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BioRxiv : the Preprint Server For... Jun 2024The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the...
The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.
PubMed: 38853924
DOI: 10.1101/2024.05.29.596533 -
BioRxiv : the Preprint Server For... Jun 2024The auditory brainstem response (ABR) is an acoustically evoked EEG potential that is an important diagnostic tool for hearing loss, especially in newborns. The ABR...
The auditory brainstem response (ABR) is an acoustically evoked EEG potential that is an important diagnostic tool for hearing loss, especially in newborns. The ABR originates from the response sequence of auditory brainstem nuclei, and a click-evoked ABR typically shows three positive peaks ('waves') within the first six milliseconds. However, an assignment of the waves of the ABR to specific sources is difficult, and a quantification of contributions to the ABR waves is not available. Here, we exploit the large size and physical separation of the barn owl first-order cochlear nucleus magnocellularis (NM) to estimate single-cell contributions to the ABR. We simultaneously recorded NM neurons' spikes and the EEG, and found that ≳ 5, 000 spontaneous single-cell spikes are necessary to isolate a significant spike-triggered average response at the EEG electrode. An average single-neuron contribution to the ABR was predicted by convolving the spike-triggered average with the cell's peri-stimulus time histogram. Amplitudes of predicted contributions of single NM cells typically reached 32.9 ± 1.1 nV (mean ± SE, range: 2.5 - 162.7 nV), or 0.07 ± 0.02% (median ± SE range: 0.01 - 4.0%) of the ABR amplitude. The time of the predicted peak coincided best with the peak of the ABR wave II, and this coincidence was independent of the click sound level. Our results suggest that wave II of the ABR is shaped by a small fraction of NM units.
PubMed: 38853863
DOI: 10.1101/2024.05.29.596509 -
Journal of Inorganic Biochemistry Sep 2024The NO dioxygenation reaction catalyzed by heme-containing globin proteins is a crucial aerobic detoxification pathway. Accordingly, the second order reaction of NO with...
The NO dioxygenation reaction catalyzed by heme-containing globin proteins is a crucial aerobic detoxification pathway. Accordingly, the second order reaction of NO with oxymyoglobin and oxyhemoglobin has been the focus of a large number of kinetic and spectroscopic studies. Stopped-flow and rapid-freeze-quench (RFQ) measurements have provided evidence for the formation of a Fe(III)-nitrato complex with millisecond lifetime prior to release of the nitrate product, but the temporal resolution of these techniques is insufficient for the characterization of precursor species. Most mechanistic models assume the formation of an initial Fe(III)-peroxynitrite species prior to homolytic cleavage of the OO bond and recombination of the resulting NO and Fe(IV)=O species. Here we report vibrational spectroscopy measurements for the reaction of oxymyoglobin with a photolabile caged NO donor at cryogenic temperatures. We show that this approach offers efficient formation and trapping of the Fe(III)-nitrato, enzyme-product, complex at 180 K. Resonance Raman spectra of the Fe(III)-nitrato complex trapped via RFQ in the liquid phase and photolabile NO release at cryogenic temperatures are indistinguishable, demonstrating the complementarity of these approaches. Caged NO is released by irradiation <180 K but diffusion into the heme pocket is fully inhibited. Our data provide no evidence for Fe(III)-peroxynitrite of Fe(IV)=O species, supporting low activation energies for the NO to nitrate conversion at the oxymyoglobin reaction site. Photorelease of NO at cryogenic temperatures allows monitoring of the reaction by transmittance FTIR which provides valuable quantitative information and promising prospects for the detection of protein sidechain reorganization events in NO-reacting metalloenzymes.
Topics: Myoglobin; Nitric Oxide; Spectrum Analysis, Raman; Cold Temperature; Animals; Kinetics; Vibration
PubMed: 38852292
DOI: 10.1016/j.jinorgbio.2024.112633 -
Cortex; a Journal Devoted To the Study... May 2024Extensive research has documented the brain networks that play an integral role in bias, or the alteration and filtration of information processing in a manner that... (Review)
Review
Extensive research has documented the brain networks that play an integral role in bias, or the alteration and filtration of information processing in a manner that fundamentally favors an individual. The roots of bias, whether self- or other-oriented, are a complex constellation of neural and psychological processes that start at the most fundamental levels of sensory processing. From the millisecond information is received in the brain it is filtered at various levels and through various brain networks in relation to extant intrinsic activity to provide individuals with a perception of reality that complements and satisfies the conscious perceptions they have for themselves and the cultures in which they were reared. The products of these interactions, in turn, are dynamically altered by the introduction of others, be they friends or strangers who are similar or different in socially meaningful ways. While much is known about the various ways that basic biases alter specific aspects of neural function to support various forms of bias, the breadth and scope of the phenomenon remains entirely unclear. The purpose of this review is to examine the brain networks that shape (i.e., bias) the self-concept and how interactions with similar (ingroup) compared to dissimilar (outgroup) others alter these network (and subsequent interpersonal) interactions in fundamental ways. Throughout, focus is placed on an emerging understanding of the brain as a complex system, which suggests that many of these network interactions likely occur on a non-linear scale that blurs the lines between network hierarchies.
PubMed: 38848651
DOI: 10.1016/j.cortex.2024.05.002 -
Journal of the American Chemical Society Jun 2024We present millisecond quantitative serial X-ray crystallography at 1.7 Å resolution demonstrating precise optical control of reversible population transfer from...
Power Density Titration of Reversible Photoisomerization of a Fluorescent Protein Chromophore in the Presence of Thermally Driven Barrier Crossing Shown by Quantitative Millisecond Serial Synchrotron X-ray Crystallography.
We present millisecond quantitative serial X-ray crystallography at 1.7 Å resolution demonstrating precise optical control of reversible population transfer from Trans-Cis and Cis-Trans photoisomerization of a reversibly switchable fluorescent protein, rsKiiro. Quantitative results from the analysis of electron density differences, extrapolated structure factors, and occupancy refinements are shown to correspond to optical measurements of photoinduced population transfer and have sensitivity to a few percent in concentration differences. Millisecond time-resolved concentration differences are precisely and reversibly controlled through intense continuous wave laser illuminations at 405 and 473 nm for the Trans-to-Cis and Cis-to-Trans reactions, respectively, while the X-ray crystallographic measurement and laser illumination of the metastable Trans chromophore conformation causes partial thermally driven reconversion across a 91.5 kJ/mol thermal barrier from which a temperature jump between 112 and 128 K is extracted.
PubMed: 38848551
DOI: 10.1021/jacs.3c12883 -
JAMA Network Open Jun 2024Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG...
IMPORTANCE
Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings.
OBJECTIVE
To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results.
MAIN OUTCOMES AND MEASURES
Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device.
RESULTS
A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R2 = 0.4; P < .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more.
CONCLUSIONS AND RELEVANCE
This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.
Topics: Humans; Female; Male; Adult; Electrocardiography; South Africa; Middle Aged; Long QT Syndrome; Reproducibility of Results; Tuberculosis, Multidrug-Resistant; Resource-Limited Settings
PubMed: 38848063
DOI: 10.1001/jamanetworkopen.2024.15576 -
Scientific Reports Jun 2024The experimental findings from the Large Helical Device have demonstrated a fast, nondiffusive behavior during the propagation of heat pulses, with an observed increase...
The experimental findings from the Large Helical Device have demonstrated a fast, nondiffusive behavior during the propagation of heat pulses, with an observed increase in speed with reduction in their temporal width. Concurrent propagation of the temperature gradient and turbulence, in a timeframe spanning from a few milliseconds to tens of milliseconds, aligned with the avalanche model. These results indicate that the more spatiotemporally localized the heat and turbulence pulses are, the greater the deviation of the plasma from its equilibrium state, coupled with faster propagation velocity. This insight is pivotal for future fusion reactors, which necessitate the maintenance of a steady-state, non-equilibrium condition.
PubMed: 38844607
DOI: 10.1038/s41598-024-63788-0 -
Regional Anesthesia and Pain Medicine Jun 2024Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait...
BACKGROUND
Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity.
METHODS
Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques.
RESULTS
SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated.
CONCLUSION
SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.
PubMed: 38844412
DOI: 10.1136/rapm-2024-105433 -
Radiology. Cardiothoracic Imaging Jun 2024Purpose To perform a systematic review and meta-analysis to assess the effect of enzyme replacement therapy on cardiac MRI parameters in patients with Fabry disease.... (Meta-Analysis)
Meta-Analysis
Purpose To perform a systematic review and meta-analysis to assess the effect of enzyme replacement therapy on cardiac MRI parameters in patients with Fabry disease. Materials and Methods A systematic literature search was conducted from January 1, 2000, through January 1, 2024, in PubMed, ClinicalTrials.gov, Embase, and Cochrane Library databases. Study outcomes were changes in the following parameters: left ventricular wall mass (LVM), measured in grams; LVM indexed to body mass index, measured in grams per meters squared; maximum left ventricular wall thickness (MLVWT), measured in millimeters; late gadolinium enhancement (LGE) extent, measured in percentage of LVM; and native T1 mapping, measured in milliseconds. A random-effects meta-analysis of the pooled mean differences between baseline and follow-up parameters was conducted. The study protocol was registered in PROSPERO (CRD42022336223). Results The final analysis included 11 studies of a total of 445 patients with Fabry disease (mean age ± SD, 41 years ± 11; 277 male, 168 female). Between baseline and follow-up cardiac MRI, the following did not change: T1 mapping (mean difference, 6 msec [95% CI: -2, 15]; two studies, 70 patients, = 88%) and LVM indexed (mean difference, -1 g/m [95% CI: -6, 3]; four studies, 290 patients, = 81%). The following measures minimally decreased: LVM (mean difference, -18 g [95% CI: -33, -3]; seven studies, 107 patients, = 96%) and MLVWT (mean difference, -1 mm [95% CI: -2, -0.02]; six studies, 151 patients, = 90%). LGE extent increased (mean difference, 1% [95% CI: 1, 1]; three studies, 114 patients, = 85%). Conclusion In patients with Fabry disease, enzyme replacement therapy was associated with stabilization of LVM, MLVWT, and T1 mapping values, whereas LGE extent mildly increased. Fabry Disease, Enzyme Replacement Therapy (ERT), Cardiac MRI, Late Gadolinium Enhancement (LGE) © RSNA, 2024.
Topics: Fabry Disease; Humans; Enzyme Replacement Therapy; Magnetic Resonance Imaging; Heart Ventricles
PubMed: 38842453
DOI: 10.1148/ryct.230154 -
Neurophotonics Apr 2024The development of genetically encoded fluorescent indicators of neural activity with millisecond dynamics has generated demand for ever faster two-photon (2P) imaging...
SIGNIFICANCE
The development of genetically encoded fluorescent indicators of neural activity with millisecond dynamics has generated demand for ever faster two-photon (2P) imaging systems, but acoustic and mechanical beam scanning technologies are approaching fundamental limits. We demonstrate that potassium tantalate niobate (KTN) electro-optical deflectors (EODs), which are not subject to the same fundamental limits, are capable of ultrafast two-dimensional (2D) 2P imaging .
AIM
To determine if KTN-EODs are suitable for 2P imaging, compatible with 2D scanning, and capable of ultrafast imaging of genetically encoded indicators with millisecond dynamics.
APPROACH
The performance of a commercially available KTN-EOD was characterized across a range of drive frequencies and laser parameters relevant to 2P microscopy. A second KTN-EOD was incorporated into a dual-axis scan module, and the system was validated by imaging signals from ASAP3, a genetically encoded voltage indicator.
RESULTS
Optimal KTN-EOD deflection of laser light with a central wavelength of 960 nm was obtained up to the highest average powers and pulse intensities tested (power: 350 mW; pulse duration: 118 fs). Up to 32 resolvable spots per line at a 560 kHz line scan rate could be obtained with single-axis deflection. The complete dual-axis EO 2P microscope was capable of imaging a by field-of-view at over 10 kHz frame rate with lateral resolution. We demonstrate imaging of neurons expressing ASAP3 with high temporal resolution.
CONCLUSIONS
We demonstrate the suitability of KTN-EODs for ultrafast 2P cellular imaging , providing a foundation for future high-performance microscopes to incorporate emerging advances in KTN-based scanning technology.
PubMed: 38841422
DOI: 10.1117/1.NPh.11.2.025005