Intensity-dependent Manner Research Articles

Optogenetic stimulation recruits cortical neurons in a morphology-dependent manner.

Single-photon optogenetics enables precise, cell-type-specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bares promise for Brain-Machine Interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cat of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.Significance Statement Sensory features, such as the position or orientation of a visual stimulus, are mapped onto the surface of cortex as functional domains. Their selective activation, that may enable eliciting complex percepts, is intensively pursued for basic science and clinical applications. However, delivery of light into one functional domain in optogenetically transfected cortex results in complex, widespread neuronal activity, spreading beyond the targeted domain. Our computational study reveals that neuron morphology contributes to this diffuse response in a cortical-layer and intensity-dependent manner. We show that enhancing the stimulator optics is more effective than soma-targeting of the opsin in increasing spatial precision of stimulation. Our simulations provide insights for designing optogenetic stimulation protocols and hardware to achieve selective activation of functional domains.

Mechanical Loading Modulates AMPK and mTOR Signaling in Muscle Cells.

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling pathway. Proteomic analysis of muscle cells subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensities of 5% and 2% as well as the control. Additionally, 10% SL suppressed RNA and protein synthesis while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with the highest expression in 2% SL. Further examination showed that the ADP/ATP ratio was increased after 10% SL compared to the control and that SL induced changes in mitochondrial biogenesis. Furthermore, Seahorse assay results indicate that 10% SL enhances mitochondrial respiration. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in muscle cells.

Electroacupuncture inhibited carrageenan-induced pain aversion by activating GABAergic neurons in the ACC

Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.

Effects of Different Eccentric Cycling Intensities on Brachial Artery Endothelial Shear Stress and Blood Flow Patterns

ABSTRACT Eccentric exercise has gained attention as a novel exercise modality that increases muscle performance at a lower metabolic demand. However, vascular responses to eccentric cycling (ECC) are unknown, thus gaining knowledge regarding endothelial shear stress (ESS) during ECC may be crucial for its application in patients. The purpose of this study was to explore ECC-induced blood flow patterns and ESS across three different intensities in ECC. Eighteen young, apparently healthy subjects were recruited for two laboratory visits. Maximum oxygen consumption, power output, and blood lactate (BLa) threshold were measured to determine workload intensities. Blood flow patterns in the brachial artery were measured via ultrasound imaging and Doppler on an eccentric ergometer during a 5 min workload steady exercise test at low (BLa of 0–2 mmol/L), moderate (BLa 2–4 mmol/L), and high intensity (BLa levels > 4 mmol/L). There was a significant increase in the antegrade ESS in an intensity-dependent manner (baseline: 44.2 ± 8.97; low: 55.6 ± 15.2; moderate: 56.0 ± 10.5; high: 70.7 ± 14.9, all dynes/cm2, all p values < 0.0002) with the exception between low and moderate and Re (AU) showed turbulent flow at all intensities. Regarding retrograde flow, ESS also increased in an intensity-dependent manner (baseline 9.72 ± 4.38; low: 12.5 ± 3.93; moderate: 15.8 ± 5.45; high: 15.7 ± 6.55, all dynes/cm2, all p values < 0.015) with the exception between high and moderate and Re (AU) showed laminar flow in all intensities. ECC produced exercise-induced blood flow patterns that are intensity-dependent. This suggests that ECC could be beneficial as a modulator of endothelial homeostasis.

Prefrontal Cortex Oxygenation During Exercise in Older Adults with Motoric Cognitive Risk Syndrome.

Motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by subjective memory complaints and gait impairments that may be related to lower prefrontal cortex (PFC) function. Acute bouts of aerobic exercise are shown to improve PFC function, however, the acute effects of exercise on PFC oxygenation have not yet been examined in MCR. This study aims to characterize the PFC oxygenation responses during acute exercise in older adults with MCR. Nineteen older adults with MCR performed a submaximal cycling exercise protocol. Functional near-infrared spectroscopy (fNIRS) is used to measure concentrations of oxygenated (OxyHb) and deoxygenated (DeoxyHb) hemoglobin from the PFC. There is a trend for increased OxyHb concentrations and decreased DeooxyHb concentrations during exercise. Exercise also induced significant increases in ratings of perceived exertion (RPEs) and heart rate. A significant, positive correlation between PFC OxyHb and RPEs during the cycling exercise are also observed. The findings reveal that PFC oxygenation increases during exercise in an intensity-dependent manner and the subjective perception of exertion is associated with the magnitude of PFC oxygenation. These results suggest that moderate-intensity cycling exercise may have beneficial effects on increasing cerebral blood flow in the PFC of older adults with MCR.

Effects of 9 Weeks of High- or Moderate-Intensity Training on Cardiorespiratory Fitness, Inhibitory Control, and Plasma Brain-Derived Neurotrophic Factor in Danish Adolescents-A Randomized Controlled Trial.

The primary aims of this study were to examine the effects of 9 weeks of aerobic training, comprising three 30-min sessions per week, on V̇O2max, inhibitory control, and plasma brain-derived neurotrophic factor (BDNF) levels among adolescents aged 16-19 years. One hundred twenty-one untrained or recreationally active adolescents from a Danish high school were enrolled in the study, with 58 females (17.8 ± 0.8 years) and 27 males (18.0 ± 0.9 years) completing it. Participants were randomly divided into three groups performing aerobic training at either moderate-intensity (MIT: 60%-70% heart rate reserve [HRR]) or high-intensity (HIT: 80%-100% HRR) or a passive control group (CON) continuing their habitual lifestyle. Both the training groups exercised for 3×30 min per week for 9 weeks using a combination of cycling and running. Before and after the intervention period maximal oxygen uptake (V̇O2max) and the primary outcomes (inhibitory control measured by a modified flanker task, and resting plasma levels of BDNF) were evaluated. After the intervention period, the HIT group demonstrated a larger increase in V̇O2max compared to both the CON and MIT groups, while no significant effects were observed on inhibitory control or plasma BDNF levels in any training group. However, compared to the CON group, the HIT group exhibited a tendency for greater improvement in the flanker interference score (accuracy), attributable to enhanced accuracy on the incongruent stimuli from pre to post. Aerobic training in adolescents increased cardiorespiratory fitness in an intensity-dependent manner, but no clear effects were observed on neither inhibitory control nor resting plasma BDNF levels. ClinicalTrials.gov: NCT02075944.

Acute exercise activates the AHR in peripheral blood mononuclear cells in an intensity-dependent manner.

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% V̇o2peak, and 3-min intervals at 50% V̇o2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.NEW & NOTEWORTHY The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.

Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30±3years; body mass index: 22.8±2.3kg/m2; : 51±6mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30min after and 90min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P<0.001) and increased plasma IL-6 (P<0.001), IL-10 (P=0.0145) and tumour necrosis factor-⍺ (TNF-⍺) (P=0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P<0.001) and inhibit TNF-⍺ secretion (P=0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P=0.0933) and HIE (P=0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P=0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.

Functional sympatholysis of Neuropeptide Y-mediated vasoconstriction in humans

Metabolic inhibition of sympathetic vasoconstriction (functional sympatholysis) is essential for adequate perfusion of skeletal muscle during exercise. Functional sympatholysis occurs primarily through post-junctional attenuation of norepinephrine and α-adrenergic-mediated vasoconstriction, though other non-adrenergic neurotransmitters are co-released with norepinephrine. Neuropeptide Y (NPY) is a neurotransmitter that elicits robust vasoconstriction and is co-released with norepinephrine during exercise in an intensity dependent manner. Evidence from animal models indicate that NPY is sensitive to metabolic inhibition, however metabolic inhibition of NPY-mediated vasoconstriction has not been tested in humans. We tested the hypothesis that NPY-mediated vasoconstriction would be attenuated during handgrip exercise in humans. In 10 healthy adults (7M:3F, age: 30±7 years, BMI: 24±5) we measured forearm blood flow (Doppler ultrasound), blood pressure (brachial artery catheter), and calculated changes in forearm vascular conductance (FVC) to local intra-arterial infusions of phenylephrine (PE; α1-agonist) or NPY (Y1R-agonist) during 1) intra-arterial infusion of sodium nitroprusside (SNP; nitric oxide donor) to serve as a non-metabolic vasodilatory control or 2) dynamic rhythmic handgrip exercise (EX; 15% maximal voluntary contraction). The vasoconstrictor responses to PE and NPY were quantified as a percent ΔFVC during each condition (SNP vs. EX) and were compared by two-way RM-ANOVA. The magnitude of sympatholysis (ΔFVC during exercise expressed as a percent of control) for PE and NPY was compared by a paired t-test. As expected, the vasoconstrictor response to PE was attenuated during handgrip exercise compared to SNP (ΔFVC: SNP: -50±24 vs. EX: -17±9 %; p=0.002). Similarly, NPY-mediated vasoconstriction was blunted during handgrip exercise compared to SNP (ΔFVC: SNP: -32±22 vs. EX: -11±7 %; p=0.029). There was no difference in the magnitude of sympatholysis between PE and NPY (PE: 68±18, NPY: 52±34 %; p=0.28). These data indicate that NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans, and the magnitude of sympatholysis is not different from α1-adrenergic vasoconstriction. Funding: NIH R00HL153777. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Genetic tools for studying cochlear inhibition.

Efferent feedback to the mammalian cochlea includes cholinergic medial olivocochlear neurons (MOCs) that release ACh to hyperpolarize and shunt the voltage change that drives electromotility of outer hair cells (OHCs). Via brainstem connectivity, MOCs are activated by sound in a frequency- and intensity-dependent manner, thereby reducing the amplification of cochlear vibration provided by OHC electromotility. Among other roles, this efferent feedback protects the cochlea from acoustic trauma. Lesion studies, as well as a variety of genetic mouse models, support the hypothesis of efferent protection from acoustic trauma. Genetic knockout and gain-of-function knockin of the unique α9α10-containing nicotinic acetylcholine receptor (nAChR) in hair cells show that acoustic protection correlates with the efficacy of cholinergic inhibition of OHCs. This protective effect was replicated by viral transduction of the gain-of-function α9L9'T nAChR into α9-knockout mice. Continued progress with "efferent gene therapy" will require a reliable method for visualizing nAChR expression in cochlear hair cells. To that end, mice expressing HA-tagged α9 or α10 nAChRs were generated using CRISPR technology. This progress will facilitate continued study of the hair cell nAChR as a therapeutic target to prevent hearing loss and potentially to ameliorate associated pathologies such as hyperacusis.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and limit of tolerance during progressive forearm exercise in men: a randomized crossover trial.

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21±2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean±standard deviation. There was a significant main effect of drink (PL<BRJ; P=0.042, ηp2=0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL<BRJ; P=0.03; ηp2= 0.197; 20%-50% and 90% LOT). BRJ did not influence oxygen delivery (P=0.893, ηp2=0.002), forearm blood flow (P=0.589, ηp2=0.03) (forearm vascular conductance (P=0.262, ηp2=0.124), mean arterial pressure (P=0.254,ηp2=0.128)), oxygen consumption (P=0.194, ηp2=0.179) or LOT (P=0.432, d=0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity.

Electromagnetic pulse induced blood-brain barrier breakdown through tight junction opening in rats.

The blood-brain barrier (BBB) is the main obstacle to hydrophilic and large molecules to enter the brain, maintaining the stability of the central nervous system (CNS). But many environmental factors may affect the permeability and structure of the BBB. Electromagnetic pulses (EMP) irradiation has been proven to enhance the permeability of the BBB, but the specific mechanism is still unclear. To explore the potential mechanism of EMP-induced BBB opening, this study investigated the permeability, fine structure and the proteins expression of the tight junction (TJ) of the BBB in the rats exposed to EMP. Using the leakage of fluorescein isothiocyanate-labeled dextran with different molecular mass under different field intensity of EMP exposure, we found that the tracer passing through the BBB is size-dependent in the rat exposed to EMP as field intensity increased. Transmission electron microscopy showed TJ of the endothelial cells in the EMP-exposed group was open, compared with the sham-irradiated group. But the levels of TJ proteins including ZO-1, claudin-5, or occludin were not changed as indicated by western blot. These data suggest that EMP induce BBB opening in a field intensity-dependent manner and probably through dysfunction of TJ proteins instead of their expression. Our findings increase the understanding of the mechanism for EMP working on the brain and are helpful for CNS protection against EMP.

Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest

BackgroundBrain injury is a leading cause of morbidity and mortality in patients resuscitated from cardiac arrest. Mitochondrial dysfunction contributes to brain injury following cardiac arrest; therefore, therapies that limit mitochondrial dysfunction have the potential to improve neurological outcomes. Generation of reactive oxygen species (ROS) during ischemia–reperfusion injury in the brain is a critical component of mitochondrial injury and is dependent on hyperactivation of mitochondria following resuscitation. Our previous studies have provided evidence that modulating mitochondrial function with specific near-infrared light (NIR) wavelengths can reduce post-ischemic mitochondrial hyperactivity, thereby reducing brain injury during reperfusion in multiple small animal models.MethodsIsolated porcine brain cytochrome c oxidase (COX) was used to investigate the mechanism of NIR-induced mitochondrial modulation. Cultured primary neurons from mice expressing mitoQC were utilized to explore the mitochondrial mechanisms related to protection with NIR following ischemia–reperfusion. Anesthetized pigs were used to optimize the delivery of NIR to the brain by measuring the penetration depth of NIR to deep brain structures and tissue heating. Finally, a model of out-of-hospital cardiac arrest with CPR in adult pigs was used to evaluate the translational potential of NIR as a noninvasive therapeutic approach to protect the brain after resuscitation.ResultsMolecular evaluation of enzyme activity during NIR irradiation demonstrated COX function was reduced in an intensity-dependent manner with a threshold of enzyme inhibition leading to a moderate reduction in activity without complete inhibition. Mechanistic interrogation in neurons demonstrated that mitochondrial swelling and upregulation of mitophagy were reduced with NIR treatment. NIR therapy in large animals is feasible, as NIR penetrates deep into the brain without substantial tissue heating. In a translational porcine model of CA/CPR, transcranial NIR treatment for two hours at the onset of return of spontaneous circulation (ROSC) demonstrated significantly improved neurological deficit scores and reduced histologic evidence of brain injury after resuscitation from cardiac arrest.ConclusionsNIR modulates mitochondrial function which improves mitochondrial dynamics and quality control following ischemia/reperfusion. Noninvasive modulation of mitochondria, achieved by transcranial treatment of the brain with NIR, mitigates post-cardiac arrest brain injury and improves neurologic functional outcomes.Graphical abstract

The intensity-dependent effects of exercise and superimposing environmental heat stress on autophagy in peripheral blood mononuclear cells from older men

We demonstrate that autophagic stimulation occurs in response to short-duration (30-min) vigorous-intensity exercise in peripheral blood mononuclear cells from older adults; however, no changes in autophagy occur during low- or moderate-intensity exercise. Moreover, older adults exhibit autophagic impairments when the same vigorous-intensity exercise is performed in hot ambient conditions. When paired with an attenuated heat shock response, as well as elevated apoptotic responses, older men may exhibit greater cellular vulnerability to exertional heat stress.

Validity and Reliability of a Linear Position Transducer to Measure Velocity, Duration, and Displacement in the Barbell Back Squat

The purpose of this investigation was to determine the validity and reliability of the Humac360 linear position transducer (LPT) as compared to Tendo Weightlifting Analyzer. Seventeen recreationally active men and women completed three visits. Visit one included maximal strength assessments via one-repetition maximum (1RM) for the barbell back squat. On visits two and three, participants completed two sets of three repetitions at 30-, 50-, 60-, and 70% 1RM. Mean Concentric Velocity (MCV), Peak Velocity (PV), Displacement (D), and Duration (T) were collected. Repetition data agreement was assessed with Intraclass Correlation Coefficients (ICCs) and were categorized as poor (&lt;0.50), moderate (0.50 – 0.75), good (0.75 – 0.90), and excellent (&gt;0.90). Significance was accepted at an alpha (p) value &lt; 0.05. Repetition-to-repetition comparisons between devices demonstrate varying degrees of agreement, with significant differences between devices across all intensities and all measurements (p &lt; 0.001). Inter-set reliability was excellent for MCV, PV, D, and T with the exceptions of MCV and PV at 70% 1RM (ICC2,k = 0.548 and 0.816). Inter-session reliability data demonstrated reduced agreeableness in an intensity-dependent manner, with ICCs decreasing and SEMs increasing with increases in intensity. The Humac360 LPT does not appear to be valid when compared to the criterion reference, though we contend it maintains construct validity. Coaches may use the Humac360 LPT as a tool to monitor fatigue, and the associated changes in trainee movement velocity on an inter-set and inter-session basis.

Optimizing statin therapy for primary prevention of cardiovascular disease in type 2 diabetes mellitus patients: Exploring dose, class, and intensity.

To investigate the impact of statin use on primary prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in a dose-, class-, and use intensity-dependent manner. We used an inverse probability treatment-weighted Cox hazards model, with statin use status as a time-dependent variable. Our results showed that statin use was associated with a significant reduction in CVD risk with an adjusted hazard ratio of 0.39. Pitavastatin was found to have the lowest CVD risk among the different classes of statins, followed by rosuvastatin, pravastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin. Our analysis also revealed that a higher cumulative defined daily dose per year of statin was associated with a lower CVD risk. Additionally, a higher intensity of daily statin dose was associated with a lower CVD risk in patients with T2DM. This study highlights the importance of statin use in reducing the risk of CVD in patients with T2DM, and the significance of dose, class, and intensity of statin use, in particular, pitavastatin class of statins was found to be the most effective in primary prevention of CVD in T2DM.

Immunity induced by vaccination with recombinant influenza B virus neuraminidase protein breaks viral transmission chains in guinea pigs in an exposure intensity-dependent manner.

Vaccines that can slow respiratory virus transmission in the population are urgently needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Here, we describe how a recombinant neuraminidase-based influenza virus vaccine reduces transmission in vaccinated guinea pigs in an exposure intensity-based manner.

Impact of a Single Episode of Different Intensity of White Light Pulse at Night on Masking Response in the Diurnal Mammal, Funambulus pennantii

Objective: Light affects mammalian circadian rhythms through entrainment and masking. Photic masking increases locomotor activity in diurnal species (positive masking) while reducing activity in nocturnal species (negative masking). Fewer studies have investigated masking in diurnal rodents. We investigated the masking response in a diurnal rodent, &lt;i&gt;Funambulus pennantii&lt;/i&gt; when subjected to white light pulses of different intensities at night between zeitgeber time (ZT) 12 and ZT 15.Methods: Adult male squirrels, &lt;i&gt;F. pennantii&lt;/i&gt; (n=10/group, three groups) were placed in individual cages with running wheels under standard 12:12 h light-dark (LD) conditions. Recording of the locomotor activity rhythm was carried out using a ClockLab setup. Following a week of stable entrainment to the LD cycle, the animals of each group were given a sham exposure. After 10 days, animals of group I, II, and III were exposed to 3-h white light pulses of 100 lux, 10 lux, and 1 lux, respectively, between ZT 12 and ZT 15. Following the exposure, the animals were allowed to run undisturbed for 7 days.Results: Compared to the shamexposed group, exposure to 3-h 1 lux, 10 lux, and 100 lux artificial light pulses at night caused positive masking, stimulating wheel running in an intensity-dependent manner. Additionally, nighttime light pulses of 100 lux and 10 lux reduced onset accuracy, reduced the amplitude of the rhythm, and also altered the phase angle relationship to light.Conclusion: The positive masking caused by light exposure at night in diurnal squirrels is intensity-dependent up to at least 100 lux and is associated with a dampening of circadian rhythms.

Acute Stress Modulates Social Approach and Social Maintenance in Adult Zebrafish.

Stress alters social functioning in a complex manner. An important variable determining the final effects of stress is stressor intensity. However, the precise relationship between stressor intensity and social behavior is not well understood. Here, we investigate the effects of varying acute stressor intensity exposure on social behavior using adult zebrafish. We first establish a novel test using adult zebrafish that allows distinguishing fish's drive to approach a social cue and its ability to engage and maintain social interaction within the same behavioral paradigm. Next, we combined this test with a new method to deliver an acute stress stimulus of varying intensities. Our results show that both social approach and social maintenance are reduced in adult zebrafish on acute stress exposure in an intensity-dependent manner. Interestingly, lower stress intensity reduces social maintenance without affecting the social approach, while a higher stress level is required to alter social approach. These results provide evidence for a direct correlation between acute stressor intensity and social functioning and suggest that distinct steps in social behavior are modulated differentially by the acute stress level.

Astrocytes adjust the dynamic range of cortical network activity to control modality-specific sensory information processing

Cortical neuron-astrocyte communication in response to peripheral sensory stimulation occurs in a topographic-, frequency-, and intensity-dependent manner. However, the contribution of this functional interaction to the processing of sensory inputs and consequent behavior remains unclear. We investigate the role of astrocytes in sensory information processing at circuit and behavioral levels by monitoring and manipulating astrocytic activity invivo. We show that astrocytes control the dynamic range of the cortical network activity, optimizing its responsiveness to incoming sensory inputs. The astrocytic modulation of sensory processing contributes to setting the detection threshold for tactile and thermal behavior responses. The mechanism of such astrocytic control is mediated through modulation of inhibitory transmission to adjust the gain and sensitivity of responding networks. These results uncover a role for astrocytes in maintaining the cortical network activity in an optimal range to control behavior associated with specific sensory modalities.