The early transcriptomic response to interleukin 1β and interleukin 33 in rat neonatal cardiomyocytes

In the heart, inflammatory cytokines including interleukin (IL) 1β are implicated in regulating adaptive and maladaptive changes, whereas IL33 negatively regulates cardiomyocyte hypertrophy and promotes cardioprotection. These agonists signal through a common co-receptor but, in cardiomyocytes, IL1β more potently activates mitogen-activated protein kinases and NFκB, pathways that regulate gene expression. We compared the effects of external application of IL1β and IL33 on the cardiomyocyte transcriptome. Neonatal rat cardiomyocytes were exposed to IL1β or IL33 (0.5, 1 or 2h). Transcriptomic profiles were determined using Affymetrix rat genome 230 2.0 microarrays and data were validated by quantitative PCR. IL1β induced significant changes in more RNAs than IL33 and, generally, to a greater degree. It also had a significantly greater effect in downregulating mRNAs and in regulating mRNAs associated with selected pathways. IL33 had a greater effect on a small, select group of specific transcripts. Thus, differences in intensity of intracellular signals can deliver qualitatively different responses. Quantitatively different responses in production of receptor agonists and transcription factors may contribute to qualitative differences at later times resulting in different phenotypic cellular responses.

Photosynthetic activity and early growth of four Cacao genotypes as influenced by different shade regimes under West African dry and wet season conditions

The physiological performance of four cacao clones was examined under three artificial shade regimes over the course of a year in Ghana. Plants under light shade had significantly higher photosynthetic rates in the rainy seasons whereas in the dry season there was a trend of higher photosynthetic rates under heavy shade. The results imply that during the wet seasons light was the main limiting factor to photosynthesis whereas in the dry season vapour pressure deficit was the major factor limiting photosynthesis through stomatal regulation. Leaf area was generally lower under heavier shade but the difference between shade treatments varied between clones. Such differences in leaf area allocation appeared to underlie genotypic differences in final biomass production in response to shade. The results suggest that shade for young cacao should be provided based on the current ambient environment and genotype.

Reduced height (Rht) and photoperiod insensitivity (Ppd) allele associations with establishment and early growth of wheat in contrasting production systems

Near isogenic lines (NILs) varying for genes for reduced height (Rht) and photoperiod insensitivity (Ppd-D1a) in a cv. Mercia background (rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht8c + Ppd-D1a, Rht-D1c, Rht12) were compared at one field site but within contrasting ('organic' vs. 'conventional') rotational and agronomic contexts, in each of 3 years. In the final year, further NILs (rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht-B1b + Rht-D1b, Rht-D1b + Rht-B1c) in both Maris Huntsman and Maris Widgeon backgrounds were added together with 64 lines of a doubled haploid (DH) population [Savannah (Rht-D1b) x Renesansa (Rht-8c + Ppd-D1a)]. Assessments included laboratory tests of germination and coleoptile length, and various field measurements of crop growth between emergence and pre jointing [plant population, tillering, leaf length, ground cover (GC), interception of photosynthetically active radiation (PAR), crop dry matter (DM) and nitrogen accumulation (N), far red: red reflectance ratio (FR:R), crop height, and weed dry matter]. All of the dwarfing alleles except Rht12 in the Mercia background and Rht8c in the DHs were associated with reduced coleoptile length. Most of the dwarfing alleles (depending on background) reduced seed viability. Severe dwarfing alleles (Rht-B1c, Rht-D1c and Rht12) were routinely associated with fewer plant numbers and reduced early crop growth (GC, PAR, DM, N, FR:R), and in 1 year, increased weed DM. In the Mercia background and the DHs the semi-dwarfing allele Rht-D1b was also sometimes associated with reductions in early crop growth; no such negative effects were associated with the marker for Rht8c. When significant interactions between cropping system and genotype did occur it was because differences between lines were more exaggerated in the organic system than in the conventional system. Ppd-D1a was associated positively with plant numbers surviving the winter and early crop growth (GC, FR:R, DM, N, PAR, height), and was the most significant locus in a QTL analysis. We conclude that, within these environmental and system contexts, genes moderating development are likely to be more important in influencing early resource capture than using Rht8c as an alternative semi-dwarfing gene to Rht-D1b.

The effect of wheat straw residue on the emergence and early growth of sugar beet (Beta vulgaris) and oilseed rape (Brassica napus)

The management of straw residue can be a concern in non-inversion tillage systems where straw tends to be incorporated at shallow depths or left on the soil surface. This can lead to poor crop establishment because straw residue can impede or hinder crop emergence and growth. Small container-based experiments were undertaken using varying amounts of wheat straw residue either incorporated or placed oil the soil surface. The effects on (lays to seedling emergence, percentage emergence, seedling dry-weight and soil temperature using sugar beet and oilseed rape were investigated because these crops often follow wheat in a cropping sequence. The position of the straw residue was found to be the primary factor in reducing crop emergence and growth. Increasing the amount of straw residue (from 3.3 t ha(-1) to 6.7 t ha(-1)) did not show any consistent trends in reducing crop emergence or growth. However, in some instances, results indicated that an interaction between the position and the amount of straw residue Occurred particularly when the straw and seed was placed on the soil surface. Straw placed on the soil surface significantly reduced mean day-time soil temperature by approximately 2.5 degrees C compared to no residue. When the seed and straw was placed on the soil Surface a lack of seed-to-soil contact caused a reduction in emergence by approximately 30% because of the restriction in available moisture that limited the ability for seed imbibition. This trend was reversed when the seed was placed in the soil, but with straw residue still on the soil surface, because the surface straw was likely to reduce moisture evaporation and improved seed-to-soil contact that led to rapid emergence. In general, when straw was mixed in or placed on the soil surface along with the seed, sugar beet and oilseed rape emergence and early growth biomass was significantly restricted by approximately 50% compared to no residue. The consequences of placing seed with or near to straw residue have been shown to cause a restriction in crop establishment. In both oilseed tape and sugar beet, this could lead to a reduction in final crop densities, poor, uneven growth and potentially lower yields that could lower financial margins. Therefore, if farmers are planning to use non-inversion tillage methods for crop establishment, the management and removal of straw residue from near or above the seed is considered important for successful crop establishment. (C) 2008 Elsevier B.V. All rights reserved.

Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome of cardiomyocytes: Egr1 is a principal Atf3 target

Endothelin-1 promotes cardiomyocyte hypertrophy by inducing changes in gene expression. Immediate early genes including activating transcription factor 3 (Atf3), Egr1 and Ptgs2 are rapidly and transiently upregulated by endothelin-1 in cardiomyocytes. Atf3 regulates expression of downstream genes and is implicated in negative feedback regulation of other immediate early genes. To identify Atf3-regulated genes, we knocked down Atf3 expression in cardiomyocytes exposed to endothelin-1 and used microarrays to interrogate the transcriptomic effects. Of upregulated mRNAs, expression of 23 (including Egr1, Ptgs2) was enhanced and expression of 25 was inhibited by Atf3 knockdown. Using quantitative PCR, we determined that knockdown of Atf3 had little effect on upregulation of Egr1 mRNA over 30 min, but abolished the subsequent decline, causing sustained Egr1 mRNA expression and enhanced protein expression. This resulted from direct binding of Atf3 to the Egr1 promoter. Mathematical modelling established that Atf3 can suffice to suppress Egr1 expression. Given the widespread co-regulation of Atf3 with Egr1, we suggest that the Atf3-Egr1 negative feedback loop is of general significance. Loss of Atf3 caused abnormal cardiomyocyte growth, presumably resulting from dysregulation of target genes. Our data therefore identify Atf3 as a nexus in cardiomyocyte hypertrophy required to facilitate the full and proper growth response.

Myostatin regulates cardiomyocyte growth through modulation of Akt signaling

Myostatin is a highly conserved, potent negative regulator of skeletal muscle hypertrophy in many species, from rodents to humans, although its mechanisms of action are incompletely understood. Transcript profiling of hearts from a genetic model of cardiac hypertrophy revealed dramatic upregulation of myostatin, not previously recognized to play a role in the heart. Here we show that myostatin abrogates the cardiomyocyte growth response to phenylephrine in vitro through inhibition of p38 and the serine - threonine kinase Akt, a critical determinant of cell size in many species from drosophila to mammals. Evaluation of male myostatin-null mice revealed that their cardiomyocytes and hearts overall were slightly smaller at baseline than littermate controls but exhibited more exuberant growth in response to chronic phenylephrine infusion. The increased cardiac growth in myostatin-null mice corresponded with increased p38 phosphorylation and Akt activation in vivo after phenylephrine treatment. Together, these data demonstrate that myostatin is dynamically regulated in the heart and acts more broadly than previously appreciated to regulate growth of multiple types of striated muscle.

Adaptation of tree growth to elevated CO2: quantitative trait loci for biomass in Populus

Information on the genetic variation of plant response to elevated CO2 (e[CO2]) is needed to understand plant adaptation and to pinpoint likely evolutionary response to future high atmospheric CO2 concentrations.• Here, quantitative trait loci (QTL) for above- and below-ground tree growth were determined in a pedigree – an F2 hybrid of poplar (Populus trichocarpa and Populus deltoides), following season-long exposure to either current day ambient CO2 (a[CO2]) or e[CO2] at 600 µl l−1, and genotype by environment interactions investigated.• In the F2 generation, both above- and below-ground growth showed a significant increase in e[CO2]. Three areas of the genome on linkage groups I, IX and XII were identified as important in determining above-ground growth response to e[CO2], while an additional three areas of the genome on linkage groups IV, XVI and XIX appeared important in determining root growth response to e[CO2].• These results quantify and identify genetic variation in response to e[CO2] and provide an insight into genomic response to the changing environment

Hypersensitivity and growth adaptation of oestrogen-deprived MCF-7 human breast cancer cells

Background: Efficacy of endocrine therapy is compromised when human breast cancer cells circumvent imposed growth inhibition. The model of long-term oestrogen-deprived MCF-7 human breast cancer cells has suggested the mechanism results from hypersensitivity to low levels of residual oestrogen. Materials and methods: MCF-7 cells were maintained for up to 30 weeks in phenol-red-free medium and charcoal-stripped serum with 10-8 M 17-oestradiol and 10 g/ml insulin (stock 1), 10-8 M 17-oestradiol (stock 2), 10 g/ml insulin (stock 3) or no addition (stock 4). Results: Loss of growth response to oestrogen was observed only in stock 4 cells. Long-term maintenance with insulin in the absence of oestradiol (stock 3) resulted in raised oestrogen receptor alpha (ERlevels (measured by western immunoblotting) and development of hypersensitivity (assayed by oestrogen-responsive reporter gene induction and dose response to oestradiol for proliferation under serum-free conditions), but with no loss of growth response to oestrogen. Conclusion: Hypersensitivity can develop without any growth adaptation and therefore is not a prerequisite for loss of growth response in MCF-7 cells.

Signaling through the extracellular signal-regulated kinase 1/2 cascade in cardiac myocytes.

The extracellular signal-regulated kinases 1/2 (ERK1/2) are particularly implicated in the growth response of cardiac myocytes. In these cells, the ERK1/2 pathway is potently activated by Gq protein-coupled receptor agonists (such as endothelin-1 or alpha-adrenergic agonists), which activate protein kinase C isoforms. Here, we review the mechanisms associated with the activation of the ERK1/2 pathway by these agonists with particular emphasis on signal integration into the pathway. Signaling to the nucleus and the regulation of transcription factor activity associated with ERK1/2 activation in cardiac myocytes are also discussed.

"Ever-growing Amman", Jordan: Urban expansion, social polarisation and contemporary urban planning issues

Amman the primate capital city of the Hashemite Kingdom of Jordan currently has a population in excess of 2 million, but in 1924 it consisted of little more than a collection of dwellings and some 2000-3000 inhabitants. The present paper sets out to document and explain the phenomenal expansion of "ever-growing Amman". The physical geography of the urban region and the early growth of the city are considered at the outset and this leads directly to consideration of the highly polarised social structuring that characterises contemporary Amman. In doing this, original data derived from the recent Greater Amman Municipality's Geographical Information System are presented. In this respect, the essential modernity of the city is exemplified. The employment and industrial bases of the city and a range of pressing contemporary issues are then considered, including transport and congestion, the provision of urban water under conditions of water stress and privatisation, and urban and regional development planning for the city. The paper concludes by emphasizing the growing regional and international geopolitical salience of the city of Amman at the start of the 21st century. (C) 2008 Elsevier Ltd. All rights reserved.

Changes in oestrogen receptor-alpha and -beta during progression to acquired resistance to tamoxifen and fulvestrant (Faslodex, ICI 182,780) in MCF7 human breast cancer cells

Cell culture models of antioestrogen resistance often involve applying selective pressures of oestrogen deprivation simultaneously with addition of tamoxifen or fulvestrant (Faslodex, ICI 182,780) which makes it difficult to distinguish events in development of antioestrogen resistance from those in loss of response to oestrogen or other components. We describe here time courses of loss of antioestrogen response using either oestrogen-maintained or oestrogen-deprived MCF7 cells in which the only alteration to the culture medium was addition of 10(-6) M tamoxifen or 10(-7) M fulvestrant. In both oestrogen-maintained and oestrogen-deprived models, loss of growth response to tamoxifen was not associated with loss of response to fulvestrant. However, loss of growth response to fulvestrant was associated in both models with concomitant loss of growth response to tamoxifen. Measurement of oestrogen receptor alpha (ER alpha) and oestrogen receptor beta (ER beta) mRNA by real-time RT-PCR together with ER alpha and ER beta protein by Western immunoblotting revealed substantial changes to ER alpha levels but very little alteration to ER beta levels following development of antioestrogen resistance. In oestrogen-maintained cells, tamoxifen resistance was associated with raised levels of ERa mRNA/protein. However by contrast, in oestrogen-deprived MCF7 cells, where oestrogen deprivation alone had already resulted in increased levels of ERa mRNA/protein, long-term tamoxifen exposure now reduced ER alpha levels. Whilst long-term exposure to fulvestrant reduced ERa. mRNA/protein levels in the oestrogen-maintained cells to a level barely detectable by Western immunoblotting and non-functional in inducing gene expression (ERE-LUC reporter or pS2), in oestrogen-deprived cells the reduction was much less substantial and these cells retained an oestrogen-induction of both the ERE-LUC reporter gene and the endogenous pS2 gene which could still be inhibited by antioestrogen. This demonstrates that whilst ER alpha can be abrogated by fulvestrant and increased by tamoxifen in some circumstances, this does not always hold true and mechanisms other than alteration to ER must be involved in the development of antioestrogen resistant growth. (c) 2006 Elsevier Ltd. All rights reserved.

Markers of intestinally-derived lipoproteins: application to studies of altered diet and meal fatty acid compositions

BACKGROUND AND AIM: The atherogenic potential of dietary derived lipids, chylomicrons (CM) and their remnants (CMr) is now becoming more widely recognised. To investigate factors effecting levels of CM and CMr and their importance in coronary heart disease risk it is essential to use a specific method of quantification. Two studies were carried out to investigate: (i) effects of increased daily intake of long chain n-3 polyunsaturated fatty acid (LC n-3 PUFA), and (ii) effects of increasing meal monounsaturated fatty acid (MUFA) content on the postprandial response of intestinally-derived lipoproteins. The contribution of the intestinally-derived lipoproteins to total lipaemia was assessed by triacylglycerol-rich lipoprotein (TRL) apolipoprotein B-48 (apo B-48) and retinyl ester (RE) concentrations. METHODS AND RESULTS: In a randomised controlled crossover trial (placebo vs LC n-3 PUFA) a mean daily intake of 1.4 g/day of LC n-3 PUFA failed to reduce fasting and postprandial triacylglycerol (TAG) response in 9 healthy male volunteers. Although the pattern and nature of the apo B-48 response was consistent with the TAG response following the two diets, the postprandial RE response differed on the LC n-3 PUFA diet with a lower early RE response and a delayed and more marked increase in RE in the late postprandial period compared with the control diet, but the differences did not reach levels of statistical significance. In the meal study there was no effect of MUFA/SFA content on the total lipaemic response to the meals nor on the contribution of intestinally derived lipoproteins evaluated as TAG, apo B-48 and RE responses in the TRL fraction. In both studies, the RE and apo B-48 measurements provided broadly similar information with respect to lack of effects of dietary or meal fatty acid composition and the presence of single or multiple peak responses. However the apo B-48 and RE measurements differed with respect to the timing of their peak response times, with a delayed RE peak, relalive to apo B-48, of approximately 2-3 hours for the LC n-3 PUFA diet (p = 0.002) study and 1-1.5 hours for the meal MUFA/SFA study. CONCLUSIONS: It was concluded that there are limitations of using RE as a specific CM marker, apo B-48 quantitation was found to be a more appropriate method for CM and CMr quantitation. However it was still considered of value to measure RE as it provided additional information regarding the incorporation of other constituents into the CM particle.

Don't we care?: the ethics and emotional labour of early years professionalism

This paper argues that early childhood education and care (ECEC) has a legitimate aspiration to be a 'caring profession' like others such as nursing or social work, defined by a moral purpose. For example, practitioners often draw on an ethic of care as evidence of their professionalism. However, the discourse of professionalism in England completely excludes the ethical vocabulary of care. Nevertheless, it necessarily depends on gendered dispositions towards emotional labour, often promoted by training programmes as 'professional' demeanours. Taking control of the professionalisation agenda therefore requires practitioners to demonstrate a critical understanding of their practice as 'emotion work'. At the same time, reconceptualising practice within a political ethic of care may allow the workforce, and new trainees in particular, to champion 'caring' as a sustainable element of professional work, expressed not only in maternal, dyadic key-working but in advocacy for care as a social principle.

Solar signal propagation: the role of gravity waves and stratospheric sudden warmings

We use a troposphere‐stratosphere model of intermediate complexity to study the atmospheric response to an idealized solar forcing in the subtropical upper stratosphere during Northern Hemisphere (NH) early winter. We investigate two conditions that could influence poleward and downward propagation of the response: (1) the representation of gravity wave effects and (2) the presence/absence of stratospheric sudden warmings (SSWs). We also investigate how the perturbation influences the timing and frequency of SSWs. Differences in the poleward and downward propagation of the response within the stratosphere are found depending on whether Rayleigh friction (RF) or a gravity wave scheme (GWS) is used to represent gravity wave effects. These differences are likely related to differences in planetary wave activity in the GWS and RF versions, as planetary wave redistribution plays an important role in the downward and poleward propagation of stratospheric signals. There is also remarkable sensitivity in the tropospheric response to the representation of the gravity wave effects. It is most realistic for GWS. Further, tropospheric responses are systematically different dependent on the absence/presence of SSWs. When only years with SSWs are examined, the tropospheric signal appears to have descended from the stratosphere, while the signal in the troposphere appears disconnected from the stratosphere when years with SSWs are excluded. Different troposphere‐stratosphere coupling mechanisms therefore appear to be dominant for years with and without SSWs. The forcing does not affect the timing of SSWs, but does result in a higher occurrence frequency throughout NH winter. Quasi‐Biennial Oscillation effects were not included.

Cigarette smoke-induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents

Cigarette smoke (CS) inhalation causes an early inflammatory response in rodent airways by stimulating capsaicin-sensitive sensory neurons that express transient receptor potential cation channel, subfamily V, member 1 (TRPV1) through an unknown mechanism that does not involve TRPV1. We hypothesized that 2 alpha,beta-unsaturated aldehydes present in CS, crotonaldehyde and acrolein, induce neurogenic inflammation by stimulating TRPA1, an excitatory ion channel coexpressed with TRPV1 on capsaicin-sensitive nociceptors. We found that CS aqueous extract (CSE), crotonaldehyde, and acrolein mobilized Ca2+ in cultured guinea pig jugular ganglia neurons and promoted contraction of isolated guinea pig bronchi. These responses were abolished by a TRPA1-selective antagonist and by the aldehyde scavenger glutathione but not by the TRPV1 antagonist capsazepine or by ROS scavengers. Treatment with CSE or aldehydes increased Ca2+ influx in TRPA1-transfected cells, but not in control HEK293 cells, and promoted neuropeptide release from isolated guinea pig airway tissue. Furthermore, the effect of CSE and aldehydes on Ca2+ influx in dorsal root ganglion neurons was abolished in TRPA1-deficient mice. These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases.