The true story of Yeti, the "abominable" heterochromatic gene of drosophila melanogaster

The Drosophila Yeti gene (CG40218) was originally identified by recessive lethal mutation and subsequently mapped to the deep pericentromeric heterochromatin of chromosome 2. Functional studies have shown that Yeti encodes a 241 amino acid protein called YETI belonging to the evolutionarily conserved family of Bucentaur (BCNT) proteins and exhibiting a widespread distribution in animals and plants. Later studies have demonstrated that YETI protein: (i) is able to bind both subunits of the microtubule-based motor kinesin-I; (ii) is required for proper chromosome organization in both mitosis and meiosis divisions; and more recently (iii) is a new subunit of dTip60 chromatin remodeling complex. To date, other functions of YETI counterparts in chicken (CENtromere Protein 29, CENP-29), mouse (Cranio Protein 27, CP27), zebrafish and human (CranioFacial Development Protein 1, CFDP1) have been reported in literature, but the fully understanding of the multifaceted molecular function of this protein family remains still unclear. In this review we comprehensively highlight recent work and provide a more extensive hypothesis suggesting a broader range of YETI protein functions in different cellular processes

Development of SMA Spring Linear Actuator for an Autonomous Lock and Release Mechanism: Application for the Gravity-Assisted Pointing System in Moon to Earth Alignment of Directional Devices

The next generation lunar reflector (NGLR) experiment is one of the experiments selected by NASA in the framework of the commercial lunar payload services (CLPS) initiative. The experiment, inspired by the lunar laser ranging (LLR) experiments of the Apollo era, is basically a single cube corner reflector (CCR) capable of reflecting a beam coming from a laser station on Earth that must be deployed on the Moon and pointed toward the mean Earth direction. In this work, a prototype of an actuator for the lock and release system of the reflector package was conceived, built, and tested in laboratory conditions. Since the entire pointing system must be passive, the actuator is designed to be operated by an SMA spring actuated by the thermal radiation of the Sun and regolith on the Moon. In lab conditions, the prototype, activated by a heat gun, howed the capability of the SMA spring to operate a lock and release pin, whose diameter is 4 mm, subjected to a preload of F = 7 N exerted by the releasing spring

Characterization in dynamic load environment of COTS synthetic sapphire bearings for application in magnetic suspension in space

The present research investigates the application of a cardan suspension making use of permanent magnet (PM) bearings employed to obtain high reliable/low-cost solutions for the permanent alignment of directional payloads such as laser reflectors for the Next Generation Lunar Retroreflector (NGLR) experiment or antennas to be deployed on the moon’s surface. According to Earnshaw’s Theorem, it is not possible to fully stabilize an object using only a stationary magnetic field. It is also necessary to provide axial control of the shaft since the PM bearings support the radial load but, they produce an unstable axial force when losing alignment between the stator and rotor magnets stack. In this work, the use of commercial off-the-shelf (COTS) sapphire as axial bearings in the cardan suspension has been investigated by testing their behavior in response to some of the dynamic loads experienced during the qualification tests for space missions. The work is innovative in the sense that COTS sapphire assembly has never been investigated for space mission qualification. As Artemis mission loads have not been yet provided for NGLR, test loads for this study are those used for the proto-qualification of the INFN INRRI payload for the ESA ExoMars EDM mission. Tests showed that, along the x and y directions, no damages were produced on the sapphire, while, unfortunately, on the z direction both sapphires were badly damaged at nominal loads

The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma

Background: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6- methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity. Methods: Tinostamustine has been tested in models of GBM by using 13 GBM cell lines and seven patient-derived GBM proliferating/stem cell lines in vitro. U87MG and U251MG (MGMT negative), as well as T98G (MGMT positive), were subcutaneously injected in nude mice, whereas luciferase positive U251MG cells and patient-derived GBM stem cell line (CSCs-5) were evaluated the orthotopic intra-brain in vivo experiments. Results: We demonstrated that tinostamustine possesses stronger antiproliferative and pro-apoptotic effects than those observed for vorinostat and bendamustine alone and similar to their combination and irrespective of MGMT expression. In addition, we observed a stronger radio-sensitization of single treatment and temozolomide used as control due to reduced expression and increased time of disappearance of γH2AX indicative of reduced signal and DNA repair. This was associated with higher caspase-3 activation and reduction of RT-mediated autophagy. In vivo, tinostamustine increased time-to-progression (TTP) and this was additive/synergistic to RT. Tinostamustine had significant therapeutic activity with suppression of tumor growth and prolongation of DFS (disease-free survival) and OS (overall survival) in orthotopic intra-brain models that was superior to bendamustine, RT and temozolomide and showing stronger radio sensitivity. Conclusions: Our data suggest that tinostamustine deserves further investigation in patients with glioblastoma

Erratum: Lipase-catalyzed regioselective acylation of resorcin[4]arenes (Journal of Molecular Catalysis B: Enzymatic (2002) 16 (24-247) PII: S1381117701000686)

10Immobilized lipase from Mucor miehei (RML) catalyzed the regioselective acylation of the C-2 side-chain of the C-alkyl resorcin[4]arene tetra-alcohol 1 in the 1,2-alternate form in organic solvents using vinyl acetate as acylating reagent. The influence of reaction parameters and solvent choice were also studied. Docking simulations allowed the determination of the binding geometry of 1, revealing the importance of Trp88 residue in stabilizing the Michaelis–Menten complex between enzyme and substrate.reservedmixedBotta, Bruno; Zappia, Giovanni; Tafi, Andrea; Botta, Maurizio; Manetti, Fabrizio; Cernia, Enrico; Milana, Giuliana; Palocci, Cleofe; Soro, Simonetta; Delle Monache, GiulianoBotta, Bruno; Zappia, Giovanni; Tafi, Andrea; Botta, Maurizio; Manetti, Fabrizio; Cernia, Enrico; Milana, Giuliana; Palocci, Cleofe; Soro, Simonetta; Delle Monache, Giulian

A Lunar Laser Ranging Retroreflector Array for the 21st Century

Abstract To date, lunar laser ranging to the Apollo retroreflector arrays, which are still operational after four decades, has produced some of the best tests of General Relativity. Since the ground Observatories have improved their accuracy by a factor of 200, the lunar hardware, due to the lunar librations, now limits the ranging accuracy. The Lunar Laser Ranging Retroreflector Array for the 21st Century program plans to deploy new packages that will improve the ranging accuracy by a factor of ten to one hundred in the next few years

The small molecule ephrin receptor inhibitor, GLPG1790, Reduces renewal capabilities of cancer stem cells, showing anti-tumour efficacy on preclinical glioblastoma models

Therapies against glioblastoma (GBM) show a high percentage of failure associated with the survival of glioma stem cells (GSCs) that repopulate treated tumours. Forced differentiation of GSCs is a promising new approach in cancer treatment. Erythropoietin-producing hepatocellular (Eph) receptors drive tumourigenicity and stemness in GBM. We tested GLPG1790, a first small molecule with inhibition activity versus inhibitor of various Eph receptor kinases, in preclinical GBM models using in vitro and in vivo assays. GLPG1790 rapidly and persistently inhibited Ephrin-A1-mediated phosphorylation of Tyr588 and Ser897, completely blocking EphA2 receptor signalling. Similarly, this compound blocks the ephrin B2-mediated EphA3 and EphB4 tyrosine phosphorylation. This resulted in anti-glioma effects. GLPG1790 down-modulated the expression of mesenchymal markers CD44, Sox2, nestin, octamer-binding transcription factor 3/4 (Oct3/4), Nanog, CD90, and CD105, and up-regulated that of glial fibrillary acidic protein (GFAP) and pro-neural/neuronal markers, βIII tubulin, and neurofilaments. GLPG1790 reduced tumour growth in vivo. These effects were larger compared to radiation therapy (RT; U251 and T98G xenografts) and smaller than those of temozolomide (TMZ; U251 and U87MG cell models). By contrast, GLPG1790 showed effects that were higher than Radiotherapy (RT) and similar to Temozolomide (TMZ) in orthotopic U87MG and CSCs-5 models in terms of disease-free survival (DFS) and overall survival (OS). Further experiments were necessary to study possible interactions with radio- and chemotherapy. GLPG1790 demonstrated anti-tumor effects regulating both the differentiative status of Glioma Initiating Cells (GICs) and the quality of tumor microenvironment, translating into efficacy in aggressive GBM mouse models. Significant common molecular targets to radio and chemo therapy supported the combination use of GLPG1790 in ameliorative antiglioma therapy