Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder characterized by motor cognitive dysfunction. Mitochondrial dysfunction and metabolic deficits are implicated in the pathophysiology of neurodegenerative diseases such as Parkinson's disease and HD and have been linked to the transcriptional dysregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a). Of the members of the PPAR family of transcription factors which require co-activation by PCG-1a, PPAR delta is the most ubiquitous and abundant in the central nervous system. Previous studies have demonstrated that PPAR-delta is dysregulated in HD leading to impairment of mitochondrial function. Furthermore, activation of the PPAR-delta pathway provided neuroprotective effects in HD models, implicating this pathway as an important therapeutic target for HD. The purpose of this study was to investigate the hypothesis that neuroprotection imparted by Bexarotene in vitro is mediated by the PPAR-delta pathway.

The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/-)white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders.

Abstract: We conducted a search for narrowband radio signals over four observing sessions in 2020–2023 with the L-band receiver (1.15–1.73 GHz) of the 100 m diameter Green Bank Telescope. We pointed the telescope in the directions of 62 TESS Objects of Interest, capturing radio emissions from a total of ∼11,680 stars and planetary systems in the ∼9′ beam of the telescope. All detections were either automatically rejected or visually inspected and confirmed to be of anthropogenic nature. We also quantified the end-to-end efficiency of radio SETI pipelines with a signal injection and recovery analysis. The UCLA SETI pipeline recovers 94.0% of the injected signals over the usable frequency range of the receiver and 98.7% of the injections when regions of dense radio frequency interference are excluded. In another pipeline that uses incoherent sums of 51 consecutive spectra, the recovery rate is ∼15 times smaller at ∼6%. The pipeline efficiency affects calculations of transmitter prevalence and SETI search volume. Accordingly, we developed an improved Drake figure of merit and a formalism to place upper limits on transmitter prevalence that take the pipeline efficiency and transmitter duty cycle into account. Based on our observations, we can state at the 95% confidence level that fewer than 6.6% of stars within 100 pc host a transmitter that is continuously transmitting a narrowband signal with an equivalent isotropic radiated power (EIRP) > 1013 W. For stars within 20,000 ly, the fraction of stars with detectable transmitters (EIRP > 5 × 1016 W) is at most 3 × 10−4. Finally, we showed that the UCLA SETI pipeline natively detects the signals detected with AI techniques by Ma et al.