e-beam evaporated MultiLayer Dielectric (MLD) mirrors. Various samples were manufactured, damage tested at a pulse duration of 500fs. Damage sites were subsequently observed by means of Nomarski microscopy and white light interferometer microscopy. The comparison of the results evidences that if MMLD design can offer damage performances rather similar to MLD design, it also exhibits lower stresses; being thus an optimal mirror substrate for a pulse compression grating operating under vacuum.
Although colistin’s clinical use is limited due to its nephrotoxicity, colistin is considered to be an antibiotic of last resort because it is used to treat patients infected with multidrug-resistant ...bacteria. In an effort to provide molecular details about colistin’s ability to kill Gram-negative (G(−)) but not Gram-positive (G(+)) bacteria, we investigated the biophysics of the interaction between colistin and lipid mixtures mimicking the cytoplasmic membrane of G(+), G(−) bacteria as well as eukaryotic cells. Two different models of the G(−) outer membrane (OM) were assayed: lipid A with two deoxy-manno-octulosonyl sugar residues, and Escherichia coli lipopolysaccharide mixed with dilaurylphosphatidylglycerol. We used circular dichroism and x-ray diffuse scattering at low and wide angle in stacked multilayered samples, and neutron reflectivity of single, tethered bilayers mixed with colistin. We found no differences in secondary structure when colistin was bound to G(−) versus G(+) membrane mimics, ruling out a protein conformational change as the cause of this difference. However, bending modulus KC perturbation was quite irregular for the G(−) inner membrane, where colistin produced a softening of the membranes at an intermediate lipid/peptide molar ratio but stiffening at lower and higher peptide concentrations, whereas in G(+) and eukaryotic mimics there was only a slight softening. Acyl chain order in G(−) was perturbed similarly to KC. In G(+), there was only a slight softening and disordering effect, whereas in OM mimics, there was a slight stiffening and ordering of both membranes with increasing colistin. X-ray and neutron reflectivity structural results reveal colistin partitions deepest to reach the hydrocarbon interior in G(−) membranes, but remains in the headgroup region in G(+), OM, and eukaryotic mimics. It is possible that domain formation is responsible for the erratic response of G(−) inner membranes to colistin and for its deeper penetration, which could increase membrane permeability.
•New method for obtaining higher orders of diffraction.•Higher resolution low-angle x-ray data for DPPC gel phase.•Direct structural evidence for mini-interdigitation of hydrocarbon chains in the ...bilayer center.•Improved modeling of low angle data to provide electron density profiles and component probabilities.
High resolution low angle x-ray data are reported for the gel phase of DPPC lipid bilayers, extending the previous q range of 1.0 Å−1 to 1.3 Å−1, and employing a new technique to obtain more accurate intensities and form factors |F(q)| for the highest orders of diffraction. Combined with previous wide angle x-ray and volumetric data, a space filling model is employed to obtain gel phase structure at a mesoscopic level. This analysis provides direct evidence that the hydrocarbon chains from opposing monolayers are mini-interdigitated, consistent with the previously well-established result that the opposing monolayers are strongly coupled with respect to their chain tilt directions. Even more detailed structural features are described that have not been obtained from experiment but that could, in principle, be obtained from simulations that would first be validated by agreement with the wide angle and the new low angle |F(q)| x-ray data.
The mechanism of action of the anti-Listeria peptide enterocin CRL35 was studied with biophysical tools by using lipid mixtures that mimicked Gram-positive plasma membranes. Langmuir monolayers and ...infrared spectroscopy indicated that the peptide readily interacted with phospholipid assembled in monolayers and bilayers to produce a dual effect, depending on the acyl chains. Indeed, short chain mixtures were disordered by enterocin CRL35, but the gel-phases of membranes composed by longer acyl chains were clearly stabilized by the bacteriocin. Structural and functional studies indicated that non-bilayer states were formed when liposomes were co-incubated with enterocin CRL35, whereas significant permeabilization could be detected when bilayer and non-bilayer states co-existed. Results can be explained by a two-step model in which the N-terminal of the peptide firstly docks enterocin CRL35 on the lipid surface by means of electrostatic interactions; then, C-terminal triggers membrane perturbation by insertion of hydrophobic α-helix.
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•Enterocin CRL35 is a 43 residues bacteriocin active against foodborne Listeria monocytogenes;•PG:PE lipid mixtures with different acyl chain length were studied in monolayer and bilayer systems;•Membrane fluidity and membrane structure upon peptide interaction were assayed;•The bacteriocin permeabilizes membranes and induces non-bilayer structures;
Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. The effect of length and ...unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air–water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch.
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