An idiotypic cross-reaction between allotype a3 and allotype a negative rabbit antibodies to streptococcal carbohydrates

Two antibodies to Group C streptococcal carbohydrate isolated from an individual rabbit had similar relative binding affinities for a Group C immuno-adsorbent column. Their light chains were similar, if not identical, as were the constant regions of their heavy chains. Differences in the variable regions of the H chains of the two antibodies were detected by chemical analysis. The two antibodies had serologically identical idiotypic determinants although one antibody possessed the a3 allotype and the other had no detectable group a marker. The occurrence of such antibodies indicates the absence of obligatory associations between group a allotypes and idiotypic specificities, despite the fact that both determinants have antigenic components in the VH region of the H chain

A Holistic Social Constructionist perspective to Enterprise Education

Purpose – Drawing on the Gestalt approach this article proposes a holistic framework for enterprise education (EE) research based on Social Constructionism, illustrating how the latter supports research into experiential learning in EE in 7 UK Higher Education (HE) pharmacy schools. Design/ Methodology/ Approach – This paper is based on a qualitative empirical study involving educators in UK Higher Education Institution (HEI) pharmacy schools in semi-structured interviews, and investigates the delivery of EE through experiential learning approaches. Social Constructionism is proposed as a suitable underlying philosophical paradigm. Findings – A Social Constructionism paradigm, which adopts relative realism ontology, transactional epistemology, and Gadamer’s Hermeneutic Phenomenology, offers a relevant, multi-perspectival philosophical foundation for EE research, supporting transactional relationships within contexts of multiple possibilities. Research limitations/implications – Social Constructionism does not necessarily support the individualistic paradigm, as advocated by Constructivists; and the values associated with the former encourage a more collaborative and cooperative approach different from the latter. Practical implications –The paper supports the understanding that applying experiential learning through inter-disciplinary and inter-professional learning is regarded as an approach beneficial for educators, institutions and learners, within the context of EE. Originality/ value – This paper offers a holistic conceptual framework of Social Constructionism that draws on the ‘Gestalt Approach’, and highlights the harmony between the ontological, epistemological and methodological underpinnings of Social Constructionism. The paper demonstrates the relevance of the proposed framework in EE research within the context of an empirical study, which is different in that it focuses on the delivery aspect of EE by considering the views of the providers (educators), an hitherto under-researched area. Paper type – Research paper Key words: Enterprise education, research philosophy, Social Constructionism, relative realism ontology, transactional epistemology, Gadamer’s Hermeneutic Phenomenology, Gestalt approach

Accurate laboratory rest frequencies of vibrationally excited CO up to varv=3varv = 3 and up to 2 THz

Astronomical observations of (sub)millimeter wavelength pure rotational emission lines of the second most abundant molecule in the Universe, CO, hold the promise of probing regions of high temperature and density in the innermost parts of circumstellar envelopes. The rotational spectrum of vibrationally excited CO up to \varv = 3 has been measured in the laboratory between 220 and 1940 GHz with relative accuracies up to $5.2 \times 10^{-9}$, corresponding to $\sim 5$ kHz near 1 THz. The rotational constant $B$ and the quartic distortion parameter $D$ have been determined with high accuracy and even the sextic distortion term $H$ was determined quite well for \varv = 1 while reasonable estimates of $H$ were obtained for \varv = 2 and 3. The present data set allows for the prediction of accurate rest frequencies of vibrationally excited CO well beyond 2 THz.Comment: Astron. Astrophys, accepted; 5 pages, 2 Figures, 2 Table

Twirling and Whirling: Viscous Dynamics of Rotating Elastica

Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by a novel pair of coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two dynamical regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.Comment: To be published in Physical Review Letter

Between- and within-population variations in thermal reaction norms of the coccolithophore Emiliania huxleyi

Thermal reaction norms for growth rates of six Emiliania huxleyi isolates originating from the central Atlantic (Azores, Portugal) and five isolates from the coastal North Atlantic (Bergen, Norway) were assessed. We used the template mode of variation model to decompose variations in growth rates into modes of biological interest: vertical shift, horizontal shift, and generalist–specialist variation. In line with the actual habitat conditions, isolates from Bergen (Bergen population) grew well at lower temperatures, and isolates from the Azores (Azores population) performed better at higher temperatures. The optimum growth temperature of the Azores population was significantly higher than that of the Bergen population. Neutral genetic differentiation was found between populations by microsatellite analysis. These findings indicate that E. huxleyi populations are adapted to local temperature regimes. Next to between-population variation, we also found variation within populations. Genotype-by-environment interactions resulted in the most pronounced phenotypic differences when isolates were exposed to temperatures outside the range they naturally encounter. Variation in thermal reaction norms between and within populations emphasizes the importance of using more than one isolate when studying the consequences of global change on marine phytoplankton. Phenotypic plasticity and standing genetic variation will be important in determining the potential of natural E. huxleyi populations to cope with global climate change

The Viscous Nonlinear Dynamics of Twist and Writhe

Exploiting the "natural" frame of space curves, we formulate an intrinsic dynamics of twisted elastic filaments in viscous fluids. A pair of coupled nonlinear equations describing the temporal evolution of the filament's complex curvature and twist density embodies the dynamic interplay of twist and writhe. These are used to illustrate a novel nonlinear phenomenon: ``geometric untwisting" of open filaments, whereby twisting strains relax through a transient writhing instability without performing axial rotation. This may explain certain experimentally observed motions of fibers of the bacterium B. subtilis [N.H. Mendelson, et al., J. Bacteriol. 177, 7060 (1995)].Comment: 9 pages, 4 figure

Detection, isolation, and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells.

Cultured hamster trachea epithelial cells were selected as an in vitro model system to study Bordetella pertussis in the respiratory tract. DNA synthesis by serum-stimulated tracheal cells, in contrast to other cell types tested, was inhibited by the supernatant from log-phase B. pertussis broth cultures. A sensitive microassay with these tracheal cells permitted the development of a chromatographic purification scheme based on aggregation of the biological activity under salt-free conditions. The active fraction from this first stage of purification caused a dose-dependent inhibition of DNA synthesis without a similar effect on RNA or protein synthesis. Organ cultures of hamster tracheal rings, when exposed to this partially purified fraction, developed epithelial cytopathology comparable to that seen during B. pertussis infection. Ciliary activity showed and eventually ceased as ciliated cells were extruded from the ring, leaving an intact but mostly nonciliated epithelium. Further purification of this biological activity was achieved with preparative-scale high-voltage paper electrophoresis. Based on ninhydrin staining and the radioactive profile of material purified from radiolabeled B. pertussis cultures, four fractions were eluted from the paper by descending chromatography. Only component B caused a dose-dependent inhibition of cultured tracheal cell DNA synthesis and epithelial cytopathology in tracheal rings. Combination experiments also demonstrated enhanced inhibition by component B in the presence of component G (oxidized glutathione), a copurifying molecule from the growth medium. Amino acid analysis (five residues), glycine (two residues), cysteine (two residues), and diaminopimelic acid (one residue), as well as muramic acid and glucosamine

Purification of a 31,000-dalton insulin-like growth factor binding protein from human amniotic fluid. Isolation of two forms with different biologic actions.

Human amniotic fluid has been shown to contain a protein that binds insulin-like growth factor I and II (IGF-I and IGF-II). Partially purified preparations of this protein have been reported to inhibit the biologic actions of the IGFs. In these studies our laboratory has used a modified purification procedure to obtain a homogeneous preparation of this protein as determined by polyacrylamide gel electrophoresis and amino acid sequence analysis. During purification the ion exchange chromatography step resulted in two peaks of material with IGF binding activity termed peaks B and C. Each peak was purified separately to homogeneity. Both peaks were estimated to be 31,000 daltons by polyacrylamide gel electrophoresis and their amino acid compositions were nearly identical. Amino acid sequence analysis showed that both peaks had identical N-terminal sequences through the first 28 residues. Neither protein had detectable carbohydrate side chains and each had a similar affinity for radiolabeled IGF-I (1.7-2.2 x 10(10) liters/mol). In contrast, these two forms had marked differences in bioactivity. Concentrations of peak C material between 2 and 20 ng/ml inhibited IGF-I stimulation of [3H]thymidine incorporation into smooth muscle cell DNA. In contrast, when peak B (100 ng/ml) was incubated with IGF-I there was a 4.4-fold enhancement of stimulation of DNA synthesis. Additionally, pure peak B was shown to adhere to cell surfaces, whereas peak C was not adherent. The non-adherent peak C inhibited IGF-I binding to its receptor and to adherent peak B. We conclude that human amniotic fluid contains two forms of IGF binding protein that have very similar physiochemical characteristics but markedly different biologic actions. Since both have similar if not identical amino acid compositions, N-terminal sequences, and do not contain carbohydrate, we conclude that they differ in some other as yet undefined post-translational modification

Antigenic and structural differences among six proteins II expressed by a single strain of Neisseria gonorrhoeae.

Gonococci express a family of related outer membrane proteins designated protein II (P.II), which undergo both phase and antigenic variation. Six P.II proteins have been identified in strain FA1090. We developed monoclonal antibodies specific for each P.II protein. Using these antibodies as probes, we purified the six different P.II proteins of this strain. Despite the relatedness of the proteins, we could not purify all of them by a single purification scheme. Four P.II proteins were purified by chromatofocusing, and the remaining two proteins were purified by hydrophobic interaction chromatography on phenyl-Sepharose. The N-terminal amino acid sequence of the proteins showed a high degree of sequence conservation. However, there was variability at specific amino acid residues, giving each P.II protein a unique N-terminal amino acid sequence. Thus P.II proteins of one strain differ among themselves not only in antigenic determinants and primary structure, but also in other characteristics affecting their properties in different chromatographic systems

Wild-Type and Mutant Hemagglutinin Fusion Peptides Alter Bilayer Structure as Well as Kinetics and Activation Thermodynamics of Stalk and Pore Formation Differently: Mechanistic Implications

Viral fusion peptides are short N-terminal regions of type-1 viral fusion proteins that are critical for virus entry. Although the importance of viral fusion peptides in virus-cell membrane fusion is established, little is known about how they function. We report the effects of wild-type (WT) hemagglutinin (HA) fusion peptide and its G1S, G1V, and W14A mutants on the kinetics of poly(ethylene glycol)(PEG)-mediated fusion of small unilamellar vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine, sphingomyelin, and cholesterol (molar ratio of 35:30:15:20). Time courses of lipid mixing, content mixing, and content leakage were obtained using fluorescence assays at multiple temperatures and analyzed globally using either a two-step or three-step sequential ensemble model of the fusion process to obtain the rate constant and activation thermodynamics of each step. We also monitored the influence of peptides on bilayer interfacial order, acyl chain order, bilayer free volume, and water penetration. All these data were considered in terms of a recently published mechanistic model for the thermodynamic transition states for each step of the fusion process. We propose that WT peptide catalyzes Step 1 by occupying bilayer regions vacated by acyl chains that protrude into interbilayer space to form the Step 1 transition state. It also uniquely contributes a positive intrinsic curvature to hemi-fused leaflets to eliminate Step 2 and catalyzes Step 3 by destabilizing the highly stressed edges of the hemi-fused microstructures that dominate the ensemble of the intermediate state directly preceding fusion pore formation. Similar arguments explain the catalytic and inhibitory properties of the mutant peptides and support the hypothesis that the membrane-contacting fusion peptide of HA fusion protein is key to its catalytic activity