Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus

The tumor suppressor protein p53 is known to be transported to the nucleus along microtubular tracks by cytoplasmic dynein. However, the connection between p53 and the dynein motor protein complex has not been established. Here, we show that hsp90.binding immunophilins link p53.hsp90 complexes to dynein and that prevention of that linkage in vivo inhibits the nuclear movement of p53. First, we show that p53.hsp90 heterocomplexes from DLD-1 human colon cancer cells contain an immunophilin (FKBP52, CyP-40, or PP5) as well as dynein. p53.hsp90.immunophilin.dynein complexes can be formed by incubating immunopurified p53 with rabbit reticulocyte lysate, and we show by peptide competition that the immunophilins link via their tetratricopeptide repeat domains to p53-bound hsp90 and by means of their PPIase domains to the dynein complex. The linkage of immunophilins to the dynein motor is indirect by means of the dynamitin component of the dynein-associated dynactin complex, and we show that purified FKBP52 binds directly by means of its PPIase domain to purified dynamitin. By using a temperature-sensitive mutant of p53 where cytoplasmic-nuclear movement occurs by shift to permissive temperature, we show that p53 movement is impeded when p53 binding to hsp90 is inhibited by the hsp90 inhibitor radicicol. Also, nuclear movement of p53 is inhibited when immunophilin binding to dynein is competed for by expression of a PPIase domain fragment in the same manner as when dynein linkage to cargo is dissociated by expression of dynamitin. This is the first demonstration of the linkage between an hsp90-chaperoned transcription factor and the system for its retrograde movement to the nucleus both in vitro and in vivo.Fil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Harrell, Jennifer M.. University of Michigan; Estados UnidosFil: O´Hagen, Heather M.. University of Michigan; Estados UnidosFil: Ljungman, Mats. University of Michigan; Estados UnidosFil: Pratt, William B.. University of Michigan; Estados Unido

Renormalization of Horava Gravity

We prove perturbative renormalizability of projectable Horava gravity. The key element of the argument is the choice of a gauge which ensures the correct anisotropic scaling of the propagators and their uniform falloff at large frequencies and momenta. This guarantees that the counterterms required to absorb the loop divergences are local and marginal or relevant with respect to the anisotropic scaling. Gauge invariance of the counterterms is achieved by making use of the background-covariant formalism. We also comment on the difficulties of this approach when addressing the renormalizability of the non-projectable model.Comment: 35 pages, no figures; references discussing gauge invariance of counterterms have been added, typos correcte

Renormalization of gauge theories in the background-field approach

Using the background-field method we demonstrate the Becchi-Rouet-Stora-Tyutin (BRST) structure of counterterms in a broad class of gauge theories. Put simply, we show that gauge invariance is preserved by renormalization in local gauge field theories whenever they admit a sensible background-field formulation and anomaly-free path integral measure. This class encompasses Yang-Mills theories (with possibly Abelian subgroups) and relativistic gravity, including both renormalizable and non-renormalizable (effective) theories. Our results also hold for non-relativistic models such as Yang-Mills theories with anisotropic scaling or Horava gravity. They strengthen and generalize the existing results in the literature concerning the renormalization of gauge systems. Locality of the BRST construction is emphasized throughout the derivation. We illustrate our general approach with several explicit examples.Comment: 45 pages, no figures; references added, changes in the Introduction and Conclusion

Local dynamics for fibered holomorphic transformations

Fibered holomorphic dynamics are skew-product transformations over an irrational rotation, whose fibers are holomorphic functions. In this paper we study such a dynamics on a neighborhood of an invariant curve. We obtain some results analogous to the results in the non fibered case

Ho\v{r}ava gravity is asymptotically free (in 2+1 dimensions)

We compute the $\beta$-functions of marginal couplings in projectable Ho\v{r}ava gravity in $2+1$ spacetime dimensions. We show that the renormalization group flow has an asymptotically-free fixed point in the ultraviolet (UV), establishing the theory as a UV-complete model with dynamical gravitational degrees of freedom. Therefore, this theory may serve as a toy-model to study fundamental aspects of quantum gravity. Our results represent a step forward towards understanding the UV properties of realistic versions of Ho\v{r}ava gravity.Comment: Updated references, minor revisions. Matches journal versio

Discrete soliton ratchets driven by biharmonic fields

Directed motion of topological solitons (kinks or antikinks) in the damped and AC-driven discrete sine-Gordon system is investigated. We show that if the driving field breaks certain time-space symmetries, the soliton can perform unidirectional motion. The phenomenon resembles the well known effects of ratchet transport and nonlinear harmonic mixing. Direction of the motion and its velocity depends on the shape of the AC drive. Necessary conditions for the occurrence of the effect are formulated. In comparison with the previously studied continuum case, the discrete case shows a number of new features: non-zero depinning threshold for the driving amplitude, locking to the rational fractions of the driving frequency, and diffusive ratchet motion in the case of weak intersite coupling.Comment: 13 pages, 13 figure

Continuous Audit: Implementasi dan Pengendalian Berbasis Teknologi Informasi dalam Menjalankan Fungsi Audit yang Lebih Efektif dan Efisien

Information Technology (IT) continues to transform how organizations function, communicate and do business with customers, partners and agents. Directors, audit committee, management and stakeholders sincerely hope their auditors more adept at using technology both in the field of audit (Audit Leveraging Technology) to develop a thorough understanding of how they control the company\u27s processes and internal controls. The research methodology to be used is quantitative observation methodology, by collecting data from various data sources such as journals and literature on Continuous Auditing, both best practice (Practical Approach) as well as theoretical and raw concept of Continuous Auditing (Teorical Approach). Impact on the internal audit process and methodology by using Continuous Audit will be very revolutionary and a major impact on the development of the company\u27s business and also the audit function which is run by the company

Excited lepton triplet contribution to electroweak observables at one loop level

In this paper, we present the one-loop radiative corrections to the electroweak precision observable ρ com ing from the IW = 1 multiplet excited leptons. We have cal culated the couplings of the exotic lepton triplet to the vector bosons and ordinary leptons using the effective Lagrangian approach. These couplings are then used to estimate the excited lepton triplet contribution to the ρ parameter. The mass degenerate excited lepton contribution to ρ is small and can be neglected. However, if the excited leptons are non degenerate, their contribution can be large which can result in more stringent constraints on the excited fermion parameter space compared to the constraints from present experimental searches and perturbative unitarity conditionM. Rehman and M. E. Gomez wish to thank the Istituto Nazionale di Fisica Nucleare, INFN, Sezione di Perugia, for kind hospitality and support for collaboration visits during the early and final stages of this work. The research of M.E.G. was supported by the Spanish MINECO, under grants FPA2017-86380 and PID2019- 107844GB-C2

Persepsi Masyarakat Terhadap Program Pengelolaan Sampah Secara Reduce, Reuse, Recycle (3r) Di Kelurahan Manembo-nembo Tengah Kecamatan Matuari Kota Bitung

Perceptions in relation to the environment, namely as the process where individuals organize and interpret their sensory impressions in order to give meaning to the environment. With the perception of the attitude that it will form a stable tendency to act a certain way in certain situations. Research on the public perception is very important because by knowing that perception would help prevent the arising problems. The purpose of this research is to determine public perception to Trash Processing Program by using 3R method viewed from aspects Socialization, facilities providing, and sorting, composting, and recycling by using instrument Likert scale. This research has been carried out for three months, from February until March 2016 from preparation till the preparation of research reports. Research located in the Manembo-nembo Tengah Sub District Matuari district Bitung City..This research using primary data and secondary data. Primary data obtained from 68 respondents by using questionnaires. While Secondary data obtained from Dinas Kebersihan and Menembo-nembo tengah office. Sampling method used in this research is purposive sampling. This research shows that public perception to trash processing socialization program with 3R still neutral, because of the low socialization from local govern, while public perception to facilities and infrastructure providing program is positive. For public perception to sorting, composting, and trash recycling is positive. So that most of public have positive perception to trash processing socialization program with 3R