Metabolic origins of spatial organization in the tumor microenvironment.

The genetic and phenotypic diversity of cells within tumors is a major obstacle for cancer treatment. Because of the stochastic nature of genetic alterations, this intratumoral heterogeneity is often viewed as chaotic. Here we show that the altered metabolism of cancer cells creates predictable gradients of extracellular metabolites that orchestrate the phenotypic diversity of cells in the tumor microenvironment. Combining experiments and mathematical modeling, we show that metabolites consumed and secreted within the tumor microenvironment induce tumor-associated macrophages (TAMs) to differentiate into distinct subpopulations according to local levels of ischemia and their position relative to the vasculature. TAMs integrate levels of hypoxia and lactate into progressive activation of MAPK signaling that induce predictable spatial patterns of gene expression, such as stripes of macrophages expressing arginase 1 (ARG1) and mannose receptor, C type 1 (MRC1). These phenotypic changes are functionally relevant as ischemic macrophages triggered tube-like morphogenesis in neighboring endothelial cells that could restore blood perfusion in nutrient-deprived regions where angiogenic resources are most needed. We propose that gradients of extracellular metabolites act as tumor morphogens that impose order within the microenvironment, much like signaling molecules convey positional information to organize embryonic tissues. Unearthing embryology-like processes in tumors may allow us to control organ-like tumor features such as tissue repair and revascularization and treat intratumoral heterogeneity

Asymptotically cylindrical 7-manifolds of holonomy G_2 with applications to compact irreducible G_2-manifolds

We construct examples of exponentially asymptotically cylindrical Riemannian 7-manifolds with holonomy group equal to G_2. To our knowledge, these are the first such examples. We also obtain exponentially asymptotically cylindrical coassociative calibrated submanifolds. Finally, we apply our results to show that one of the compact G_2-manifolds constructed by Joyce by desingularisation of a flat orbifold T^7/\Gamma can be deformed to one of the compact G_2-manifolds obtainable as a generalized connected sum of two exponentially asymptotically cylindrical SU(3)-manifolds via the method given by the first author (math.DG/0012189).Comment: 36 pages; v2: corrected trivial typos; v3: some arguments corrected and improved; v4: a number of improvements on presentation, paritularly in sections 4 and 6, including an added picture

Inverse Power Law Quintessence with Non-Tracking Initial Conditions

A common property of popular models of quintessence dark energy is the convergence to a common solution from a large range of the initial conditions. We re-examine the popular inverse power-law model of quintessence (where the common solution is dubbed as the 'tracker') with particular attention to the initial conditions for the field and their influence on the evolution. We find that previously derived limits on the parameters of the potential in this model are valid only in a range of initial conditions. A reasonably sharp boundary lies where the initial energy density of the scalar field is equal to that of the background radiation component. An initial quintessence energy density above this equipartition value lead to a solution that will not have joined the tracker solution by the present epoch. These non-tracker solutions possess the property that their present equation of state is very compatible with the observed bounds and independent of the exponent of the potential.Comment: RevTEX4, 9 figure

Management of European floodplain grasslands for plant biodiversity

Available from British Library Document Supply Centre-DSC:DXN025637 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

The effect of cognitive-behavioral therapy for bulimia nervosa on temperament and character as measured by the temperament and character inventory

Cognitive-behavioral therapy (CBT) is a successful treatment method for reducing symptomatology associated with bulimia nervosa (BN). Less is known regarding the impact of CBT on measures of temperament and character across treatment. We explore changes on the Temperament and Character Inventory (TCI) from pretreatment to 1-year follow-up in a sample of women with bulimia nervosa (BN). Ninety-one women who met DSM-III-R criteria for BN, completed pretreatment measures, and participated in a randomized clinical trial with a core treatment of CBT were available for follow-up at 1 year. Participants were assessed at pretreatment using the TCI as part of a larger assessment battery, and received eight sessions of CBT and eight sessions of exposure with response prevention or relaxation training. The TCI was readministered at the 1-year follow-up point. We compared TCI scores across the two administrations and explored the relation between clinical status at 1 year and TCI scores. Significant decreases in the TCI temperament scale of harm avoidance and increases in the character scale of self-directedness were observed between pretreatment and 1-year follow-up. Observed differences in these scales were independent of change in depression scores as well as other measures of therapeutic change (i.e., binge and purge frequency). We conclude that self-directedness and harm avoidance scores are positively affected by CBT. Higher scores on self-directedness not only predict treatment outcome for BN, but overall self-directedness is improved with CBT in women with BN. These results suggest that the elements of CBT affecting self-directedness may hold promise for enhancing the effectiveness of treatment for BN

A review of seagrass ecosystem services: providing nature-based solutions for a changing world

Seagrasses are marine flowering plants, which form extensive meadows in intertidal and shallow water marine environments. They provide a wide range of ecosystem services, which directly or indirectly benefit humans and can be grouped into four broad categories: provisioning (e.g. food production); regulating (e.g. carbon sequestration); supporting (e.g. primary production); and cultural (e.g. recreational, and eco-tourism). This study provides a review of publications focusing on seagrass ecosystem services provision to identify knowledge gaps and improve our understanding of the use of these habitats as nature-based solutions to societal challenges, such as climate change. Results showed that some ecosystem services, namely food provision, carbon sequestration, and maintenance of biodiversity/nursery habitats receive a higher level of focus and attention than others, such as regulation of diseases and social relations, which are rarely, if ever, included in studies. It is clear that in order to fully comprehend the nature-based solution potential held by seagrass ecosystems, studies need to consider ecosystem services as a whole, and also combine and share results across global regions, to better understand the potential impacts of degradation and loss of these ecosystems worldwide. Suggestions include applying novel technologies such as remote sensing and ecological niche modelling to address some of the main gaps in seagrass research, like meadow extent and connectivity within landscapes, to better incorporate preservation of seagrass ecosystems in marine management plans

Expression of PAL and HSPs in fresh-cut banana fruit

Wounding of plants is a widespread stress in nature. Physical damage frequently occurs during harvesting, handling and marketing of fresh produce. Phenylalanine ammonia-lyase (PAL) is a key enzyme involved in plant wound related phenylpropanoid metabolism while heat shock proteins (HSPs) are involved in abiotic, including wounding, and biotic stress responses in plants. However, little is known about postharvest expression at gene and protein levels of PAL and HSPs in wounding (fresh-cut) fruits. In the present study, expression patterns of PAL and HSPs in fresh-cut and intact banana fruit pulp were characterized by Northern and Western blot analyses. Cuting enhanced Ma-PAL2 mRNA accumulation, new PAL protein synthesis, and PAL activity; thereby resulting in accumulation of total phenolics. HSP70 protein and Ma-HSP70-2 transcript were constitutively expressed and were not affected by cutting. However, Ma-HSP70-1 transcript levels increased in fresh-cut pulp tissue at 2–18 h after cutting. Ma-sHSP-1-CI, Ma-sHSP-3-CII, Ma-HSP90, and Ma-HSP101 transcripts also accumulated in fresh-cut tissues at 2–18 h after cuting, but Ma-sHSP-2-CI did not accumulate. Accumulation of sHSP (HSP17.6), HSP90 and HSP101 proteins exhibited the same pattern of expression as their mRNA. There was no evidence of a possible suppressive effect of HSPs synthesis on PAL protein accumulation. Thus, PAL, sHSP, HSP90 and HSP101 were regulated by cutting both at translational and transcriptional levels while HSP70 (Ma-HSP70-1) was regulated by cutting only at transcription level

Mercury exposure of children living in Amazonian villages: influence of geographical location where they lived during prenatal and postnatal development

Abstract: Introduction: In some Amazonian river basins, hair mercury concentration is above the recommended levels. We evaluated the influence of birth geographical location in the hair mercury level of Amazonian riverine children. Materials and Methods: Hair mercury concentration was measured in 219 children living in four Amazonian riverine communities: Tapajós River (São Luiz do Tapajós and Barreiras villages, n = 110), Tocantins River (Limoeiro do Ajurú village, n = 61), and Caeté River (Caratateua village, n = 48). We used Poisson regression analysis to evaluate the association between native and non-native children from each village and its hair mercury concentration. Results: Higher mercury exposure was found in native children from São Luiz do Tapajós (range = 0.81-22.38 µg/g) followed by native children from Barreiras (range = 0.48-13.46 µg/g), non-native children from São Luiz do Tapajós (range = 0.26-22.18 µg/g), non-native children from Barreiras (range = 0.43-20.76 µg/g), followed by the children from Caeté and Tocantins river basins. We observed that Tapajós villages’ native children had higher prevalence of mercury exposure children than other children (p < 0.05). Conclusions: Birth geographical location has association to mercury levels in the hair of children who lived in a same community with history of mercury exposure