Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is the most rapidly turned over mammalian enzyme. We have shown that its degradation is accelerated by ODC antizyme, an inhibitory protein induced by polyamines. This is a new type of enzyme regulation and may be a model for selective protein degradation. Here we report the identification of the protease responsible for ODC degradation. Using a cell-free degradation system, we demonstrate that immunodepletion of proteasomes from cell extracts causes almost complete loss of ATP- and antizyme-dependent degradation of ODC. In addition, purified 26S proteasome complex, but not the 20S proteasome, catalyses ODC degradation in the absence of ubiquitin. These results strongly suggest that the 26S proteasome, widely viewed as specific for ubiquitin-conjugated proteins, is the main enzyme responsible for ODC degradation. The 26S proteasome may therefore have a second role in ubiquitin-independent proteolysis.

This publication describes the methods used to measure the centrality of inelastic Pb-Pb collisions at a center-of-mass energy of 2.76 TeV per colliding nucleon pair with ALICE. The centrality is a key parameter in the study of the properties of QCD matter at extreme temperature and energy density, because it is directly related to the initial overlap region of the colliding nuclei. Geometrical properties of the collision, such as the number of participating nucleons and the number of binary nucleon-nucleon collisions, are deduced from a Glauber model with a sharp impact parameter selection and shown to be consistent with those extracted from the data. The centrality determination provides a tool to compare ALICE measurements with those of other experiments and with theoretical calculations.

In this paper measurements are presented of π ± , K ± , p, andp production at midrapidity (|y| < 0.5), in Pb-Pb collisions at √ s NN = 2.76 TeV as a function of centrality. The measurement covers the transverse-momentum (p T ) range from 100, 200, and 300 MeV/c up to 3, 3, and 4.6 GeV/c for π , K, and p, respectively. The measured p T distributions and yields are compared to expectations based on hydrodynamic, thermal and recombination models. The spectral shapes of central collisions show a stronger radial flow than measured at lower energies, which can be described in hydrodynamic models. In peripheral collisions, the p T distributions are not well reproduced by hydrodynamic models. Ratios of integrated particle yields are found to be nearly independent of centrality. The yield of protons normalized to pions is a factor ∼1.5 lower than the expectation from thermal models.

At su ciently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP) 1 . Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed 2-6 . Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions 7 , is more pronounced for multi-strange baryons. Several e ects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions 8,9 , but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results 10,11 , indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.The production of strange hadrons in high-energy hadronic interactions provides a way to investigate the properties of quantum chromodynamics (QCD), the theory of strongly interacting matter. Unlike up (u) and down (d) quarks, which form ordinary matter, strange (s) quarks are not present as valence quarks in the initial state, yet they are sufficiently light to be abundantly created during the course of the collisions. In the early stages of high-energy collisions, strangeness is produced in hard (perturbative) 2 → 2 partonic scattering processes by flavour creation (gg → ss, qq → ss) and flavour excitation (gs → gs, qs → qs). Strangeness is also created

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.

The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.

Previous studies on mice bearing various mutations within the c‐kit gene, dominant white spotting (W), indicate the functional role of this tyrosine kinase receptor in the development of melanocytes, germ cells and hematopoietic cells. Despite the availability of mice defective in the c‐kit gene and a respectable understanding of the molecular nature of c‐kit, however, it is not clear at what stage of gestation c‐kit is functionally required for the development of each of these cell lineages. To address this question, we have used a monoclonal anti‐c‐kit antibody, ACK2, as an antagonistic blocker of c‐kit function to interfere with the development of melanocytes during embryonic and postnatal life. ACK2 injected intradermally into pregnant mice entered the embryos where it blocked the proper development of melanocytes. This inhibitory effect was manifested as coat color alteration in the offspring. Furthermore, ACK2 injection also altered the coat color of neonatal and adult mice. Based on the coat color patterns produced by ACK2 administration at various stages before or after birth, the following conclusions are drawn: (i) during mid‐gestation, c‐kit is functionally required during a restricted period around day 14.5 post‐coitum when a sequence of events leading to melanocyte entry into the epidermal layer occurs; (ii) during postnatal life, c‐kit is required for melanocyte activation which occurs concomitantly with the hair cycle which continues throughout life after neonatal development of the first hair.

Background & Aims-The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology