Plasmodium falciparum glutamate dehydrogenase a is dispensable and not a drug target during erythrocytic development

<p>Background: Plasmodium falciparum contains three genes encoding potential glutamate dehydrogenases. The protein encoded by gdha has previously been biochemically and structurally characterized. It was suggested that it is important for the supply of reducing equivalents during intra-erythrocytic development of Plasmodium and, therefore, a suitable drug target.</p> <p>Methods: The gene encoding the NADP(H)-dependent GDHa has been disrupted by reverse genetics in P. falciparum and the effect on the antioxidant and metabolic capacities of the resulting mutant parasites was investigated.</p> <p>Results: No growth defect under low and elevated oxygen tension, no up-or down-regulation of a number of antioxidant and NADP(H)-generating proteins or mRNAs and no increased levels of GSH were detected in the D10(Delta gdha) parasite lines. Further, the fate of the carbon skeleton of [(13)C] labelled glutamine was assessed by metabolomic studies, revealing no differences in the labelling of a-ketoglutarate and other TCA pathway intermediates between wild type and mutant parasites.</p> <p>Conclusions: First, the data support the conclusion that D10(Delta gdha) parasites are not experiencing enhanced oxidative stress and that GDHa function may not be the provision of NADP(H) for reductive reactions. Second, the results imply that the cytosolic, NADP(H)-dependent GDHa protein is not involved in the oxidative deamination of glutamate but that the protein may play a role in ammonia assimilation as has been described for other NADP(H)dependent GDH from plants and fungi. The lack of an obvious phenotype in the absence of GDHa may point to a regulatory role of the protein providing glutamate (as nitrogen storage molecule) in situations where the parasites experience a limiting supply of carbon sources and, therefore, under in vitro conditions the enzyme is unlikely to be of significant importance. The data imply that the protein is not a suitable target for future drug development against intra-erythrocytic parasite development.</p&gt

Rotation of Hot Horizontal Branch Stars in the Globular Clusters NGC 1904, NGC 2808, NGC 6093 and NGC 7078

We present high resolution UVES+VLT spectroscopic observations of 56 stars in the extended horizontal branch (EHB) of the Galactic globular clusters NGC 1904, NGC 2808, NGC 6093, and NGC 7078. Our data reveal for the first time the presence in NGC 1904 of a sizable population of fast (vsini > 20 km/s) horizontal branch (HB) rotators, confined to the cool end of the EHB, similar to that found in M13. We also confirm the fast rotators already observed in NGC 7078. The cooler stars (Teff < 11,500 K) in these three clusters show a range of rotation rates, with a group of stars rotating at ~ 15 km/s or less, and a fast rotating group at ~ 30 km/s. Apparently, the fast rotators are relatively more abundant in NGC 1904 and M13, than in NGC 7078. No fast rotators have been identified in NGC 2808 and NGC 6093. All the stars hotter than Teff ~ 11,500 K have projected rotational velocities vsini < 12 km/s, but less than 20% have vsini < 2 km/s. The connection between photometric gaps in the HB and the change in the projected rotational velocities is not confirmed by the new data. However, our data are consistent with a relation between this discontinuity and the HB jump. We discuss a number of possibilities for the origin of the stellar rotation distribution along the HB. We conclude that none of them can yet provide a satisfactory explanation of the observations.Comment: 12 pages, 3 figures, ApJ Letter, accepte

Accretion and photodesorption of CO ice as a function of the incident angle of deposition

Non-thermal desorption of inter- and circum-stellar ice mantles on dust grains, in particular ultraviolet photon-induced desorption, has gained importance in recent years. These processes may account for the observed gas phase abundances of molecules like CO toward cold interstellar clouds. Ice mantle growth results from gas molecules impinging on the dust from all directions and incidence angles. Nevertheless, the effect of the incident angle for deposition on ice photo-desorption rate has not been studied. This work explores the impact on the accretion and photodesorption rates of the incidence angle of CO gas molecules with the cold surface during deposition of a CO ice layer. Infrared spectroscopy monitored CO ice upon deposition at different angles, ultraviolet-irradiation, and subsequent warm-up. Vacuum-ultraviolet spectroscopy and a Ni-mesh measured the emission of the ultraviolet lamp. Molecules ejected from the ice to the gas during irradiation or warm-up were characterized by a quadrupole mass spectrometer. The photodesorption rate of CO ice deposited at 11 K and different incident angles was rather stable between 0 and 45$^{\circ}$. A maximum in the CO photodesorption rate appeared around 70$^{\circ}$-incidence deposition angle. The same deposition angle leads to the maximum surface area of water ice. Although this study of the surface area could not be performed for CO ice, the similar angle dependence in the photodesorption and the ice surface area suggests that they are closely related. Further evidence for a dependence of CO ice morphology on deposition angle is provided by thermal desorption of CO ice experiments

Strategies for analyzing highly enriched IP-chip datasets

BACKGROUND: Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult. RESULTS: Here we present strategies for analyzing such experiments, focusing our discussion on the analysis of Bromodeoxyruridine (BrdU) immunoprecipitation on tiling array (BrdU-IP-chip) datasets. BrdU-IP-chip experiments map large, recently replicated genomic regions and have similar characteristics to histone modification/location data. To prepare such data for downstream analysis we employ a dynamic programming algorithm that identifies a set of putative unenriched probes, which we use for both within-array and between-array normalization. We also introduce a second dynamic programming algorithm that incorporates a priori knowledge to identify and quantify positive signals in these datasets. CONCLUSION: Highly enriched IP-chip datasets are often difficult to analyze with traditional array normalization and analysis strategies. Here we present and test a set of analytical tools for their normalization and quantification that allows for accurate identification and analysis of enriched regions

A conceptual model for building design coordination using open source tools

Building Design Coordination is the process of communicating and integrating multidisciplinary designs into a single, coherent set of information that can be used for construction, to anticipate problems that would otherwise only be raised on the construction site. As projects grow in complexity and size, digital communication tools and other technological improvements have made it possible for physically distant design teams to collaborate in novel ways. More recently, BIM (Building Information Modelling), has opened even greater possibilities, although the design process nevertheless is often one of trial and error, demanding on each small change multiple possibilities to be considered, with decisions requiring to be validated among designers and other project stakeholders. Regardless of all the advantages that BIM has brought to the industry, testing for design changes in BIM models often requires a big effort and is a time-consuming activity that should be avoided whenever simpler processes can be used. Further developments on this study will propose a framework for building design coordination, using a non-relational graph database. The system can track design issues between unlimited users, organized into teams, handling formal project documents and keeping an historical record of the design development timeline. Since all the information regarding the design development process is stored in the form of Nodes and Relationships these can be intuitively be manipulated making it easier for teams to provide input on design decisions in real time with least cost impact to the project, providing at the same time access to pertinent information on the status of design issues and how the various stakeholders are contributing to the project. Through the use of reliable open source tools, a prototype can be implemented and made available to the industry professionals for testing, providing guidelines for modelling a Building Design Coordination system.info:eu-repo/semantics/publishedVersio

Lattice-Energy Calculations on Organometallic Compounds

Lattice-energy calculations in the atom-atom approach have been performed for five organometallic com­ pounds of previously determined crystal structure. Minimization of energy in terms of positional, orienta­ tional, torsional and cell parameters gave satisfactory results. Computation of energy as a function of torsion angle gave two-dimensional cross sections which o108-7681/88/030259-04$03.00 present minimum-energy conformations at maximum deviations of 10° from the experimental conforma­ tions

The Stellar Structures around Disk Galaxies

We present a brief summary of our current results on the stellar distribution and population gradients of the resolved stars in the surroundings of ~50 nearby disk galaxies, observed with space- (Hubble & Spitzer) and ground-based telescopes (Subaru, VLT, BTA, Palomar, CFHT & INT). We examine the radial (in-plane) and vertical (extraplanar) distributions of resolved stars as a function of stellar age and metallicity by tracking changes in the color-magnitude diagram of face-on and edge-on galaxies. Our data show, that the scale length and height of a stellar population increases with age, with the oldest detected stellar populations identified at a large galactocentric radius or extraplanar height, out to typically a few kpc. In the most massive of the studied galaxies there is evidence for a break in number density and color gradients of evolved stars, which plausibly correspond to the thick disk and halo components of the galaxies. The ratio of intermediate-age to old stars in the outermost fields correlate with the gas fraction, while relative sizes of the thick-to-thin disks anticorrelate with galactic circular velocity.Comment: To appear in the proceedings for the IAUS 241 'Stellar Populations as Building Blocks of Galaxies' held in La Palma, Spain, December 10-16 200

The spatial and age distribution of stellar populations in DDO 190

The spatial distribution of stellar populations, the star formation history, and other properties of the dIrr galaxy DDO 190 have been analyzed using color--magnitude diagrams (CMDs) of about 3900 resolved stars and the Ha fluxes of HII regions. From the mean color index of the red giant branch, a mean metallicity [Fe/H]=-2.0 is obtained. The I magnitude of the TRGB has been used to estimate the distance. DDO 190 is 2.9+/-0.2 Mpc from the Milky Way, 2.1 Mpc from the M 94 group (CnV-I), 2.4 Mpc from the M 81 group and 2.9 Mpc from the barycenter of the Local Group, all indicating that it is an isolated, field galaxy. The surface-brightness distribution of the galaxy is well fitted by ellipses of ellipticity e=1-a/b=0.1 and P.A.=82deg. The radial star density distribution follows an exponential law of scale length a=43."4, corresponding to 611 pc. The Holmberg semi-major axis to mu_B=26.5 is estimated to be r^B_(26.5)=3.'0. Stellar populations of different ages in DDO 190 show strong spatial decoupling, the oldest population appearing much more extended than the youngest. Stars younger than 0.1 Gyr occupy only the central 40'' (0.55 kpc); stars younger than a few (~4) Gyr extend out to ~80'' (125 kpc), and for larger galactocentric distances only older stars seem to be present. This behavior is found in all the dIrr galaxies for which spatially extended studies have been performed and could be related with the kinematical history of the galaxy.Comment: To be published in the AJ. 29 pages, 13 figure