Swift UVOT grism observations of nearby Type Ia supernovae – II. Probing the progenitor metallicity of SNe Ia with ultraviolet spectra

Ultraviolet (UV) observations of Type Ia supernovae (SNe Ia) are crucial for constraining the properties of their progenitor systems. Theoretical studies predicted that the UV spectra, which probe the outermost layers of an SN, should be sensitive to the metal content of the progenitor. Using the largest SN Ia UV (λ < 2900 Å) spectroscopic sample obtained from Neil Gehrels Swift Observatory, we investigate the dependence of UV spectra on metallicity. For the first time, our results reveal a correlation (∼2σ) between SN Ia UV flux and hostgalaxy metallicities, with SNe in more metal-rich galaxies (which are likely to have higher progenitor metallicities) having lower UV flux level. We find that this metallicity effect is only significant at short wavelengths (λ 2700 Å), which agrees well with the theoretical predictions. We produce UV spectral templates for SNe Ia at peak brightness. With our sample, we could disentangle the effect of light-curve shape and metallicity on the UV spectra. We also examine the correlation between the UV spectra and SN luminosities as parametrized by Hubble residuals. However, we do not see a significant trend with Hubble residuals. This is probably due to the large uncertainties in SN distances, as the majority of our sample members are extremely nearby (redshift z 0.01). Future work with SNe discovered in the Hubble flow will be necessary to constrain a potential metallicity bias on SN Ia cosmology

Immediate and sustained increases in the activity of vagal preganglionic neurons during exercise and after exercise training.

AIMS: The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the development of cardiovascular responses during exercise, however, the patterns of changes in the activity of the two autonomic limbs, and their functional interactions in orchestrating physiological responses during exercise, are not fully understood. The aim of this study was to characterize changes in vagal parasympathetic drive in response to exercise and exercise training by directly recording the electrical activity of vagal preganglionic neurons in experimental animals (rats). METHODS AND RESULTS: Single unit recordings were made using carbon-fibre microelectrodes from the populations of vagal preganglionic neurons of the nucleus ambiguus (NA) and the dorsal vagal motor nucleus of the brainstem. It was found that (i) vagal preganglionic neurons of the NA and the dorsal vagal motor nucleus are strongly activated during bouts of acute exercise, and (ii) exercise training markedly increases the resting activity of both populations of vagal preganglionic neurons and augments the excitatory responses of NA neurons during exercise. CONCLUSIONS: These data show that central vagal drive increases during exercise and provide the first direct neurophysiological evidence that exercise training increases vagal tone. The data argue against the notion of exercise-induced central vagal withdrawal during exercise. We propose that robust increases in the activity of vagal preganglionic neurons during bouts of exercise underlie activity-dependent plasticity, leading to higher resting vagal tone that confers multiple health benefits associated with regular exercise

Transcriptional response of the heart to vagus nerve stimulation.

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF, and stimulated using light. RNA sequencing of left ventricular myocardium identified 294 differentially expressed genes (DEGs, false discovery rate <0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z-score of ≥2/≤-2, including EIF-2, IL-2, Integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signalling, inflammation, and hypertrophy. IPA further predicted that the identified DEGs were the targets of 50 upstream regulators, including transcription factors (e.g., MYC, NRF1) and microRNAs (e.g., miR-335-3p, miR-338-3p). These data demonstrate that the vagus nerve has a major impact on myocardial expression of genes involved in regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart

Synthetic Fragments of Receptor for Advanced Glycation End Products Bind Beta-Amyloid 1-40 and Protect Primary Brain Cells From Beta-Amyloid Toxicity

Receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of Alzheimer’s disease. We have previously revealed that RAGE fragment sequence (60–76) and its shortened analogs sequence (60–70) and (60–65) under intranasal insertion were able to restore memory and improve morphological and biochemical state of neurons in the brain of bulbectomized mice developing major AD features. In the current study, we have investigated the ability of RAGE peptide (60–76) and five shortened analogs to bind beta-amyloid (Aβ) 1–40 in an fluorescent titration test and show that all the RAGE fragments apart from one [sequence (65–76)] were able to bind Aβ in vitro. Moreover, we show that all RAGE fragments apart from the shortest one (60–62), were able to protect neuronal primary cultures from amyloid toxicity, by preventing the caspase 3 activation induced by Aβ 1–42. We have compared the data obtained in the present research with the previously published data in the animal model of AD, and offer a probable mechanism of neuroprotection of the RAGE peptide