Dissection of GTPase activating proteins reveals functional asymmetry in the COPI coat of budding yeast.

The Arf GTPase controls formation of the COPI vesicle coat. Recent structural models of COPI revealed the positioning of two Arf1 molecules in contrasting molecular environments. Each of these pockets for Arf1 is expected to also accommodate an Arf GTPase-activating protein (ArfGAP). Structural evidence and protein interactions observed between isolated domains indirectly suggests that each niche may preferentially recruit one of the two ArfGAPs known to affect COPI, Gcs1/ArfGAP1 and Glo3/ArfGAP2/3, although only partial structures are available. The functional role of the unique non-catalytic domain of either ArfGAP has not been integrated into the current COPI structural model. Here, we delineate key differences in the consequences of triggering GTP hydrolysis via the activity of one versus the other ArfGAP. We demonstrate that Glo3/ArfGAP2/3 specifically triggers Arf1 GTP hydrolysis impinging on the stability of the COPI coat. We show that the yeast homologue of AMP kinase, Snf1, phosphorylates the region of Glo3 that is critical for this effect and thereby regulates its function in the COPI-vesicle cycle. Our results revise the model of ArfGAP function in the molecular context of COPI

Energy use for urban water management by utilities and Households in Los Angeles

Reducing energy consumption for urban water management may yield economic and environmental benefits. Few studies provide comprehensive assessments of energy needs for urban water sectors that include both utility operations and household use. Here, we evaluate the energy needs for urban water management in metropolitan Los Angeles (LA) County. Using planning scenarios that include both water conservation and alternative supply options, we estimate energy requirements of water imports, groundwater pumping, distribution in pipes, water and wastewater treatment, and residential water heating across more than one hundred regional water agencies covering over 9 million people. Results show that combining water conservation with alternative local supplies such as stormwater capture and water reuse (nonpotable or indirect potable) can reduce the energy consumption and intensity of water management in LA. Further advanced water treatment for direct potable reuse could increase energy needs. In aggregate, water heating represents a major source of regional energy consumption. The heating factor associated with grid-supplied electricity drives the relative contribution of energy-for-water by utilities and households. For most scenarios of grid operations, energy for household water heating significantly outweighs utility energy consumption. The study demonstrates how publicly available and detailed data for energy and water use supports sustainability planning. The method is applicable to cities everywhere

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts.

Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were examined. All tumours but one expressed both cadherin and NCAM. The tumours expressed one, two or rarely three cadherin bands, and different combinations of two major isoforms of NCAM with M(r)'s of approximately 190,000 and 135,000. Polysialylation of NCAM, a feature characteristic of NCAM during embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression

The Cdc31p-binding protein Kar1p is a component of the half bridge of the yeast spindle pole body

KAR1 has been identified as an essential gene which is involved in karyogamy of mating yeast cells and in spindle pole body duplication of mitotic cells (Rose, M. D., and G. R. Fink. 1987. Cell. 48:1047-1060). We investigated the cell cycle-dependent localization of the Kar1 protein (Kar1p) and its interaction with other SPB components. Kar1p is associated with the spindle pole body during the entire cell cycle of yeast. Immunoelectron microscopic studies with anti-Kar1p antibodies or with the monoclonal antibody 12CA5 using an epitope-tagged, functional Kar1p revealed that Kar1p is associated with the half bridge or the bridge of the spindle pole body. Cdc31p, a Ca(2+)-binding protein, was previously identified as the first component of the half bridge of the spindle pole body (Spang, A., I. Courtney, U. Fackler, M. Matzner, and E. Schiebel. 1993. J. Cell Biol. 123:405-416). Using an in vitro assay we demonstrate that Cdc31p specifically interacts with a short sequence within the carboxyl terminal half of Kar1p. The potential Cdc31p-binding sequence of Kar1p contains three acidic amino acids which are not found in calmodulin-binding peptides, explaining the different substrate specificities of Cdc31p and calmodulin. Cdc31p was also able to bind to the carboxy terminus of Nuflp/Spc110p, another component of the SPB (Kilmartin, J. V., S. L. Dyos, D. Kershaw, and J. T. Finch. 1993. J. Cell Biol. 123:1175-1184). The association of Kar1p with the spindle pole body was independent of Cdc31p. Cdc31p, on the other hand, was not associated with SPBs of kar1 cells

Fundamental parameters of 16 late-type stars derived from their angular diameter measured with VLTI/AMBER

Thanks to their large angular dimension and brightness, red giants and supergiants are privileged targets for optical long-baseline interferometers. Sixteen red giants and supergiants have been observed with the VLTI/AMBER facility over a two-years period, at medium spectral resolution (R=1500) in the K band. The limb-darkened angular diameters are derived from fits of stellar atmospheric models on the visibility and the triple product data. The angular diameters do not show any significant temporal variation, except for one target: TX Psc, which shows a variation of 4% using visibility data. For the eight targets previously measured by Long-Baseline Interferometry (LBI) in the same spectral range, the difference between our diameters and the literature values is less than 5%, except for TX Psc, which shows a difference of 11%. For the 8 other targets, the present angular diameters are the first measured from LBI. Angular diameters are then used to determine several fundamental stellar parameters, and to locate these targets in the Hertzsprung-Russell Diagram (HRD). Except for the enigmatic Tc-poor low-mass carbon star W Ori, the location of Tc-rich stars in the HRD matches remarkably well the thermally-pulsating AGB, as it is predicted by the stellar-evolution models. For pulsating stars with periods available, we compute the pulsation constant and locate the stars along the various sequences in the Period -- Luminosity diagram. We confirm the increase in mass along the pulsation sequences, as predicted by the theory, except for W Ori which, despite being less massive, appears to have a longer period than T Cet along the first-overtone sequence.Comment: 15 pages, 9 figures, 6 table

Chemical modification of epibatidine causes a switch from agonist to antagonist and modifies its selectivity for neuronal nicotinic acetylcholine receptors

AbstractBackground: Studies of ligand gated channels strongly rely on the availability of compounds that can activate or inhibit with high selectivity one set or a subset of defined receptors. The alkaloid epibatidine (EPB), originally isolated from the skin of an Ecuadorian poison frog, is a very specific agonist for the neuronal nicotinic acetylcholine receptors (nAChRs). We used EPB derivatives to investigate the pharmacophore of nAChR subtypes.Results: Optically pure enantiomers of EPB analogues were synthesised. Analogues were obtained altered in the aromatic part: the chlorine was eliminated and the relative position of the pyridyl nitrogen changed. Voltage clamp electrophysiology was performed with these compounds on neuronal nAChRs reconstituted in Xenopus oocytes. The EPB derivatives show different activities towards the various nAChR subtypes.Conclusions: Small changes in the molecular structure of EPB produce marked changes in its capacity to activate the nAChRs. Subtype specificity can be obtained by changing the position of or by eliminating the pyridyl nitrogen

The water consumption of energy production: an international comparison

Producing energy resources requires significant quantities of fresh water. As an energy sector changes or expands, the mix of technologies deployed to produce fuels and electricity determines the associated burden on regional water resources. Many reports have identified the water consumption of various energy production technologies. This paper synthesizes and expands upon this previous work by exploring the geographic distribution of water use by national energy portfolios. By defining and calculating an indicator to compare the water consumption of energy production for over 150 countries, we estimate that approximately 52 billion cubic meters of fresh water is consumed annually for global energy production. Further, in consolidating the data, it became clear that both the quality of the data and global reporting standards should be improved to track this important variable at the global scale. By introducing a consistent indicator to empirically assess coupled water–energy systems, it is hoped that this research will provide greater visibility into the magnitude of water use for energy production at the national and global scales

Multiple metrics for quantifying the intensity of water consumption of energy production

Discussion of the environmental implications of worldwide energy demand is currently dominated by the effects of carbon dioxide (CO[subscript 2]) emissions on global climate. At the regional scale, however, water resource challenges associated with energy systems are a growing concern. This paper, based on an inventory of national energy portfolios, posits an indicator-based framework for characterizing regional energy portfolios' relative water intensity. These calculations extend upon a previous paper that established a method for calculating the national water consumption of energy production (WCEP) at the global level. Intensity indicators are based on normalizing the WCEP results with a set of additional indicators (including population, gross domestic product, total energy production, and regional water availability). The results show great variability in water consumption across nations, as well as across the various water intensity measures that were applied. Therefore, it is best to apply this full suite of indicators to each country to develop an integrated understanding of the intensity of water use for energy across countries