Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna

Background: Ibuprofen and other nonsteroidal anti-inflammatory drugs have been designed to interrupt eicosanoid metabolism in mammals, but little is known of how they affect nontarget organisms. Here we report a systems biology study that simultaneously describes the transcriptomic and phenotypic stress responses of the model crustacean Daphnia magna after exposure to ibuprofen. Results: Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis. Conclusion: Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role.

Litomosoides sigmodontis: vaccine-induced immune responses against Wolbachia surface protein can enhance the survival of filarial nematodes during primary infection

Wolbachia are bacteria present within the tissues of most filarial nematodes. Filarial nematode survival is known to be affected by immune responses generated during filarial nematode infection and immune responses to Wolbachia can be found in different species harbouring filarial nematode infections, including humans. Using the rodent filarial model Litomosoides sigmodontis, we show that pre-exposure to wolbachia surface protein in a Th1 context (but not in a Th2-context) enhances worm survival on subsequent challenge. This study suggests that despite abundant evidence that pro-inflammatory reactions to the endosymbiont have detrimental effects on the both the nematode and mammalian host, they may under some circumstances be beneficial to the nematode.

Avoidance responses of an aphidophagous ladybird, Adalia bipunctata, to aphid-tending ants

1. Insect predators often aggregrate to patches of high prey density and use prey chemicals as cues for oviposition. If prey have mutualistic guardians such as ants, however, then these patches may be less suitable for predators. 2. Ants often tend aphids and defend them against predators such as ladybirds. Here, we show that ants can reduce ladybird performance by destroying eggs and physically attacking larvae and adults. 3. Unless ladybirds are able to defend against ant attacks they are likely to have adaptations to avoid ants. We show that Adalia bipunctata ladybirds not only move away from patches with Lasius niger ants, but also avoid laying eggs in these patches. Furthermore, ladybirds not only respond to ant presence, but also detect ant semiochemicals and alter oviposition strategy accordingly. 4. Ant semiochemicals may signal the extent of ant territories allowing aphid predators to effectively navigate a mosaic landscape of sub-optimal patches in search of less well-defended prey. Such avoidance probably benefits both ants and ladybirds, and the semiochemicals could be regarded as a means of cooperative communication between enemies. 5. Overall, ladybirds respond to a wide range of positive and negative oviposition cues that may trade-off with each other and internal motivation to determine the overall oviposition strategy.

Crosstalk between plant responses to pathogens and herbivores: a view from the outside in

Plants encounter numerous pests and pathogens in the natural environment. An appropriate response to attack by such organisms can lead to tolerance or resistance mechanisms that enable the plant to survive. Many studies concentrate on the signalling pathways that enable plants to recognize and respond to attack, and measure the downstream effect in either biochemical or molecular terms. At the whole plant level, ecologists examine the fitness costs of attack not only for the plant but also over a range of trophic levels. The links between these differing levels of study are beginning to be addressed by the adoption of molecular approaches in more ecologically relevant settings. This review will describe the different approaches used by ecologists and cell biologists in this field and will try to address the question of how we can explore the response to, and consequences, of attack by multiple enemies.

Lack of effect of dietary n-6 : n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Background: Indian Asians living in Western Countries have an over 50% increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim: To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods: Twenty-nine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL- cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results: Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n-3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/22.5] (P = 0.02) reaching significance. Conclusion: The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Regulation of cell cycle and stress responses to hydrostatic pressure in fission yeast

We have investigated the cellular responses to hydrostatic pressure by using the fission yeast Schizosaccharomyces pombe as a model system. Exposure to sublethal levels of hydrostatic pressure resulted in G2 cell cycle delay. This delay resulted from Cdc2 tyrosine-15 (Y-15) phosphorylation, and it was abrogated by simultaneous disruption of the Cdc2 kinase regulators Cdc25 and Wee1. However, cell cycle delay was independent of the DNA damage, cytokinesis, and cell size checkpoints, suggesting a novel mechanism of Cdc2-Y15 phosphorylation in response to hydrostatic pressure. Spc1/Sty1 mitogen-activated protein (MAP) kinase, a conserved member of the eukaryotic stress-activated p38, mitogen-activated protein (MAP) kinase family, was rapidly activated after pressure stress, and it was required for cell cycle recovery under these conditions, in part through promoting polo kinase (Plo1) phosphorylation on serine 402. Moreover, the Spc1 MAP kinase pathway played a key role in maintaining cell viability under hydrostatic pressure stress through the bZip transcription factor, Atf1. Further analysis revealed that prestressing cells with heat increased barotolerance, suggesting adaptational cross-talk between these stress responses. These findings provide new insight into eukaryotic homeostasis after exposure to pressure stress.

A novel experimental method for measuring vergence and accommodation responses to the main near visual cues in typical and atypical groups

Binocular disparity, blur, and proximal cues drive convergence and accommodation. Disparity is considered to be the main vergence cue and blur the main accommodation cue. We have developed a remote haploscopic photorefractor to measure simultaneous vergence and accommodation objectively in a wide range of participants of all ages while fixating targets at between 0.3 and 2 m. By separating the three main near cues, we can explore their relative weighting in three-, two-, one-, and zero-cue conditions. Disparity can be manipulated by remote occlusion; blur cues manipulated by using either a Gabor patch or a detailed picture target; looming cues by either scaling or not scaling target size with distance. In normal orthophoric, emmetropic, symptom-free, naive visually mature participants, disparity was by far the most significant cue to both vergence and accommodation. Accommodation responses dropped dramatically if disparity was not available. Blur only had a clinically significant effect when disparity was absent. Proximity had very little effect. There was considerable interparticipant variation. We predict that relative weighting of near cue use is likely to vary between clinical groups and present some individual cases as examples. We are using this naturalistic tool to research strabismus, vergence and accommodation development, and emmetropization.

Occupants' adaptive responses and perception of thermal environment in naturally conditioned university classrooms

A year-long field study of the thermal environment in university classrooms was conducted from March 2005 to May 2006 in Chongqing, China. This paper presents the occupants’ thermal sensation votes and discusses the occupants’ adaptive response and perception of the thermal environment in a naturally conditioned space. Comparisons between the Actual Mean Vote (AMV) and Predicted Mean Vote (PMV) have been made as well as between the Actual Percentage of Dissatisfied (APD) and Predicted Percentage of Dissatisfied (PPD). The adaptive thermal comfort zone for the naturally conditioned space for Chongqing, which has hot summer and cold winter climatic characteristics, has been proposed based on the field study results. The Chongqing adaptive comfort range is broader than that of the ASHRAE Standard 55-2004 in general, but in the extreme cold and hot months, it is narrower. The thermal conditions in classrooms in Chongqing in summer and winter are severe. Behavioural adaptation such as changing clothing, adjusting indoor air velocity, taking hot/cold drinks, etc., as well as psychological adaptation, has played a role in adapting to the thermal environment.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

Translationally controlled tumour protein (TCTP) is a highly conserved protein present in all eukaryotic organisms. Various cellular functions and molecular interactions have been ascribed to this protein, many related to its growth-promoting and antiapoptotic properties. TCTP levels are highly regulated in response to various cellular stimuli and stresses. We have shown recently that the double-stranded RNA-dependent protein kinase, PKR, is involved in translational regulation of TCTP. Here we extend these studies by demonstrating that TCTP is downregulated in response to various proapoptotic treatments, in particular agents that induce Ca++ stress, in a PKR-dependent manner. This regulation requires phosphorylation of protein synthesis factor eIF2α. Since TCTP has been characterized as an antiapoptotic and Ca++-binding protein, we asked whether it is involved in protecting cells from Ca++-stress-induced apoptosis. Overexpression of TCTP partially protects cells against thapsigargin-induced apoptosis, as measured using caspase-3 activation assays, a nuclear fragmentation assay, using fluorescence-activated cell sorting analysis, and time-lapse video microscopy. TCTP also protects cells against the proapoptotic effects of tunicamycin and etoposide, but not against those of arsenite. Our results imply that cellular TCTP levels influence sensitivity to apoptosis and that PKR may exert its proapoptotic effects at least in part through downregulation of TCTP via eIF2α phosphorylation.