Amino acids induce peptide uptake via accelerated degradation of CUP9, the transcriptional repressor of the PTR2 peptide transporter

Multiple pathways link expression of PTR2, the transporter of di- and tripeptides in the yeast Saccharomyces cerevisiae, to the availability and quality of nitrogen sources. Previous work has shown that induction of PTR2 by extracellular amino acids requires, in particular, SSY1 and PTR3. SSY1 is structurally similar to amino acid transporters, but functions as a sensor of amino acids. PTR3 acts downstream of SSY1. Expression of the PTR2 peptide transporter is induced not only by amino acids but also by dipeptides with destabilizing N-terminal residues. These dipeptides bind to UBR1, the ubiquitin ligase of the N-end rule pathway, and allosterically accelerate the UBR1-dependent degradation of CUP9, a transcriptional repressor of PTR2. UBR1 targets CUP9 through its internal degron. Here we demonstrate that the repression of PTR2 by CUP9 requires TUP1 and SSN6, the corepressor proteins that form a complex with CUP9. We also show that the induction of PTR2 by amino acids is mediated by the UBR1-dependent acceleration of CUP9 degradation that requires both SSY1 and PTR3. The acceleration of CUP9 degradation is shown to be attained without increasing the activity of the N-end rule pathway toward substrates with destabilizing N-terminal residues. We also found that GAP1, a general amino acid transporter, strongly contributes to the induction of PTR2 by Trp. While several aspects of this complex circuit remain to be understood, our findings establish new functional links between the amino acids-sensing SPS system, the CUP9-TUP1-SSN6 repressor complex, the PTR2 peptide transporter and the UBR1-dependent N-end rule pathway

Percolation transition of hydration water at hydrophilic surfaces

An analysis of water clustering is used to study the quasi-2D percolation transition of water adsorbed at planar hydrophilic surfaces. Above the critical temperature of the layering transition (quasi-2D liquid-vapor phase transition of adsorbed molecules) a percolation transition occurs at some threshold surface coverage, which increases with increasing temperature. The location of the percolation line is consistent with the existence of a percolation transition at the critical point. The percolation threshold at a planar surface is weakly sensitive to the size of the system when its lateral dimension increases from 80 to 150 A. The size distribution of the largest water cluster shows a specific two-peaks structure in a wide range of surface coverage : the lower- and higher-size peaks represent contributions from non-spanning and spanning clusters, respectively. The ratio of the average sizes of spanning and non-spanning largest clusters is about 1.8 for all studied planes. The two-peak structure becomes more pronounced with decreasing size of the planar surface and strongly enhances at spherical surfaces.Comment: 17 pages, 11 figure

A circular polarimeter for the Cosmic Microwave Background

A primordial degree of circular polarization of the Cosmic Microwave Background is not observationally excluded. The hypothesis of primordial dichroism can be quantitatively falsified if the plasma is magnetized prior to photon decoupling since the initial V-mode polarization affects the evolution of the temperature fluctuations as well as the equations for the linear polarization. The observed values of the temperature and polarization angular power spectra are used to infer constraints on the amplitude and on the spectral slope of the primordial V-mode. Prior to photon decoupling magnetic fields play the role of polarimeters insofar as they unveil the circular dichroism by coupling the V-mode power spectrum to the remaining brightness perturbations. Conversely, for angular scales ranging between 4 deg and 10 deg the joined bounds on the magnitude of circular polarization and on the magnetic field intensity suggest that direct limits on the V-mode power spectrum in the range of 0.01 mK could directly rule out pre-decoupling magnetic fields in the range of 10-100 nG. The frequency dependence of the signal is located, for the present purposes, in the GHz range.Comment: 28 pages, 12 included figures

Weather and Climate Information for Tourism

The tourism sector is one of the largest and fastest growing global industries and is a significant contributor to national and local economies around the world. The interface between climate and tourism is multifaceted and complex, as climate represents both a vital resource to be exploited and an important limiting factor that poses risks to be managed by the tourism industry and tourists alike. All tourism destinations and operators are climate-sensitive to a degree and climate is a key influence on travel planning and the travel experience. This chapter provides a synopsis of the capacities and needs for climate services in the tourism sector, including current and emerging applications of climate services by diverse tourism end-users, and a discussion of key knowledge gaps, research and capacity-building needs and partnerships that are required to accelerate the application of climate information to manage risks to climate variability and facilitate successful adaptation to climate change

Raman spectrum and lattice parameters of MgB2 as a function of pressure

We report Raman spectra and synchrotron x-ray diffraction measurements of lattice parameters of polycrystalline MgB2 under hydrostatic pressure conditions up to 15 GPa. An anomalously broadened Raman band at 620 cm-1 is observed that exhibits a large linear pressure shift of its frequency. The large mode damping and Gruneisen parameter indicate a highly anharmonic nature of the mode, broadly consistent with theoretical predictions for the E2g in-plane boron stretching mode. The results obtained may provide additional constraints on the electron-phonon coupling in the system.Comment: 3 pages, 3 figure

The Hubble Constant and the Expansion Age of the Universe

The Hubble constant, which measures the expansion rate, together with the total energy density of the Universe, sets the size of the observable Universe, its age, and its radius of curvature. Excellent progress has been made recently toward the measurement of the Hubble constant: a number of different methods for measuring distances have been developed and refined, and a primary project of the Hubble Space Telescope has been the accurate calibration of this difficult-to-measure parameter. The recent progress in these measurements is summarized, and areas where further work is needed are discussed. Currently, for a wide range of possible cosmological models, the Universe appears to have a kinematic age less than about 14 +/- 2 billion years. Combined with current estimates of stellar ages, the results favor a low-matter-density universe. They are consistent with either an open universe, or a flat universe with a non-zero value of the cosmological constant.Comment: 25 page review, 3 figures, to be published in the David Schramm Memorial Volume of Physics Reports, latex file; elsar

Evolution of substrate specificity in a recipient's enzyme following horizontal gene transfer

Despite the prominent role of horizontal gene transfer (HGT) in shaping bacterial metabolism, little is known about the impact of HGT on the evolution of enzyme function. Specifically, what is the influence of a recently acquired gene on the function of an existing gene? For example, certain members of the genus Corynebacterium have horizontally acquired a whole L-tryptophan biosynthetic operon, whereas in certain closely related actinobacteria, for example, Mycobacterium, the trpF gene is missing. In Mycobacterium, the function of the trpF gene is performed by a dual-substrate (βα)8 phosphoribosyl isomerase (priA gene) also involved in L-histidine (hisA gene) biosynthesis. We investigated the effect of a HGT-acquired TrpF enzyme upon PriA’s substrate specificity in Corynebacterium through comparative genomics and phylogenetic reconstructions. After comprehensive in vivo and enzyme kinetic analyses of selected PriA homologs, a novel (βα)8 isomerase subfamily with a specialized function in L-histidine biosynthesis, termed subHisA, was confirmed. X-ray crystallography was used to reveal active-site mutations in subHisA important for narrowing of substrate specificity, which when mutated to the naturally occurring amino acid in PriA led to gain of function. Moreover, in silico molecular dynamic analyses demonstrated that the narrowing of substrate specificity of subHisA is concomitant with loss of ancestral protein conformational states. Our results show the importance of HGT in shaping enzyme evolution and metabolism

Position-Space Description of the Cosmic Microwave Background and Its Temperature Correlation Function

We suggest that the cosmic microwave background (CMB) temperature correlation function C(theta) as a function of angle provides a direct connection between experimental data and the fundamental cosmological quantities. The evolution of inhomogeneities in the prerecombination universe is studied using their Green's functions in position space. We find that a primordial adiabatic point perturbation propagates as a sharp-edged spherical acoustic wave. Density singularities at its wavefronts create a feature in the CMB correlation function distinguished by a dip at theta ~ 1.2 deg. Characteristics of the feature are sensitive to the values of cosmological parameters, in particular to the total and the baryon densities.Comment: The version accepted for publication in Phys. Rev. Letters. 4 pages, 3 figure

A deep spectroscopic study of the filamentary nebulosity in NGC4696, the brightest cluster galaxy in the Centaurus cluster

We present results of deep integral field spectroscopy observations using high resolution optical (4150-7200 A) VIMOS VLT spectra, of NGC 4696, the dominant galaxy in the Centaurus cluster (Abell 3526). After the Virgo cluster, this is the second nearest (z=0.0104) example of a cool core cluster. NGC 4696 is surrounded by a vast, luminous H alpha emission line nebula (L = 2.2 \times 10^40 ergs per second). We explore the origin and excitation of the emission-line filaments and find their origin consistent with being drawn out, under rising radio bubbles, into the intracluster medium as in other similar systems. Contrary to previous observations we do not observe evidence for shock excitation of the outer filaments. Our optical spectra are consistent with the recent particle heating excitation mechanism of Ferland et al.Comment: 21 pages, 23 figures, accepted for publication in MNRA