Evaluation of serotype prediction by cpsA-cpsB gene polymorphism in Streptococcus pneumoniae

New pneumococcal conjugate vaccines covering a limited number of serotypes are likely to come into widespread use over the next few years. It is unknown what effect this will have on the relative importance of different serotypes as causes of pneumococcal infection. Hence, it will be important to monitor serotype prevalence before, during, and after the introduction of new vaccines. We have investigated the ability of a PCR method based on polymorphisms in two genes common to the different capsule loci to predict the serotype of 93 clinical isolates of Streptococcus pneumoniae submitted to the Central Public Health Laboratory in 1997. Of 70 isolates with vaccine serotypes, 65 were predicted to belong to the correct serotype; this number was improved to 69 with the inclusion of two additional patterns to the database. Of 23 isolates with other serotypes, 19 were correctly predicted as non-vaccine serotypes, the discrepancy lying with four isolates of 6A (non-vaccine serotype) that were indistinguishable from isolates of 6B (vaccine serotype). In situations in which culture of the organism is not feasible, this method could potentially be applicable directly to clinical specimens and could be a valuable aid to the surveillance of pneumococcal serotypes.     

Selectin catch–slip kinetics encode shear threshold adhesive behavior of rolling leukocytes

The selectin family of leukocyte adhesion receptors is principally recognized for mediating transient rolling interactions during the inflammatory response. Recent studies using ultrasensitive force probes to characterize the force–lifetime relationship between P- and L-selectin and their endogenous ligands have underscored the ability of increasing levels of force to initially extend the lifetime of these complexes before disrupting bond integrity. This so-called “catch–slip” transition has provided an appealing explanation for shear threshold phenomena in which increasing levels of shear stress stabilize leukocyte rolling under flow. We recently incorporated catch–slip kinetics into a mechanical model for cell adhesion and corroborated this hypothesis for neutrophils adhering via L-selectin. Here, using adhesive dynamics simulations, we demonstrate that biomembrane force probe measurements of various P- and L-selectin catch bonds faithfully predict differences in cell adhesion patterns that have been described extensively in vitro. Using phenomenological parameters to characterize the dominant features of molecular force spectra, we construct a generalized phase map that reveals that robust shear-threshold behavior is possible only when an applied force very efficiently stabilizes the bound receptor complex. This criteria explains why only a subset of selectin catch bonds exhibit a shear threshold and leads to a quantitative relationship that may be used to predict the magnitude of the shear threshold for families of catch–slip bonds directly from their force spectra. Collectively, our results extend the conceptual framework of adhesive dynamics as a means to translate complex single-molecule biophysics to macroscopic cell behavior.     

Deep brain stimulation in the globus pallidus compensates response inhibition deficits: evidence from pantothenate kinase-associated neurodegeneration

Fronto-striatal loops are important for many cognitive control processes, like response inhibition, and it has been suggested that the globus pallidus is of particular importance for these processes. In the current study, we investigate the effect of deep brain stimulation in the GP on response inhibition processes by means of neurophysiological (EEG) methods. We perform a case–control study in neuroaxonal dystrophy pantothenate kinase-associated neurodegeneration (PKAN) using single-case statistics. We control the signal-to-noise ratio of the EEG data. The data show that disease-related changes in the globus pallidus lead to dysfunctions in response inhibition processes. Dysfunctions in the GP seem to affect controlled, but not automatized behavior as evidenced by an increased rate of false alarms and attenuation of inhibition-related neurophysiological correlates. With respect to controlled behavior in terms of response inhibition, it seems that pre-motor subprocesses and not evaluation subprocesses are affected. Deep brain stimulation in the globus pallidus seems to be able to compensate the effects of disease-related changes in this structure and normalizes response inhibition performance and their electrophysiological correlates in PKAN.