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Journal of Biomolecular NMR Jun 2024Solution NMR spectroscopy is a particularly powerful technique for characterizing the functional dynamics of biomolecules, which is typically achieved through the...
Solution NMR spectroscopy is a particularly powerful technique for characterizing the functional dynamics of biomolecules, which is typically achieved through the quantitative characterization of chemical exchange processes via the measurement of spin relaxation rates. In addition to the conventional nuclei such as N and C, which are abundant in biomolecules, fluorine-19 (F) has recently garnered attention and is being widely used as a site-specific spin probe. While F offers the advantages of high sensitivity and low background, it can be susceptible to artifacts in quantitative relaxation analyses due to a multitude of dipolar and scalar coupling interactions with nearby H spins. In this study, we focused on the ribose 2'-F spin probe in nucleic acids and investigated the effects of H-F spin interactions on the quantitative characterization of slow exchange processes on the millisecond time scale. We demonstrated that the H-F dipolar coupling can significantly affect the interpretation of F chemical exchange saturation transfer (CEST) experiments when H decoupling is applied, while the H-F interactions have a lesser impact on Carr-Purcell-Meiboom-Gill relaxation dispersion applications. We also proposed a modified CEST scheme to alleviate these artifacts along with experimental verifications on self-complementary RNA systems. The theoretical framework presented in this study can be widely applied to various F spin systems where H-F interactions are operative, further expanding the utility of F relaxation-based NMR experiments.
PubMed: 38918317
DOI: 10.1007/s10858-024-00446-7 -
Neuron Jun 2024The hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive...
The hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive autoencoder model of the hippocampus including the trisynaptic and monosynaptic circuits from the entorhinal cortex (EC). CA3 was trained as a self-supervised recurrent neural network to predict its next input. We confirmed that CA3 is predicting ahead by analyzing the spike coupling between simultaneously recorded neurons in the dentate gyrus, CA3, and CA1 of the mouse hippocampus. In the model, CA1 neurons signal prediction errors by comparing CA3 predictions to the next direct EC input. The model exhibits the rapid appearance and slow fading of CA1 place cells and displays replay and phase precession from CA3. The model could be learned in a biologically plausible way with error-encoding neurons. Similarities between the hippocampal and thalamocortical circuits suggest that such computation motif could also underlie self-supervised sequence learning in the cortex.
PubMed: 38917804
DOI: 10.1016/j.neuron.2024.05.024 -
Proceedings of the National Academy of... Jul 2024Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for...
Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for tracing rapid conformational evolutions in proteins. However, linking spectral characteristics to dynamic structures poses a formidable challenge. Here, we present a pretrained machine learning model based on 2DIR spectra analysis. This model has learned signal features from approximately 204,300 spectra to establish a "spectrum-structure" correlation, thereby tracing the dynamic conformations of proteins. It excels in accurately predicting the dynamic content changes of various secondary structures and demonstrates universal transferability on real folding trajectories spanning timescales from microseconds to milliseconds. Beyond exceptional predictive performance, the model offers attention-based spectral explanations of dynamic conformational changes. Our 2DIR-based pretrained model is anticipated to provide unique insights into the dynamic structural information of proteins in their native environments.
Topics: Machine Learning; Proteins; Spectrophotometry, Infrared; Protein Conformation; Protein Folding; Protein Structure, Secondary
PubMed: 38917009
DOI: 10.1073/pnas.2409257121 -
The Journal of Head Trauma... Jun 2024We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but...
OBJECTIVES
We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls.
METHODS
We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups.
RESULTS
Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00).
CONCLUSION
Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.
PubMed: 38916433
DOI: 10.1097/HTR.0000000000000979 -
Cureus May 2024Cognitive communication abilities, such as working memory (WM), are vital for accomplishing daily activities and are also important for higher-order processes such as...
BACKGROUND
Cognitive communication abilities, such as working memory (WM), are vital for accomplishing daily activities and are also important for higher-order processes such as planning and problem-solving. The current study investigates the simultaneous effect of kapalabhati (KBH) on WM and phasic heart rate variability (HRV).
METHODS
Twenty participants who fulfilled the inclusion and exclusion criteria, with an average age of 23.65±3.07 years (mean±SD), were recruited for the study. Prior to data collection, the participants underwent a seven-day orientation to maintain uniformity in KBH practice. EKGs were assessed using a 16-channel polygraph system arranged in a standard limb lead II configuration. WM was assessed using E-Prime version 2.0 (Psychology Software Tools, Sharpsburg, PA, USA).
RESULTS
There was a significant increase in accuracy after the immediate KBH practice in all three conditions of the WM task (i.e., n-back task: 0-back, 1-back, and 2-back). However, there was also an increase in reaction time. Repeated measures ANOVA of HRV measures showed statistically significant changes in mean rhythm-to-rhythm (RR) intervals, heart rate (HR), number of adjacent N-N intervals over 50 milliseconds (NN50), percentage of successive normal sinus RR intervals greater than 50 milliseconds (pNN50 RR), low frequency (LF), and high frequency (HF), with HR, NN50, pNN50, LF, and HF all significant at p<0.001 and the LF/HF ratio significant at the p<0.01 level.
CONCLUSION
The results of the current study suggest that KBH practice can modulate vagal tone or parasympathetic activity and improve WM performance. Furthermore, the parasympathetic shift found in the present study may promote better cardioprotective health and longevity.
PubMed: 38915978
DOI: 10.7759/cureus.61027 -
BioRxiv : the Preprint Server For... Jun 2024Natural visual scenes are dominated by sequences of transforming images. Spatial visual information is thought to be processed by detection of elemental stimulus...
Natural visual scenes are dominated by sequences of transforming images. Spatial visual information is thought to be processed by detection of elemental stimulus features which are recomposed into scenes. How image information is integrated over time is unclear. We explored visual information encoding in the optic tectum. Unbiased stimulus presentation shows that the majority of tectal neurons recognize image sequences. This is achieved by temporally dynamic response properties, which encode complex image transitions over several hundred milliseconds. Calcium imaging reveals that neurons that encode spatiotemporal image sequences fire in spike sequences that predict a logical diagram of spatiotemporal information processing. Furthermore, the temporal scale of visual information is tuned by experience. This study indicates how neurons recognize dynamic visual scenes that transform over time.
PubMed: 38915552
DOI: 10.1101/2024.06.10.598314 -
Communications Biology Jun 2024Chromatin organization and dynamics play important roles in governing the regulation of nuclear processes of biological cells. However, due to the constant diffusive...
Chromatin organization and dynamics play important roles in governing the regulation of nuclear processes of biological cells. However, due to the constant diffusive motion of chromatin, examining chromatin nanostructures in living cells has been challenging. In this study, we introduce interferometric scattering correlation spectroscopy (iSCORS) to spatially map nanoscopic chromatin configurations within unlabeled live cell nuclei. This label-free technique captures time-varying linear scattering signals generated by the motion of native chromatin on a millisecond timescale, allowing us to deduce chromatin condensation states. Using iSCORS imaging, we quantitatively examine chromatin dynamics over extended periods, revealing spontaneous fluctuations in chromatin condensation and heterogeneous compaction levels in interphase cells, independent of cell phases. Moreover, we observe changes in iSCORS signals of chromatin upon transcription inhibition, indicating that iSCORS can probe nanoscopic chromatin structures and dynamics associated with transcriptional activities. Our scattering-based optical microscopy, which does not require labeling, serves as a powerful tool for visualizing dynamic chromatin nano-arrangements in live cells. This advancement holds promise for studying chromatin remodeling in various crucial cellular processes, such as stem cell differentiation, mechanotransduction, and DNA repair.
Topics: Chromatin; Humans; Spectrum Analysis; Interferometry; Chromatin Assembly and Disassembly; Cell Nucleus
PubMed: 38914653
DOI: 10.1038/s42003-024-06457-2 -
Optometry and Vision Science : Official... Jun 2024Prior studies with large, highly visible targets report low smooth pursuit gains in individuals with macular degeneration (MD). We show that lower gains persist even...
SIGNIFICANCE
Prior studies with large, highly visible targets report low smooth pursuit gains in individuals with macular degeneration (MD). We show that lower gains persist even when observers are pursuing a target that requires discrimination at the acuity limit. This low gain causes retinal slip, potentially leading to motion blur and target disappearance in the scotoma, which further compromise the visibility of moving object.
PURPOSE
In this study, we examine whether the characteristics of smooth pursuit (pursuit gain and placement of the fixational locus relative to the target) change when the task requires dynamic visual acuity.
METHODS
Using the scanning laser ophthalmoscope, we recorded smooth pursuit eye movements in 10 eyes of 6 MD participants and 7 eyes of 4 age-matched controls in response to leftward- or rightward-moving annular targets (O) that briefly (300 milliseconds) changed to a Landolt C at one of several time points during the pursuit trial. Participants were asked to pursue the target and indicate the direction of the C opening.
RESULTS
Individuals with MD had lower pursuit gains and fewer saccades during the C presentation than during the O, compared with their age-matched peers. Further, pursuit gain, but not the distance of the retinal pursuit locus from the target, predicted task performance in the MD group.
CONCLUSIONS
Our findings suggest that compromised pursuit gain in MD participants likely further compromises their dynamic visual acuity and thus ability to view moving targets.
PubMed: 38913934
DOI: 10.1097/OPX.0000000000002144 -
ACS Nano Jun 2024Several fabrication methods have been developed for label-free detection in various fields. However, fabricating high-density and highly ordered nanoscale architectures...
Several fabrication methods have been developed for label-free detection in various fields. However, fabricating high-density and highly ordered nanoscale architectures by using soluble processes remains a challenge. Herein, we report a biosensing platform that integrates deep learning with surface-enhanced Raman scattering (SERS), featuring large-area, close-packed three-dimensional (3D) architectures of molybdenum disulfide (MoS)-assisted gold nanoparticles (AuNPs) for the on-site screening of coronavirus disease (COVID-19) using human tears. Some AuNPs are spontaneously synthesized without a reducing agent because the electrons induced on the semiconductor surface reduce gold ions when the Fermi level of MoS and the gold electrolyte reach equilibrium. With the addition of polyvinylpyrrolidone, a two-dimensional large-area MoS layer assisted in the formation of close-packed 3D multistacked AuNP structures, resembling electroless plating. This platform, with a convolutional neural network-based deep learning model, achieved outstanding SERS performance at subterascale levels despite the microlevel irradiation power and millisecond-level acquisition time and accurately assessed susceptibility to COVID-19. These results suggest that our platform has the potential for rapid, low-damage, and high-throughput label-free detection of exceedingly low analyte concentrations.
PubMed: 38913718
DOI: 10.1021/acsnano.4c00978 -
Brain Stimulation Jun 2024Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation...
BACKGROUND
Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons.
METHODS
In 25 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment.
RESULTS
We observed an early positive EEG deflection starting after approx. 2 ms followed by a series of superimposed peaks with an inter-peak interval of ∼1.1-1.4 ms in multiple electrodes surrounding the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1 region and was modified by changes in stimulation intensity and current direction.
DISCUSSION
Single-pulse TMS of the M1 evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.
PubMed: 38909748
DOI: 10.1016/j.brs.2024.06.008