"Spoon-feeding" an AGN

Tidal disruption events (TDEs) occur when a star, passing too close to a massive black hole, is ripped apart by tidal forces. A less dramatic event occurs if the star orbits just outside the tidal radius, resulting in a mild stripping of mass. Thus, if a star orbits a central black hole on one of these bound eccentric orbits, weaker outbursts will occur recurring every orbital period. Thanks to five Swift observations, we observed a recent flare from the close by (92 Mpc) galaxy IC 3599, where a possible TDE was already observed in December 1990 during the Rosat All-Sky Survey. By light curve modeling and spectral fitting, we account for all these events as the non-disruptive tidal stripping of a single star into a 9.5 yr highly eccentric bound orbit. This is the first example of periodic partial tidal disruptions, possibly spoon-feeding the central black hole.Comment: 7 pages, 3 figures, to appear in "Swift:10 years of discovery", Proceedings of Scienc

Investigation of ancient DNA to enhance natural history museum collections: misidentification of smooth-coated otter (Lutrogale perspicillata) specimens across multiple museums

Historical and modern natural museum collections are storehouses of extraordinary value for scientific research in a wide range of fields. Recent advances in molecular biotechnology (e.g., next generation genomics) have increased the range of collection material employable for DNA-based analyses to unprecedented levels. Nevertheless, the value of museum specimens strictly depends on reliability of data associated with them. We report on investigations of ancient DNA from specimens of smooth-coated otter (Lutrogale perspicillata, Mustelidae), the largest otter species living in Asia, in US and European mammal collections. Mitochondrial DNA Cytochrome-b gene sequencing proved that the studied specimens were not the expected taxon. Indeed, they actually belonged to three different species, namely the Asian small-clawed (Aonyx cinereus), Eurasian (Lutra lutra) and African clawless (Aonyx capensis) otters. This represents the first record of mustelid misidentification from museum collections. Detection of errors can be extremely difficult when based only on collectors’ notes and data. Hence, we warn scientists involved in otter research about potential challenges when dealing with museum specimens. We recommend curators pursue a multidisciplinary approach, including DNA analyses, to accurately catalogue the resources under their management and uphold the value of biodiversity information

Osteoinductive effects of preoperative dexamethasone in human dental pulp stem cells primary culture

Aim: The use of dexamethasone (DEX) in mesenchymal cell culture induces osteoblastic differentiation and, consequently, formation of mineralized tissues. Tissue engineering proposes the development of therapeutic strategies aimed at structural and functional regeneration of biological tissues. In this sense, cell characterization in vitro is critical to ensure the development of such techniques. Our objective was to evaluate the osteoinductive effect of DEX administered as a preoperative medication in primary cell culture of human dental pulp stem cell. Methodology: Cells from the third molar pulp were divided into two experimental groups, each with two preoperative medication protocols used in dental practice and differentiated by the intake of DEX in one of them. The assessment of proliferation, differentiation and viability through trypan blue, methylthiazol tetrazolium, and von Kossa and alizarin red assays, respectively, were held within fixed intervals: 7, 14, 21 and 28 days. Conclusion: This study has shown that DEX may influence in vitro human dental pulp stem cell behavior. Lay abstract: Dexamethasone (DEX) is often used as a preoperative drug in dental surgeries because it reduces pain and has favorable effects on other symptoms caused by the surgery. Additionally, when used in cell culture, its osteoinductor effect is observed. In vitro cell characterization is critical to ensure the development of therapeutic strategies used in tissue engineering. In this sense, this study used two preoperative medication protocols regularly used in dental practice. In Protocol A, patients did not intake DEXin Protocol B, patients took in tablets of DEX. It was possible to assess in vitro behavior of human dental pulp stem cells by applying those protocols.UNIFESP Univ Fed São Paulo, Escola Paulista Med, CTCMol, Ctr Cellular & Mol Therapy, São Paulo, BrazilUNIFESP Univ Fed São Paulo, Escola Paulista Med, Translat Surg, Dept Surg, São Paulo, BrazilBIOFABRIS, Natl Inst Sci & Technol, Biofabricat Inst, São Paulo, BrazilHosp Ipiranga, Oral & Maxillofacial Surg Dept, São Paulo, BrazilUNIFESP Univ Fed São Paulo, Escola Paulista Med, CTCMol, Ctr Cellular & Mol Therapy, São Paulo, BrazilUNIFESP Univ Fed São Paulo, Escola Paulista Med, Translat Surg, Dept Surg, São Paulo, BrazilWeb of Scienc

Evaluation of in vivo labelled dendritic cell migration in cancer patients

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with (99m)Tc-HMPAO or (111)In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20–60 min after inoculation and the maximum concentration was reached after 48–72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC

The structure of DNA by direct imaging

The structure of DNA was determined in 1953 by x-ray fiber diffraction. Several attempts have been made to obtain a direct image of DNA with alternative techniques. The direct image is intended to allow a quantitative evaluation of all relevant characteristic lengths present in a molecule. A direct image of DNA, which is different from diffraction in the reciprocal space, is difficult to obtain for two main reasons: the intrinsic very low contrast of the elements that form the molecule and the difficulty of preparing the sample while preserving its pristine shape and size. We show that through a preparation procedure compatible with the DNA physiological conditions, a direct image of a single suspended DNA molecule can be obtained. In the image, all relevant lengths of A-form DNA are measurable. A high-resolution transmission electron microscope that operates at 80 keV with an ultimate resolution of 1.5 Å was used for this experiment. Direct imaging of a single molecule can be used as a method to address biological problems that require knowledge at the single-molecule level, given that the average information obtained by x-ray diffraction of crystals or fibers is not sufficient for detailed structure determination, or when crystals cannot be obtained from biological molecules or are not sufficient in understanding multiple protein configurations

Variability and star formation in Leo T, the lowest luminosity star-forming galaxy known today

We present results from the first combined study of variable stars and star formation history (SFH) of the Milky Way (MW) "ultra-faint" dwarf (UFD) galaxy Leo T, based on F606W and F814W multi-epoch archive observations obtained with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope. We have detected 14 variable stars in the galaxy. They include one fundamental-mode RR Lyrae star and 10 Anomalous Cepheids with periods shorter than 1 day, thus suggesting the occurrence of multiple star formation episodes in this UFD, of which one about 10 Gyr ago produced the RR Lyrae star. A new estimate of the distance to Leo T of 409 $^{+29}_{-27}$ kpc (distance modulus of 23.06 $\pm$ 0.15 mag) was derived from the galaxy's RR Lyrae star. Our V, V-I color-magnitude diagram of Leo T reaches V~29 mag and shows features typical of a galaxy in transition between dwarf irregular and dwarf spheroidal types. A quantitative analysis of the star formation history, based on the comparison of the observed V,V-I CMD with the expected distribution of stars for different evolutionary scenarios, confirms that Leo T has a complex star formation history dominated by two enhanced periods about 1.5 and 9 Gyr ago, respectively. The distribution of stars and gas shows that the galaxy has a fairly asymmetric structure.Comment: 31 pages, 14 figures, accepted for publication in Ap

Mafic magma feeds degassing unrest at Vulcano Island, Italy

The benign fuming activity of dormant volcanoes is punctuated by phases of escalating degassing activity that, on some occasions, ultimately prelude to eruption. However, understanding the drivers of such unrest is complicated by complex interplay between magmatic and hydrothermal processes. Some of the most comprehensively characterised degassing unrest have recently been observed at La Fossa cone on Vulcano Island, but whether or not these episodes involve new, volatile-rich ascending magma remains debated. Here, we use volcanic gas measurements, in combination with melt inclusion information, to propose that heightened sulphur dioxide flux during the intense fall 2021 La Fossa unrest is sourced by degassing of volatile-rich mafic magma. Calculations using a numerical model indicate observations are consistent with the unrest being triggered by the emplacement of ∼3·106 m3 of mafic magma at ∼4–5 km depth. Degassing of mafic magma is argued as a recurrent driver of unrest at dormant volcanoes worldwide

Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo

Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. The aim of this study was to evaluate the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (Afatinib)-mediated signaling pathways, when used alone or in combination, on growth, cell cycle, cell death and autophagy, modulation of molecules involved in transduction pathways, in three human MM cell lines of different histotypes. The efficacy of the combined treatment was also evaluated in a murine epithelioid MM cell line both in vitro and in vivo. This study demonstrated that combined treatment with two inhibitors counteracting the activation of two different signaling pathways involved in neoplastic transformation and progression, such as those activated by ErbB and Hh signaling, is more effective than the single treatments in reducing MM growth in vitro and in vivo. This study may have clinical implications for the development of targeted therapy approaches for MM

Stability Program in Dendritic Cell Vaccines: A “Real-World” Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics