A differential genome-wide transcriptome analysis : impact of cellular copper on complex biological processes like aging and development

The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development

Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain

Mitochondrial maintenance crucially depends on the quality control of proteins by various chaperones, proteases and repair enzymes. While most of the involved components have been studied in some detail, little is known on the biological role of the CLPXP protease complex located in the mitochondrial matrix. Here we show that deletion of PaClpP, encoding the CLP protease proteolytic subunit CLPP, leads to an unexpected healthy phenotype and increased lifespan of the fungal ageing model organism Podospora anserina. This phenotype can be reverted by expression of human ClpP in the fungal deletion background, demonstrating functional conservation of human and fungal CLPP. Our results show that the biological role of eukaryotic CLP proteases can be studied in an experimentally accessible model organism

Improved preparation of 9-octadecenes

Organic synthesis of cis-9 and trans-9 octadecenes from oleyl alcohol and elaidyl alcohol, respectively, by conversion to tosylates followed by lithium aluminum hydride reductio

fMRI Evidence for Modality-Specific Processing of Conceptual Knowledge on Six Modalities

Traditional theories assume that amodal representations, such as feature lists and semantic networks, represent conceptual knowledge about the world. According to this view, the sensory, motor, and introspective states that arise during perception and action are irrelevant to representing knowledge. Instead the conceptual system lies outside modality-specific systems and operates according to different principles. Increasingly, however, researchers report that modality-specific systems become active during purely conceptual tasks, suggesting that these systems play central roles in representing knowledge (for a review, see Martin, 2001, Handbook of Functional Neuroimaging of Cognition). In particular, researchers report that the visual system becomes active while processing visual properties, and that the motor system becomes active while processing action properties. The present study corroborates and extends these findings. During fMRI, subjects verified whether or not properties could potentially be true of concepts (e.g., BLENDER-loud). Subjects received only linguistic stimuli, and nothing was said about using imagery. Highly related false properties were used on false trials to block word association strategies (e.g., BUFFALOwinged). To assess the full extent of the modality-specific hypothesis, properties were verified on each of six modalities. Examples include GEMSTONE-glittering (vision), BLENDER-loud (audition), FAUCET-turned (motor), MARBLE-cool (touch), CUCUMBER-bland (taste), and SOAP-perfumed (smell). Neural activity during property verification was compared to a lexical decision baseline. For all six sets of the modalityspecific properties, significant activation was observed in the respective neural system. Finding modality-specific processing across six modalities contributes to the growing conclusion that knowledge is grounded in modality-specific systems of the brain

The Quasar-frame Velocity Distribution of Narrow CIV Absorbers

We report on a survey for narrow (FWHM < 600 km/s) CIV absorption lines in a sample of bright quasars at redshifts $1.8 \le z < 2.25$ in the Sloan Digital Sky Survey. Our main goal is to understand the relationship of narrow CIV absorbers to quasar outflows and, more generally, to quasar environments. We determine velocity zero-points using the broad MgII emission line, and then measure the absorbers' quasar-frame velocity distribution. We examine the distribution of lines arising in quasar outflows by subtracting model fits to the contributions from cosmologically intervening absorbers and absorption due to the quasar host galaxy or cluster environment. We find a substantial number ($\ge 43\pm6$ per cent) of absorbers with REW $> 0.3$ \AA in the velocity range +750 km/s \la v \la +12000 km/s are intrinsic to the AGN outflow. This `outflow fraction' peaks near $v=+2000$ km/s with a value of $f_{outflow} \simeq 0.81 \pm 0.13$. At velocities below $v \approx +2000$ km/s the incidence of outflowing systems drops, possibly due to geometric effects or to the over-ionization of gas that is nearer the accretion disk. Furthermore, we find that outflow-absorbers are on average broader and stronger than cosmologically-intervening systems. Finally, we find that $\sim 14$ per cent of the quasars in our sample exhibit narrow, outflowing CIV absorption with REW $> 0.3$\AA, slightly larger than that for broad absorption line systems.Comment: 11 pages, 9 figures, accepted for publication in MNRA

systemfit: A Package for Estimating Systems of Simultaneous Equations in R

Many statistical analyses (e.g., in econometrics, biostatistics and experimental design) are based on models containing systems of structurally related equations. The systemfit package provides the capability to estimate systems of linear equations within the R programming environment. For instance, this package can be used for "ordinary least squares" (OLS), "seemingly unrelated regression" (SUR), and the instrumental variable (IV) methods "two-stage least squares" (2SLS) and "three-stage least squares" (3SLS), where SUR and 3SLS estimations can optionally be iterated. Furthermore, the systemfit package provides tools for several statistical tests. It has been tested on a variety of datasets and its reliability is demonstrated.