Photosynthetic metabolism of propionate in Rhodospirillum rubrum

Summary As in the case of oxidative metabolism, the photosynthetic metabolism of propionate in Rhodospirillum rubrum begins with a carboxylation yielding succinate. This conclusion is based on experiments in which radioactive propionate (1-C¹⁴ and 2-C¹⁴) is administered in the presence of carrier lactate, pyruvate, succinate, and acrylate, and on studies of the inhibitory action of malonate.     

Reduced protein adsorption at solid interfaces by sugar excipients

Sugar excipients are shown to reduce the adsorption of ribonuclease A, bovine serum albumin, and hen egg white lysozyme at the liquid-solid interface. The amount of protein adsorbed decreased as the concentration of the sugar increased. At the same sugar concentration, the ability of sugars to reduce protein adsorption followed the trend: trisaccharides > disaccharides > 6-carbon polyols > monosaccharides. This trend in adsorbed protein amounts among sugars was explained by stabilization of the protein native state in solution by the sugar excipients. The heat of solution of the amorphous saccharide was found to correlate with the amount of protein adsorbed.     

Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of the heat shock response in HeLa cells

It has been established that non-steroidal anti-inflammatory drugs (NSAIDs), such as sodium salicylate, sulindac, ibuprofen, and indomethacin, induce anti-inflammatory and anti-proliferative effects independent of cyclooxygenase. These cyclooxygenase-independent pharmacodynamic effects appear to regulate several signaling pathways involving proliferation, apoptosis, and heat shock response. However, the mechanisms of these actions remain an area of ongoing investigation. Hsc70 is a cytoplasmic chaperone protein involved in folding and trafficking of client proteins to different subcellular compartments, plays roles in signal transduction and apoptosis processes, and translocates to the nucleus following exposure to heat shock. Since NSAIDs induce some aspects of the heat shock response, we hypothesized that they may also induce Hsc70 nuclear translocation. Western immunoblotting and indirect cellular immunofluorescence showed that indomethacin and ibuprofen induce Hsc70 nuclear translocation at concentrations previously shown to induce HSF DNA-binding activity. Chemical inhibition of both p38(MAPK) and Erk42/44 had no effect on localization patterns. In addition, while indomethacin has been shown to behave as an oxidative stressor, the radical scavenging agent, N-acetyl cysteine, did not inhibit nuclear translocation. These results indicate that induction of the heat shock response by NSAIDs occurs at concentrations fivefold greater than those required to inhibit cyclooxygenase activity, suggesting a cyclooxygenase-independent mechanism, and in the presence or absence of kinase inhibitors and a free radical scavenger, suggesting independence of Erk42/44 or p38(MAPK) activities and intracellular oxidoreductive state.     

Linkage analysis using co-phenotypes in the BRIGHT study reveals novel potential susceptibility loci for hypertension

Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD = 4.24) and with parameters of renal function on chromosome 5p (maximum LOD = 3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.     

Data standards for flow cytometry

Flow cytometry (FCM) is an analytical tool widely used for cancer and HIV/AIDS research, and treatment, stem cell manipulation and detecting microorganisms in environmental samples. Current data standards do not capture the full scope of FCM experiments and there is a demand for software tools that can assist in the exploration and analysis of large FCM datasets. We are implementing a standardized approach to capturing, analyzing, and disseminating FCM data that will facilitate both more complex analyses and analysis of datasets that could not previously be efficiently studied. Initial work has focused on developing a community-based guideline for recording and reporting the details of FCM experiments. Open source software tools that implement this standard are being created, with an emphasis on facilitating reproducible and extensible data analyses. As well, tools for electronic collaboration will assist the integrated access and comprehension of experiments to empower users to collaborate on FCM analyses. This coordinated, joint development of bioinformatics standards and software tools for FCM data analysis has the potential to greatly facilitate both basic and clinical research--impacting a notably diverse range of medical and environmental research areas.     

Elasmobranch immune cells as a source of novel tumor cell inhibitors: Implications for public health

Reports that elasmobranchs (sharks, skates, and rays) may havea low incidence of disease have stimulated interest in understandingthe role of their immune system in this apparent resistance.Although research in this area may potentially translate intoapplications for human health, a basic understanding of theelasmobranch immune system components and how they functionis essential. As in higher vertebrates, elasmobranch fishespossess thymus and spleen, but in the absence of bone marrowand lymph nodes, these fish have evolved unique lymphomyeloidtissues, namely epigonal and Leydig organs. As conditions forshort-term culture of elasmobranch immune cells have becomebetter understood, the opportunity to examine functional activityof cytokine-like factors derived from conditioned culture mediumhas resulted in the identification of growth inhibitory activityagainst a variety of tumor cell lines. Specifically, the mediumenriched by short term culture of bonnethead shark (Sphyrnatiburo) epigonal cells (epigonal conditioned medium, ECM) hasbeen shown to inhibit the growth of mammalian tumor cell lines,including fibrosarcoma (WEHI-164), melanoma (A375.S2), B-celllymphoma (Daudi), T-cell leukemia (Jurkat), pancreatic cancer(PANC-1), ovarian cancer (NIH:OVCAR-3), and three breast carcinomacell lines (MCF7, HCC38, Hs578T). Of the cell lines tested,WEHI-164, A375.S2, Daudi, and Jurkat cells were among the mostsensitive to growth inhibitory activity of ECM whereas PANC-1and NIH:OVCAR-3 cells were among the least sensitive. In addition,ECM demonstrated preferential growth inhibition of malignantcells in assays against two different malignant/non-malignantcell line pairs (HCC38/HCC38 BL and Hs 578T/Hs 578Bst). Separationof protein components of ECM using SDS-PAGE resulted in a veryreproducible pattern of three major bands corresponding to molecularsizes of approximately 40–42 kD, 24 kD, and 17 kD. Activityis lost after heating at 75°C for 30 min, and can be diminishedby treatment with proteinase K and protease. Activity is notaffected by treating with trypsin, DNase I or RNase A.     

Problems faced by food-caching corvids and the evolution of cognitive solutions

The scatter hoarding of food, or caching, is a widespread and well-studied behaviour. Recent experiments with caching corvids have provided evidence for episodic-like memory, future planning and possibly mental attribution, all cognitive abilities that were thought to be unique to humans. In addition to the complexity of making flexible, informed decisions about caching and recovering, this behaviour is underpinned by a motivationally controlled compulsion to cache. In this review, we shall first discuss the compulsive side of caching both during ontogeny and in the caching behaviour of adult corvids. We then consider some of the problems that these birds face and review the evidence for the cognitive abilities they use to solve them. Thus, the emergence of episodic-like memory is viewed as a solution for coping with food perishability, while the various cache-protection and pilfering strategies may be sophisticated tools to deprive competitors of information, either by reducing the quality of information they can gather, or invalidating the information they already have. Finally, we shall examine whether such future-oriented behaviour involves future planning and ask why this and other cognitive abilities might have evolved in corvids.