Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.

Experimental confirmation of transformation pathways between inverse double diamond and gyroid cubic phases

A macroscopically oriented double diamond inverse bicontinuous cubic phase (QIID) of the lipid glycerol monooleate is reversibly converted into a gyroid phase (QIIG). The initial QIID phase is prepared in the form of a film coating the inside of a capillary, deposited under flow, which produces a sample uniaxially oriented with a ⟨110⟩ axis parallel to the symmetry axis of the sample. A transformation is induced by replacing the water within the capillary tube with a solution of poly(ethylene glycol), which draws water out of the QIID sample by osmotic stress. This converts the QIID phase into a QIIG phase with two coexisting orientations, with the ⟨100⟩ and ⟨111⟩ axes parallel to the symmetry axis, as demonstrated by small-angle X-ray scattering. The process can then be reversed, to recover the initial orientation of QIID phase. The epitaxial relation between the two oriented mesophases is consistent with topologypreserving geometric pathways that have previously been hypothesized for the transformation. Furthermore, this has implications for the production of macroscopically oriented QIIG phases, in particular with applications as nanomaterial templates.

Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice

Mammalian aging is accompanied by a progressive loss of skeletal muscle, a process called sarcopenia. Myostatin, a secreted member of the transforming growth factor-β family of signaling molecules, has been shown to be a potent inhibitor of muscle growth. Here, we examined whether muscle growth could be promoted in aged animals by antagonizing the activity of myostatin through the neutralizing activity of the myostatin propeptide. We show that a single injection of an AAV8 virus expressing the myostatin propeptide induced an increase in whole body weights and all muscles examined within 7 weeks of treatment. Our cellular studies demonstrate that muscle enlargement was due to selective fiber type hypertrophy, which was accompanied by a shift toward a glycolytic phenotype. Our molecular investigations elucidate the mechanism underpinning muscle hypertrophy by showing a decrease in the expression of key genes that control ubiquitin-mediated protein breakdown. Most importantly, we show that the hypertrophic muscle that develops as a consequence of myostatin propeptide in aged mice has normal contractile properties. We suggest that attenuating myostatin signaling could be a very attractive strategy to halt and possibly reverse age-related muscle loss.

The housing pathways of young people in the UK

The authors examine the housing pathways of young people in the UK in the years 1999 to 2008, and consider the changing nature of these pathways in the run up to 2020. They employ a highly innovative methodology, which begins with the identification and description of key drivers likely to affect young people’s housing circumstances in the future. The empirical identification and analysis of housing pathways is then achieved using multiple-sequence analysis and cluster analysis of the British Household Panel Survey, contextualised by qualitative interviews with a large sample of young people. The authors describe how the interactions between the meanings, perceptions, and aspirations of young people, and the opportunities and constraints imposed by the drivers, are having a major impact on young people’s housing pathways, resulting in considerable housing policy challenges, particularly in relation to the private rented sector

Investigations into plant biochemical wound-response pathways involved in the production of aphid-induced plant volatiles

Feeding damage to plants by insect herbivores induces the production of plant volatiles, which are attractive to the herbivores natural enemies. Little is understood about the plant biochemical pathways involved in aphid-induced plant volatile production. The aphid parasitoid Diaeretiella rapae can detect and respond to aphid-induced volatiles produced by Arabidopsis thaliana. When given experience of those volatiles, it can learn those cues and can therefore be used as a novel biosensor to detect them. The pathways involved in aphid-induced volatile production were investigated by comparing the responses of D. rapae to volatiles from a number of different transgenic mutants of A. thaliana, mutated in their octadecanoid, ethylene or salicylic acid wound-response pathways and also from wild-type plants. Plants were either undamaged or infested by the peach-potato aphid, Myzus persicae. It is demonstrated that the octadecanoid pathway and specifically the COI1 gene are required for aphid-induced volatile production. The presence of salicylic acid is also involved in volatile production. Using this model system, in combination with A. thaliana plants with single point gene mutations, has potential for the precise dissection of biochemical pathways involved in the production of aphid-induced volatiles

Full effects of land use change in the representative concentration pathways

Future land use change (LUC) is an important component of the IPCC representative concentration pathways (RCPs), but in these scenarios' radiative forcing targets the climate impact of LUC only includes greenhouse gases. However, climate effects due to physical changes of the land surface can be as large. Here we show the critical importance of including non-carbon impacts of LUC when considering the RCPs. Using an ensemble of climate model simulations with and without LUC, we show that the net climate effect is very different from the carbon-only effect. Despite opposite signs of LUC, all the RCPs assessed here have a small net warming from LUC because of varying biogeophysical effects, and in RCP4.5 the warming is outside of the expected variability. The afforestation in RCP4.5 decreases surface albedo, making the net global temperature anomaly over land around five times larger than RCPs 2.6 and 8.5, for around twice the amount of LUC. Consequent changes to circulation in RCP4.5 in turn reduce Arctic sea ice cover. The small net positive temperature effect from LUC could make RCP4.5's universal carbon tax, which incentivizes retaining and growing forest, counter productive with respect to climate. However, there are spatial differences in the balance of impacts, and potential climate gains would need to be assessed against other environmental aims.

Quantifying the relative importance of land cover change from climate and land-use in the representative concentration pathways

Climate change is projected to cause substantial alterations in vegetation distribution, but these have been given little attention in comparison to land-use in the Representative Concentration Pathway (RCP) scenarios. Here we assess the climate-induced land cover changes (CILCC) in the RCPs, and compare them to land-use land cover change (LULCC). To do this, we use an ensemble of simulations with and without LULCC in earth system model HadGEM2-ES for RCP2.6, RCP4.5 and RCP8.5. We find that climate change causes an expansion poleward of vegetation that affects more land area than LULCC in all of the RCPs considered here. The terrestrial carbon changes from CILCC are also larger than for LULCC. When considering only forest, the LULCC is larger, but the CILCC is highly variable with the overall radiative forcing of the scenario. The CILCC forest increase compensates 90% of the global anthropogenic deforestation by 2100 in RCP8.5, but just 3% in RCP2.6. Overall, bigger land cover changes tend to originate from LULCC in the shorter term or lower radiative forcing scenarios, and from CILCC in the longer term and higher radiative forcing scenarios. The extent to which CILCC could compensate for LULCC raises difficult questions regarding global forest and biodiversity offsetting, especially at different timescales. This research shows the importance of considering the relative size of CILCC to LULCC, especially with regard to the ecological effects of the different RCPs.

Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703.

Microbial Recognition Via Toll-Like Receptor-Dependent and -Independent Pathways Determines the Cytokine Response of Murine Dendritic Cell Subsets to CD40 Triggering

Dendritic cells (DC) can produce Th-polarizing cytokines and direct the class of the adaptive immune response. Microbial stimuli, cytokines, chemokines, and T cell-derived signals all have been shown to trigger cytokine synthesis by DC, but it remains unclear whether these signals are functionally equivalent and whether they determine the nature of the cytokine produced or simply initiate a preprogrammed pattern of cytokine production, which may be DC subtype specific. Here, we demonstrate that microbial and T cell-derived stimuli can synergize to induce production of high levels of IL-12 p70 or IL-10 by individual murine DC subsets but that the choice of cytokine is dictated by the microbial pattern recognition receptor engaged. We show that bacterial components such as CpG-containing DNA or extracts from Mycobacterium tuberculosis predispose CD8alpha(+) and CD8alpha(-)CD4(-) DC to make IL-12 p70. In contrast, exposure of CD8alpha(+), CD4(+) and CD8alpha(-)CD4(-) DC to heat-killed yeasts leads to production of IL-10. In both cases, secretion of high levels of cytokine requires a second signal from T cells, which can be replaced by CD40 ligand. Consistent with their differential effects on cytokine production, extracts from M. tuberculosis promote IL-12 production primarily via Toll-like receptor 2 and an MyD88-dependent pathway, whereas heat-killed yeasts activate DC via a Toll-like receptor 2-, MyD88-, and Toll/IL-1R domain containing protein-independent pathway. These results show that T cell feedback amplifies innate signals for cytokine production by DC and suggest that pattern recognition rather than ontogeny determines the production of cytokines by individual DC subsets.

Motivational trajectories for early language learning across the primary-secondary school transition

The transition from primary to secondary school is an area of concern across a range of curriculum subjects, and this is no less so for foreign language learning. Indeed problems with transition have been identified in England as an important barrier to the introduction of language learning to the primary school curriculum, with implications for learners’ longer-term motivation for the subject. This longitudinal study investigated, through a questionnaire, the development of 233 learners’ motivation for learning French in England, during the transition from primary to secondary schooling. It also explored whether levels and patterns of motivation differed according to the type of language teaching experienced, comparing a largely oracy-focused approach with one with greater emphasis on literacy activities. Learners showed high and increasing levels of motivation across transition, placing particular value on learning French for travel. Being taught through an oracy or a literacy-focused approach had less impact on learners’ motivation than broader classroom experiences, with the development of a sense of progress and feeling that instruction met their learning needs being especially important. A growing disjuncture emerged between valuing the learning of French for travel/communication and learners’ low levels of self-efficacy for communication with native speakers, together with a desire for more communication-based activities. By the end of the first year of secondary school less positive attitudes towards learning French and less optimism about the possibility of future progress were beginning to emerge. The paper concludes by outlining the implications of the study for classroom practice in language learning.

Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy.

Maximally effective concentrations of endothelin-1 (ET-1), acidic FGF (aFGF), or 12-O-tetradecanoylphorbol-13-acetate (TPA) activated mitogen-activated protein kinase (MAPK) by 3-4-fold in crude extracts of myocytes cultured from neonatal rat heart ventricles. Maximal activation was achieved after 5 min. Thereafter, MAPK activity stimulated by ET-1 or aFGF declined to control values within 1-2 h, whereas activation by TPA was more sustained. Two peaks of MAPK activity (a 42- and a 44-kDa MAPK) were resolved in cells exposed to ET-1 or aFGF by fast protein liquid chromatography on a Mono Q column. One major and one minor peak of MAPK kinase (MAPKK) was stimulated by ET-1 or aFGF. Cardiac myocytes expressed protein kinase C (PKC)-alpha, -delta, -epsilon and -zeta as shown immunoblotting. Exposure to 1 microM TPA for 24 h down-regulated PKC-alpha, -delta, and -epsilon, but not PKC-zeta. This maneuver wholly abolished the activation of MAPK on re-exposure to TPA but did not affect the response to aFGF. The effect of ET-1 was partially down-regulated. ET-1 stimulated phospho[3H]inositide hydrolysis 18-fold, whereas aFGF stimulated by only 30%. Agonists which initially utilize dissimilar signaling pathways may therefore converge at the level of MAPKK/MAPK and this may be relevant to the hypertrophic response of the heart.