Evidence of widespread degradation of gene control regions in hominid genomes

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human¿chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees

CS J = 2 yields 1 emission toward the central region of M82

M82 is an irregular (Type II) galaxy located at a distance of approximately 3.5 Mpc. Its unusual appearance and high luminosity, particularly in the infrared, has led many astronomers to classify it as a starburst galaxy. This interpretation is supported by the observation of a large number of radio continuum sources within the central arcminute of the galaxy. These sources are thought to be associated with supernova remnants. The starburst in the central region of the galaxy is believed to have been triggered by tidal interaction with either M81 or the HI cloud surrounding the M81 group. High angular resolution CO-12 J=1 to 0 maps by Nakai (1984) and Lo et al. (1987) indicate the existence of a 400 to 450 pc rotating ring of molecular material about the central region of M82. Red- and blue-shifted absorption components of the HI and OH lines measured by Weliachew et al. (1984) provided the first evidence for the presence of the ring. Many astronomers, each using a different angular resolution, have compared CO-12 J=1 to 0, J=2 to 1, and J=3 to 2 emission and concluded that a large fraction of the CO emission is optically thin. Additional observations suggest that the molecular material toward the center of M82 is clumpy and dense. Unlike the lower rotational transitions of CO, CS is excited only at relatively high densities, n sub H sub 2 greater than or equal to 10(exp 4) cm(-3). It is in clouds with these densities that stars are expected to form. This makes CS an excellent probe of star formation regions. Researchers observed the CS J=2 to 1 transition (97.981 GHz) toward 52 positions in M82 using the National Radio Astronomy Observatory (NRAO) 12 m telescope

Cnemidophorus tigris punctatus: A new whiptailed lizard from northwestern Sonora, Mexico

Gecorrigeerd via dispense

Hierarchical strategies for efficient fault recovery on the reconfigurable PAnDA device

A novel hierarchical fault-tolerance methodology for reconfigurable devices is presented. A bespoke multi-reconfigurable FPGA architecture, the programmable analogue and digital array (PAnDA), is introduced allowing fine-grained reconfiguration beyond any other FPGA architecture currently in existence. Fault blind circuit repair strategies, which require no specific information of the nature or location of faults, are developed, exploiting architectural features of PAnDA. Two fault recovery techniques, stochastic and deterministic strategies, are proposed and results of each, as well as a comparison of the two, are presented. Both approaches are based on creating algorithms performing fine-grained hierarchical partial reconfiguration on faulty circuits in order to repair them. While the stochastic approach provides insights into feasibility of the method, the deterministic approach aims to generate optimal repair strategies for generic faults induced into a specific circuit. It is shown that both techniques successfully repair the benchmark circuits used after random faults are induced in random circuit locations, and the deterministic strategies are shown to operate efficiently and effectively after optimisation for a specific use case. The methods are shown to be generally applicable to any circuit on PAnDA, and to be straightforwardly customisable for any FPGA fabric providing some regularity and symmetry in its structure

Routine data linkage to identify and monitor diabetes in clozapine-treated patients with schizophrenia

No abstract available

16S rRNA gene-based profiling of the human infant gut microbiota is strongly influenced by sample processing and PCR primer choice

Acknowledgements The authors acknowledge the assistance of Grietje Holtrop (RINH-BioSS) with the statistical analysis of the data and the Wellcome Trust Sanger Institute’s 454 pyrosequencing team for generating 16S rRNA gene data. AWW, PS and JP received core funding support from the Wellcome Trust [grant number 098051]. AWW, JCM, HJF and KPS are funded by the Scottish Government (SG-RESAS).Peer reviewedPublisher PD

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7WT cells or a drug-resistant, P-gp-expressing derivative MCF7Adr. Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TSWT, whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TSAdr resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TSWT. The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds

Ordering our world: the quest for traces of temporal organization in autobiographical memory

An experiment examined the idea, derived from the Self Memory System model (Conway & Pleydell-Pearce, 2000), that autobiographical events are sometimes tagged in memory with labels reflecting the life era in which an event occurred. The presence of such labels should affect the ease of judgments of the order in which life events occurred. Accordingly, 39 participants judged the order of two autobiographical events. Latency data consistently showed that between-era judgments were faster than within-era judgments, when the eras were defined in terms of either: (a) college versus high school, (b) academic quarter within year, or (c) academic year within school. The accuracy data similarly supported the presence of a between-era judgment effect for the college versus high school dichotomy