Malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew; these cells are known as cancer stem-like cells (CSCs) or tumor-initiating cells. Primitive ...mammary CSCs/progenitor cells can be propagated in culture as floating spherical colonies termed 'mammospheres'. We show here that the expression of the autophagy protein Beclin 1 is higher in mammospheres established from human breast cancers or breast cancer cell lines (MCF-7 and BT474) than in the parental adherent cells. As a result, autophagic flux is more robust in mammospheres. We observed that basal and starvation-induced autophagy flux is also higher in aldehyde dehydrogenase 1-positive (ALDH1(+)) population derived from mammospheres than in the bulk population. Beclin 1 is critical for CSC maintenance and tumor development in nude mice, whereas its expression limits the development of tumors not enriched with breast CSCs/progenitor cells. We found that decreased survival in autophagy-deficient cells (MCF-7 Atg7 knockdown cells) during detachment does not contribute to an ultimate deficiency in mammosphere formation. This study demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance, and that Beclin 1 plays a dual role in tumor development.
Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin‐related disorders. We report a ...patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation.
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Since 1990, we have maintained a database of historical information on landslides and floods in Italy, known as the National Research Council's AVI (Damaged Urban Areas) archive. The database was ...originally designed to respond to a request of the Minister of Civil Protection, and was aimed at helping the regional assessment of landslide and flood risk in Italy. The database was compiled in 1991-1992 to cover the period 1917 to 1990, and then updated to cover systematically the period 1917 to 2000, and non-systematically the periods 1900 to 1916 and 2001 to 2002. The database currently contains information on more than 32000 landslide events occurred at more than 21000 sites, and on more than 29000 flood events occurred at more than 14000 sites. Independently from the AVI archive, we have obtained other databases containing information on damage caused by mass movements and inundations, daily discharge measurements and solid-transport measurements at selected gauging stations, bibliographical and reference information on landslides and inundations, and a catalogue of National legislation on hydrological and geological hazards and risk in Italy. The databases are part of an information system known as SICI (an Italian acronym for Sistema Informativo sulle Catastrofi Idrogeologiche, Information System on Hydrological and Geomorphological Catastrophes), which is currently the largest single repository of historical information on landslides and floods in Italy. After an outline of the history and evolution of the AVI Project archive, we present and discuss: (a) the structure of the SICI information system, including the hardware and software solutions adopted to maintain, manage, update, use and disseminate the information stored in the various databases, (b) the type and amount of information stored in each database, including an estimate of their completeness, and (c) examples of recent applications of the information system, including a web-based GIS system to show the location of sites historically affected by landslides and floods, and an estimate of geo-hydrological (i.e. landslide and flood) risk in Italy based on the available historical information.
A historical and metallurgical characterization of a “falchion” sword manufactured in Caino (Brescia, northern Italy) and dating from the early 17th century was performed to understand the ...manufacture methods of a Renaissance sword. At first, a set of size measurements was carried out to look for the existence of constant and/or recurring macroscopic sizes, which would indicate a standardized production, or of any type of proportionality between different parts of a sword, which would prove an intentional design activity. Light optical microscopy, scanning electron microscopy, energy-dispersive x-ray spectroscopy, quantometer analyses, and Vickers microhardness tests were then employed to analyze the microstructure and obtain the mechanical properties. All the metallurgical work is supported by an accurate study on the chemical composition of both metal-matrix and nonmetallic inclusions, which allowed for rebuilding and evaluating the efficiency of the whole production process.
The objective of this study was to verify whether phenytoin modifies methylphenidate‐induced hyperlocomotion, an animal model for screening antimanic‐like drugs, and also evaluate the effect of ...veratrine, a voltage‐gated sodium channel opener, pretreatment on the effect of phenytoin in this model. Carbamazepine was used as a positive control. Methylphenidate (5 mg/kg, s.c.) increased open‐field locomotion, and phenytoin (5–10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.) blocked this effect. Veratrine (0.4 mg/kg, s.c.) pretreatment reversed the effects of phenytoin (10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.). Phenytoin (1–50 mg/kg, i.p.) and carbamazepine (10–20 mg/kg i.p.) alone did not change spontaneous locomotor activity. These results indicate that voltage‐gated sodium channels play an important role in antimanic‐like effects of phenytoin and carbamazepine on psychostimulant‐induced hyperlocomotion model.
Abstract
Spontaneous coronary artery dissection (SCAD) is recently emerging as an increasingly frequent cause of myocardial infarction and among the main triggering factors we found hypertension, ...pregnancy, fibromuscular dysplasia and connective tissue diseases (e.g. Marfan syndrome). Recent studies also suggest that even bicuspid aortic valve may be a predisposing condition for the development of spontaneous coronary artery dissection. We report the case of a 45–year–old Caucasian man with no cardiovascular risk factors; his clinical history begins in August 2019, when he was hospitalized for acute coronary syndrome (NSTEMI). Echocardiography showed preserved left ventricular ejection fraction, bicuspid aortic valve (fusion of right and left cusps) with mild to moderate regurgitation without stenosis and mild dilatation of the aortic bulb (38 mm). The coronary angiography showed no significant stenoses and an anomalous origin of the right coronary artery from the common trunk. The patient was discharged two days later with a diagnosis of MINOCA and an indication to perform a coronary CT scan, which confirmed the anomalous origin of the right coronary artery with a retro–aortic course, and a cardiac MRI, which showed myocardial edema of the infero–lateral wall, mainly with sub–endocardial distribution and LGE in the same sites, compatible with ischemic damage. In September 2022 there was a new hospitalization for inferior–posterior–lateral STEMI with coronarographic finding of a large marginal branch collateral stenosis, with recovery of distal caliber. The angiographic pattern was consistent with type II SCAD (no intracoronary imaging has been performed because of vascular tortuosity and lesion distality). A retrospective comparative analysis of the 2019 angiography allowed to find a distal occlusion of the same branch, now healed, also compatible with SCAD. The patient was discharged on single antiplatelet therapy after one week of DAPT with acetylsalicylic acid and clopidogrel and indication to perform a genetic test for connective tissue diseases. The case described prompts the cardiologists to suspect an uncommon etiology (connective tissue disease, bicuspid aortic valve) in case of SCAD detection, especially if associated with anomalous origin of the coronary arteries.
The Compact Muon Solenoid (CMS) is one of the experiments at the Large Hadron Collider (LHC) under construction at CERN. Its inner tracking system consist of the world largest Silicon Strip Tracker ...(SST). In total it implements 24,244 silicon sensors covering an area of
206
m
2
. To construct a large system of this size and ensure its functionality for the full lifetime of 10 years under LHC condition, the CMS collaboration developed an elaborate design and a detailed quality assurance program. This paper describes the strategy and shows first results on sensor qualification.
The effect of 1,2-benzisoxazole-3-acetic acid (BOA), compared to 1-naphthaleneacetic acid (NAA), on adventitious shoot formation in leaf portions and compared to indolebutyric acid (IBA), on in vitro ...rooting in the apple (Malus domestica Borkh) cultivars McIntosh and Gala, and one rootstock, Jork 9, was investigated. BOA at 43.0 micrometers or 2.7 micrometers at NAA in combination with 17.8 micrometers benzyladenine (BA), induced the highest number of explants to produce adventitious shoots in Jork 9. In Gala, the combination of 21.5 micrometers BOA with 1.0 micrometers thidiazuron (TDZ) or with 22.0 micrometers BA induced the highest regeneration percentages, 58 and 54%, respectively, giving more satisfactory results than NAA (where only 42% of leaf explants exhibited shoot formation). In McIntosh, the highest percentage of regeneration was obtained with 1.3 micrometers NAA and 22.0 micrometers BA, while 51% was the highest response obtained with the BOA treatment. The combination of BOA with TDZ completely inhibited regeneration activity in leaf portions of this cultivar. The shoots of all the genotypes obtained with the most morphogenetic NAA or BOA treatments were excised, multiplied and successfully rooted and hardened. The results demonstrate that the synthetic auxin BOA is active in inducing shoot regeneration from leaf explants of apple and that the activity of BOA in plant regeneration is genotype dependent. When BOA was used to induce rooting in apple microcuttings, lower rooting percentages were obtained than with IBA, showing that the effect of BOA in inducing root formation is very low and that it cannot be used routinely to replace IBA in the in vitro rooting of microcuttings.
To cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), scheduled to start operation in 2029, CMS will replace its entire tracking ...system. The requirements for the tracker are largely determined by the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 1034cm−2s−1 in the ultimate performance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluence corresponding to a non-ionising energy loss of up to Φeq= 3.5 × 1016cm−2. This paper focuses on planar pixel sensor design and qualification up to a fluence of Φeq = 1.4 × 1016cm−2.
For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150mm (6”) wafers with an active thickness of 150µm with pixel sizes of 100×25 µm2 and 50×50 µm2 manufactured by Hamamatsu Photonics K.K. (HPK). Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was an extensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly with ROC4Sens readout chips. It demonstrates that multiple designs fulfil the requirements in terms of breakdown voltage, leakage current and efficiency. The single point resolution for 50×50 µm2 pixels is measured as 4.0µm for non-irradiated samples, and 6.3µm after irradiation to Φeq = 7.2 × 1015cm−2.
Shoot regeneration was obtained from leaves of in vitro cultures of wild pear genotypes. The highest regeneration rates, ranging from 40% to 64%, depending on the genotype, were obtained using leaves ...wounded by three cuts transversely to the mid-rib, a Quoirin and Lepoivre macro-salt composition, 250 mg l(-1) cefotaxime and maintaining the explants in darkness for the first 30 days (induction phase), then transferring them to an auxin-free medium in light (expression phase). A concentration of 8.8 micromolar BA induced the highest number of explants to produce adventitious shoots. TDZ was less effective than BA and induced hyperhydricity in regenerated shoots. The histological studies revealed that the regenerated shoots originated mainly from callus formed by epidermal and sub-epidermal cells and by cells of the vascular tissue. The regenerated shoots were micropropagated, rooted and transplanted to the soil.
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