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

No significant improvement of cardiovascular disease risk indicators by a lifestyle intervention in people with familial hypercholesterolemia compared to usual care: results of a randomised controlled trial

Background: People with Familial Hypercholesterolemia (FH) may benefit from lifestyle changes supporting their primary treatment of dyslipidaemia. This project evaluated the efficacy of an individualised tailored lifestyle intervention on lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides), systolic blood pressure, glucose, body mass index (BMI) and waist circumference in people with FH. Methods: Adults with FH (n= 340), recruited from a Dutch cascade screening program, were randomly assigned to either a control group or an intervention group. The personalised intervention consisted of web-based tailored lifestyle advice and personal counselling. The control group received care as usual. Lipids, systolic blood pressure, glucose, BMI, and waist circumference were measured at baseline and after 12 months. Regression analyses were conducted to examine differences between both groups. Results: After 12 months, no significant between-group differences of cardiovascular disease (CVD) risk indicators were observed. LDL-C levels had decreased in both the intervention and control group. This difference between intervention and control group was not statistically significant. Conclusions: This project suggests that an individually tailored lifestyle intervention did not have an additional effect in improving CVD risk indicators among people with FH. The cumulative effect of many small improvements in all indicators on long term CVD risk remains to be assessed in future studies. Trial registration: NTR1899 at ww.trialregister.nl.© 2012 Broekhuizen et al

First Steps in Using Multi-Voxel Pattern Analysis to Disentangle Neural Processes Underlying Generalization of Spider Fear

A core symptom of anxiety disorders is the tendency to interpret ambiguous information as threatening. Using electroencephalography and blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI), several studies have begun to elucidate brain processes involved in fear-related perceptual biases, but thus far mainly found evidence for general hypervigilance in high fearful individuals. Recently, multi-voxel pattern analysis (MVPA) has become popular for decoding cognitive states from distributed patterns of neural activation. Here, we used this technique to assess whether biased fear generalization, characteristic of clinical fear, is already present during the initial perception and categorization of a stimulus, or emerges during the subsequent interpretation of a stimulus. Individuals with low spider fear (n = 20) and high spider fear (n = 18) underwent functional MRI scanning while viewing series of schematic flowers morphing to spiders. In line with previous studies, individuals with high fear of spiders were behaviorally more likely to classify ambiguous morphs as spiders than individuals with low fear of spiders. Univariate analyses of BOLD-MRI data revealed stronger activation toward spider pictures in high fearful individuals compared to low fearful individuals in numerous areas. Yet, neither average activation, nor support vector machine classification (i.e., a form of MVPA) matched the behavioral results – i.e., a biased response toward ambiguous stimuli – in any of the regions of interest. This may point to limitations of the current design, and to challenges associated with classifying emotional and neutral stimuli in groups that differ in their judgment of emotionality. Improvements for future research are suggested

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals

Enlargement of ribbons in zebrafish hair cells increases calcium currents, but disrupts afferent spontaneous activity and timing of stimulus onset.

In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure-the synaptic ribbon-that organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Taken together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons.SIGNIFICANCE STATEMENTNumerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset-a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence sensory encoding, and give further insight into how hair cells transduce signals that cover a wide dynamic range of stimuli

Thermodynamics and structure of self-assembled networks

We study a generic model of self-assembling chains which can branch and form networks with branching points (junctions) of arbitrary functionality. The physical realizations include physical gels, wormlike micells, dipolar fluids and microemulsions. The model maps the partition function of a solution of branched, self-assembling, mutually avoiding clusters onto that of a Heisenberg magnet in the mathematical limit of zero spin components. The model is solved in the mean field approximation. It is found that despite the absence of any specific interaction between the chains, the entropy of the junctions induces an effective attraction between the monomers, which in the case of three-fold junctions leads to a first order reentrant phase separation between a dilute phase consisting mainly of single chains, and a dense network, or two network phases. Independent of the phase separation, we predict the percolation (connectivity) transition at which an infinite network is formed that partially overlaps with the first-order transition. The percolation transition is a continuous, non thermodynamic transition that describes a change in the topology of the system. Our treatment which predicts both the thermodynamic phase equilibria as well as the spatial correlations in the system allows us to treat both the phase separation and the percolation threshold within the same framework. The density-density correlation correlation has a usual Ornstein-Zernicke form at low monomer densities. At higher densities, a peak emerges in the structure factor, signifying an onset of medium-range order in the system. Implications of the results for different physical systems are discussed.Comment: Submitted to Phys. Rev.

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Ising Universality in Three Dimensions: A Monte Carlo Study

We investigate three Ising models on the simple cubic lattice by means of Monte Carlo methods and finite-size scaling. These models are the spin-1/2 Ising model with nearest-neighbor interactions, a spin-1/2 model with nearest-neighbor and third-neighbor interactions, and a spin-1 model with nearest-neighbor interactions. The results are in accurate agreement with the hypothesis of universality. Analysis of the finite-size scaling behavior reveals corrections beyond those caused by the leading irrelevant scaling field. We find that the correction-to-scaling amplitudes are strongly dependent on the introduction of further-neighbor interactions or a third spin state. In a spin-1 Ising model, these corrections appear to be very small. This is very helpful for the determination of the universal constants of the Ising model. The renormalization exponents of the Ising model are determined as y_t = 1.587 (2), y_h = 2.4815 (15) and y_i = -0.82 (6). The universal ratio Q = ^2/ is equal to 0.6233 (4) for periodic systems with cubic symmetry. The critical point of the nearest-neighbor spin-1/2 model is K_c=0.2216546 (10).Comment: 25 pages, uuencoded compressed PostScript file (to appear in Journal of Physics A

A single particle model to simulate the dynamics of entangled polymer melts

We present a computer simulation model of polymer melts representing each chain as one single particle. Besides the position coordinate of each particle, we introduce a parameter nij for each pair of particles i and j within a specified distance from each other. These numbers, called entanglement numbers, describe the deviation of the system of ignored coordinates from its equilibrium state for the given configuration of the centers of mass of the polymers. The deviations of the entanglement numbers from their equilibrium values give rise to transient forces, which, together with the conservative forces derived from the potential of mean force, govern the displacements of the particles. We have applied our model to a melt of C800H1602 chains at 450 K and have found good agreement with experiments and more detailed simulations. Properties addressed in this paper are radial distribution functions, dynamic structure factors, and linear as well as nonlinear rheological properties