This study describes the effects of chip-scale gigahertz (GHz) ultrasound (US) and electrical stimulus on the morphology, functionality, and viability of neural cells in vitro . The GHz frequency ...stimulation is achieved using aluminum nitride piezoelectric transducers fabricated on a silicon wafer, operating at 1.47 GHz, corresponding to the film's thickness mode resonance. These devices are used to stimulate SH-SY5Y neural cells in vitro and observe effects on the morphology and viability of the stimulated cells. It is possible to use these devices to deliver either ultrasonic stimulus alone or US stimulus in conjunction with electrical stimulus. Viability tests demonstrated that the neurons retained structural integrity and viability across a wide range of GHz US stimulus intensities (0-1.2 W/cm 2 ), validating that measurements occur at nontoxic doses of US. Neural stimulation is validated with these devices following the outputs of a previous study, with the normalized fluorescence intensity of activated cells between 1.9 and 2.4. The 300-s ultrasonic stimulation at 1.47 GHz and 0.05 W/cm 2 peak intensity led to a decrease in nuclear elongation by 17.5% and a cross-sectional area decrease by 17.8% across three independent trials of over 150 cells per category (<inline-formula> <tex-math notation="LaTeX">{p} < 0.01 </tex-math></inline-formula>). The F-actin governed cellular elongation increased in length by up to 16.3% in cells exposed to an ultrasonic stimulus or costimulus (<inline-formula> <tex-math notation="LaTeX">{p} < 0.01 </tex-math></inline-formula>). Neurite length increased following ultrasonic stimulation compared with control by 75.8% (<inline-formula> <tex-math notation="LaTeX">{p} < 0.01 </tex-math></inline-formula>). This article demonstrates new GHz US and electrical chip-scale arrays with apparent effects in both neural excitation and cell morphology.
Cellular microstructural changes due to ultrasound exposure are critical to understand and characterize in order to further the establishment of ultrasonics in cell and tissue engineering and ...medicine. In this study, neurite length, nuclear morphology, and cellular toxicity are assessed at varying intensities of 92 kHz ultrasound provided by a piezoceramic disk element and incident upon SH- SY5Y neurons in vitro. Findings suggest that stimulation increases neurite length up to 2.73 fold tested at α = 0.05 in an intensity dependent manner. Additionally, stimulation causes a statistically significant (α = 0.05) decrease in nuclear area and less elongated nuclei, by 1.78 fold and 1.38 fold respectively, also in an intensity dependent manner. For maximum transducer surface intensities ranging from 0 to 39.11 W/cm2, the toxicity of 92 kHz ultrasound is assessed and a nontoxic range is determined using Caspase-3 and Annexin V staining, in addition to Calcium imaging via Calcein-AM staining. Intensities of up to 1.6 W/cm2 are found to be nontoxic for the cells under the parameters used in this study.
Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To develop therapies rationally that ...improve vascular health and thereby increase health span and life span in older adults, it will be essential to understand the cellular and molecular mechanisms contributing to vascular aging. Preclinical studies in model organisms demonstrate that NAD
availability decreases with age in multiple tissues and that supplemental NAD
precursors can ameliorate many age-related cellular impairments. Here, we provide a comprehensive overview of NAD
-dependent pathways including the NAD
-using silent information regulator-2-like enzymes and poly(ADP-ribose) polymerase enzymes and the potential consequences of endothelial NAD
deficiency in vascular aging. The multifaceted vasoprotective effects of treatments that reverse the age-related decline in cellular NAD
levels, as well as their potential limitations, are discussed. The preventive and therapeutic potential of NAD
intermediates as effective, clinically relevant interventions in older adults at risk for ischemic heart disease, vascular cognitive impairment, and other common geriatric conditions and diseases that involve vascular pathologies (e.g., sarcopenia, frailty) are critically discussed. We propose that NAD
precursors e.g., nicotinamide (Nam) riboside, Nam mononucleotide, niacin should be considered as critical components of combination therapies to slow the vascular aging process and increase cardiovascular health span.
Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, ...and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10-20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves Formula: see text caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03
C for Formula: see text This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.
Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy ...aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects of CR. Overall, the prospect for further research in both NHP and humans is highly encouraging.
•Calorie restriction is a promising intervention for attenuating age-related changes.•Highlights from the first human calorie restriction studies are presented.•Moderate calorie restriction is feasible and well tolerated in non-obese humans.•Findings in humans are highly encouraging of further research.
Sleep deprivation (SD) is a common condition and an important health concern. In addition to metabolic and cardiovascular risks, SD associates with decreases in cognitive performance. Neurovascular ...coupling (NVC, "functional hyperemia") is a critical homeostatic mechanism, which maintains adequate blood supply to the brain during periods of intensive neuronal activity. To determine whether SD alters NVC responses and cognitive performance, cognitive and hemodynamic NVC assessments were conducted prior to and 24 h post-SD in healthy young male individuals (n = 10, 27 ± 3 years old). Cognition was evaluated with a battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Hemodynamic components of NVC were measured by transcranial Doppler sonography (TCD) during cognitive stimulation, dynamic retinal vessel analysis (DVA) during flicker light stimulation, and functional near infrared spectroscopy (fNIRS) during finger tapping motor task. Cognitive assessments revealed impairments in reaction time and sustained attention after 24 h of SD. Functional NIRS analysis revealed that SD significantly altered hemodynamic responses in the prefrontal cortex and somatosensory cortex during a motor task. NVC-related vascular responses measured by DVA and TCD did not change significantly. Interestingly, TCD detected decreased task-associated cerebral blood flow (CBF) in the right middle cerebral artery in sleep deprived participants. Our results demonstrate that 24 h of SD lead to impairments in cognitive performance together with altered CBF and hemodynamic components of cortical NVC responses.
Chronic activation of β3-adrenergic receptors (β3-ARs) expands the catabolic activity of both brown and white adipose tissue by engaging uncoupling protein 1 (UCP1)-dependent and UCP1-independent ...processes. The present work examined de novo lipogenesis (DNL) and TG/glycerol dynamics in classic brown, subcutaneous “beige,” and classic white adipose tissues during sustained β3-AR activation by CL 316,243 (CL) and also addressed the contribution of TG hydrolysis to these dynamics. CL treatment for 7 days dramatically increased DNL and TG turnover similarly in all adipose depots, despite great differences in UCP1 abundance. Increased lipid turnover was accompanied by the simultaneous upregulation of genes involved in FAS, glycerol metabolism, and FA oxidation. Inducible, adipocyte-specific deletion of adipose TG lipase (ATGL), the rate-limiting enzyme for lipolysis, demonstrates that TG hydrolysis is required for CL-induced increases in DNL, TG turnover, and mitochondrial electron transport in all depots. Interestingly, the effect of ATGL deletion on induction of specific genes involved in FA oxidation and synthesis varied among fat depots. Overall, these studies indicate that FAS and FA oxidation are tightly coupled in adipose tissues during chronic adrenergic activation, and this effect critically depends on the activity of adipocyte ATGL.
We experimentally demonstrate the protection of a room-temperature hybrid spin register against environmental decoherence by performing repeated quantum error correction whilst maintaining ...sensitivity to signal fields. We use a long-lived nuclear spin to correct multiple phase errors on a sensitive electron spin in diamond and realize magnetic field sensing beyond the time scales set by natural decoherence. The universal extension of sensing time, robust to noise at any frequency, demonstrates the definitive advantage entangled multiqubit systems provide for quantum sensing and offers an important complement to quantum control techniques.
Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of ...this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.
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