5-Lipoxygenase contributes to PPARγ activation in macrophages in response to apoptotic cells

Macrophage polarization to an anti-inflammatory phenotype upon contact with apoptotic cells is a contributing hallmark to immune suppression during the late phase of sepsis. Although the peroxisome proliferator-activated receptor γ (PPARγ) supports this macrophage phenotype switch, it remains elusive how apoptotic cells activate PPARγ. Assuming that a molecule causing PPARγ activation in macrophages originates in the cell membrane of apoptotic cells we analyzed lipid rafts from apoptotic, necrotic, and living human Jurkat T cells which showed the presence of 5-lipoxygenase (5-LO) in lipid rafts of apoptotic cells only. Incubating macrophages with lipid rafts of apoptotic, but not necrotic or living cells, induced PPAR responsive element (PPRE)-driven mRuby reporter gene expression in RAW 264.7 macrophages stably transduced with a 4xPPRE containing vector. Experiments with lipid rafts of apoptotic murine EL4 T cells revealed similar results. To verify the involvement of 5-LO in activating PPARγ in macrophages, Jurkat T cells were incubated with the 5-LO inhibitor MK-866 prior to induction of apoptosis, which failed to induce mRuby expression. Similar results were obtained with lipid rafts of apoptotic EL4 T cells preexposed to the 5-LO inhibitors zileuton and CJ-13610. Interestingly, Jurkat T cells overexpressing 5-LO failed to activate PPARγ in macrophages, while their 5-LO overexpressing apoptotic counterparts did. Our results suggest that during apoptosis 5-LO gets associated with lipid rafts and synthesizes ligands that in turn stimulate PPARγ in macrophages.     

UN system efforts to support the response to AIDS in China

INTRODUCTION China has made considerable progress in the response to the AIDS epidemic in the past years, particularly in terms of commitment by the national leadership, the establish- ment of a supportive policy framework, improved under- standing of the…     

Myosins in melanocytes: to move or not to move?

The actin network has been implicated in the intracellular transport and positioning of the melanosomes, organelles that are specialized in the biosynthesis and the storage of melanin. It contributes also to molecular mechanisms that underlie the intracellular membrane dynamics and thereby can control the biogenesis of melanosomes. Two mechanisms for actin‐based movements have been identified: one is dependent on the motors associated to actin namely the myosins; the other is dependent on actin polymerization. This review will focus on to the role of the actin cytoskeleton and myosins in the transport and in the biogenesis of melanosomes. Myosins involved in membrane traffic are largely seen as transporters of organelles or membrane vesicles containing cargos along the actin networks. Yet increasing evidence suggests that some of the myosins contribute to the dynamics of internal membrane by using other mechanisms. The role of the myosins and the different molecular mechanisms by which they contribute or may contribute to the distribution, the movement and the biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented epithelial (RPE) cells will be discussed.     

Adaptation to stress in yeast: to translate or not?

For most eukaryotic organisms, including Saccharomyces cerevisiae, the rapid inhibition of protein synthesis forms part of a response to stress. In order to balance the changing conditions, precise stress-specific alterations to the cell's proteome are required. Therefore, in the background of a global down-regulation in protein synthesis, specific proteins are induced. Given the level of plasticity required to enable stress-specific alterations of this kind, it is surprising that the mechanisms of translational regulation are not more diverse. In the present review, we summarize the impact of stress on translation initiation, highlighting both the similarities and distinctions between various stress responses. Finally, we speculate as to how yeast cells generate stress-responsive programmes of protein production when regulation is focused on the same steps in the translation pathway.     

Myosins in melanocytes: to move or not to move?

The actin network has been implicated in the intracellular transport and positioning of the melanosomes, organelles that are specialized in the biosynthesis and the storage of melanin. It contributes also to molecular mechanisms that underlie the intracellular membrane dynamics and thereby can control the biogenesis of melanosomes. Two mechanisms for actin-based movements have been identified: one is dependent on the motors associated to actin namely the myosins; the other is dependent on actin polymerization. This review will focus on to the role of the actin cytoskeleton and myosins in the transport and in the biogenesis of melanosomes. Myosins involved in membrane traffic are largely seen as transporters of organelles or membrane vesicles containing cargos along the actin networks. Yet increasing evidence suggests that some of the myosins contribute to the dynamics of internal membrane by using other mechanisms. The role of the myosins and the different molecular mechanisms by which they contribute or may contribute to the distribution, the movement and the biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented epithelial (RPE) cells will be discussed.     

Neurobehavioral Effects in Relation to Endocrine Alterations Caused by Exposure to Brominated Flame Retardants in Rats—Comparison to Polychlorinated Biphenyls

The widespread use of brominated flame retardants (BFRs) has led to increasing concentrations in environmental samples. Previous reports suggested endocrine activity of these compounds. Because thyroid hormones and sex steroids are known to regulate the development of the nervous system, we examined neurobehavioral and endocrine effects of gestational exposure to 2,2′4,4′,5-pentabrominated diphenyl ether (PBDE99) and lifetime exposure to tetrabromobisphenol A (TBBPA) or hexabromocyclododecane (HBCD) in rats. Treatment with PBDE99 (0, 1, or 10 mg/kg bw) reduced serum testosterone and estradiol in male offspring and affected sexual development in both sexes. Exposed males exhibited increased sweet preference, indicating feminization of this sexually dimorphic behavior. In TBBPA and HBCD experiments, a benchmark design was used with dose ranges of 0-3000 mg/kg bw/day and 0–100 mg/kg bw/day, respectively. Because thyroid hormones are critical for auditory development, brainstem auditory evoked potentials (BAEPs) were recorded in young adult offspring. TBBPA exposure elevated BAEP thresholds in females and prolonged latencies in both sexes. Benchmark doses were comparable for auditory effects and decreased plasma T4. HBCD increased BAEP thresholds and delayed BAEP waves only in males, but the relation to thyroid hormones remains to be determined. HBCD also reduced latencies in haloperidol-induced catalepsy, suggesting effects on the dopaminergic system.     

A methodology to identify sustainability indicators in construction project management—Application to infrastructure projects in Spain

Since the birth of the sustainable development concept and its application to urban planning and construction projects, countless sustainability indicator sets have appeared. This paper analyses the problems posed by these sets and the need to establish a method to identify and select an indicator set which includes every participant involved in the life cycle of a project, to find a proper balance between all actors. Sustainability is proposed as an opportunity for improvement throughout the project. Thus, we have developed a methodology to identify, classify and prioritise sustainability indicators based on risk management standards. The application of this method to infrastructure projects in Spain will reveal the strengths and weaknesses of the proposed method and is the first step to develop an indicator set for civil engineering projects.     

What to do in marine biotechnology?

During the symposium "Marine Biotechnology: Basics and Applications", held 25 February-1 March, 2003 in Matalasca?as, Spain, a special brainstorm session was organized. Two questions were addressed: 1, "What is the most desirable development in marine biotechnology"?; 2, "What is the most spectacular development in this field in your 'wildest' dreams"? The outcome of this session is reported in this paper. From the more than 250 ideas generated, concern for the environment and human health emerged as the most significant issues.     

Grooming in Barbary macaques: better to give than to receive?

It is well established that grooming underpins sociality in group-living primates, and a number of studies have documented the stress-reducing effects of being groomed. In this study, we quantified grooming behaviour and physiological stress (assessed by faecal glucocorticoid analysis) in free-ranging Barbary macaques, Macaca sylvanus. Our results indicate that it is the giving rather than the receiving of grooming that is associated with lower stress levels. These findings shed important new light on the benefits of this key behaviour in primate social life.     

Is plasticity in mating preferences adapted to perceived exposure to pathogens?

Humans are unique among primates due to a lack of typical thermally insulating fur. The ectoparasite avoidance mediated by the mate choice hypothesis suggests that the loss of body hair reduces the risk of infection by ectoparasites and that the movement toward nudity may have been enforced by parasite-mediated sexual selection. In this study, we investigated two possible predictions of this hypothesis: (1) that preferences for hairless bodies increase with exposure to environmental pathogens and (2) that disgust sensitivity to the pathogens’ threat predicts the degree to which a woman will prefer hairless bodies. Using an experiment comparing the preferences of 88 women for shaved vs. hairy pictured versions of 20 male torsos, we found that exposure to the visual cues of pathogens does not predict preferences for a male chest nor does the individual disgust sensitivity to disease-related invertebrates. Overall, the results suggest that female perception of male trunk hair is not associated with a risk of contamination, which questions the salience of the ectoparasite avoidance hypothesis in explaining the loss of body hair in humans.     

Patterns of Plasma Oestradiol-17ß in Relation to the Interval from Weaning to Oestrus in Sows

Sows generally are anoestrus during lactation. Weaning the litter normally results in a rapid increase in follicular growth that terminates in oestrus and ovulation. Follicular development after weaning is characterized by an elevation in the blood concentrations of oestradiol-17ß (E2). Although the post-weaning patterns of E2 in blood circulation have been reported previously (Cox & Britt 1982, Edwards & Foxcroft 1983, Rojanasthien 1988), the plasma patterns of E2 in relation to the interval from weaning to oestrus (WOI), to our knowledge, have not been assessed. The purpose of this study was therefore to relate the blood patterns of E2 to the WOI in sows exhibiting their first oestrus within 10 days after weaning.     

Expression of α-amylase in response to wounding in mung bean

The activity of -amylase (EC 3.2.1.1) in mung bean (Vigna radiata (L.) Wilczek) cotyledons increased markedly in response to wounding. The changes in enzyme activity were in parallel with those in enzyme content. The level of -amylase mRNA also notably increased in wounded cotyledons and attained its maximum level during the period between 1 and 2 d after wounding. The level of mRNA for phenylalanine ammonia-lyase, which is one of the well-characterized stress-inducible proteins, also increased after wounding, but the increase in mRNA level was faster than that of -amylase mRNA. On the other hand, the content of mRNA for actin, a housekeeping protein, was almost the same in wounded and unwounded cotyledons. The increase in -amylase mRNA level in wounded cotyledons was severely inhibited by -amanitin and cordycepin. -Amylase expression in the first leaves of mung-bean seedlings was also induced by wounding.Abbreviations PAL phenylalanine ammonia-lyase - SSC standard saline citrate We greatly acknowledge Prof. Richard Meagher, Department of Genetics, University of Georgia, Athens, USA for the gift of soybean actin gene clone. We also thank Mr. Kaoru Ishiwata for technical assistance.     

When do parasites fail to speciate in response to host speciation?

Cospeciation generally increases the similarity between host and parasite phylogenies. Incongruence between host and parasite phylogenies has previously been explained in terms of host switching, sorting, and duplication events. Here, we describe an additional process, failure of the parasite to speciate in response to host speciation, that may be important in some host-parasite systems. Failure to speciate is likely to occur when gene flow among parasite populations is much higher than that of their hosts. We reconstructed trees from mitochondrial and nuclear DNA sequences for pigeons and doves (Aves: Columbiformes) and their feather lice in the genus Columbicola (Insecta: Phthiraptera). Although comparisons of the trees from each group revealed a significant amount of cospeciation, there was also a significant degree of incongruence. Cophylogenetic analyses generally indicated that host switching may be an important process in the history of this host-parasite association. Using terminal sister taxon comparisons, we also identified three apparent cases where the host has speciated but the associated parasite has not. In two of these cases of failure to speciate, these comparisons involve allopatric sister taxa of hosts whose lice also occur on hosts sympatric with both of the allopatric sisters. These additional hosts for generalist lice may promote gene flow with lice on the allopatric sister species. Relative rate comparisons for the mitochondrial cytochrome oxidase I gene indicate that molecular substitution occurs about 11 times faster in lice than in their avian hosts.     

United Nations system efforts to support the response to AIDS in China

In the last two years, we have seen a remarkable intensification in the response to AIDS in China. A number of organizations have joined and contributed to the efforts of the Chinese government in responding the AIDS epidemic in China. This article specifically describes the role of the United Nations in supporting and strengthening those responses. Achievements of the United Nations （UN） highlighted in the article include： strengthened leadership and political commitment to respond to AIDS; improved HIV/AIDS surveillance and information; expanded prevention efforts; improved treatment, care and support to people living with HIV and increased resources for AIDS programs. Additional roles of the United Nations system in the near future include strengthening national leadership by supporting the ‘three ones＇, i. e., one national plan on AIDS; one national coordinating authority for AIDS; and one monitoring and evaluation system for AIDS. In addition, the UN system is expected to strengthen alignment and harmonization of activities of all international organizations and improved accountability and oversight. Remaining challenges identified include increasing awareness of AIDS and reducing stigma and discrimination; reducing vulnerability and risk behaviour among specific groups; providing improved treatment, care and support for people living with HIV; promoting stronger engagement by civil society, and; addressing the gender dimensions of AIDS.     

Do We Need to Detect Isoniazid Resistance in Addition to Rifampicin Resistance in Diagnostic Tests for Tuberculosis?

Background

Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain.

Methods

We developed a transmission model to evaluate three tests in a population similar to that of India: a rapid molecular test for TB, the same test plus RIF-resistance detection (“TB+RIF”), and detection of RIF and INH-resistance (“TB+RIF/INH”). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years.

Results

Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17–54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3–7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%).

Conclusion

When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB.     

Human α-globin maps to pter-p13.3 in chromosome 16 distal to PGP

Summary Fibroblasts from a fetus with an unbalanced karyotype 46(XY),-16,+(16qter-16p13.3::4q31.1-4qter) were found to possess only one allele at the 3 hypervariable region (3HVR) close to the -globin locus and two alleles at the PGP locus. This places the -globin locus at the very tip of 16p, distal to PGP.