158 research outputs found
Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam
The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy
Large Isoforms of UNC-89 (Obscurin) Are Required for Muscle Cell Architecture and Optimal Calcium Release in Caenorhabditis elegans
Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction
Metal alloys, matrix inclusions and manufacturing techniques of Moinhos de Golas collection (North Portugal): a study by micro-EDXRF, SEM–EDS, optical microscopy and X-ray radiography
"Article:820"A collection of 35 metallic artefacts comprising
various typologies, some of which can be attributed to the
Bronze Age and others to later periods, were studied to
provide detailed information on elemental composition,
manufacturing techniques and preservation state. Elemental
analysis by micro-EDXRF and SEM–EDS was performed
to investigate the use of different alloys and to
study the presence of microstructural heterogeneities, as
inclusions. X-ray radiography, optical microscopy and
SEM–EDS were used to investigate manufacturing techniques
and degradation features. Results showed that most
of the artefacts were produced in a binary bronze alloy
(Cu–Sn) with 10–15 wt% Sn and a low concentration of
impurities. Other artefacts were produced in copper or in
brass, the latest with varying contents of Zn, Sn and Pb. A
variety of inclusions in the metal matrices were also found,
some related to specific types of alloys, as (Cu–Ni)S2 in
coppers, or ZnS in brasses. Microstructural observations
revealed that the majority of the artefacts were subjected to
cycles of thermomechanical processing after casting, being
evident that among some artefacts different parts were
subjected to distinct treatments. The radiographic images
revealed structural heterogeneities related to local corrosion
processes and fissures that seem to have developed in
wear-tension zones, as in the handle of some daggers.
Radiographic images were also useful to detect the use of
different materials in one particular brass artefact, revealing
the presence of a possible Cu–Sn solder.This work was funded by FEDER funds through
the COMPETE 2020 Programme and National Funds through FCT—
Fundação para a Ciência e a Tecnologia under the project UID/CTM/
50025/2013 to CENIMAT/I3N. C2
TN/IST authors gratefully
acknowledge the FCT support through the UID/Multi/04349/2013
project. EF acknowledges FCT for the grant SFRH/BPD/97360/2013.
JF acknowledge FCT for the grant SFRH/BD/65143/2009. Part of this
project has been done in the framework of the FCT project ENARDAS
(PTDC/HISARQ/112983/2009).info:eu-repo/semantics/publishedVersio
T2K ECAL Test–beam Proposal
The T2K experiment will search for the last unknown element of the neutrino mixing matrix. An crucial component of the near detector for this experiment is the electromagnetic calorimeter which is being built in the UK. Testbeam time is requested to test the full ECAL system, validate calibration techniques, and determine the hadronic and electromagnetic energy scale of the calorimeter
Syntaxin 5 Is Required for Copper Homeostasis in Drosophila and Mammals
Copper is essential for aerobic life, but many aspects of its cellular uptake and distribution remain to be fully elucidated. A genome-wide screen for copper homeostasis genes in Drosophila melanogaster identified the SNARE gene Syntaxin 5 (Syx5) as playing an important role in copper regulation; flies heterozygous for a null mutation in Syx5 display increased tolerance to high dietary copper. The phenotype is shown here to be due to a decrease in copper accumulation, a mechanism also observed in both Drosophila and human cell lines. Studies in adult Drosophila tissue suggest that very low levels of Syx5 result in neuronal defects and lethality, and increased levels also generate neuronal defects. In contrast, mild suppression generates a phenotype typical of copper-deficiency in viable, fertile flies and is exacerbated by co-suppression of the copper uptake gene Ctr1A. Reduced copper uptake appears to be due to reduced levels at the plasma membrane of the copper uptake transporter, Ctr1. Thus Syx5 plays an essential role in copper homeostasis and is a candidate gene for copper-related disease in humans
Tryptophan Scanning Analysis of the Membrane Domain of CTR-Copper Transporters
Membrane proteins of the CTR family mediate cellular copper uptake in all eukaryotic cells and have been shown to participate in uptake of platinum-based anticancer drugs. Despite their importance for life and the clinical treatment of malignancies, directed biochemical studies of CTR proteins have been difficult because high-resolution structural information is missing. Building on our recent 7Å structure of the human copper transporter hCTR1, we present the results of an extensive tryptophan-scanning analysis of hCTR1 and its distant relative, yeast CTR3. The comparative analysis supports our previous assignment of the transmembrane helices and shows that most functionally and structurally important residues are clustered around the threefold axis of CTR trimers or engage in helix packing interactions. The scan also identified residues that may play roles in interactions between CTR trimers and suggested that the first transmembrane helix serves as an adaptor that allows evolutionarily diverse CTRs to adopt the same overall structure. Together with previous biochemical and biophysical data, the results of the tryptophan scan are consistent with a mechanistic model in which copper transport occurs along the center of the trimer
Rad51 Inhibits Translocation Formation by Non-Conservative Homologous Recombination in Saccharomyces cerevisiae
Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in mammalian cells also reduce DSB repair by conservative gene conversion and stimulate non-conservative repair by SSA, this mechanism may also operate in humans and, perhaps contribute to the genome instability that propels the development of cancer
- …