The Tor Vergata Synoptic Solar Telescope (TSST): A robotic, compact facility for solar full disk imaging

By the continuous multi-line observation of the solar atmosphere, it is possible to infer the magnetic and dynamical status of the Sun. This activity is essential to identify the possible precursors of space weather events, such as flare or coronal mass ejections. We describe the design and assembly of TSST (Tor Vergata Synoptic Solar Telescope), a robotic synoptic telescope currently composed of two main full-disk instruments, a Hα telescope and a Potassium (KI D1) magneto-optical filter (MOF)-based telescope operating at 769.9 nm. TSST is designed to be later upgraded with a second MOF channel. This paper describes the TSST concepts and presents the first light observation carried out in February 2020. We show that TSST is a low-cost robotic facility able to achieve the necessary data for the study of precursors of space weather events (using the magnetic and velocity maps by the MOF telescope) and fast flare detection (by the Hα telescope) to support Space Weather investigation and services

Data reduction pipeline for MOF-based synoptic telescopes

There are strong scientific cases and practical reasons for building ground-based solar synoptic telescopes. Some issues, like the study of solar dynamics and the forecasting of solar flares, benefit from the 3D reconstruction of the Sun’s atmosphere and magnetic field. Others, like the monitoring and prediction of space weather, require full disk observations, at the proper sampling rate, combining H-alpha images and Doppler velocity and magnetic field. The synoptic telescopes based on Magneto Optical Filters (MOF) using different lines are capable of measuring the line-of-sight Doppler velocity and magnetic field over the full solar disk at different ranges of height in the Sun’s photosphere and low chromosphere. Instruments like the MOTH (Magneto-Optical filters at Two Heights), using a dual-channel based on MOFs operating at 589.0 nm (Na D2 line) and 769.9 nm (K D1 line), the VAMOS instrument (Velocity And Magnetic Observations of the Sun), operating at 769.9 nm (K D1 line), and the future TSST (Tor Vergata Synoptic Solar Telescope), using a dual-channel telescope operating at 656.28 nm (H-alpha line) and at 769.9 nm (K D1 line), allow to face both aspects, the scientific and the operative related to Space Weather applications. The MOTH, VAMOS and TSST data enable a wide variety of studies of the Sun, from seismic probing of the solar interior (sound speed, rotation, details of the tachocline, sub-surface structure of active regions), to the dynamics and magnetic evolution of the lower part of the solar atmosphere (heating of the solar atmosphere, identification of the signatures of solar eruptive events, atmospheric gravity waves, etc.), to the 3D reconstruction of the solar atmosphere and flare locations. However, the use of MOF filters requires special care in calibrating the data for scientific or operational use. This work presents a systematic pipeline that derives from the decennial use of MOF’s technology. More in detail, the pipeline is based on data reduction procedures tested and validated on MOTH data acquired at Mees Solar Observatory of the University of Hawaii Haleakala Observatories and at South Pole Solar Observatory (SPSO), at the Amundsen-Scott South Pole Station in Antarctica, during Antarctica Summer Campaign 2016/17

STAT3 induces breast cancer growth via ANGPTL4, MMP13 and STC1 secretion by cancer associated fibroblasts

In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6, act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among these, ANGPTL4, MMP13 and STC-1 were functionally validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. Both in vitro and in vivo CAFs activities were moreover impaired by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The clinical potential of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease

STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca2+ fluxes and apoptotic responses

STAT3 is an oncogenic transcription factor exerting its functions both as a canonical transcriptional activator and as a non-canonical regulator of energy metabolism and mitochondrial functions. While both activities are required for cell transformation downstream of different oncogenic stimuli, they rely on different post-translational activating events, namely phosphorylation on either Y705 (nuclear activities) or S727 (mitochondrial functions). Here, we report the discovery of the unexpected STAT3 localization to the endoplasmic reticulum (ER), from where it modulates ER-mitochondria Ca2+ release by interacting with the Ca2+ channel IP3R3 and facilitating its degradation. The release of Ca2+ is of paramount importance for life/death cell decisions, as excessive Ca2+ causes mitochondrial Ca2+ overload, the opening of the mitochondrial permeability transition pore, and the initiation of the intrinsic apoptotic program. Indeed, STAT3 silencing enhances ER Ca2+ release and sensitivity to apoptosis following oxidative stress in STAT3-dependent mammary tumor cells, correlating with increased IP3R3 levels. Accordingly, basal-like mammary tumors, which frequently display constitutively active STAT3, show an inverse correlation between IP3R3 and STAT3 protein levels. These results suggest that STAT3-mediated IP3R3 downregulation in the ER crucially contributes to its anti-apoptotic functions via modulation of Ca2+ fluxes

RICTOR/mTORC2 downregulation in BRAFV600E melanoma cells promotes resistance to BRAF/MEK inhibition

Background: The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM. Methods: After analyzing The Cancer Genome Atlas MM patients' database to explore both overall survival and molecular signatures as a function of intra-tumor RICTOR levels, we investigated the effects of RICTOR downregulation in BRAFV600E MM cell lines on their response to BRAF/MEKi. We performed proteomic screening to identify proteins modulated by changes in RICTOR expression, and Seahorse analysis to evaluate the effects of RICTOR depletion on mitochondrial respiration. The combination of BRAFi with drugs targeting proteins and processes emerged in the proteomic screening was carried out on RICTOR-deficient cells in vitro and in a xenograft setting in vivo. Results: Low RICTOR levels in BRAF-mutated MM correlate with a worse clinical outcome. Gene Set Enrichment Analysis of low-RICTOR tumors display gene signatures suggestive of activation of the mitochondrial Electron Transport Chain (ETC) energy production. RICTOR-deficient BRAFV600E cells are intrinsically tolerant to BRAF/MEKi and anticipate the onset of resistance to BRAFi upon prolonged drug exposure. Moreover, in drug-naïve cells we observed a decline in RICTOR expression shortly after BRAFi exposure. In RICTOR-depleted cells, both mitochondrial respiration and expression of nicotinamide phosphoribosyltransferase (NAMPT) are enhanced, and their pharmacological inhibition restores sensitivity to BRAFi. Conclusions: Our work unveils an unforeseen tumor-suppressing role for mTORC2 in the early adaptation phase of BRAFV600E melanoma cells to targeted therapy and identifies the NAMPT-ETC axis as a potential therapeutic vulnerability of low RICTOR tumors. Importantly, our findings indicate that the evaluation of intra-tumor RICTOR levels has a prognostic value in metastatic melanoma and may help to guide therapeutic strategies in a personalized manner