Gravity darkening and tidally perturbed stellar pulsation in the misaligned exoplanet system WASP-33

WASP-33 is one of the few $\delta$ Sct stars with a known planetary companion. By analyzing the stellar oscillations, we search for possible star-planet interactions in the pattern of the pulsation. We made use of the Transit and Light Curve Modeller (TLCM) to solve the light curve from the Transiting Exoplanet Survey Satellite (TESS). We include gravity darkening into our analysis. The stellar oscillation pattern of WASP-33 clearly shows signs of several tidally perturbed modes. We find that there are peaks in the frequency spectrum that are at or near the $3$rd, $12$th and $25$th orbital harmonics ($f_{orb} \sim 0.82$ d$^{-1}$). Also, there is a prominent overabundance of pulsational frequencies rightwards of the orbital harmonics, being characteristic of a tidally perturbed stellar pulsation, which is an outcome of star-planet interactions in the misaligned system. There are peaks in both the $\delta$ Sct and $\gamma$ Dor ranges of the Fourier spectrum, implying that WASP-33 is a $\gamma$ Dor -- $\delta$ Sct hybrid pulsator. The transit light curves are best fitted by a gravity darkened stellar model, and the planet parameters are consistent with earlier determinations.Comment: Accepted in A&A on 12 March 2022, 6 pages, 4 figure

Novel Neuroprotective Strategies in Ischemic Retinal Lesions

Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques

The impact of network sharing on competition: The challenges posed by early versus mature 5G

The rollout of fifth generation mobile networks is progressing around the world, but 5G looks especially expensive compared to previous generations. Network sharing between two or more mobile operators is an obvious way to attain significant cost savings, but may also raise competition concerns. This paper first distinguishes between early and mature 5G, and then discusses the expected changes mature 5G brings to the assessment of active mobile network sharing agreements from a competition policy point of view. We focus on the three main concerns where 5G may bring the most significant changes in the evaluation compared to 4G: service differentiation, cost commonality between the parties and the parties' ability and incentives to grant access to critical inputs to downstream competitors. For each of these concerns, we show that they are not easy to substantiate and in some cases the concerns may even become less grave than under 4G

BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species.

Reactive oxygen species (ROS) play a critical role in the progression of mitochondria-related diseases. A novel insulin sensitizer drug candidate, BGP-15, has been shown to have protective effects in several oxidative stress-related diseases in animal and human studies. In this study, we investigated whether the protective effects of BGP-15 are predominantly via preserving mitochondrial integrity and reducing mitochondrial ROS production. BGP-15 was found to accumulate in the mitochondria, protect against ROS-induced mitochondrial depolarization and attenuate ROS-induced mitochondrial ROS production in a cell culture model, and also reduced ROS production predominantly at the complex I-III system in isolated mitochondria. At physiologically relevant concentrations, BGP-15 protected against hydrogen peroxide-induced cell death by reducing both apoptosis and necrosis. Additionally, it attenuated bacterial lipopolysaccharide (LPS)-induced collapse of mitochondrial membrane potential and ROS production in LPS-sensitive U-251 glioma cells, suggesting that BGP-15 may have a protective role in inflammatory diseases. However, BGP-15 did not have any antioxidant effects as shown by in vitro chemical and cell culture systems. These data suggest that BGP-15 could be a novel mitochondrial drug candidate for the prevention of ROS-related and inflammatory disease progression

Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure.

In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure. In mitochondria, oxidative stress causes a shift toward fission which leads to mitochondrial fragmentation and cell death. Protecting mitochondria from oxidative stress, and the regulation of mitochondrial dynamics by drugs that shift the balance toward fusion, could be a novel therapeutic approach for heart failure. On the basis of our findings, we raise the possibility that DOX could be a novel therapeutic agent in the future treatment of heart failure

Regulation of type I interferon responses by mitochondria-derived reactive oxygen species in plasmacytoid dendritic cells

Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation. Therefore, pDCs provide an ideal model to study the impact of elevated mtROS on the antiviral signaling pathways initiated by receptors with distinct subcellular localization. We found that elevated level of mtROS alone did not change the phenotype and the baseline cytokine profile of resting pDCs. Nevertheless increased mtROS levels in pDCs lowered the TLR9-induced secretion of pro-inflammatory mediators slightly, whereas reduced type I IFN production markedly via blocking phosphorylation of interferon regulatory factor 7 (IRF7), the key transcription factor of the TLR9 signaling pathway. The TLR9-induced expression of RIG-I in pDCs was also negatively regulated by enhanced mtROS production. On the contrary, elevated mtROS significantly augmented the RIG-I-stimulated expression of type I IFNs, as well as the expression of mitochondrial antiviral-signaling (MAVS) protein and the phosphorylation of Akt and IRF3 that are essential components of RIG-I signaling. Collectively, our data suggest that increased mtROS exert diverse immunoregulatory functions in pDCs both in the early and late phase of type I IFN responses depending on which type of viral sensing pathway is stimulated