The effect of the year of wheat variety release on productivity and stability of performance on two organic and two non-organic farms

Nineteen wheat cultivars, released from 1934 to 2000, were grown at two organic and two non-organic sites in each of 3 years. Assessments included grain yield, grain protein concentration, protein yield, disease incidence and green leaf area. The superiority of each cultivar (the sum of the squares of the differences between its mean in each environment and the mean of the best cultivar there, divided by twice the number of environments; CS) was calculated for yield, grain protein concentration and protein yield, and ranked in each environment. The yield and grain protein concentration CS were more closely correlated with cultivar release date at the non-organic sites than at organic sites. This difference may be attributed to higher yield levels with larger differences among cultivars at the non-organic sites, rather than to improved stability (i.e. similar ranks) across sites. The significant difference in the correlation of protein yield CS and cultivar age between organic and non-organic sites would support evidence that the ability to take up mineral nitrogen (N) compared to soil N has been a component of the selection conditions of more modern cultivars (released after 1989). This is supported by assessment of green leaf area (GLA), where more modern cultivars in the non-organic systems had greater late-season GLA, a trend that was not identified in organic conditions. This effect could explain the poor correlation between age and protein yield CS in organic compared to non-organic conditions where modern cultivars are selected to benefit from later nitrogen (N) availability which includes the spring nitrogen applications tailored to coincide with peak crop demand. Under organic management, N release is largely based on the breakdown of fertility-building crops incorporated (ploughed-in) in the previous autumn. The release of nutrients from these residues is dependent on the soil conditions, which includes temperature and microbial populations, in addition to the potential leaching effect of high winter rainfall in the UK. In organic cereal crops, early resource capture is a major advantage for maximizing the utilization of nutrients from residue breakdown. It is concluded that selection of cultivars under conditions of high agrochemical inputs selects for cultivars that yield well under maximal conditions in terms of nutrient availability and pest, disease and weed control. The selection conditions for breeding have a tendency to select cultivars which perform relatively better in non-organic compared to organic systems.

Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity.

Recombinant expression systems differ in the type of glycosylation they impart on expressed antigens such as the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, potentially affecting their biological properties. We performed head-to-head antigenic, immunogenic and molecular profiling of two distantly related Env surface (gp120) antigens produced in different systems: (a) mammalian (293 FreeStyle cells; 293F) cells in the presence of kifunensine, which impart only high-mannose glycans; (b) insect cells (Spodoptera frugiperda, Sf9), which confer mainly paucimannosidic glycans; (c) Sf9 cells recombinant for mammalian glycosylation enzymes (Sf9 Mimic), which impart high-mannose, hybrid and complex glycans without sialic acid; and (d) 293F cells, which impart high-mannose, hybrid and complex glycans with sialic acid. Molecular models revealed a significant difference in gp120 glycan coverage between the Sf9-derived and wild-type mammalian-cell-derived material that is predicted to affect ligand binding sites proximal to glycans. Modeling of solvent-exposed surface electrostatic potentials showed that sialic acid imparts a significant negative surface charge that may influence gp120 antigenicity and immunogenicity. Gp120 expressed in systems that do not incorporate sialic acid displayed increased ligand binding to the CD4 binding and CD4-induced sites compared to those expressed in the system that do, and imparted other more subtle differences in antigenicity in a gp120 subtype-specific manner. Non-sialic-acid-containing gp120 was significantly more immunogenic than the sialylated version when administered in two different adjuvants, and induced higher titers of antibodies competing for CD4 binding site ligand-gp120 interaction. These findings suggest that non-sialic-acid-imparting systems yield gp120 immunogens with modified antigenic and immunogenic properties, considerations that should be considered when selecting expression systems for glycosylated antigens to be used for structure-function studies and for vaccine use.

Enhanced second order non-linear optical properties of silica sol-gel thin films through photo-induced poling

Sol-gel derived inorganic materials are of interest as hosts for non-linear optically active guest molecules and they offer particular advantages in the field of non-linear optics. Orientationally ordered glasses have been prepared using a sol-gel system based on tetramethoxysilane, methyltrimethoxysilane and a non-linear optical chromophore Disperse Red 1. The novel technique of photo-induced poling was used to generate enhanced levels of polar order. The level of enhancement is strongly dependent on the extent of gelation and an optimum preparation time of ∼100 h led to an enhancement factor of ∼5. Films prepared in this manner exhibited a high stability of the polar order.

Response theory for equilibrium and non-equilibrium statistical mechanics: causality and generalized Kramers-Kronig relations

We consider the general response theory recently proposed by Ruelle for describing the impact of small perturbations to the non-equilibrium steady states resulting from Axiom A dynamical systems. We show that the causality of the response functions entails the possibility of writing a set of Kramers-Kronig (K-K) relations for the corresponding susceptibilities at all orders of nonlinearity. Nonetheless, only a special class of directly observable susceptibilities obey K-K relations. Specific results are provided for the case of arbitrary order harmonic response, which allows for a very comprehensive K-K analysis and the establishment of sum rules connecting the asymptotic behavior of the harmonic generation susceptibility to the short-time response of the perturbed system. These results set in a more general theoretical framework previous findings obtained for optical systems and simple mechanical models, and shed light on the very general impact of considering the principle of causality for testing self-consistency: the described dispersion relations constitute unavoidable benchmarks that any experimental and model generated dataset must obey. The theory exposed in the present paper is dual to the time-dependent theory of perturbations to equilibrium states and to non-equilibrium steady states, and has in principle similar range of applicability and limitations. In order to connect the equilibrium and the non equilibrium steady state case, we show how to rewrite the classical response theory by Kubo so that response functions formally identical to those proposed by Ruelle, apart from the measure involved in the phase space integration, are obtained. These results, taking into account the chaotic hypothesis by Gallavotti and Cohen, might be relevant in several fields, including climate research. In particular, whereas the fluctuation-dissipation theorem does not work for non-equilibrium systems, because of the non-equivalence between internal and external fluctuations, K-K relations might be robust tools for the definition of a self-consistent theory of climate change.

Influence of a non-ionic amphiphilic copolymer on the self-assembly of a peptide amphiphile that forms nanotapes

The influence of a non-ionic polymeric surfactant on the self-assembly of a peptide amphiphile (PA) that forms nanotapes is investigated using a combination of microscopic, scattering and spectroscopic techniques. Mixtures of Pluronic copolymer P123 with the PA C16-KTTKS in aqueous solution were studied at a fixed concentration of the PA at which it is known to self-assemble into extended nanotapes, but varying P123 concentration. We find that P123 can disrupt the formation of C16- KTTKS nanotapes, leading instead to cylindrical nanofibril structures. The spherical micelles formed by P123 at room temperature are disrupted in the presence of the PA. There is a loss of cloudiness in the solutions as the large nanotape aggregates formed by C16-KTTKS are broken up, by P123 solubilization. At least locally, b-sheet structure is retained, as confirmed by XRD and FTIR spectroscopy, even for solutions containing 20 wt% P123. This indicates, unexpectedly, that peptide secondary structure can be retained in solutions with high concentration of non-ionic surfactant. Selfassembly in this system exhibits slow kinetics towards equilibrium, the initial self-assembly being dependent on the order of mixing. Heating above the lipid chain melting temperature assists in disrupting trapped non-equilibrium states.

Variable and strain dependent colonisation of chickens by Escherichia coli O157

The prevalence of enterohaemorrhagic Escherichia coli (EHEC) O157 in poultry is considered minimal compared with other species, especially ruminants. However, deliberate inoculation studies have shown that poultry are readily and persistently infected by this organism but that the mechanism of colonisation is independent of intimin, a recognised factor in host-EHEC interactions in mammalian species, and may be dependent upon flagella. Few strains of EHEC O157 have been tested in poultry and here 1-day-old and 6-week-old chicks were inoculated with seven non-toxigenic E. coli O157 strains in separate experiments. Persistence was measured semi-quantitatively by bacteriological assessment of E. coli O157 cultured from cloacal swabs (shedding score). In the 1-day-old chick model that was monitored for 43 days, all seven strains established well after inoculation. In the 6-week-old chicken model, one strain established and gave consistently high shedding for the duration of the experiment (156 days). Whereas of the remaining six strains, two persisted for 113 days, two persisted for 43 days, one persisted for 22 days and one strain was never detected.

Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice

Proteases that are released during inflammation and injury cleave protease-activated receptor 2 (PAR2) on primary afferent neurons to cause neurogenic inflammation and hyperalgesia. PAR2-induced thermal hyperalgesia depends on sensitization of transient receptor potential vanilloid receptor 1 (TRPV1), which is gated by capsaicin, protons and noxious heat. However, the signalling mechanisms by which PAR2 sensitizes TRPV1 are not fully characterized. Using immunofluorescence and confocal microscopy, we observed that PAR2 was colocalized with protein kinase (PK) Cepsilon and PKA in a subset of dorsal root ganglia neurons in rats, and that PAR2 agonists promoted translocation of PKCepsilon and PKA catalytic subunits from the cytosol to the plasma membrane of cultured neurons and HEK 293 cells. Subcellular fractionation and Western blotting confirmed this redistribution of kinases, which is indicative of activation. Although PAR2 couples to phospholipase Cbeta, leading to stimulation of PKC, we also observed that PAR2 agonists increased cAMP generation in neurons and HEK 293 cells, which would activate PKA. PAR2 agonists enhanced capsaicin-stimulated increases in [Ca2+]i and whole-cell currents in HEK 293 cells, indicating TRPV1 sensitization. The combined intraplantar injection of non-algesic doses of PAR2 agonist and capsaicin decreased the latency of paw withdrawal to radiant heat in mice, indicative of thermal hyperalgesia. Antagonists of PKCepsilon and PKA prevented sensitization of TRPV1 Ca2+ signals and currents in HEK 293 cells, and suppressed thermal hyperalgesia in mice. Thus, PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. These mechanisms may underlie inflammatory pain, where multiple proteases are generated and released.

Enhanced affective brain representations of chocolate in cravers vs. non-cravers

To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.

Non-Refoulement between 'Common Article 1' and 'Common Article 3'

This article considers whether, in the context of armed conflicts, certain non-refoulement obligations of non-belligerent States can be derived from the 1949 Geneva Conventions. According to Common Article 1 (CA1) thereof, all High Contracting Parties (HCPs) undertake to ‘respect and to ensure respect’ for the four conventions ‘in all circumstances’. It is contended that CA1 applies both in international armed conflicts (IACs) and in non-international armed conflicts (NIACs). In turn, it is suggested that Common Article 3 (CA3) which regulates conduct in NIACs serves as a ‘minimum yardstick’ also applicable in IACs. It is widely (though not uniformly) acknowledged that the undertaking to ‘ensure respect’ in a given armed conflict extends to HCPs that are not parties to it; nevertheless, the precise scope of this undertaking is subject to scholarly debate. This article concerns situations where, in the course of an (international or non-international) armed conflict, persons ’taking no active part in hostilities’ flee from States where violations of CA3 are (likely to be) occurring to a non-belligerent State. Based on the undertaking in CA1, the central claim of this article is that, as long as risk of exposure to these violations persists, persons should not be refouled notwithstanding possible assessment of whether they qualify as refugees based on the 1951 Refugee Convention definition, or could be eligible for complementary or subsidiary forms of protection that are regulated in regional arrangements. The analysis does not affect the explicit protection from refoulement that the Fourth Geneva Convention accords to ‘protected persons’ (as defined in Article 4 thereof). It is submitted that CA1 should be read in tandem with other obligations of non-belligerent States under the 1949 Geneva Conventions. Most pertinently, all HCPs are required to take specific measures to repress ‘grave breaches’ and to take measures necessary for the suppression of all acts contrary to the 1949 Geneva Conventions other than the grave breaches. A HCP that is capable of protecting displaced persons from exposure to risks of violations of CA3 and nonetheless refoules them to face such risks is arguably failing to take lawful measures at its disposal in order to suppress acts contrary to the conventions and, consequently, fails to ‘ensure respect’ for the conventions. KEYWORDS Non-refoulement; International Armed Conflict; Non-International Armed Conflict; Common Article 1; Common Article 3

Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

The modelled occurrence of non-thermal plasma in the ionospheric F-region and the possible consequences for ion outflows into the magnetosphere

A global, time-dependent, three-dimensional, coupled ionosphere-thermosphere model is used to predict the spatial distribution of non-thermal plasma in the F-layer. It is shown that, even for steady-state conditions with Kp as low as 3, the difference between the ion and neutral velocities often exceeds the neutral thermal speed by a factor, D', which can be as large as 4. Theoretically, highly non-Maxwellian, and probably toroidal, ion velocity distributions are expected when D' exceeds about 1.5. The lack of response of the neutral winds to sunward ion drifts in the dawn sector of the auroral oval cause this to be the region most likely to contain toroidal distributions. The maximum in D' is found in the throat region of the convection pattern, where the strong neutral winds of the afternoon sector meet the eastward ion flows of the morning sector. These predictions are of interest, not only to radar scientists searching for non-thermal ionospheric plasma, but also as one possible explanation of the initial heating and upward flows of ions in the cleft ion fountain and nightside auroral oval, both of which are a major source of plasma for the magnetosphere.

Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35yrs) and 20 elderly (50-80yrs) healthy, male non- smokers consumed either a CF-containing drink (450mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1±0.7% vs. 7.6±0.7%, p<0.001) and elderly (4.9±0.6% vs. 6.3±0.9%, p<0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, increased arteriolar- and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial stiffness-related augmentation. CF intake decreased aortic augmentation index (-9%), and thus systolic blood pressure (-7mmHg). (Clinicaltrials.gov:NCT01639781) CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.

Estrogens and thyroid hormone: Non-genomic effects are coupled to transcription.

Estrogens and thyroid hormones are regulators of important diverse physiological processes such as reproduction, thermogenesis, neural development, neural differentiation and cardiovascular functions. Both are ligands for receptors in the nuclear receptor superfamily, which act as ligand-dependent transcription factors, regulating transcription. However, estrogens and thyroid hormones also rapidly (within minutes or seconds) activate kinase cascades and calcium increases, presumably initiated at the cell membrane. We discuss the relevance of both modes of hormone action, including the membrane estrogen receptor, to physiology, with particular reference to lordosis behavior. We first showed that estrogen restricted to the membrane can, in fact, lead to subsequent increases in transcription from a consensus estrogen response element-based reporter in the neuroblastoma cell line, SK-N-BE(2)C. Using a novel hormonal paradigm, we also showed that the activation of protein kinase A, protein kinase C, mitogen activated protein kinase and increases in calcium were important in the ability of the membrane-limited estrogen to potentiate transcription. We discuss the source of calcium important in transcriptional potentiation. Since estrogens and thyroid hormones have common effects on neuroprotection, cognition and mood, we also hypothesized that crosstalk could occur between the rapid actions of thyroid hormones and the genomic actions of estrogens. In neural cells, we showed that triiodothyronine acting rapidly via MAPK can increase transcription by the nuclear estrogen receptor ERa from a consensus estrogen response element, possibly by the phosphorylation of the ERa. Novel mechanisms that link signals initiated by hormones from the membrane to the nucleus are physiologically relevant and can achieve neuroendocrine integration

Polymerization-dependent activation of porcine γδ T-cells by proanthocyanidins

Plant-derived proanthocyanidins (PAC) have been promoted as a natural method of improving health and immune function in livestock. It has previously been shown that PAC are effective agonists for activating ruminant γδ T-cells in vitro, however effects on other livestock species are not yet clear. Moreover, the fine structural characteristics of the PAC which contribute to this stimulatory effect have not been elucidated. Here, we demonstrate activation of porcine γδ T-cells by PAC via up-regulation of CD25 (IL-2Rα) and show that 1) activation is dependent on degree of polymerization (DP), with PAC fractions containing polymers with mean DP >6 significantly more effective than fractions with mean DP <6, whilst flavan-3-ol monomers (the constituent monomeric units of PAC) did not induce CD25 expression and 2) both procyanidin and prodelphinidin-type PAC are effective agonists. Furthermore, we show that this effect of PAC is restricted to the γδ T-cell population within porcine peripheral mononuclear cells as significant CD25 up-regulation was not observed in non γδ T-cells, and no activation (via CD80/86 up-regulation) was evident in monocytes. Our results show that dietary PAC may contribute to enhancement of innate immunity in swine via activation of γδ T-cells.