Different domains cooperate to target the human ribosomal L7a protein to the nucleus and to the nucleoli.

The human ribosomal protein L7a is a component of the major ribosomal subunit. We transiently expressed in HeLa cells L7a-β-galactosidase fusion proteins and studied their subcellular localization by indirect immunofluorescence staining with anti-β-galactosidase antibodies. We have identified three distinct domains responsible for the nuclear targeting of the protein: domain I, amino acids 23-51; domain II, amino acids 52-100; domain III, amino acids 101-220, each of which contains at least one nuclear localization signal (NLS). Through subcellular localization analysis of deletion mutants of L7a-β-galactosidase chimeras, we demonstrate that domain II plays a special role because it is necessary, although not sufficient, to target the chimeric β-galactosidase to the nucleoli. In fact, we demonstrate that the nucleolar targeting process requires the presence of domain II plus an additional basic domain that can be represented by an NLS or a basic stretch of amino acids without NLS activity. Thus, when multiple NLS are present, each NLS exerts distinct functions. Domain II drives nucleolar accumulation of a reporter protein with the cooperative action of a short basic amino acid sequence, suggesting a mechanism requiring protein-protein or protein-nucleic acid interactions

Possible, alternative explanations of the T2K observation of the nu_e appearance from an initial nu_mu

An alternative explanation to the emergence of sin^2(2 theta_13) > 0 is discussed. It is pointed out that the recorded T2K events might have been due to some other new physics in the neutrino sector, related to the LSND/MiniBooNE sterile neutrino anomalies, for which there is nowadays a growing evidence. The presently running ICARUS detector with the CNGS beam will be able to distinguish between these two possible sources of the effectComment: 5 pages, 1 figur

COVID-19. Update of the Italian situation

On the March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus disease 2019 (COVID-19) outbreak as a pandemic. The first cases in Italy were reported on January 30, 2020, and quickly the number of cases escalated. On March 20, 2020, according to the Italian National Institute of Health (ISS) and National Institute of Statistics (ISTAT), the peak of COVID-19 cases reported in Italy reached the highest number, surpassing those in China. The Italian government endorsed progressively restrictive measures initially at the local level, and finally, at the national level with a lockdown of the entire Italian territory up to 3 May 2020. The complete Italian territory closing slowed down the contagion. This review retraces the main numbers of the pandemic in Italy. Although in decline, the new reported cases remain high in the northern regions. Since drugs or vaccines are still not available, the described framework highlights the importance of the containment measures to be able to quickly identify all the potential transmission hotspots and keep control subsequent epidemic waves of COVID-19

cis-acting sequences and trans-acting factors in the localization of mRNA for mitochondrial ribosomal proteins

mRNA localization is a conserved post-transcriptional process crucial for a variety of systems. Although several mechanisms have been identified, emerging evidence suggests that most transcripts reach the protein functional site by moving along cytoskeleton elements. We demonstrated previously that mRNA for mitochondrial ribosomal proteins are asymmetrically distributed in the cytoplasm, and that localization in the proximity of mitochondria is mediated by the 3′-UTR. Here we show by biochemical analysis that these mRNA transcripts are associated with the cytoskeleton through the microtubule network. Cytoskeleton association is functional for their intracellular localization near the mitochondrion, and the 3′-UTR is involved in this cytoskeleton-dependent localization. To identify the minimal elements required for localization, we generated DNA constructs containing, downstream from the GFP gene, deletion mutants of mitochondrial ribosomal protein S12 3′-UTR, and expressed them in HeLa cells. RT-PCR analysis showed that the localization signals responsible for mRNA localization are located in the first 154 nucleotides. RNA pulldown assays, mass spectrometry, and RNP immunoprecipitation assay experiments, demonstrated that mitochondrial ribosomal protein S12 3′-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and α-tubulin in vitro and in vivo

Constant-q data representation in Neutron Compton scattering on the VESUVIO spectrometer

Standard data analysis on the VESUVIO spectrometer at ISIS is carried out within the Impulse Approximation framework, making use of the West scaling variable y. The experiments are performed using the time-of-flight technique with the detectors positioned at constant scattering angles. Line shape analysis is routinely performed in the y-scaling framework, using two different (and equivalent) approaches: (I) fitting the parameters of the recoil peaks directly to fixed-angle time-of-flight spectral (2) transforming the time-of-flight spectra into fixed-angle y spectra, referred to as the Neutron Compton Profiles, and then fitting the line shape parameters. The present work shows that scattering signals from different fixed-angle detectors can be collected and rebinned to obtain Neutron Compton Profiles at constant wave vector transfer, q, allowing for a suitable interpretation of data in terms of the dynamical structure factor, S(q, w). The current limits of applicability of such a procedure are discussed in terms of the available q-range and relative uncertainties for the VESUVIO experimental set up and of the main approximations involved. (C) 2008 Elsevier B.V. All rights reserved

Genetic Diversity of the Noncoding Control Region of the Novel Human Polyomaviruses.

The genomes of polyomaviruses are characterized by their tripartite organization with an early region, a late region and a noncoding control region (NCCR). The early region encodes proteins involved in replication and transcription of the viral genome, while expression of the late region generates the capsid proteins. Transcription regulatory sequences for expression of the early and late genes, as well as the origin of replication are encompassed in the NCCR. Cell tropism of polyomaviruses not only depends on the appropriate receptors on the host cell, but cell-specific expression of the viral genes is also governed by the NCCR. Thus far, 15 polyomaviruses have been isolated from humans, though it remains to be established whether all of them are genuine human polyomaviruses (HPyVs). The sequences of the NCCR of these HPyVs show high genetic variability and have been best studied in the human polyomaviruses BK and JC. Rearranged NCCRs in BKPyV and JCPyV, the first HPyVs to be discovered approximately 30 years ago, have been associated with the pathogenic properties of these viruses in nephropathy and progressive multifocal leukoencephalopathy, respectively. Since 2007, thirteen novel PyVs have been isolated from humans: KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, HPyV10, STLPyV, HPyV12, NJPyV, LIPyV and QPyV. This review describes all NCCR variants of the new HPyVs that have been reported in the literature and discusses the possible consequences of NCCR diversity in terms of promoter strength, putative transcription factor binding sites and possible association with diseases

A new search for anomalous neutrino oscillations at the CERN-PS

The LSND experiment has observed a 3.8 sigma excess of anti-nu_e events from an anti-nu_mu beam coming from pions at rest. If confirmed, the LSND anomaly would imply new physics beyond the standard model, presumably in the form of some additional sterile neutrinos. The MiniBooNE experiment at FNAL-Booster has further searched for the LSND anomaly. Above 475 MeV, the nu_e result is excluding the LSND anomaly to about 1.6 sigma but it introduces an unexplained, new 3.0 sigma anomaly at lower energies, down to 200 MeV. The nu_e data have so far an insufficient statistics to be conclusive with LSND's anti-nu_e. The present proposal at the CERN-PS is based on two strictly identical LAr-TPC detectors in the near and far positions, respectively at 127 and 850 m from the neutrino (or antineutrino) target and focussing horn, observing the electron-neutrino signal. This project will benefit from the already developed technology of ICARUS T600, well tested on surface in Pavia, without the need of any major R&D activity and without the added problems of an underground experiment (CNGS-2). The superior quality of the Liquid Argon imaging TPC and its unique electron - pi-zero discrimination allow full rejection of the NC background, without efficiency loss for electron neutrino detection. In two years of exposure, the far detector mass of 600 tons and a reasonable utilization of the CERN-PS with the refurbished previous TT7 beam line will allow to collect about 10^6 charged current events, largely adequate to settle definitely the LSND anomaly.Comment: 23 pages, 17 figures, added watermark, better referencin

The 3'-untranslated region directs ribosomal protein-encoding mRNAs to specific cytoplasmic regions

mRNA localization is a conserved post-transcriptional process crucial for a variety of systems. We have analyzed the subcellular distribution of mRNAs encoding human cytosolic and mitochondrial ribosomal proteins. Biochemical fractionation experiments showed that the transcripts for cytosolic ribosomal proteins associate preferentially with the cytoskeleton via actin microfilaments. Transfection in HeLa cells of a GFP reporter construct containing the cytosolic ribosomal protein L4 3'-UTR showed that the 3'-UTR is necessary for the association of the transcript to the cytoskeleton. Using confocal analysis we demonstrate that the chimeric transcript is specifically associated with the perinuclear cytoskeleton. We also show that mRNA for mitochondrial ribosomal protein S12 is asymmetrically distributed in the cytoplasm. In fact, this transcript was localized mainly in the proximity of mitochondria, and the localization was 3'-UTR-dependent. In summary, ribosomal protein mRNAs constitute a new class of localized transcripts that share a common localization mechanism

Facility for fast neutron irradiation tests of electronics at the ISIS spallation neutron source

The VESUVIO beam line at the ISIS spallation neutron source was set up for neutron irradiation tests in the neutron energy range above 10 MeV. The neutron flux and energy spectrum were shown, in benchmark activation measurements, to provide a neutron spectrum similar to the ambient one at sea level, but with an enhancement in intensity of a factor of 107. Such conditions are suitable for accelerated testing of electronic components, as was demonstrated here by measurements of soft error rates in recent technology field programable gate arrays