An MD2-derived peptide promotes LPS aggregation,facilitates its internalization in THP-1 cells,and inhibits LPS-induced pro-inflammatory responses

MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS. An MD54 analog of the same size was also designed in which a leucine residue at a heptadic position was replaced with an alanine residue. MD54 but not its analog, MMD54 induced aggregation of LPS and aided in its internalization within THP-1 monocytes. Furthermore, MD54 inhibited LPS-induced nuclear translocation of NF-κB in PMA-treated THP-1 and TLR4/MD2/CD14-transfected HEK-293T cells and the production of pro-inflammatory cytokines. In addition, in in vivo experiments, MD54 showed marked protection and survival of mice against LPS-induced inflammation and death. Overall, we have identified a short peptide with heptad repeat sequence from MD2 that can cause aggregation of LPS and abet in its internalization within THP-1 cells, resulting in attenuation of LPS-induced pro-inflammatory responses in vitro and in vivo.     

Three-dimensional structure of an antigen-antibody complex at 6 A resolution

Present understanding of the three-dimensional structure of antibody combining sites is based on X-ray diffraction studies of myeloma immunoglobulins. The structures of the antigen-binding fragment (Fab) complexes of two of these immunoglobulins with small ligands have also been determined. However, there is no crystallographic information concerning the interactions of an antibody with an antigen, nor do we know the precise structure of antigenic determinants on protein molecules. We now report the first structure determination of an antigen-antibody complex at 6 A resolution. The structure of the complex between hen egg-white lysozyme and the Fab of a monoclonal anti-lysozyme antibody (D1.3) shows that the combining site of antibodies is not merely a cleft delineated by the complementarity-determining regions of the variable regions of the light and heavy chains, but is a larger area extending beyond it. A correspondingly large area of the antigen makes close contacts with the antibody, in agreement with the notion of a 'topographical' rather than 'sequential' antigenic determinant. The structural basis of cross-reactivities of an antibody with heterologous antigens and the effect of a single amino acid substitution on antigenic specificity can thus be visualized in the structural model presented here.     

Experimental : The double standard in the quantum-information approach to the foundations of quantum theory

Among the alternatives of non-relativistic quantum mechanics (NRQM) there are those that give different predictions than quantum mechanics in yet-untested circumstances, while remaining compatible with current empirical findings. In order to test these predictions, one must isolate one's system from environmental induced decoherence, which, on the standard view of NRQM, is the dynamical mechanism that is responsible for the ‘apparent’ collapse in open quantum systems. But while recent advances in condensed-matter physics may lead in the near future to experimental setups that will allow one to test the two hypotheses, namely genuine collapse vs. decoherence, hence make progress toward a solution to the quantum measurement problem, those philosophers and physicists who are advocating an information-theoretic approach to the foundations of quantum mechanics are still unwilling to acknowledge the empirical character of the issue at stake. Here I argue that in doing so they are displaying an unwarranted double standard.     

Seasonal dynamics of recurrent epidemics

Seasonality is a driving force that has a major effect on the spatio-temporal dynamics of natural systems and their populations. This is especially true for the transmission of common infectious diseases (such as influenza, measles, chickenpox and pertussis), and is of great relevance for host-parasite relationships in general. Here we gain further insights into the nonlinear dynamics of recurrent diseases through the analysis of the classical seasonally forced SIR (susceptible, infectious or recovered) epidemic model. Our analysis differs from other modelling studies in that the focus is more on post-epidemic dynamics than the outbreak itself. Despite the mathematical intractability of the forced SIR model, we identify a new threshold effect and give clear analytical conditions for predicting the occurrence of either a future epidemic outbreak, or a 'skip'-a year in which an epidemic fails to initiate. The threshold is determined by the population's susceptibility measured after the last outbreak and the rate at which new susceptible individuals are recruited into the population. Moreover, the time of occurrence (that is, the phase) of an outbreak proves to be a useful parameter that carries important epidemiological information. In forced systems, seasonal changes can prevent late-peaking diseases (that is, those having high phase) from spreading widely, thereby increasing population susceptibility, and controlling the triggering and intensity of future epidemics. These principles yield forecasting tools that should have relevance for the study of newly emerging and re-emerging diseases controlled by seasonal vectors.     

Photo-induced optical changes in GexAs40Se60-x thin films

Ge-As-Se chalcogenide thin films show a wide range of photosensitivity, which is utilized for the fabrication of micro-optical elements for integrated optics. The photosensitivity of GexAs40Se60?x(x=0,15) chalcogenide thin films for UV light was presented. For that purpose, the bulk samples of GexAs40Se60?x(x=0,15) chalcogenide glasses were prepared using conventional melt quenching technique, and thin films were prepared using thermal evaporation technique. These thin films were exposed to UV light for two hours. Amorphous natures of bulk samples and thin films were verified by XRD and chemical compositions were verified by EDX measurements. The thicknesses of the thin films were measured using a thickness profilometer. Linear optical analysis of these thin films was done using transmission spectra in wavelength range of 300?900 nm. Optical bandgap was determined by first peak of transmission derivative as well as extrapol ation of Tauc’s plot. R2 analysis was done using R software to ensure that the material is indirect bandgap material. It is observed that two hours UV exposure causes photo-darkening along with photo-expansion in As40Se60 thin films, while photo-bleach ing and photo-densification for Ge15As40Se45 thin films. However, the amounts of photo-induced optical changes for Ge15As40Se45 thin films are smaller than those for As40Se60 thin films. The changes in optical absorption, bandgap and thickness are understood base d on the bonding rearrangement caused by UV exposure.     

Forecasting daily foreign exchange rates using genetically optimized neural networks

Forecasting currency exchange rates is an important financial problem that has received much attention especially because of its intrinsic difficulty and practical applications. The statistical distribution of foreign exchange rates and their linear unpredictability are recurrent themes in the literature of international finance. Failure of various structural econometric models and models based on linear time series techniques to deliver superior forecasts to the simplest of all models, the simple random walk model, have prompted researchers to use various non‐linear techniques. A number of non‐linear time series models have been proposed in the recent past for obtaining accurate prediction results, in an attempt to ameliorate the performance of simple random walk models. In this paper, we use a hybrid artificial intelligence method, based on neural network and genetic algorithm for modelling daily foreign exchange rates. A detailed comparison of the proposed method with non‐linear statistical models is also performed. The results indicate superior performance of the proposed method as compared to the traditional non‐linear time series techniques and also fixed‐geometry neural network models. Copyright © 2002 John Wiley & Sons, Ltd.     

Use of nonalpine anthropogenic habitats by American pikas ( Ochotona princeps ) in western Oregon

The American pika ( Ochotona princeps Richardson) has long been characterized in field guides and popular literature as an obligate inhabitant of alpine talus and as having relatively low dispersal capability. However, recent work reveals pikas to have broader habitat associations than previously reported. Over a large portion of the western slope of the Cascade Range in Oregon, pikas inhabit relatively low-elevation sites far from alpine areas and frequently occur in rocky man-made habitats such as roadcuts or rock quarries. We present observations of pikas in these previously overlooked habitats and discuss implications for (1) the proposed listing of the American pika as an endangered or threatened species; (2) furthering our understanding of pika population dynamics, habitat associations, and dispersal capabilites; and (3) management of federal, state, and private forest lands. Por mucho tiempo la pika americana ( Ochotona princeps Richardson) ha sido caracterizada en guías de campo y literatura popular como un habitante obligado de taludes alpinos y por tener una capacidad de dispersión relativamente baja. Sin embargo, trabajo reciente ha revelado que las pikas tienen asociaciones de hábitat más amplias de lo que hasta ahora se creía. En una gran parte de la vertiente occidental de la cordillera Cascade en Oregón, las pikas habitan sitios de elevación relativamente baja, lejos de las áreas alpinas y frecuentemente aparecen en hábitats rocosos artificiales tales como canteras y cortes de carretera. Presentamos observaciones de pikas en estos hábitats pasados por alto anteriormente y discutimos las implicaciones para (1) la propuesta de agregar la pika americana a la lista de especies amenazadas o en peligro; (2) ampliar nuestro conocimiento sobre la dinámica poblacional, las asociaciones de hábitat y la capacidad de dispersión; y (3) la gestión de tierras forestales federales, estatales y privadas.