Phase-lags in large scale brain synchronization : Methodological considerations and in-silico analysis

Architecture of phase relationships among neural oscillations is central for their functional significance but has remained theoretically poorly understood. We use phenomenological model of delay-coupled oscillators with increasing degree of topological complexity to identify underlying principles by which the spatio-temporal structure of the brain governs the phase lags between oscillatory activity at distant regions. Phase relations and their regions of stability are derived and numerically confirmed for two oscillators and for networks with randomly distributed or clustered bimodal delays, as a first approximation for the brain structural connectivity. Besides in-phase, clustered delays can induce anti-phase synchronization for certain frequencies, while the sign of the lags is determined by the natural frequencies and by the inhomogeneous network interactions. For in-phase synchronization faster oscillators always phase lead, while stronger connected nodes lag behind the weaker during frequency depression, which consistently arises for in-silico results. If nodes are in antiphase regime, then a distance Pi is added to the in-phase trends. The statistics of the phases is calculated from the phase locking values (PLV), as in many empirical studies, and we scrutinize the method's impact. The choice of surrogates do not affects the mean of the observed phase lags, but higher significance levels that are generated by some surrogates, cause decreased variance and might fail to detect the generally weaker coherence of the interhemispheric links. These links are also affected by the non-stationary and intermittent synchronization, which causes multimodal phase lags that can be misleading if averaged. Taken together, the results describe quantitatively the impact of the spatio-temporal connectivity of the brain to the synchronization patterns between brain regions, and to uncover mechanisms through which the spatio-temporal structure of the brain renders phases to be distributed around 0 and Pi.Peer reviewe

Crystallization and X-ray diffraction analysis of SpaE, a basal pilus protein from the gut-adapted Lactobacillus rhamnosus GG

SpaE is the predicted basal pilin subunit in the sortase-dependent SpaFED pilus from the gut-adapted and commensal Lactobacillus rhamnosus GG. Thus far, structural characterization of the cell-wall-anchoring basal pilins has remained difficult and has been limited to only a few examples from pathogenic genera and species. To gain a further structural understanding of the molecular mechanisms that are involved in the anchoring and assembly of sortase-dependent pili in less harmful bacteria, L. rhamnosus GG SpaE for crystallization was produced by recombinant expression in Escherichia coli. Although several attempts to crystallize the SpaE protein were unsuccessful, trigonal crystals that diffracted to a resolution of 3.1 angstrom were eventually produced using PEG 3350 as a precipitant and high protein concentrations. Further optimization with a combination of additives led to the generation of SpaE crystals in an orthorhombic form that diffracted to a higher resolution of 1.5 angstrom. To expedite structure determination by SAD phasing, selenium-substituted (orthorhombic) SpaE crystals were grown and X-ray diffraction data were collected to 1.8 angstrom resolution.Peer reviewe

The structure of Lactobacillus brevis surface layer reassembled on liposomes differs from native structure as revealed by SAXS

AbstractThe reassembly of the S-layer protein SlpA of Lactobacillus brevis ATCC 8287 on positively charged liposomes was studied by small angle X-ray scattering (SAXS) and zeta potential measurements. SlpA was reassembled on unilamellar liposomes consisting of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-3-trimethylammonium-propane, prepared by extrusion through membranes with pore sizes of 50nm and 100nm. Similarly extruded samples without SlpA were used as a reference. The SlpA-containing samples showed clear diffraction peaks in their SAXS intensities. The lattice constants were calculated from the diffraction pattern and compared to those determined for SlpA on native cell wall fragments. Lattice constants for SlpA reassembled on liposomes (a=9.29nm, b=8.03nm, and γ=84.9°) showed a marked change in the lattice constants b and γ when compared to those determined for SlpA on native cell wall fragments (a=9.41nm, b=6.48nm, and γ=77.0°). The latter are in good agreement with values previously determined by electron microscopy. This indicates that the structure formed by SlpA is stable on the bacterial cell wall, but SlpA reassembles into a different structure on cationic liposomes. From the (10) reflection, the lower limit of crystallite size of SlpA on liposomes was determined to be 92nm, corresponding to approximately ten aligned lattice planes

Molecular ecology of the yet uncultured bacterial Ct85-cluster in the mammalian gut

In our previous studies on irritable bowel syndrome (IBS) –associated microbiota by molecular methods, we demonstrated that a particular 16S rRNA gene amplicon was more abundant in the feces of healthy subjects or mixed type IBS (IBS-M) –sufferers than in the feces of individuals with diarrhea-type IBS (IBS-D). In the current study, we demonstrated that this, so called Ct85-amplicon, consists of a cluster of very heterogeneous 16S rRNA gene sequences, and defined six 16S rRNA gene types, a to f, within this cluster, each representing a novel species-, genus- or family level taxon. We then designed specific PCR primers for these sequence types, mapped the distribution of the Ct85-cluster sequences and that of the newly defined sequence types in several animal species and compared the sequence types present in the feces of healthy individuals and IBS sufferers using two IBS study cohorts, Finnish and Dutch. Various Ct85-cluster sequence types were detected in the fecal samples of several companion and production animal species with remarkably differing prevalences and abundances. The Ct85 sequence type composition of swine closely resembled that of humans. One of the five types (d) shared between humans and swine was not present in any other animals tested, while one sequence type (b) was found only in human samples. In both IBS study cohorts, one type (e) was more prevalent in healthy individuals than in the IBS-M group. By revealing various sequence types in the widespread Ct85-cluster and their distribution, the results improve our understanding of these uncultured bacteria, which is essential for future efforts to cultivate representatives of the Ct85-cluster and reveal their roles in IBS.Peer reviewe

BopA does not have a major role in the adhesion of bifidobacterium bifidum to intestinal epithelial cells, extracellular matrix proteins, and mucus

he ability of bifidobacteria to adhere to the intestine of the human host is considered to be important for efficient colonization and achieving probiotic effects. Bifidobacterium bifidum strains DSM20456 and MIMBb75 adhere well to the human intestinal cell lines Caco-2 and HT-29. The surface lipoprotein BopA was previously described to be involved in mediating adherence of B. bifidum to epithelial cells, but thioacylated, purified BopA inhibited the adhesion of B. bifidum to epithelial cells in competitive adhesion assays only at very high concentrations, indicating an unspecific effect. In this study, the role of BopA in the adhesion of B. bifidum was readdressed. The gene encoding BopA was cloned and expressed without its lipobox and hydrophobic signal peptide in Escherichia coli, and an antiserum against the recombinant BopA was produced. The antiserum was used to demonstrate the abundant localization of BopA on the cell surface of B. bifidum. However, blocking of B. bifidum BopA with specific antiserum did not reduce adhesion of bacteria to epithelial cell lines, arguing that BopA is not an adhesin. Also, adhesion of B. bifidum to human colonic mucin and fibronectin was found to be BopA independent. The recombinant BopA bound only moderately to human epithelial cells and colonic mucus, and it failed to bind to fibronectin. Thus, our results contrast the earlier findings on the major role of BopA in adhesion, indicating that the strong adhesion of B. bifidum to epithelial cell lines is BopA independent

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1

Peer reviewedPublisher PD

Cochlear implantation in patients with chronic otitis media: 7 years’ experience in Maastricht

The purpose of this paper is to propose management options for cochlear implantation in chronic otitis media (COM) based on our 7-year experience. Thirteen patients with COM who were candidates for cochlear implantation were identified. COM was divided in an inactive and an active form based on clinical and radiological findings. One major complications and one minor complication were identified in the study group. In case of an active infection or in case of a unstable cavity we advise cochlear implantation as a staged procedure. A single stage procedure is recommended in case of patients with COM presenting with a dry perforation or a stable cavity

Cross-Frequency Integration for Consonant and Vowel Identification in Bimodal Hearing

Purpose: Improved speech recognition in binaurally combined acoustic–electric stimulation (otherwise known as bimodal hearing) could arise when listeners integrate speech cues from the acoustic and electric hearing. The aims of this study were (a) to identify speech cues extracted in electric hearing and residual acoustic hearing in the low-frequency region and (b) to investigate cochlear implant (CI) users' ability to integrate speech cues across frequencies. Method: Normal-hearing (NH) and CI subjects participated in consonant and vowel identification tasks. Each subject was tested in 3 listening conditions: CI alone (vocoder speech for NH), hearing aid (HA) alone (low-pass filtered speech for NH), and both. Integration ability for each subject was evaluated using a model of optimal integration—the PreLabeling integration model (Braida, 1991). Results: Only a few CI listeners demonstrated bimodal benefit for phoneme identification in quiet. Speech cues extracted from the CI and the HA were highly redundant for consonants but were complementary for vowels. CI listeners also exhibited reduced integration ability for both consonant and vowel identification compared with their NH counterparts. Conclusion: These findings suggest that reduced bimodal benefits in CI listeners are due to insufficient complementary speech cues across ears, a decrease in integration ability, or both.National Organization for Hearing ResearchNational Institute on Deafness and Other Communication Disorders (U.S.) (Grant R03 DC009684-01)National Institute on Deafness and Other Communication Disorders (U.S.) (Grant R01 DC007152-02

Covert Waking Brain Activity Reveals Instantaneous Sleep Depth

The neural correlates of the wake-sleep continuum remain incompletely understood, limiting the development of adaptive drug delivery systems for promoting sleep maintenance. The most useful measure for resolving early positions along this continuum is the alpha oscillation, an 8–13 Hz electroencephalographic rhythm prominent over posterior scalp locations. The brain activation signature of wakefulness, alpha expression discloses immediate levels of alertness and dissipates in concert with fading awareness as sleep begins. This brain activity pattern, however, is largely ignored once sleep begins. Here we show that the intensity of spectral power in the alpha band actually continues to disclose instantaneous responsiveness to noise—a measure of sleep depth—throughout a night of sleep. By systematically challenging sleep with realistic and varied acoustic disruption, we found that sleepers exhibited markedly greater sensitivity to sounds during moments of elevated alpha expression. This result demonstrates that alpha power is not a binary marker of the transition between sleep and wakefulness, but carries rich information about immediate sleep stability. Further, it shows that an empirical and ecologically relevant form of sleep depth is revealed in real-time by EEG spectral content in the alpha band, a measure that affords prediction on the order of minutes. This signal, which transcends the boundaries of classical sleep stages, could potentially be used for real-time feedback to novel, adaptive drug delivery systems for inducing sleep