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Bioelectricity Mar 2019This review covers the use of pulsed electric fields in cancer therapy. It is organized into three sections based on pulse length, millisecond domain, microsecond... (Review)
Review
This review covers the use of pulsed electric fields in cancer therapy. It is organized into three sections based on pulse length, millisecond domain, microsecond domain, and nanosecond domain. The predominant application of pulsed electric fields is the modification of the permeability of cellular membranes, sometimes referred to as electroporation. This has been used in many different ways for cancer treatment. These include introducing genes into the tumor cells to activate an immune response, introducing poisons into the tumor cells, initiating necrosis using irreversible electroporation, and initiating immunogenic cell death with nanopulse stimulation.
PubMed: 34471806
DOI: 10.1089/bioe.2018.0001 -
Molecules (Basel, Switzerland) Aug 2023Rods and cones are the photoreceptor cells containing the visual pigment proteins that initiate visual phototransduction following the absorption of a photon. Photon... (Review)
Review
Rods and cones are the photoreceptor cells containing the visual pigment proteins that initiate visual phototransduction following the absorption of a photon. Photon absorption induces the photochemical transformation of a visual pigment, which results in the sequential formation of distinct photo-intermediate species on the femtosecond to millisecond timescales, whereupon a visual electrical signal is generated and transmitted to the brain. Time-resolved spectroscopic studies of the rod and cone photo-intermediaries enable the detailed understanding of initial events in vision, namely the key differences that underlie the functionally distinct scotopic (rod) and photopic (cone) visual systems. In this paper, we review our recent ultrafast (picoseconds to milliseconds) transient absorption studies of rod and cone visual pigments with a detailed comparison of the transient molecular spectra and kinetics of their respective photo-intermediaries. Key results include the characterization of the porphyropsin (carp fish rhodopsin) and human green-cone opsin photobleaching sequences, which show significant spectral and kinetic differences when compared against that of bovine rhodopsin. These results altogether reveal a rather strong interplay between the visual pigment structure and its corresponding photobleaching sequence, and relevant outstanding questions that will be further investigated through a forthcoming study of the human blue-cone visual pigment are discussed.
Topics: Animals; Cattle; Humans; Rhodopsin; Kinetics; Retinal Cone Photoreceptor Cells; Vision, Ocular
PubMed: 37570798
DOI: 10.3390/molecules28155829 -
Proceedings of the National Academy of... Oct 2019Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as...
Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as it is heard, in terms of complex multilevel representations of relevant linguistic and nonlinguistic knowledge. Central to this process are the neural computations involved in semantic combination, whereby the meanings of words are combined into more complex representations, as in the combination of a verb and its following direct object (DO) noun (e.g., "eat the apple"). These combinatorial processes form the backbone for incremental interpretation, enabling listeners to integrate the meaning of each word as it is heard into their dynamic interpretation of the current utterance. Focusing on the verb-DO noun relationship in simple spoken sentences, we applied multivariate pattern analysis and computational semantic modeling to source-localized electro/magnetoencephalographic data to map out the specific representational constraints that are constructed as each word is heard, and to determine how these constraints guide the interpretation of subsequent words in the utterance. Comparing context-independent semantic models of the DO noun with contextually constrained noun models reflecting the semantic properties of the preceding verb, we found that only the contextually constrained model showed a significant fit to the brain data. Pattern-based measures of directed connectivity across the left hemisphere language network revealed a continuous information flow among temporal, inferior frontal, and inferior parietal regions, underpinning the verb's modification of the DO noun's activated semantics. These results provide a plausible neural substrate for seamless real-time incremental interpretation on the observed millisecond time scales.
Topics: Adolescent; Adult; Auditory Perception; Brain; Comprehension; Electroencephalography; Female; Humans; Linguistics; Magnetoencephalography; Male; Semantics; Speech Perception; Young Adult
PubMed: 31570590
DOI: 10.1073/pnas.1903402116 -
Frontiers in Physiology 2015Mechanisms underlying pacemaker activity in the sinus node remain controversial, with some ascribing a dominant role to timing events in the surface membrane ("membrane... (Review)
Review
Mechanisms underlying pacemaker activity in the sinus node remain controversial, with some ascribing a dominant role to timing events in the surface membrane ("membrane clock") and others to uptake and release of calcium from the sarcoplasmic reticulum (SR) ("calcium clock"). Here we discuss recent evidence on mechanisms underlying pacemaker activity with a particular emphasis on the many roles of calcium. There are particular areas of controversy concerning the contribution of calcium spark-like events and the importance of I(f) to spontaneous diastolic depolarisation, though it will be suggested that neither of these is essential for pacemaking. Sodium-calcium exchange (NCX) is most often considered in the context of mediating membrane depolarisation after spark-like events. We present evidence for a broader role of this electrogenic exchanger which need not always depend upon these spark-like events. Short (milliseconds or seconds) and long (minutes) term influences of calcium are discussed including direct regulation of ion channels and NCX, and control of the activity of calcium-dependent enzymes (including CaMKII, AC1, and AC8). The balance between the many contributory factors to pacemaker activity may well alter with experimental and clinical conditions, and potentially redundant mechanisms are desirable to ensure the regular spontaneous heart rate that is essential for life. This review presents evidence that calcium is central to the normal control of pacemaking across a range of temporal scales and seeks to broaden the accepted description of the "calcium clock" to cover these important influences.
PubMed: 25859219
DOI: 10.3389/fphys.2015.00080 -
BioRxiv : the Preprint Server For... Oct 2023The temporal dynamics of visual information processing varies with the stimulus being processed and with the retinal location that initiates the processing. Here, we...
The temporal dynamics of visual information processing varies with the stimulus being processed and with the retinal location that initiates the processing. Here, we present psychophysical data with sub-millisecond precision showing that increasing eccentricity decreases the delay with which stimuli are processed. We show that, even within the central +/-6° of the visual field, processing delays change by a factor of up to three times. A simple model, grounded in retinal physiology, provides a good account of the data. The relative delays are on the order of only milliseconds. But if later processing leaves the delays unresolved, they can cause dramatic misperceptions of motion and 3D layout. We discuss the implications for how the human visual system solves the temporal binding problem across eccentricity. The results highlight the severe computational challenge of obtaining accurate, temporally-unified percepts of the environment with spatiotemporally-staggered processing across the visual field.
PubMed: 37808845
DOI: 10.1101/2023.09.30.559991 -
BMB Reports Dec 2015Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions:... (Review)
Review
Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca2+ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.
Topics: Animals; Circadian Rhythm; Heart Rate; Humans; Myocardial Contraction; Sinoatrial Node
PubMed: 25999176
DOI: 10.5483/bmbrep.2015.48.12.061 -
Trends in Neurosciences Oct 2018The ability to detect time intervals and temporal patterns is critical to some of the most fundamental computations the brain performs, including the ability to... (Review)
Review
The ability to detect time intervals and temporal patterns is critical to some of the most fundamental computations the brain performs, including the ability to communicate and appraise a dynamically changing environment. Many of these computations take place on the scale of tens to hundreds of milliseconds. Electrophysiological evidence shows that some neurons respond selectively to duration, interval, rate, or order. Because the time constants of many time-varying neural and synaptic properties, including short-term synaptic plasticity (STP), are also in the range of tens to hundreds of milliseconds, they are strong candidates to underlie the formation of temporally selective neurons. Neurophysiological studies indicate that STP is indeed one of the mechanisms that contributes to temporal selectivity, and computational models demonstrate that neurons embedded in local microcircuits exhibit temporal selectivity if their synapses undergo STP. Converging evidence suggests that some forms of temporal selectivity emerge from the dynamic changes in the balance of excitation and inhibition imposed by STP.
Topics: Action Potentials; Animals; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity; Neurons; Synapses
PubMed: 30274605
DOI: 10.1016/j.tins.2018.08.001 -
Biomedicines Jan 2023The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABA)-mediated...
BACKGROUND
The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABA)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths.
METHODS
We analyzed data from three previous studies of youth who underwent CSP and LICI measurements with transcranial magnetic stimulation and electromyography. We assessed CSP and LICI association using Spearman rank correlation tests and multiple linear regression analyses adjusted for demographic and clinical covariates.
RESULTS
The sample included 16 healthy participants and 45 participants with depression. The general mean (SD) age was 15.5 (1.7), 14.3 (1.7) for healthy participants, and 15.9 (1.6) years for participants with depression. Measures were nonnormally distributed (Shapiro-Wilk, < 0.001). CSP and LICI were not correlated at 100-millisecond (ρ = -0.2421, = 0.06), 150-millisecond (ρ = -0.1612, = 0.21), or 200-millisecond (ρ = -0.0507, = 0.70) interstimulus intervals using Spearman rank correlation test. No correlations were found in the multiple regression analysis ( = 0.35).
CONCLUSIONS
Although previous studies suggest that cortical silent period and long-interval intracortical inhibition measure GABA receptor-mediated activity, these biomarkers were not associated in our sample of youths. Future studies should focus on the specific physiologic and pharmacodynamic properties assessed by CSP and LICI in younger populations.
PubMed: 36830945
DOI: 10.3390/biomedicines11020409 -
International Journal of Molecular... Dec 2020An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active... (Review)
Review
An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active zone (AZ). The AP simultaneously controls the release site replenishment with SV for sustainable synaptic transmission in response to incoming neuronal signals. Although many studies have suggested that the replenishment time is relatively slow, recent studies exploring high speed resolution have revealed SV dynamics with milliseconds timescale after an AP. Accurate regulation is conferred by proteins sensing Ca entering through voltage-gated Ca channels opened by an AP. This review summarizes how millisecond Ca dynamics activate multiple protein cascades for control of the release site replenishment with release-ready SVs that underlie presynaptic short-term plasticity.
Topics: Animals; Humans; Neuronal Plasticity; Neurotransmitter Agents; Presynaptic Terminals; Synaptic Transmission
PubMed: 33396919
DOI: 10.3390/ijms22010327 -
Ear, Nose, & Throat Journal Feb 2023Fatigue is thought of as a leading cause of iatrogenic accidents. A significant deterioration in qualitative balance function has been shown in sleep deprived...
BACKGROUND
Fatigue is thought of as a leading cause of iatrogenic accidents. A significant deterioration in qualitative balance function has been shown in sleep deprived individuals.
AIM/OBJECTIVES
To quantify the degree to which balance is impaired by sleep deprivation (SD) in post-call medical residents.
METHODS
Medical residents voluntarily underwent computed dynamic posturography (CDP) before and after an on-call night, at an identical time of the day. Order of test performance was random to avoid behavioral learning. Each participant served as his or her own control.
RESULTS
Seventeen residents were enrolled (median age 32years). Average sleeping duration the night before and during the night shift was 6.5 and 1 hour, respectively. The average response times difference between alert and fatigued was 10.15 milliseconds (95% CI: 6.81-13.49 milliseconds), yielding a significantly prolonged response times from 120 milliseconds before to 130 milliseconds after the night shift ( < .001). Comparison of additional measurements of CDP performance did not differ between test conditions.
CONCLUSION
Medical residents are fatigued due to the effect of on-call nights. Sleep deprivation prolongs response times to vestibular stimuli. This finding probably has an effect on execution of manual skills and may reflect a more generalized slowing of responses and overall performance impairment.
SIGNIFICANCE
The vestibular system is susceptible to SD.
Topics: Humans; Male; Female; Adult; Sleep Deprivation; Internship and Residency; Sleep; Sleep Duration; Work Schedule Tolerance; Fatigue
PubMed: 33393818
DOI: 10.1177/0145561320980242