-
Nature Communications May 2024
PubMed: 38769306
DOI: 10.1038/s41467-024-48805-0 -
BioRxiv : the Preprint Server For... May 2024Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we...
UNLABELLED
Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we performed simultaneous electrophysiology and two-photon calcium imaging through transparent NeuroGrids and mapped touch-evoked cortical traveling waves and their underlying microcircuit dynamics. In awake mice, both passive and active whisker touch elicited traveling waves within and across barrels, with a fast early component followed by a variable late wave that lasted hundreds of milliseconds post-stimulus. Strikingly, late-wave dynamics were modulated by stimulus value and correlated with task performance. Mechanistically, the late wave component was i) modulated by motor feedback, ii) complemented by a sparse ensemble pattern across layer 2/3, which a balanced-state network model reconciled via inhibitory stabilization, and iii) aligned to regenerative Layer-5 apical dendritic Ca events. Our results reveal a translaminar spacetime pattern organized by cortical feedback in the sensory cortex that supports touch-evoked traveling waves.
GRAPHICAL ABSTRACT AND HIGHLIGHTS
Whisker touch evokes both early- and late-traveling waves in the barrel cortex over 100's of millisecondsReward reinforcement modulates wave dynamics Late wave emergence coincides with network sparsity in L23 and time-locked L5 dendritic Ca spikes Experimental and computational results link motor feedback to distinct translaminar spacetime patterns.
PubMed: 38766232
DOI: 10.1101/2024.05.09.593381 -
BioRxiv : the Preprint Server For... May 2024Site-directed spin labeling electron paramagnetic resonance (SDSL-EPR) using nitroxide spin labels is a well-established technology for mapping site-specific secondary...
Site-directed spin labeling electron paramagnetic resonance (SDSL-EPR) using nitroxide spin labels is a well-established technology for mapping site-specific secondary and tertiary structure and for monitoring conformational changes in proteins of any degree of complexity, including membrane proteins, with high sensitivity. SDSL-EPR also provides information on protein dynamics in the time scale of ps-µs using continuous wave lineshape analysis and spin lattice relaxation time methods. However, the functionally important time domain of µs-ms, corresponding to large-scale protein motions, is inaccessible to those methods. To extend SDSL-EPR to the longer time domain, the perturbation method of pressure-jump relaxation is implemented. Here, we describe a complete high-pressure EPR system at Q-band for both static pressure and millisecond-timescale pressure-jump measurements on spin-labeled proteins. The instrument enables pressure jumps both up and down from any holding pressure, ranging from atmospheric pressure to the maximum pressure capacity of the system components (~3500 bar). To demonstrate the utility of the system, we characterize a local folding-unfolding equilibrium of T4 lysozyme. The results illustrate the ability of the system to measure thermodynamic and kinetic parameters of protein conformational exchange on the millisecond timescale.
PubMed: 38766191
DOI: 10.1101/2024.05.07.593074 -
Neuropsychologia May 2024Current research suggests that menstruating female athletes might be at greater risk of musculoskeletal injury in relation to hormonal changes throughout the menstrual...
Current research suggests that menstruating female athletes might be at greater risk of musculoskeletal injury in relation to hormonal changes throughout the menstrual cycle. A separate body of work suggests that spatial cognition might also fluctuate in a similar manner. Changes in spatial cognition could, in theory, be a contributing risk factor for injury, especially in fast-paced sports that require precise, millisecond accuracy in interactions with moving objects in the environment. However, existing theories surrounding causes for increased injury risk in menstruating females largely focus on biomechanical mechanisms, with little consideration of possible cognitive determinants of injury risk. Therefore, the aim of this proof-of-principle study was to explore whether menstruating females exhibit fluctuations in cognitive processes throughout their cycle on a novel sport-oriented cognitive test battery, designed to measure some of the mental processes putatively involved in these sporting situations. A total of 394 participants completed an online cognitive battery, a mood scale and a symptom questionnaire twice, 14 days apart. After exclusions, 248 eligible participants were included in the analyses (mean: 28 ± 6 years) (male = 96, female(menstruating) = 105, female(contraception) = 47). Cycle phase for menstruating females was based on self-reported information. The cognitive battery was designed to measure reaction times, attention, visuospatial functions (including 3D mental rotation) and timing anticipation. Three composite scores were generated using factor analysis with varimax rotation (Errors, Reaction Time, Intra-Individual Variability). Mixed model ANOVAs and repeated measures ANOVAs were performed to test for between and within-subject effects. There was no group difference in reaction times and accuracy between males and females (using contraception and not). However, within subject analyses revealed that regularly menstruating females performed better during menstruation compared to being in any other phase, with faster reaction times (10ms c.ca, p < 0.01), fewer errors (p < 0.05) and lower dispersion intra-individual variability (p < 0.05). In contrast they exhibited slower reaction times (10ms c.ca, p < 0.01) and poorer timing anticipation (p < 0.01) in the luteal phase, and more errors in the predicted ovulatory phase (p < 0.01). Self-reported mood, cognitive and physical symptoms were all worst during menstruation (p < 0.01), and a significant proportion of females felt that their symptoms were negatively affecting their cognitive performance during menstruation on testing day, which was incongruent with their actual performance. These findings suggest that visuospatial and anticipatory processes may fluctuate throughout the menstrual cycle in the general population, with better performance during the menstrual phase and poorer performance during the luteal phase. If these extend to associations between phase-specific cognitive performance and injury incidence, they would support a cognitive theory of determinants of injury risk in cycling female athletes, opening an opportunity to develop mitigation strategies where appropriate.
PubMed: 38762068
DOI: 10.1016/j.neuropsychologia.2024.108909 -
Langmuir : the ACS Journal of Surfaces... May 2024Air bubbles in pure water appear to coalesce much faster compared to oil emulsion droplets at the same water solution conditions. The main factors explaining this...
Air bubbles in pure water appear to coalesce much faster compared to oil emulsion droplets at the same water solution conditions. The main factors explaining this difference in coalescence times could be interface mobility and/or pH-dependent surface charge at the water interface. To quantify the relative importance of these effects, we use high-speed imaging to monitor the coalescence of free-rising air bubbles with the water-air interface as well as free-falling fluorocarbon-oil emulsion droplets with a water-oil interface. We measure the coalescence times of such bubbles and droplets over a range of different water pH values (3.0, 5.6, 11.0). In the case of bubbles, a very fast coalescence (milliseconds) is observed for the entire pH range in pure water, consistent with the hydrodynamics of fully mobile interfaces. However, when the water-air interface is immobilized by the deposition of a monolayer of arachidic acid, the coalescence is significantly delayed. Furthermore, the coalescence times increase with increasing pH. In the case of fluorocarbon-oil droplets, the coalescence is always much slower (seconds) and consistent with immobile interface coalescence. The fluorocarbon droplet's coalescence time is also pH-dependent, with a complete stabilization (no coalescence) observed at pH 11. In the high electrolyte concentration, a 0.6 M NaCl water solution, bubbles, and droplets have similar coalescence times, which could be related to the bubble interface immobilization at the late stage of the coalescence process. Numerical simulations are used to evaluate the time scale of mobile and immobile interface film drainage.
PubMed: 38748812
DOI: 10.1021/acs.langmuir.4c01247 -
BioRxiv : the Preprint Server For... Apr 2024The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain...
The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain RNA-guided endonuclease, the intricate molecular crosstalk within the Cas9 protein hinges on its conformational dynamics, but a comprehensive understanding of the extent and timescale of the motions that drive its allosteric function and association with nucleic acids remains elusive. Here, we investigated the structure and multi-timescale molecular motions of the recognition (Rec) lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. Our results provide new atomic details about the GeoRec subdomains (GeoRec1, GeoRec2) and the full-length domain in solution. Two single-point mutants, K267E and R332A, enhanced and redistributed micro-millisecond flexibility throughout GeoRec, and NMR studies of the interaction between GeoRec and its guide RNA showed that mutations reduced this affinity and the stability of the ribonucleoprotein complex. Despite measured biophysical differences due to the mutations, DNA cleavage assays reveal only modest functional differences in on-target activity, and similar specificity. These data highlight how guide RNA interactions can be tuned in the absence of major functional losses, but also raise questions about the underlying mechanism of GeoCas9, since analogous single-point mutations have significantly impacted on- and off-target DNA editing in mesophilic S. pyogenes Cas9. A K267E/R332A double mutant did modestly enhance GeoCas9 specificity, highlighting the robust evolutionary tolerance of Cas9 and species-dependent complexity. Ultimately, this work provides an avenue by which to modulate the structure, motion, and nucleic acid interactions at the level of the Rec lobe of GeoCas9, setting the stage for future studies of GeoCas9 variants and their effect on its allosteric mechanism.
PubMed: 38746279
DOI: 10.1101/2024.04.26.591382 -
BioRxiv : the Preprint Server For... May 2024Epilepsy, a neurological disorder affecting millions worldwide, poses great challenges in precisely delineating the epileptogenic zone - the brain region generating...
UNLABELLED
Epilepsy, a neurological disorder affecting millions worldwide, poses great challenges in precisely delineating the epileptogenic zone - the brain region generating seizures - for effective treatment. High-frequency oscillations (HFOs) are emerging as promising biomarkers; however, the clinical utility is hindered by the difficulties in distinguishing pathological HFOs from non- epileptiform activities at single electrode and single patient resolution and understanding their dynamic role in epileptic networks. Here, we introduce an HFO-sequencing approach to analyze spontaneous HFOs traversing cortical regions in 40 drug-resistant epilepsy patients. This data- driven method automatically detected over 8.9 million HFOs, pinpointing pathological HFO- networks, and unveiled intricate millisecond-scale spatiotemporal dynamics, stability, and functional connectivity of HFOs in prolonged intracranial EEG recordings. These HFO sequences demonstrated a significant improvement in localization of epileptic tissue, with an 818.47% increase in concordance with seizure-onset zone (mean error: 2.92 mm), compared to conventional benchmarks. They also accurately predicted seizure outcomes for 90% AUC based on pre-surgical information using generalized linear models. Importantly, this mapping remained reliable even with short recordings (mean standard deviation: 3.23 mm for 30-minute segments). Furthermore, HFO sequences exhibited distinct yet highly repetitive spatiotemporal patterns, characterized by pronounced synchrony and predominant inward information flow from periphery towards areas involved in propagation, suggesting a crucial role for excitation-inhibition balance in HFO initiation and progression. Together, these findings shed light on the intricate organization of epileptic network and highlight the potential of HFO-sequencing as a translational tool for improved diagnosis, surgical targeting, and ultimately, better outcomes for vulnerable patients with drug-resistant epilepsy.
ONE SENTENCE SUMMARY
Pathological fast brain oscillations travel like traffic along varied routes, outlining recurrently visited neural sites emerging as critical hotspots in epilepsy network.
PubMed: 38746136
DOI: 10.1101/2024.05.02.592202 -
Materials (Basel, Switzerland) Apr 2024Experimental research and numerical simulations of the structural response to shock waves with pulse durations of hundreds of milliseconds, or even seconds, are...
Experimental research and numerical simulations of the structural response to shock waves with pulse durations of hundreds of milliseconds, or even seconds, are extremely challenging. This paper takes typical single-layer and sandwich cylindrical shells as the research objects. The response rules of cylindrical shells under long-duration blast loadings were studied. The results show that when the pulse duration is greater than or equal to 4~5 times the first-order period of the structure, the maximum response of the structure tends to be consistent, that is, the maximum response of the cylindrical shells with different vibration shapes shows a saturation effect as the pulse duration increases. This study established the relationship between the saturation loading time and the inherent characteristics of the structure. It was found that the saturation effect was applicable under the following conditions, including different load waveforms, elastic-plastic deformation of the structure, and the loading object being a sandwich shell. This will help transform the long-duration explosion wave problem into a finite pulse-duration shock wave problem that can be realized by both experiments and numerical simulations.
PubMed: 38730796
DOI: 10.3390/ma17091990 -
Chemical Science May 2024The accumulation and deposition of amyloid fibrils, also known as amyloidosis, in tissues and organs of patients has been found to be linked to numerous devastating...
The accumulation and deposition of amyloid fibrils, also known as amyloidosis, in tissues and organs of patients has been found to be linked to numerous devastating neurodegenerative diseases. The aggregation of proteins to form amyloid fibrils, however, is a slow pathogenic process, and is a major issue for the evaluation of the effectiveness of inhibitors in new drug discovery and screening. Here, we used microdroplet reaction technology to accelerate the amyloid fibrillation process, monitored the process to shed light on the fundamental mechanism of amyloid self-assembly, and demonstrated the value of the technology in the rapid screening of potential inhibitor drugs. Proteins in microdroplets accelerated to form fibrils in milliseconds, enabling an entire cycle of inhibitor screening for Aβ40 within 3 minutes. The technology would be of broad interest to drug discovery and therapeutic design to develop treatments for diseases associated with protein aggregation and fibrillation.
PubMed: 38725489
DOI: 10.1039/d4sc00437j -
Journal of Vision May 2024Image differences between the eyes can cause interocular discrepancies in the speed of visual processing. Millisecond-scale differences in visual processing speed can...
Image differences between the eyes can cause interocular discrepancies in the speed of visual processing. Millisecond-scale differences in visual processing speed can cause dramatic misperceptions of the depth and three-dimensional direction of moving objects. Here, we develop a monocular and binocular continuous target-tracking psychophysics paradigm that can quantify such tiny differences in visual processing speed. Human observers continuously tracked a target undergoing Brownian motion with a range of luminance levels in each eye. Suitable analyses recover the time course of the visuomotor response in each condition, the dependence of visual processing speed on luminance level, and the temporal evolution of processing differences between the eyes. Importantly, using a direct within-observer comparison, we show that continuous target-tracking and traditional forced-choice psychophysical methods provide estimates of interocular delays that agree on average to within a fraction of a millisecond. Thus, visual processing delays are preserved in the movement dynamics of the hand. Finally, we show analytically, and partially confirm experimentally, that differences between the temporal impulse response functions in the two eyes predict how lateral target motion causes misperceptions of motion in depth and associated tracking responses. Because continuous target tracking can accurately recover millisecond-scale differences in visual processing speed and has multiple advantages over traditional psychophysics, it should facilitate the study of temporal processing in the future.
Topics: Humans; Motion Perception; Psychophysics; Vision, Binocular; Photic Stimulation; Adult; Depth Perception; Male; Vision, Monocular; Female; Young Adult; Reaction Time
PubMed: 38722274
DOI: 10.1167/jov.24.5.4