Front dynamics in fractional-order epidemic models

A number of recent studies suggest that human and animal mobility patterns exhibit scale-free, Lévy-flight dynamics. However, current reaction-diffusion epidemics models do not account for the superdiffusive spread of modern epidemics due to Lévy flights. We have developed a SIR model to simulate the spatial spread of a hypothetical epidemic driven by long-range displacements in the infective and susceptible populations. The model has been obtained by replacing the second-order diffusion operator by a fractional-order operator. Theoretical developments and numerical simulations show that fractional-order diffusion leads to an exponential acceleration of the epidemic's front and a power-law decay of the front's leading tail. Our results indicate the potential of fractional-order reaction-diffusion models to represent modern epidemics.     

Non-normal Statistics of DNA Sequences of Prokaryotes

The n-rule of Schrödinger in his discussion of DNA is based onnormal statistics and equilibrium physics. Herein the kurtosis is used tomeasure the deviation from normality of the stistics of non-equilibrium DNAsequences. A pattern for this deviation from normality is identified andthis signature is found in prokaryotes. The signature is explained by atheory of DNA sequences that involves finite length DNA walks withdynamically generated long-range correlations.     

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers

 Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems. Received: 1 December 1999 / Revised version: 2 March 2000 / Accepted: 2 March 2000     

Interaction of α-lactalbumin with dimyristoylphosphatidylcholine vesicles. III. Influence of the temperature and of the lipid-to-protein molar ratio on the complex formation

We investigated the interaction between α-lactalbumin and sonicated dimyristoylphosphatidylcholine at pH 4 and different temperatures. (1) At 23°C and lipid-to-protein molar ratios below 170, the interaction results in a disruption of the original vesicles to form smaller complex particles. By the sedimentation velocity method we determined for this particle a molar mass of (1.05 ± 0.16) · 10⁶ g·mol^?1. The lipid-to-protein molar ratio within the complex particle is 70/1, as earlier estimated. It follows that there are approximately 1200 lipid and 17 α-lactalbumin molecules per particle. At molar ratios above 170, α-lactalbumin strongly associates with the vesicles. In this case the vesicle entity remains. The ability of α-lactalbumin to break up the vesicles at this temperature is determined by the number of protein molecules which are required in the complex particle. (2) By means of fluorescence polarization of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene and energy transfer of the tryptophan groups of the protein to 1,3-(1,1′-dipyrenyl)propane located in the hydrocarbon region of the vesicles, it is shown that with increasing temperature above 25°C, complexes of decreasing internal lipid-to-protein molar ratio are formed. However, by electron microscopy we show that the overall size of these complexes remains approximately the same, i.e., bars with dimensions $\text{70 × 220}\text{A}\text{?}$. A temperature-reversible transformation occurs between these complexes, which cannot be isolated by gel chromatography. In contrast, the complex of molar ratio 70/1 remains stable at lower temperatures.     

L’art Paléolithique est-il un « art » ?: Réflexions autour d’une question d’actualité

During the last years, an international debate about the concept of “Palaeolithic art” has taken place. On one hand, several specialists have critiqued the use of the concept of “art” in naming the images created by Homo sapiens during the Palaeolithic era. They claim that the use of this term implies the projection of a modern category to a world - that of prehistoric humans - which is completely different from our own. On the other hand, some archaeologists consider that the term “Palaeolithic art” does not imply an anachronistic interpretation of prehistoric representations. In presenting the historical context, which has made such a discussion possible, we consider the causes and effects of this controversy. Firstly, we analyze the traditional interpretation, which considered Palaeolithic images as “works of art”. Secondly, we examine the connections, which can be found between the debate about “Palaeolithic art” and certain polemics, which have arisen from the history of art and anthropological frameworks. Thirdly, we consider the arguments utilized by those who are for and those who are against the term “Palaeolithic art”. Finally, we emphasize the importance of this debate to better understand the categories and the concepts, which determine the scientific practice.     

The structure and orientation of class-A amphipathic peptides on a phospholipid bilayer surface

The amphipathic α-helix is a recognised structural motif that is shared by membrane-associating proteins and peptides of diverse function. The aim of this paper is to determine the orientation of an α-helical amphipathic peptide on the bilayer surface. We use five amphipathic 18-residue peptide analogues of a class A amphipathic peptide that is known to associate with a bilayer surface. Tyrosine and tryptophan are used as spectroscopic probes to sense local environments in the peptide in solution and when bound to the surface of unilamellar phosphatidylcholine vesicles. In a series of peptides, tryptophan is moved progressively along the sequence from the nonpolar face (positions 3, 7, 4) to the polar face of the peptide (positions 2, 12). The local environment of the tryptophan residue at each position is determined using fluorescence spectroscopy employing quantum yield, and the wavelength of the emission maximum as indicators of micropolarity. The exposure of the tryptophan residues at each site is assessed by acrylamide quenching. On association with vesicles, the tryptophan residues at positions 3, 7 and 14 are in nonpolar water-shielded environments, and the tryptophan at position 12 is in an exposed polar environment. The tryptophan at position 2, which is located near the bilayer-water interface, exhibits intermediate behaviour. Analysis of the second-derivative absorption spectrum confirmed that the tyrosine residue at position 7 is in a nonpolar water-shielded environment in the peptide-lipid complex. We conclude that these class A amphipathic peptides lie parallel to the lipid surface and penetrate no deeper than the ester linkages of the phospholipids. Received: 8 April 1998 / Revised version: 6 July 1998 / Accepted: 7 August 1998     

Lipid-ion channel interactions: Increasing phospholipid headgroup size but not ordering acyl chains alters reconstituted channel behavior

We have recently shown (Chang et al., 1995) that lipid-channel interactions, exemplified by the effects of cholesterol on the calcium-activated potassium (BK) channel, profoundly affect channel properties. The present study further explores such interactions by monitoring changes in BK channel behavior after reconstitution into bilayers where the size of phospholipid (PL) headgroups is increased and where the freedom of motion (inverse order) of fatty acid chains is incremented. Increasing the PL headgroup cross-sectional area, from that of N-meth-DOPE to that of DOPC (an increase from ca. 60 to 70 Ų), is associated with a doubling of the channel mean opentime. Channel conductance, however, was unaffected. Increasing the order of the fatty acid chains, from that of DOPE to POPE and to that of DEPE, had no significant effect on channel properties (at 22°C). We interpret the changes reported here to reflect lipid-protein interactions through the induction of structural stress related to the headgroup structures of phospholipids.This research was funded in part by a grant (82–2687) from the Arizona Disease Control Research Commission, and a BRSG grant (to R.G.). R.R. was supported by National Institutes of Health Training grant HL-07249.     

Interaction of recombinant human epidermal growth factor with phospholipid vesicles. A steady-state and time-resolved fluorescence study of the bis-tryptophan sequence (TRP49-TRP50)

The interaction of recombinant human epidermal growth factor with small unilamellar phospholipid vesicles was studied by steady-state and time-resolved fluorescence of the bis-tryptophan sequence (Trp₄₉-Trp₅₀). Steady-state anisotropy measurements demonstrate that strong binding occurred with small unilamellar vesicles made up of acidic phospholipids at acidic pH only (pH 4.7). An apparent stoichiometry for 1,2-dimyristoyl-sn-phosphoglycerol of about 12 phospholipid molecules per molecule of human epidermal growth factor was estimated. The binding appears to be more efficient at temperatures above the gel to liquid-crystalline phase transition. The conformation and the environment of the Trp-Trp sequence are not greatly modified after binding, as judged from the invariance of the excited state lifetime distribution and from that of the fast processes affecting the anisotropy decay. This suggests that the Trp-Trp sequence is not embedded within the bilayer, in contrast to the situation in surfactant micelles (Mayo et al. 1987; Kohda and Inigaki 1992).Abbreviations DMPG 1,2-dimyristoyl-sn-phosphoglycerol - hEGF human Epidermal Growth Factor - HPLC high performance liquid chromatography - MEM Maximum Entropy Method - POPC 1-palmitoyl, 2-oleoyl-sn-phosphocholine - POPS 1-palmitoyl, 2-oleoyl-sn-phosphoserine - SUV small unilamellar vesicles - Trp tryptophan - Trp-Trp bis-tryptophan     

Real-time assay method of lipid extraction activity

Intracellular lipid translocation is mediated by lipid transfer proteins and their functional impairments cause severe disorder in lipid metabolism. However, molecular mechanisms of protein-mediated lipid transfer remain unclear since conventional assay methods could not observe elementary processes in the lipid transfer reaction, such as lipid bilayer binding and lipid uptake. In this study, we found that ceramide extraction mediated by a ceramide trafficking protein (CERT) could be detected as decreasing the response of surface plasmon resonance (SPR). Based on this finding, we developed a novel real-time assay method that enables quantitative evaluation of the ceramide extraction activity of CERT, using the SPR technique. Performing this SPR-based assay using ceramide-embedded and ceramide-free lipid bilayers as ligands allows for the exclusive investigation of ceramide uptake processes, differentiating them from other CERT-membrane binding events. Furthermore, mutagenesis experiments of CERT using this SPR-based assay clearly elucidated whether an amino acid residue plays a role in the ceramide uptake process or the lipid bilayer binding process. This SPR-based assay method can separately evaluate the lipid extraction activity and lipid bilayer binding activity of the lipid transfer proteins, and provide more detailed information about lipid transfer phenomena.     

Notes and tips for improving quality of lipid-protein overlay assays

To reduce costs of lipid-binding assays, allow for multiple lipids to be screened for protein binding simultaneously, and to make lipid binding more user friendly, lipids have been dotted onto membranes to investigate lipid-protein interactions. These assays are similar to a western blot where the membrane is blocked, incubated with a protein of interest and detected using antibodies. Although the assay is inexpensive and straightforward, problems with promiscuous or poor binding, as well as insufficient blocking occur frequently. In this technical note, we share several specific improvements to ensure lipid-protein overlay assays are of high quality and contain proper controls.     

Identification of a segment in the precursor of pulmonary surfactant protein SP-B, potentially involved in pH-dependent membrane assembly of the protein

In the present work, the hydrophobic properties of proSP-B, the precursor of pulmonary surfactant protein SP-B, have been analyzed under different pH conditions, and the sequence segment at position 111-135 of the N-terminal domain of the precursor has been detected as potentially possessing pH-dependent hydrophobic properties. We have studied the structure and lipid-protein interactions of the synthetic peptides BpH, with sequence corresponding to the segment 111-135 of proSP-B, and BpH-W, bearing the conservative substitution F127W to use the tryptophan as an intrinsic fluorescent probe. Peptide BpH-W interacts with both zwitterionic and anionic phospholipid vesicles at neutral pH, as monitored by the blue-shifted maximum emission of its tryptophan reporter. Insertion of tryptophan into the membranes is further improved at pH 5.0, especially in negatively-charged membranes. Peptides BpH and BpH-W also showed pH-dependent properties to insert into phospholipid monolayers. We have also found that the single sequence variation F120K decreases substantially the interaction of this segment with phospholipid surfaces as well as its pH-dependent insertion into deeper regions of the membranes. We hypothesize that this region could be involved in pH-triggered conformational changes occurring in proSP-B along the exocytic pathway of surfactant in type II cells, leading to the exposure of the appropriate segments for processing and assembly of SP-B within surfactant lipids.