Localization of cortico-peripheral coherence with electroencephalography.

Background The analysis of coherent networks from continuous recordings of neural activity with functional MRI or magnetoencephalography has provided important new insights into brain physiology and pathology. Here we assess whether valid localizations of coherent cortical networks can also be obtained from high-resolution electroencephalography (EEG) recordings. Methods EEG was recorded from healthy subjects and from patients with ischemic brain lesions during a tonic hand muscle contraction task and during continuous visual stimulation with an alternating checkerboard. These tasks induce oscillations in the primary hand motor area or in the primary visual cortex, respectively, which are coherent with extracerebral signals (hand muscle electromyogram or visual stimulation frequency). Cortical oscillations were reconstructed with different inverse solutions and the coherence between oscillations at each cortical voxel and the extracerebral signals was calculated. Moreover, simulations of coherent point sources were performed. Results Cortico-muscular coherence was correctly localized to the primary hand motor area and the steady-state visual evoked potentials to the primary visual cortex in all subjects and patients. Sophisticated head models tended to yield better localization accuracy than a single sphere model. A Minimum Variance Beamformer (MVBF) provided more accurate and focal localizations of simulated point sources than an L2 Minimum Norm (MN) inverse solution. In the real datasets, the MN maps had less localization error but were less focal than MVBF maps. Conclusions EEG can localize coherent cortical networks with sufficient accuracy

Background EEG connectivity captures the time-course of epileptogenesis in a mouse model of epilepsy

This is the author accepted manuscript. The final version is available from Society for Neuroscience via the DOI in this recordLarge-scale brain networks are increasingly recognized as important for the generation of seizures in epilepsy. However, how a network evolves from a healthy state through the process of epileptogenesis remains unclear. To address this question, here, we study longitudinal epicranial background EEG recordings (30 electrodes, EEG free from epileptiform activity) of a mouse model of mesial temporal lobe epilepsy. We analyse functional connectivity networks and observe that over the time-course of epileptogenesis the networks become increasingly asymmetric. Furthermore, computational modelling reveals that a set of nodes, located outside of the region of initial insult, emerges as particularly important for the network dynamics. These findings are consistent with experimental observations, thus demonstrating that ictogenic mechanisms can be revealed on the EEG, that computational models can be used to monitor unfolding epileptogenesis and that both the primary focus and epileptic network play a role in epileptogenesis.Epilepsy Research UKEngineering and Physical Sciences Research Council (EPSRC)Wellcome Trus

Craniometric variation among Brazilian and Scottish populations: a physical anthropology approach

The present investigation intended to compare the craniometric variations of two samples of different nationalities (Brazilian and Scottish). Materials and methods: The Brazilian sample consisted of 100 modern complete skulls, including 53 female skulls and 47 male skulls, and the Scottish sample consisted of 100 historical skulls (61 males, 39 females) and 36 mandibles (24 males, 12 females). The cranial measurement protocol was composed of 40 measurements, 11 bilateral and 29 unilateral, and the measurement protocol of the mandible was composed of 15 measurements, with six that were bilateral and nine that were unique. The comparative analysis of the metric variability between the two samples was performed using the means and medians analysis, the t-test, the Wilcoxon test, and the coefficient of variance, with a significance level of 5%. Results: The results showed that, among the 72 analysed variables, 44 measurements (61.11%) presented statistical differences between the samples. The Scottish skull tends to have a cranial length (GOL diff=5.53), breadth (XCB diff=3.78) and height (NPH diff=5.33) greater than the Brazilian skulls, and the Scottish mandibles tend to show a higher mandibular ramus height (MRH diff=9.25), a higher mandibular body height (HMB diff=6.37) and a larger bigonial breadth (BGB diff=5.29) than the Brazilians. The discriminant analysis of the 51 cranial measurements and 21 mandibular measurements showed a variation of the percentage of accuracy between 46.3- 83.8%. Conclusion: The metric analysis demonstrated that there is variability between the two samples studied (61.11%), but a concrete cause cannot be determined considering the multifactorial aspects of the variations of form and size

Sex Differences in Semantic Processing: Event-Related Brain Potentials Distinguish between Lower and Higher Order Semantic Analysis during Word Reading

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processin

Initial steps towards a production platform for DNA sequence analysis on the grid

ABSTRACT: BACKGROUND: Bioinformatics is confronted with a new data explosion due to the availability of high throughput DNA sequencers. Data storage and analysis becomes a problem on local servers, and therefore it is needed to switch to other IT infrastructures. Grid and workflow technology can help to handle the data more efficiently, as well as facilitate collaborations. However, interfaces to grids are often unfriendly to novice users. RESULTS: In this study we reused a platform that was developed in the VL-e project for the analysis of medical images. Data transfer, workflow execution and job monitoring are operated from one graphical interface. We developed workflows for two sequence alignment tools (BLAST and BLAT) as a proof of concept. The analysis time was signicantly reduced. All workflows and executables are available for the members of the Dutch Life Science Grid and the VL-e Medical virtual organizations. All components are open source and can be transported to other grid infrastructures. CONCLUSIONS: The availability of in-house expertise and tools facilitates the usage of grid resources by new users. Our first results indicate that this is a practical, powerful and scalable solution to address the capacity and collaboration issues raised by the deployment of next generation sequencers. We currently adopt this methodology on a daily basis for DNA sequencing and other applications. More information and source code is available via http://www.bioinformaticslaboratory.nl

Relationship between location and activity in injurious falls: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Knowledge about the circumstances under which injurious falls occur could provide healthcare workers with better tools to prevent falls and fall-related injuries. Therefore, we assessed whether older persons who sustain an injurious fall can be classified into specific fall types, based on a combination of fall location and activity up to the moment of the fall. In addition, we assessed whether specific injurious fall types are related to causes of the fall, consequences of the fall, socio-demographic characteristics, and health-related characteristics.</p> <p>Methods</p> <p>An exploratory, cross-sectional study design was used to identify injurious fall types. The study population comprised 333 community-dwelling Dutch elderly people aged 65 years or over who attended an accident and emergency department after a fall. All participants received a self-administered questionnaire after being discharged home. The questionnaire comprised items concerning circumstances of the injurious fall, causes of the fall, consequences of the fall, socio-demographic characteristics and health-related characteristics. Injurious fall types were distinguished by analyzing data by means of HOMALS (homogeneity analysis by means of alternating least squares).</p> <p>Results</p> <p>We identified 4 injurious fall types: 1) Indoor falls related to lavatory visits (hall and bathroom); 2) Indoor falls during other activities of daily living; 3) Outdoor falls near the home during instrumental activities of daily living; 4) Outdoor falls away from home, occurring during walking, cycling, and shopping for groceries. These injurious fall types were significantly related to age, cause of the fall, activity avoidance and daily functioning.</p> <p>Conclusion</p> <p>The face validity of the injurious fall typology is obvious. However, we found no relationship between the injurious fall types and severity of the consequences of the fall. Nevertheless, there appears to be a difference between the prevalence of fractures and the cause of the fall between the injurious fall types. Our data suggests that with regard to prevention of serious injuries, we should pay special attention to outdoor fallers and indoor fallers during lavatory visits. In addition, we should have special attention for causes of the fall. However, the conclusions reached in this exploratory analysis are tentative and need to be validated in a separate dataset.</p

Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

Combination of electroweak and QCD corrections to single W production at the Fermilab Tevatron and the CERN LHC

Precision studies of the production of a high-transverse momentum lepton in association with missing energy at hadron colliders require that electroweak and QCD higher-order contributions are simultaneously taken into account in theoretical predictions and data analysis. Here we present a detailed phenomenological study of the impact of electroweak and strong contributions, as well as of their combination, to all the observables relevant for the various facets of the p\smartpap \to {\rm lepton} + X physics programme at hadron colliders, including luminosity monitoring and Parton Distribution Functions constraint, $W$ precision physics and search for new physics signals. We provide a theoretical recipe to carefully combine electroweak and strong corrections, that are mandatory in view of the challenging experimental accuracy already reached at the Fermilab Tevatron and aimed at the CERN LHC, and discuss the uncertainty inherent the combination. We conclude that the theoretical accuracy of our calculation can be conservatively estimated to be about 2% for standard event selections at the Tevatron and the LHC, and about 5% in the very high $W$ transverse mass/lepton transverse momentum tails. We also provide arguments for a more aggressive error estimate (about 1% and 3%, respectively) and conclude that in order to attain a one per cent accuracy: 1) exact mixed ${\cal O}(\alpha \alpha_s)$ corrections should be computed in addition to the already available NNLO QCD contributions and two-loop electroweak Sudakov logarithms; 2) QCD and electroweak corrections should be coherently included into a single event generator.Comment: One reference added. Final version to appear in JHE

Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation

A critical step in X-chromosome inactivation (XCI), which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s) are strongly downregulated, while the levels of unspliced form(s) of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process

Pseudoclavibacter-like subcutaneous infection: a case report

<p>Abstract</p> <p>Background</p> <p><it>Arthrobacter</it>-like organisms, including <it>Pseudoclavibacter </it>organisms, have rarely been documented as being responsible for infection in humans.</p> <p>Case presentation</p> <p>An 81-year-old French man developed a subcutaneous infection despite antibiotic treatment combining clindamycin and metronidazole for chronic wound infection. A skin biopsy showed numerous polymorphonuclear cells and no bacteria, but a subcutaneous swab yielded numerous polymorphonuclear cells, a few Gram-positive cocci, Gram-negative cocci, and Gram-positive rods. The Gram-positive rod sequence exhibited 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419350" ext-link-type="gen">EF419350</ext-link>] and 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419347" ext-link-type="gen">EF419347</ext-link>]. The genetic data and unique peptide profile of this <it>Pseudoclavibacter</it>-like isolate, determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry, underscored its uniqueness.</p> <p>Conclusions</p> <p><it>Pseudoclavibacter</it>-like organisms are identifiable in cutaneous and subcutaneous infections in humans.</p