Uncoupling of p97 ATPase activity has a dominant negative effect on protein extraction

p97 is a highly abundant, homohexameric AAA+ ATPase that performs a variety of essential cellular functions. Characterized as a ubiquitin-selective chaperone, p97 recognizes proteins conjugated to K48-linked polyubiquitin chains and promotes their removal from chromatin and other molecular complexes. Changes in p97 expression or activity are associated with the development of cancer and several related neurodegenerative disorders. Although pathogenic p97 mutations cluster in and around p97's ATPase domains, mutant proteins display normal or elevated ATPase activity. Here, we show that one of the most common p97 mutations (R155C) retains ATPase activity, but is functionally defective. p97-R155C can be recruited to ubiquitinated substrates on chromatin, but is unable to promote substrate removal. As a result, p97-R155C acts as a dominant negative, blocking protein extraction by a similar mechanism to that observed when p97's ATPase activity is inhibited or inactivated. However, unlike ATPase-deficient proteins, p97-R155C consumes excess ATP, which can hinder high-energy processes. Together, our results shed new insight into how pathogenic mutations in p97 alter its cellular function, with implications for understanding the etiology and treatment of p97-associated diseases

Probing neutrino and Higgs sectors in SU(2)1×SU(2)2×U(1)YSU(2)_1 \times SU(2)_2 \times U(1)_Y model with lepton-flavor non-universality

The neutrino and Higgs sectors in the \mbox{SU(2)}_1 \times \mbox{SU(2)}_2 \times \mbox{U(1)}_Y model with lepton-flavor non-universality are discussed. We show that active neutrinos can get Majorana masses from radiative corrections, after adding only new singly charged Higgs bosons. The mechanism for generation of neutrino masses is the same as in the Zee models. This also gives a hint to solving the dark matter problem based on similar ways discussed recently in many radiative neutrino mass models with dark matter. Except the active neutrinos, the appearance of singly charged Higgs bosons and dark matter does not affect significantly the physical spectrum of all particles in the original model. We indicate this point by investigating the Higgs sector in both cases before and after singly charged scalars are added into it. Many interesting properties of physical Higgs bosons, which were not shown previously, are explored. In particular, the mass matrices of charged and CP-odd Higgs fields are proportional to the coefficient of triple Higgs coupling $\mu$. The mass eigenstates and eigenvalues in the CP-even Higgs sector are also presented. All couplings of the SM-like Higgs boson to normal fermions and gauge bosons are different from the SM predictions by a factor $c_h$, which must satisfy the recent global fit of experimental data, namely $0.995<|c_h|<1$. We have analyzed a more general diagonalization of gauge boson mass matrices, then we show that the ratio of the tangents of the $W-W'$ and $Z-Z'$ mixing angles is exactly the cosine of the Weinberg angle, implying that number of parameters is reduced by 1. Signals of new physics from decays of new heavy fermions and Higgs bosons at LHC and constraints of their masses are also discussed.Comment: 40 pages, 1 figure; Journal vesio

General one-loop formulas for decay h→Zγh\rightarrow Z\gamma

Radiative corrections to the $h\rightarrow Z\gamma$ are evaluated in the one-loop approximation. The unitary gauge gauge is used. The analytic result is expressed in terms of the Passarino-Veltman functions. The calculations are applicable for the Standard Model as well for a wide class of its gauge extensions. In particular, the decay width of a charged Higgs boson $H^\pm \rightarrow W^\pm\gamma$ can be derived. The consistence of our formulas and several specific earlier results is shown.Comment: 33 pages, 3 figures, a new section (V) and references were improved in the published versio

The conceptual evolution of responsible research and innovation in China:A systematic literature review

Within the contemporary global economy, research and innovation are just as likely to come from non-western economic and political powers, such as China, as from western powers more traditionally associated with research and innovation production, such as in Europe and North America. Subsequently, how Responsible Research and Innovation (RRI) is conceptualised and applied in these alternative contexts is an important question. This review aims to contribute to a better understanding of the evolution and application of RRI in China by reviewing Chinese academic literature. Our analysis indicates that, on the one hand, there is wariness that a complete transplantation of a European conception of RRI to China might lead to cultural imperialism. On the other hand, it is hoped that RRI will improve the ethical governance of technological innovation in China. By analysing Chinese scholarship, the paper also attempts to define distinctive features of RRI in China.</p

Hubble space telescope STIS spectroscopy of the peculiar nova-like variables BK Lyn, V751 Cygni, and V380 Oph

We obtained Hubble STIS spectra of three nova-like variables: V751 Cygni, V380 Oph, and—the only confirmed nova-like variable known to be below the period gap—BK Lyn. In all three systems, the spectra were taken during high optical brightness state, and a luminous accretion disk dominates their far-ultraviolet (FUV) light. We assessed a lower limit of the distances by applying the infrared photometric method of Knigge. Within the limitations imposed by the poorly known system parameters (such as the inclination, white dwarf mass, and the applicability of steady state accretion disks) we obtained satisfactory fits to BK Lyn using optically thick accretion disk models with an accretion rate of for a white dwarf mass of Mwd = 1.2M and for Mwd = 0.4M. However, for the VY Scl-type nova-like variable V751 Cygni and for the SW Sex star V380 Oph, we are unable to obtain satisfactory synthetic spectral fits to the high state FUV spectra using optically thick steady state accretion disk models. The lack of FUV spectra information down to the Lyman limit hinders the extraction of information about the accreting white dwarf during the high states of these nova-like systems

Single Z' production at CLIC based on e^- gamma collisions

We analyze the potential of CLIC based on e- gamma collisions to search for new $Z'$ gauge boson. Single Z' production at e-gamma colliders in two SU(3)_C X SU(3)_L X U(1)_N models: the minimal model and the model with right-handed (RH) neutrinos is studied in detail. Results show that new Z' gauge bosons can be observed at the CLIC, and the cross sections in the model with RH neutrinos are bigger than those in the minimal one.Comment: 11 pages, 4 figures, To appear in JET

Quartic Gauge Boson Couplings and Tree Unitarity in the SU(3)_C X SU(3)_L X U(1)_N Models

The quartic gauge boson couplings in the ${SU(3)}_C \otimes {SU(3)}_L \otimes {U(1)}_N$ models are presented. We find that the couplings of four {\it differrent} gauge bosons may have unusual Lorentz structure and the couplings sastify the tree unitarity requirement at high energy limit.Comment: 13 pages, Latex, axodraw.st

Quantum-Mechanical Detection of Non-Newtonian Gravity

In this work the possibility of detecting the presence of a Yukawa term, as an additional contribution to the usual Newtonian gravitational potential, is introduced. The central idea is to analyze the effects at quantum level employing interference patterns (at this respect the present proposal resembles the Colella, Overhauser and Werner experiment), and deduce from it the possible effects that this Yukawa term could have. We will prove that the corresponding interference pattern depends on the phenomenological parameters that define this kind of terms. Afterwards, using the so called restricted path integral formalism, the case of a particle whose position is being continuously monitored, is analyzed, and the effects that this Yukawa potential could have on the measurement outputs are obtained. This allows us to obtain another scheme that could lead to the detection of these terms. This last part also renders new theoretical predictions that could enable us to confront the restricted path integral formalism against some future experiments.Comment: 17 pages, accepted in International Journal of Modern Physics

Carbonate Hydroxyapatite and Silicon-Substituted Carbonate Hydroxyapatite: Synthesis, Mechanical Properties, and Solubility Evaluations

The present study investigates the chemical composition, solubility, and physical and mechanical properties of carbonate hydroxyapatite (CO3Ap) and silicon-substituted carbonate hydroxyapatite (Si-CO3Ap) which have been prepared by a simple precipitation method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF) spectroscopy, and inductively coupled plasma (ICP) techniques were used to characterize the formation of CO3Ap and Si-CO3Ap. The results revealed that the silicate (SiO4 4−) and carbonate (CO3 2−) ions competed to occupy the phosphate (PO4 3−) site and also entered simultaneously into the hydroxyapatite structure.TheSi-substitutedCO3Ap reduced the powder crystallinity and promoted ion release which resulted in a better solubility compared to that of Si-free CO3Ap. The mean particle size of Si-CO3Ap was much finer than that of CO3Ap. At 750∘C heat-treatment temperature, the diametral tensile strengths (DTS) of Si-CO3Ap and CO3Ap were about 10.8 ± 0.3 and 11.8 ± 0.4 MPa, respectively