Auditory cortical responses in the cat to sounds that produce spatial illusions

Humans and cats can localize a sound source accurately if its spectrum is fairly broad and flat(1-3), as is typical of most natural sounds. However, if sounds are filtered to reduce the width of the spectrum, they result:in illusions of sources that are very different from the actual locations, particularly in the up/down and front/back dimensions(4-6). Such illusions reveal that the auditory system relies on specific characteristics of sound spectra to obtain cues for localization(7). In the-auditory cortex of cats, temporal firing patterns of neurons can signal the locations of broad-band sounds(8-9). Here we show that such spike patterns systematically mislocalize sounds that have been passed through a narrow-band filter. Both correct and incorrect locations signalled by neurons can be predicted quantitatively by a model of spectral processing that also predicts correct and incorrect localization judgements by human listeners(6). Similar cortical mechanisms, if present in humans, could underlie human auditory spatial perception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62778/1/399688a0.pd

Minor differences in haplotype frequency estimates can produce very large differences in heterogeneity test statistics

<p>Abstract</p> <p>Background</p> <p>Tests for association between a haplotype and disease are commonly performed using a likelihood ratio test for heterogeneity between case and control haplotype frequencies. Using data from a study of association between heroin dependence and the DRD2 gene, we obtained estimated haplotype frequencies and the associated likelihood ratio statistic using two different computer programs, MLOCUS and GENECOUNTING. We also carried out permutation testing to assess the empirical significance of the results obtained.</p> <p>Results</p> <p>Both programs yielded similar, though not identical, estimates for the haplotype frequencies. MLOCUS produced a p value of 1.8*10^-15and GENECOUNTING produced a p value of 5.4*10^-4. Permutation testing produced a p value 2.8*10^-4.</p> <p>Conclusion</p> <p>The fact that very large differences occur between the likelihood ratio statistics from the two programs may reflect the fact that the haplotype frequencies for the combined group are not constrained to be equal to the weighted averages of the frequencies for the cases and controls, as they would be if they were directly observed rather than being estimated. Minor differences in haplotype frequency estimates can result in very large differences in the likelihood ratio statistic and associated <it>p </it>value.</p

Corticospinal excitability modulation by pairing peripheral nerve stimulation with cortical states of movement initiation

KEY POINTS: We compare the effects on corticospinal excitability of repeatedly delivering peripheral nerve stimulation at three time points (-30 ms, 0 ms, +50 ms) relative to muscle onset in a cue-guided task. Plastic changes in excitability are only observed when stimuli are delivered immediately before the time when muscles activate, while stimuli delivered at muscle onset or shortly later (0, +50 ms) have no effect. Plastic effects are abolished if there is ongoing volitional EMG activity in the muscles prior to onset of the phasic contraction. The plastic effects induced by timing peripheral stimulation relative to electromyographic markers of muscle activation are as effective as those that occur if stimulation is timed relative to electroencephalographic markers of motor cortical activation. We provide a simple alternative protocol to induce plasticity in people in whom EEG recording is difficult. ABSTRACT: Plastic changes in corticospinal excitability (CSE) and motor function can be induced in a targeted and long-term manner if afferent volleys evoked by peripheral nerve stimulation are repeatedly associated with the peak of premovement brain activity assessed with electroencephalography (EEG). Here we ask whether other factors might also characterise this optimal brain state for plasticity induction. In healthy human volunteers (N = 24) we find that the same reliable changes in CSE can be induced by timing peripheral afferent stimulation relative to the electromyography (EMG) onset rather than using the EEG peak. Specifically, we observed an increase in CSE when peripheral stimulation activated the cortex just before movement initiation. By contrast, there was no effect on CSE if the afferent input reached the cortex at the same time or after EMG onset, consistent with the idea that the temporal order of synaptic activation from afferent input and voluntary movement is important for production of plasticity. Finally, in 14 volunteers we found that background voluntary muscle activity prior to movement also abolished the effect on CSE. One possible explanation is that the intervention strengthens synapses that are inactive at rest, but change their activity in anticipation of movement, and that the intervention fails when the synapses are tonically active during background EMG activity. Overall, we demonstrate that, in individuals with voluntary control of muscles targeted by our intervention, EMG signals are a suitable alternative to EEG to induce plasticity by coupling movement-related brain states with peripheral afferent input. This article is protected by copyright. All rights reserved

Mechanics and dynamics of X-chromosome pairing at X inactivation

At the onset of X-chromosome inactivation, the vital process whereby female mammalian cells equalize X products with respect to males, the X chromosomes are colocalized along their Xic (X-inactivation center) regions. The mechanism inducing recognition and pairing of the X’s remains, though, elusive. Starting from recent discoveries on the molecular factors and on the DNA sequences (the so-called "pairing sites") involved, we dissect the mechanical basis of Xic colocalization by using a statistical physics model. We show that soluble DNA-specific binding molecules, such as those experimentally identified, can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomes but only when their concentration, or chemical affinity, rises above a threshold value as a consequence of a thermodynamic phase transition. We derive the likelihood of pairing and its probability distribution. Chromosome dynamics has two stages: an initial independent Brownian diffusion followed, after a characteristic time scale, by recognition and pairing. Finally, we investigate the effects of DNA deletion/insertions in the region of pairing sites and compare model predictions to available experimental data

Cut-free Calculi and Relational Semantics for Temporal STIT Logics

We present cut-free labelled sequent calculi for a central formalism in logics of agency: STIT logics with temporal operators. These include sequent systems for Ldm , Tstit and Xstit. All calculi presented possess essential structural properties such as contraction- and cut-admissibility. The labelled calculi G3Ldm and G3Tstit are shown sound and complete relative to irreflexive temporal frames. Additionally, we extend current results by showing that also Xstit can be characterized through relational frames, omitting the use of BT+AC frames

How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

Cytosine-to-Uracil Deamination by SssI DNA Methyltransferase

The prokaryotic DNA(cytosine-5)methyltransferase M.SssI shares the specificity of eukaryotic DNA methyltransferases (CG) and is an important model and experimental tool in the study of eukaryotic DNA methylation. Previously, M.SssI was shown to be able to catalyze deamination of the target cytosine to uracil if the methyl donor S-adenosyl-methionine (SAM) was missing from the reaction. To test whether this side-activity of the enzyme can be used to distinguish between unmethylated and C5-methylated cytosines in CG dinucleotides, we re-investigated, using a sensitive genetic reversion assay, the cytosine deaminase activity of M.SssI. Confirming previous results we showed that M.SssI can deaminate cytosine to uracil in a slow reaction in the absence of SAM and that the rate of this reaction can be increased by the SAM analogue 5’-amino-5’-deoxyadenosine. We could not detect M.SssI-catalyzed deamination of C5-methylcytosine (m5C). We found conditions where the rate of M.SssI mediated C-to-U deamination was at least 100-fold higher than the rate of m5C-to-T conversion. Although this difference in reactivities suggests that the enzyme could be used to identify C5-methylated cytosines in the epigenetically important CG dinucleotides, the rate of M.SssI mediated cytosine deamination is too low to become an enzymatic alternative to the bisulfite reaction. Amino acid replacements in the presumed SAM binding pocket of M.SssI (F17S and G19D) resulted in greatly reduced methyltransferase activity. The G19D variant showed cytosine deaminase activity in E. coli, at physiological SAM concentrations. Interestingly, the C-to-U deaminase activity was also detectable in an E. coli ung+ host proficient in uracil excision repair