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Figure 2—figure supplement 2. Structural analysis of a single-headed filament of the NLoop. ; (A) Typical cryo-EM micrograph of the NLoop (enlarged view of Figure 3C). Two representative round-shaped particles were selected (circled) and one 2D averaged class is shown in the top right corner, with 13 protomers recognized. One single-headed filament is marked in the rectangular box and used in further analysis. (B) Power spectrum and 2D classification analysis of a single-headed filament. A single-headed filament is divided into head, middle and tail parts (left), 2D classes of which are shown (middle). Power spectrum analysis of selected filament clearly indicates a 1/60 Å layer line (right). (C) 3D reconstruction of a single-headed filament and the respective pseudo-atomic model. (D) 3D projection of pseudo-atomic model of (C) after a 15 Å low-pass filter with sharp herringbone shape.

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Figure 5. STN – M1 functional and effective connectivity during conflict. ; (A) Functional connectivity, phase-locking value. Left panel shows the full-spectrum PLV analysis, specifically, a comparison of incongruent minus congruent trials. Significant (pM1 connectivity from the full-spectrum analysis. Right panels show individual subject data for the significant time-frequency window.

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Figure 4. Bayesian spectrum analysis (BSA) of anterior digastric EMG recordings - probability of gaping calculated in terms of the total posterior probability of 4–6Hz movements. ; (A1-A2) Two representative Conc Qui trials. The animal’s mouth movements can be seen as bursts of higher-amplitude (y-axis) EMG activity (blue) following taste delivery - the onset of gaping, as detected on video, is marked. The time series of the envelope of the EMG signal (black line) are the data subjected to BSA. (B1-B2) Result of BSA brought to bear on a pair of individual Conc Qui trials. The calculated probability of gaping (y-axis, black lines) matches up with individual gapes (grey vertical hash marks) picked by a previously published quadratic classifier that achieved 75% accuracy. (C1-C2) The trial-averaged probability of gaping (across a set of no-laser control trials) calculated with BSA (solid line) matches up with the peri-stimulus ‘gaping rate’ produced from the gapes identified by the quadratic classifier (dotted line, same set of control trials) in response to both Dil Qui (C1) and Conc Qui (C2). While correlating well with the quadratic classifier, BSA avoids multiple pitfalls of that technique (and is easier to apply, see Materials and methods). (D) The probability of gaping calculated with BSA rises reliably just before the first gape, detected either on video (black) or by the quadratic classifier (grey). The black dashed line (0 on the x axis) indicates the time of the first gape. (E) KL divergence between the probability of gaping to Conc and Dil Qui (higher values indicate larger differences in their gaping distributions, same trials as in (C1, C2). As expected, the distributions of gaping probability on Conc and Dil Qui trials are initially similar (while non-specific investigative licks happen) and diverge out at ∼1s post stimulus once gaping begins. (F) The cumulative sum of the KL divergence in E across time. The jump in KL divergence around the mean onset time of gaping is seen as a change in slope of its cumulative sum. We fit two straight lines to the cumulative sum and pick their intersection as the mean onset of gaping across this set of trials.

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Figure 7—figure supplement 1. Resting activity in GB1-cKO and control littermate mice. ; (A) Normalized power spectrum analysis of the LFP recordings in hippocampal CA1 region in GB1-cKO (red, n = 6) and control littermate mice (black, n = 6) in unstimulated conditions. (B) Relative changes of power at different oscillation frequencies for GB1-cKO and control littermate mice. No significant differences in network activity were observed in resting conditions between those mice. Theta band, p=0.485; unpaired t-test. Low gamma p=0.937; Wilcoxon rank-sum test. High gamma oscillations, p=0.158; Wilcoxon rank-sum test. (C) PVL index in resting conditions for GB1-cKO and control littermate mice did not show significant changes (PVL = 0.30 ± 0.03 and 0.39 ± 0.03 for control and GB1-cKO; n = 24 and 36 epochs, respectively; p=0.06; unpaired t test). Error bars indicate SEM.

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Figure 7. Astrocyte GABAB receptors participate in hippocampal theta and gamma oscillations in vivo. ; (A) Schematic illustration of the hippocampal recording configuration and whisker stimulation in anesthetized mice. (B) Representative LFP recordings and corresponding analysis of theta-phase and gamma-amplitude relation for control littermate (left) and GB1-cKO (right) mice. The raw signals (black) were high-pass filtered (1st row; grey and red, respectively) and then computed to extract the theta phase (second row) and gamma envelope (third row; grey and red, respectively) for control and GB1-cKO mice. (C) Normalized LFP power spectrum analysis for theta (4–8 Hz) and gamma frequencies (30–50 Hz, low gamma; 70–90 Hz, high gamma) in control littermate (n = 6) and GB1-cKO mice (n = 6) after whisker stimulation. Inset, Relative power changes for GB1-cKO and control littermate mice (theta band, p=0.007; unpaired t test; low gamma, p=0.042; Wilcoxon rank-sum test; and high gamma oscillations, p=0.738; Wilcoxon rank-sum test). (D) Gamma-amplitude modulation by theta-phase for wild-type (left) and GB1-cKO mice (right), before (control) and after whisker stimulation (post stim). Note the enhancement of theta-gamma coupling in wild-type after stimulus that does not appeared in GB1-cKO mice. (E) Normalized Phase-Lock Value (PLV), either in control and after stimulation for wild-type (p=0.017; paired t test), and GB1-cKO mice (p=0.62; paired t test). See also Figure 7—figure supplement 1. *p

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Author response image 3. Power spectrum analysis of the current traces in Figure 5—figure supplement 1 A-20% and B-1% revealed no ~10Hz rPSCs burst phase in B-1%.

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Figure 7. PI3K activity acutely modulates epileptic seizures. ; (a) Schematic shows electrode placement for EEG recordings. LF=Left Frontal, LP= Left Posterior, RF=Right Frontal, RP= Right Posterior. Only 2 electrodes were placed in P35 Nestin-cre;E545K. (b) EEG-EMG tracings of Nestin-cre;E545K mutant showed bilateral spikes/polyspikes, myoclonic (MC) seizures, fast and slow wave discharges, not associated with movement on video or EMG activity. (c) Generalized (G) and regional (R) spike and wave discharges were observed in Nestin-creER;E545K mice. Scale: 1s,1mV. (d,e) Sleep deprivation (SD) enhances epileptiform EEG activity in Nestin-creER;E545K mutant. EEG tracings of a Nestin-creER;E545K mutant mouse after 5 hr of normal sleep (Pre SD) and after 5 hr of total sleep deprivation (Post SD) in the same mouse (d), the mutant showing myoclonic (MC) seizures and isolated regional spikes (R). Power spectrum analysis, representing the frequency distribution for EEG activity over time, also displayed increased activity of the mutant post SD (e). (f) Bar chart showing average number of seizures (SZ) in PTZ-induced P35 Nestin-cre;E545K and control over time. (g) Experimental outline for BKM120-PTZ test. (h) Total number of seizures was significantly higher in P35 mutants than controls. Acute administration of BKM120 reduced number of seizures in mutants. (i) Duration of sustained generalized tonic-clonic seizure state (Racine 5), normalized to the total time of test, was significantly longer in P35 Nestin-cre;E545K mutants than controls. BKM120 significantly reduced the duration. Data are represented as mean ± SEM. *p

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Figure 2. HSN, VC, and vulval muscle activity is rhythmic and phased with animal locomotion. ; (A) Active-state segments, such as the one shown here, were extracted from Ca2+ recordings, and analyzed for rhythmicity by power spectrum analysis. Underlying rhythm frequencies and peak inter-transient intervals were thus extracted for HSN (B), VC (C), and vulval muscle (D) traces, and the peak of maximum rhythm for each active state is indicated in bold. (E) The average vulval muscle Ca2+ peak interval (~10 s) was significantly different than the ~20 s rhythm observed in HSN (p0.9999; one-way ANOVA). (F) The position of the vulva within a sinusoidal locomotor body bend at the moment a Ca2+ transient peaked was used to assign a body bend ‘phase’, in units of degrees, with 180° representing ventral relaxation and 0/360° representing ventral contraction. Plots show the percent of Ca2+ transients observed in each of eight 45° bins for HSN (G), VC (H), and vulval muscle (I), with data for transients accompanied by an egg-laying event (‘egg transient’) plotted in different colors from data for transients not accompanied by an egg-laying event (‘no egg transient’). These plots show data pooled from recordings of 8–11 animals, and Figure 2—figure supplement 1 shows plots for each animal separately. The phasing of VC and vulval muscle transients that did not lead to egg laying is significantly different from an equal number of randomly distributed events (R, at 12.5%; p

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Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study

• Authors : Yang, Bingyi; García-Carreras, Bernardo; Lessler, Justin ...

Subjects: General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine

• Source: eLife ; volume 11 ; ISSN 2050-084X

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• Authors : Rodríguez-Lorenzo, Sabela; van Olst, Lynn; Rodriguez-Mogeda, Carla ...

Subjects: General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine

• Source: eLife ; volume 11 ; ISSN 2050-084X

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