Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis

Caveolin-1, the structural protein component of caveolae, acts as a scaffolding protein that functionally regulates signaling molecules. We show that knockdown of caveolin-1 protein expression enhances chemotherapeutic drug-induced apoptosis and inhibits long-term survival of colon cancer cells. In vitro studies demonstrate that caveolin-1 is a novel Ku70-binding protein, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101) to the caveolin-binding domain (CBD) of Ku70 (amino acids 471-478). Cell culture data show that caveolin-1 binds Ku70 after treatment with chemotherapeutic drugs. Mechanistically, we found that binding of caveolin-1 to Ku70 inhibits the chemotherapeutic drug-induced release of Bax from Ku70, activation of Bax, translocation of Bax to mitochondria and apoptosis. Potentiation of apoptosis by knockdown of caveolin-1 protein expression is greatly reduced in the absence of Bax expression. Finally, we found that overexpression of wild type Ku70, but not a mutant form of Ku70 that cannot bind to caveolin-1 (Ku70 Φ→A), limits the chemotherapeutic drug-induced Ku70/Bax dissociation and apoptosis. Thus, caveolin-1 acts as an anti-apoptotic protein in colon cancer cells by binding to Ku70 and inhibiting Bax-dependent cell death. © 2012 Zou et al

Law, human capital, and the emergence of free city-states in medieval Italy

In this paper, we study how the birth of the first universities in Italy affected the emergence of the Italian free cities-states (the commune) in the period 1000-1300 a.d. Exploiting a panel dataset of 121 cities, we show that after the foundation of a new university the distance between each city in the sample and the university negatively predicts the timing of the birth of communal institutions in the city. Our evidence is consistent with the idea that universities in the Middle Ages provided the necessary juridical knowledge and skills to build legal capacity and develop broader-based institutions.This paper considers how the foundation of the first universities in Italy affected the emergence of free city-states (the communes) in the period 1000-1300 CE. Exploiting a panel dataset of 121 cities, we show that the time variant distance of the sample cities to their closest university is inversely correlated with the probability of their transition to communal institutions. Our evidence is consistent with the hypothesis that the medieval universities provided the useful juridical knowledge and skills for building legal capacity and developing communal institutions

REGULATORY NETWORK CONTROLLING OVULE DEVELOPMENT IN Arabidopsis thaliana

In flowering plants ovules develop as lateral organ from the placenta and, once fertilized, give rise to seeds. My Ph.D. was mainly focused on the identification of the mechanisms controlling ovule number and development in Arabidopsis thaliana. AINTEGUMENTA (ANT), CUP-SHAPED COTYLEDON 1 (CUC1) and CUC2 are involved in ovule primordia initiation, since ant single and cuc1 cuc2 double mutant produce fewer ovule compared to wild type. Through the contemporary silencing of ANT, CUC1 and CUC2 we showed that these genes have additive roles in the determination of ovule number. Among all the developmental processes in which hormones are involved, their role in ovule primordia formation have been proposed for auxin and cytokinins. We show that CUC1 and CUC2 are required for correct auxin transport and that they, together with ANT are direct target of MP, a member of AUXIN RESPONSIVE FACTOR (ARF) family. Interestingly we saw that cytokinin treatments restore ovule number defects in our mutants increasing the expression of PINFORMED1 (PIN1), an auxin efflux carrier. Once the primordium is formed, the three MADS box transcription factors SEEDSTICK (STK), SHATTERPROOF1 (SHP1), and SHP2 redundantly regulate ovule development and, together with the SEPALLATA proteins determine ovule identity. I have contributed to the characterization of VERDANDI (VDD), the first direct target of the Arabidopsis ovule identity complex

Orthodontic-surgical treatment: electromyographic and kinesiographic evaluation in follow up period : Experimental study

Introduction. The aim of this study was to investigate muscular function and mandibular kinesiology of patients undergoing orthodontic-surgical treatment by electromyography and kinesiography. Electromyographic evaluation is essential to estimate masticatory forces in patients undergoing combined surgical-orthodontic treatment. Materials and methods. 60 patients referred for orthodontic surgical treatment were included in the study, 43 patients presented a class III while 17 presented a class II. The patients underwent electromyographic and kinesiographic examinations during all the therapeutic orthodontic-surgical phases. Results. The relationship between fundamental electromyographic values and age, weight, asymmetry and activation was weak. A strong and positive relationship was observed between the relaxation percentage after TENS (transcutaneous electrical neuromuscular stimulation), the steepness of the post-surgery rehabilitation curve, the initial POC (percentage overlapping coefficient), and for the values in microvolts of the right and left temporal and masseters at the beginning of treatment. Conclusions. Patients with dentofacial deformities corrected by surgical treatment, have a significant positive treatment outcome in respect of masticatory activity and performance electromyographic evaluation on, before, during and follow up period of the analized patients permit to underline that this examination can predict long term stability

Dual-domain reporter approach for multiplex identification of major SARS-CoV-2 variants of concern in a microarray-based assay

: Since the emergence of the COVID-19 pandemic in December 2019, the SARS-CoV-2 virus continues to evolve into many variants emerging around the world. To enable regular surveillance and timely adjustments in public health interventions, it is of the utmost importance to accurately monitor and track the distribution of variants as rapidly as possible. Genome sequencing is the gold standard for monitoring the evolution of the virus, but it is not cost-effective, rapid and easily accessible. We have developed a microarray-based assay that can distinguish known viral variants present in clinical samples by simultaneously detecting mutations in the Spike protein gene. In this method, the viral nucleic acid, extracted from nasopharyngeal swabs, after RT-PCR, hybridizes in solution with specific dual-domain oligonucleotide reporters. The domains complementary to the Spike protein gene sequence encompassing the mutation form hybrids in solution that are directed by the second domain ("barcode" domain) at specific locations on coated silicon chips. The method utilizes characteristic fluorescence signatures to unequivocally differentiate, in a single assay, different known SARS-CoV-2 variants. In the nasopharyngeal swabs of patients, this multiplex system was able to genotype the variants which have caused waves of infections worldwide, reported by the WHO as being of concern (VOCs), namely Alpha, Beta, Gamma, Delta and Omicron variants

The Nylon Scintillator Containment Vessels for the Borexino Solar Neutrino Experiment

Borexino is a solar neutrino experiment designed to observe the 0.86 MeV Be-7 neutrinos emitted in the pp cycle of the sun. Neutrinos will be detected by their elastic scattering on electrons in 100 tons of liquid scintillator. The neutrino event rate in the scintillator is expected to be low (~0.35 events per day per ton), and the signals will be at energies below 1.5 MeV, where background from natural radioactivity is prominent. Scintillation light produced by the recoil electrons is observed by an array of 2240 photomultiplier tubes. Because of the intrinsic radioactive contaminants in these PMTs, the liquid scintillator is shielded from them by a thick barrier of buffer fluid. A spherical vessel made of thin nylon film contains the scintillator, separating it from the surrounding buffer. The buffer region itself is divided into two concentric shells by a second nylon vessel in order to prevent inward diffusion of radon atoms. The radioactive background requirements for Borexino are challenging to meet, especially for the scintillator and these nylon vessels. Besides meeting requirements for low radioactivity, the nylon vessels must also satisfy requirements for mechanical, optical, and chemical properties. The present paper describes the research and development, construction, and installation of the nylon vessels for the Borexino experiment

Direct WIMP identification: Physics performance of a segmented noble-liquid target immersed in a Gd-doped water veto

We evaluate background rejection capabilities and physics performance of a detector composed of two diverse elements: a sensitive target (filled with one or two species of liquefied noble gasses) and an active veto (made of Gd-doped ultra-pure water). A GEANT4 simulation shows that for a direct WIMP search, this device can reduce the neutron background to O(1) event per year per tonne of material. Our calculation shows that an exposure of one tonne $\times$ year will suffice to exclude spin-independent WIMP-nucleon cross sections ranging from $10^{-9}$ pb to $10^{-10}$ pb.Comment: 17 pages, 5 figures. Version accepted for publication in JCA

Demonstration and Comparison of Operation of Photomultiplier Tubes at Liquid Argon Temperature

Liquified noble gases are widely used as a target in direct Dark Matter searches. Signals from scintillation in the liquid, following energy deposition from the recoil nuclei scattered by Dark Matter particles (e.g. WIMPs), should be recorded down to very low energies by photosensors suitably designed to operate at cryogenic temperatures. Liquid Argon based detectors for Dark Matter searches currently implement photo multiplier tubes for signal read-out. In the last few years PMTs with photocathodes operating down to liquid Argon temperatures (87 K) have been specially developed with increasing Quantum Efficiency characteristics. The most recent of these, Hamamatsu Photonics Mod. R11065 with peak QE up to about 35%, has been extensively tested within the R&D program of the WArP Collaboration. During these testes the Hamamatsu PMTs showed superb performance and allowed obtaining a light yield around 7 phel/keVee in a Liquid Argon detector with a photocathodic coverage in the 12% range, sufficient for detection of events down to few keVee of energy deposition. This shows that this new type of PMT is suited for experimental applications, in particular for new direct Dark Matter searches with LAr-based experiments

Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 4: Cosmic Frontier

These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 4, on the Cosmic Frontier, discusses the program of research relevant to cosmology and the early universe. This area includes the study of dark matter and the search for its particle nature, the study of dark energy and inflation, and cosmic probes of fundamental symmetries.Comment: 61 page