Prion expression is activated by Adenovirus 5 infection and affects the adenoviral cycle in human cells

The prion protein is a cell surface glycoprotein whose physiological role remains elusive, while its implication in transmissible spongiform encephalopathies (TSEs) has been demonstrated. Multiple interactions between the prion protein and viruses have been described: viruses can act as co-factors in TSEs and life cycles of different viruses have been found to be controlled by prion modulation. We present data showing that human Adenovirus 5 induces prion expression. Inactivated Adenovirus did not alter prion transcription, while variants encoding for early products did, suggesting that the prion is stimulated by an early adenoviral function. Down-regulation of the prion through RNA interference showed that the prion controls adenovirus replication and expression. These data suggest that the prion protein could play a role in the defense strategy mounted by the host during viral infection, in a cell autonomous manner. These results have implications for the study of the prion protein and of associated TSEs

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5\u2032 phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as \u3b1-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Interplay of the nuclear envelope with chromatin in physiology and pathology

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer

Objective assessment of walking impairments in myotonic dystrophy by means of a wearable technology and a novel severity index

Myotonic dystrophy type 1 (DM1) is a genetic inherited autosomal dominant disease characterized by multisystem involvement, including muscle, heart, brain, eye, and endocrine system. Although several methods are available to evaluate muscle strength, endurance, and dexterity, there are no validated outcome measures aimed at objectively evaluating qualitative and quantitative gait alterations. Advantageously, wearable sensing technology has been successfully adopted in objectifying the assessment of motor disabilities in different medical occurrences, so that here we consider the adoption of such technology specifically for DM1. In particular, we measured motor tasks through inertial measurement units on a cohort of 13 DM1 patients and 11 healthy control counterparts. The motor tasks consisted of 16 meters of walking both at a comfortable speed and fast pace. Measured data consisted of plantar-flexion and dorsi-flexion angles assumed by both ankles, so to objectively evidence the footdrop behavior of the DM1 disease, and to define a novel severity index, termed SI-Norm2, to rate the grade of walking impairments. According to the obtained results, our approach could be useful for a more precise stratification of DM1 patients, providing a new tool for a personalized rehabilitation approach

Cross-verification of independent quantum devices

Quantum computers are on the brink of surpassing the capabilities of even the most powerful classical computers. This naturally raises the question of how one can trust the results of a quantum computer when they cannot be compared to classical simulation. Here we present a verification technique that exploits the principles of measurement-based quantum computation to link quantum circuits of different input size, depth, and structure. Our approach enables consistency checks of quantum computations within a device, as well as between independent devices. We showcase our protocol by applying it to five state-of-the-art quantum processors, based on four distinct physical architectures: nuclear magnetic resonance, superconducting circuits, trapped ions, and photonics, with up to 6 qubits and 200 distinct circuits

Genuine Counterfactual Communication with a Nanophotonic Processor

In standard communication information is carried by particles or waves. Counterintuitively, in counterfactual communication particles and information can travel in opposite directions. The quantum Zeno effect allows Bob to transmit a message to Alice by encoding information in particles he never interacts with. The first suggested protocol not only required thousands of ideal optical components, but also resulted in a so-called "weak trace" of the particles having travelled from Bob to Alice, calling the scalability and counterfactuality of previous proposals and experiments into question. Here we overcome these challenges, implementing a new protocol in a programmable nanophotonic processor, based on reconfigurable silicon-on-insulator waveguides that operate at telecom wavelengths. This, together with our telecom single-photon source and highly-efficient superconducting nanowire single-photon detectors, provides a versatile and stable platform for a high-fidelity implementation of genuinely trace-free counterfactual communication, allowing us to actively tune the number of steps in the Zeno measurement, and achieve a bit error probability below 1%, with neither post-selection nor a weak trace. Our demonstration shows how our programmable nanophotonic processor could be applied to more complex counterfactual tasks and quantum information protocols.Comment: 6 pages, 4 figure

Changes in gene expression in human skeletal stem cells transduced with constitutively active Gs\u3b1 correlates with hallmark histopathological changes seen in fibrous dysplastic bone

Fibrous dysplasia (FD) of bone is a complex disease of the skeleton caused by dominant activating mutations of the GNAS locus encoding for the \u3b1 subunit of the G protein-coupled receptor complex (Gs\u3b1). The mutation involves a substitution of arginine at position 201 by histidine or cysteine (Gs\u3b1R201H or R201C), which leads to overproduction of cAMP. Several signaling pathways are implicated downstream of excess cAMP in the manifestation of disease. However, the pathogenesis of FD remains largely unknown. The overall FD phenotype can be attributed to alterations of skeletal stem/progenitor cells which normally develop into osteogenic or adipogenic cells (in cis), and are also known to provide support to angiogenesis, hematopoiesis, and osteoclastogenesis (in trans). In order to dissect the molecular pathways rooted in skeletal stem/progenitor cells by FD mutations, we engineered human skeletal stem/progenitor cells with the Gs\u3b1R201C mutation and performed transcriptomic analysis. Our data suggest that this FD mutation profoundly alters the properties of skeletal stem/progenitor cells by pushing them towards formation of disorganized bone with a concomitant alteration of adipogenic differentiation. In addition, the mutation creates an altered in trans environment that induces neovascularization, cytokine/chemokine changes and osteoclastogenesis. In silico comparison of our data with the signature of FD craniofacial samples highlighted common traits, such as the upregulation of ADAM (A Disintegrin and Metalloprotease) proteins and other matrix-related factors, and of PDE7B (Phosphodiesterase 7B), which can be considered as a buffering process, activated to compensate for excess cAMP. We also observed high levels of CEBPs (CCAAT-Enhancer Binding Proteins) in both data sets, factors related to browning of white fat. This is the first analysis of the reaction of human skeletal stem/progenitor cells to the introduction of the FD mutation and we believe it provides a useful background for further studies on the molecular basis of the disease and for the identification of novel potential therapeutic targets

Body-worn triaxial accelerometer coherence and reliability related to static posturography in unilateral vestibular failure

Poichè le alterazioni della funzione vestibolare possono essere causa di disequilibrio, i principali reperti sviluppati ad oggi per misurare il controllo posturale e lintegrazione sensoriale nel danno vestibolare sono stati ottenuti grazie alla posturografia. Tuttavia, al fine di superare i problemi legati a tale genere di tecnologia, sono stati proposti gli accelerometri indossabili (ACC) come unalternativa portatile e a basso costo per la misurazione delloscillazione corporea in ambienti confortevoli. Daltro canto, nessuno studio ad oggi ha dimostrato la validità sperimentale delle misurazioni ottenute con ACC - rispetto a quelle derivanti dalla posturografia - in soggetti affetti da deficit vestibolare. Pertanto, lobiettivo del presente lavoro è stato quello di i) sviluppare e validare una strumentazione pratica che potesse consentire la misurazione dei disordini delloscillazione corporea nellambito della valutazione otoneurologica attraverso gli ACC e ii) fornire unanalisi delle oscillazioni affidabile ed automatica, che potesse implementare in modo sensibile ed accurato la possibile discriminazione di pazienti affetti da deficit vestibolare unilaterale (UVF). A tale scopo, un gruppo di 13 pazienti (sette femmine, 6 maschi; età media 48.6 ± 6.4 anni) affetti da UVF da almeno 6 mesi e un altro omogeneo di 13 soggetti sani sono stati invitati a mantenere la posizione eretta durante lesecuzione della posturografia statica (FBP) mentre indossavano a livello lombare - vicino al centro di massa - un sensore Movit® (by Captiks) costituito da accelerometri 3-D. La correlazione product-moment secondo Pearson ha dimostrato un elevato livello di corrispondenza di quattro misure, estratte da ACC e da FBP, nel dominio del tempo e di tre in quello della frequenza. Inoltre il t-test ha evidenziato che due parametri nel dominio del tempo e due in quello della frequenza si sono dimostrati affidabili nel discriminare i soggetti affetti da UVF. Tali aspetti, nel loro complesso, dovrebbero focalizzare lattenzione in ambito clinico e di ricerca su tale tecnica di registrazione, considerato larricchimento quantitativo e qualitativo di informazioni utili nella discriminazione, diagnosi e trattamento di pazienti affetti da UVF. In conclusione, noi riteniamo che la misurazione basata su ACC offra unalternativa confortevole, affidabile, economica ed efficiente utile, assieme ai test clinici di equilibrio e mobilità, in molteplici circostanze così come negli studi implicati nella diagnosi, controllo e riabilitazione di pazienti affetti da UVF

Search for MSSM Higgs bosons decaying to μ+μ-in proton-proton collisions at √s=13TeV

A search is performed for neutral non-standard-model Higgs bosons decaying to two muons in the context of the minimal supersymmetric standard model (MSSM). Proton-proton collision data recorded by the CMS experiment at the CERN Large Hadron Collider at a center-of-mass energy of 13TeVwere used, corresponding to an integrated luminosity of 35.9fb-1. The search is sensitive to neutral Higgs bosons produced via the gluon fusion process or in association with a bbquark pair. No significant deviations from the standard model expectation are observed. Upper limits at 95% confidence level are set in the context of the mmod+hand phenomenological MSSM scenarios on the parameter tanβas a function of the mass of the pseudoscalar Aboson, in the range from 130 to 600GeV. The results are also used to set a model-independent limit on the product of the branching fraction for the decay into a muon pair and the cross section for the production of a scalar neutral boson, either via gluon fusion, or in association with bquarks, in the mass range from 130 to 1000GeV