Search

Abstract Monocytes represent key cellular elements that contribute to the neurological sequela following brain injury. The current study reveals that trauma induces the augmented release of a transcriptionally distinct CD115+/Ly6Chi monocyte population into the circulation of mice pre-exposed to clodronate depletion conditions. This phenomenon correlates with tissue protection, blood–brain barrier stability, and cerebral blood flow improvement. Uniquely, this shifted the innate immune cell profile in the cortical milieu and reduced the expression of pro-inflammatory Il6, IL1r1, MCP-1, Cxcl1, and Ccl3 cytokines. Monocytes that emerged under these conditions displayed a morphological and gene profile consistent with a subset commonly seen during emergency monopoiesis. Single-cell RNA sequencing delineated distinct clusters of monocytes and revealed a key transcriptional signature of Ly6Chi monocytes enriched for Apoe and chitinase-like protein 3 (Chil3/Ym1), commonly expressed in pro-resolving immunoregulatory monocytes, as well as granule genes Elane, Prtn3, MPO, and Ctsg unique to neutrophil-like monocytes. The predominate shift in cell clusters included subsets with low expression of transcription factors involved in monocyte conversion, Pou2f2, Na4a1, and a robust enrichment of genes in the oxidative phosphorylation pathway which favors an anti-inflammatory phenotype. Transfer of this monocyte assemblage into brain-injured recipient mice demonstrated their direct role in neuroprotection. These findings reveal a multifaceted innate immune response to brain injury and suggest targeting surrogate monocyte subsets may foster tissue protection in the brain.

Chronic sleep/wake disturbances (SWDs) are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong SWDs. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in 4-month-old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. Sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at 3 months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Further, TBI mice showed extensive brain tissue loss and increased glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 levels in the hypothalamus and vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes post-TBI early in life.

Abstract SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to mitochondrial DNA (mtDNA). These past findings on the mitochondrial toxicity of ribonucleoside analogues motivated us to investigate what effects RDV may have on mitochondrial function. Using in vitro and in vivo rodent models treated with RDV, we observed increases in mtDNA copy number in Mv1Lu cells (35.26% increase ± 11.33%) and liver (100.27% increase ± 32.73%) upon treatment. However, these increases only resulted in mild changes to mitochondrial function. Surprisingly, skeletal muscle and heart were extremely resistant to RDV treatment, tissues that have preferentially been affected by other nucleoside analogues. Although our data suggest that RDV does not greatly impact mitochondrial function, these data are insightful for the treatment of RDV for individuals with mitochondrial disease.

A piezoelectric tuning fork sensor is evaluated as a physical excitation and sensing device aiming at the detection of crystals and their nucleation behavior in joint fluids, as observed in gout. This device allows to study the crystallization tendency at varying temperatures or at increased uric acid concentrations as predominant in real human joints. In this work, a tuning fork resonator is characterized to enable spatially resolved viscosity and density measurements by calculating the mode shape of the vibration from resonance frequency measurements when immersed in test liquids.

We introduce an analysis platform for the viscoelastic properties of biological fluids such as the synovia found in articular joints. Small sample volumes are available for diagnostic purpose. Our approach uses a thickness shear mode quartz crystal integrated in an electrodynamically actuated spring structure. This combines the sensitivity of the quartz resonator operating at several overtones in the MHz range with previously introduced low kHz frequency multimode resonators. The latter is not only advantageous for characterizing viscoelastic fluids but is also used as an acoustic streaming actuator. Particulate matter in the sample thus can be resuspended and their settling is observed by tracking the resonance frequencies and Q-factors of both the quartz and electrodynamic resonator sensors.

The modulation response of injection-locked lasers has been carefully analyzed, theoretically and experimentally, with a focus on the strong optical injection regime. We derive closed-form solutions to the relaxation oscillation (resonance) frequency and damping term, as well as the low-frequency damping term, and discuss design rules for maximizing resonance frequency and broadband performance. A phasor model is described in order to better explain the enhancement of the resonance frequency. Experimental curves match closely to theory. Record resonance frequency of 72 GHz and broadband results are shown.

It has been shown that strong optical injection locking can significantly enhance the resonance frequency of semiconductor lasers. In this Letter, we describe the trade-off between the maximum resonance frequency enhancement and the quality factor (Q) of the lossless laser cavity and show that the time-bandwidth product (product of photon lifetime and maximum resonance frequency) is equal to one half the square root of the external power injection ratio. The theoretical model agrees well with our experimental data. (C) 2007 Optical Society of America.

The optical properties and the frequency responses of ultrastrong (injection ratio > 10 dB) injection-locked distributed feedback lasers are investigated experimentally and theoretically. We have observed three distinctive modulation regimes under different frequency detuning between the master and the slave lasers. At large negative frequency detuning, the laser exhibits enhanced modulation efficiency at low frequencies. At intermediate frequency detuning, a flat frequency response with large 3 dB bandwidth is observed. At large positive frequency detuning, the modulation response shows a pronounced resonance peak at high frequencies. These phenomena can be explained by the resonance enhancement of the slave laser cavity mode, with the resonance frequency equal to the difference between the injection-locked frequency and the cavity mode. The experimental results agree well with theoretical calculations based on three coupled rate equations. Depending on the applications, the injection locking conditions can be optimized to achieve high RF link gain, broadband, or high resonance frequency operations.

We report on the experimental demonstration of optical single sideband (SSB) modulation using a directly modulated semiconductor laser under strong optical injection-locking. Modulation sidebands with 15-dB power ratio between the lower and upper sidebands have been achieved. The longer wavelength sideband is resonantly amplified by the injection-locked laser cavity mode. The radio-frequency performance of the optical SSB after 80-km fiber transmission is significantly improved compared with a typical symmetric sideband modulation of a free-running laser. A 622-Mb/s data transmission on a 20-GHz subcarrier is demonstrated over an 80-km fiber link.