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Obesity exacerbates aging-induced adipose tissue dysfunction. This study aimed to investigate the effects of long-term exercise on inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) of aged obese mice. Two-month-old female mice received a high-fat diet for 4 months. Then, six-month-old diet-induced obese animals were allocated to sedentarism (DIO) or to a long-term treadmill training (DIOEX) up to 18 months of age. In exercised mice, iWAT depot revealed more adaptability, with an increase in the expression of fatty acid oxidation genes (Cpt1a, Acox1), and an amelioration of the inflammatory status, with a favorable modulation of pro/antiinflammatory genes and lower macrophage infiltration. Additionally, iWAT of trained animals showed an increment in the expression of mitochondrial biogenesis (Pgc1a, Tfam, Nrf1), thermogenesis (Ucp1), and beige adipocytes genes (Cd137, Tbx1). In contrast, iBAT of aged obese mice was less responsive to exercise. Indeed, although an increase in functional brown adipocytes genes and proteins (Pgc1a, Prdm16 and UCP1) was observed, few changes were found on inflammation-related and fatty acid metabolism genes. The remodeling of iWAT and iBAT depots occurred along with an improvement in the HOMA index for insulin resistance and in glucose tolerance. In conclusion, long-term exercise effectively prevented the loss of iWAT and iBAT thermogenic properties during aging and obesity. In iWAT, the long-term exercise program also reduced the inflammatory status and stimulated a fat-oxidative gene profile. These exercise-induced adipose tissue adaptations could contribute to the beneficial effects on glucose homeostasis in aged obese mice. [ABSTRACT FROM AUTHOR]

This paper discusses the science case for a sensitive spectro-polarimetric survey of the microwave sky. Such a survey would provide a tomographic and dynamic census of the three-dimensional distribution of hot gas, velocity flows, early metals, dust, and mass distribution in the entire Hubble volume, exploit CMB temperature and polarisation anisotropies down to fundamental limits, and track energy injection and absorption into the radiation background across cosmic times by measuring spectral distortions of the CMB blackbody emission. In addition to its exceptional capability for cosmology and fundamental physics, such a survey would provide an unprecedented view of microwave emissions at sub-arcminute to few-arcminute angular resolution in hundreds of frequency channels, a data set that would be of immense legacy value for many branches of astrophysics. We propose that this survey be carried out with a large space mission featuring a broad-band polarised imager and a moderate resolution spectro-imager at the focus of a 3.5 m aperture telescope actively cooled to about 8K, complemented with absolutely-calibrated Fourier Transform Spectrometer modules observing at degree-scale angular resolution in the 10–2000 GHz frequency range. We propose two observing modes: a survey mode to map the entire sky as well as a few selected wide fields, and an observatory mode for deeper observations of regions of specific interest. [ABSTRACT FROM AUTHOR]

Background and Objective: Morton neuroma is a common cause of metatarsalgia of neuropathic origin. Systematic reviews suggest that insufficient studies have been performed on the efficacy of the different treatments available. OnabotulinumtoxinA has shown a degree of usefulness in other conditions associated with neuropathic pain. The aim of this study was to investigate the therapeutic potential of onabotulinumtoxinA in Morton neuroma. Patients and Methods: We present an open-label, pilot study with 17 consecutive patients with Morton neuroma and pain of more than 3 months' duration that had not responded to conservative treatment with physical measures or corticosteroid injection. Patients received one onabotulinumtoxinA injection in the area of the neuroma. The main outcome measure was the variation in the pain on walking evaluated using a visual analogue scale (VAS) before treatment and at 1 and 3 months after treatment. The secondary outcome was the change in foot function, which was assessed using the Foot Health Status Questionnaire. Results: In the overall group, the mean initial VAS score on walking was 7. This mean score had fallen to 4.8 at 1 month after treatment and to 3.7 at 3 months. Twelve patients (70.6 %) reported an improvement in their pain and five patients (29.4 %) reported no change; exacerbation of the pain did not occur in any patient. Improvements were also observed in two of the dimensions of the Foot Health Status Questionnaire: foot pain, which improved from a mean of 38.88 before treatment to 57 at 3 months, and foot function, which improved from a mean of 42.27 before treatment to 59.9 at 3 months. Clinical variables including age, sex, site and size of the lesion, standing activity, weekly duration of walking, footwear, foot type and footprint had no influence on the outcome. No adverse effects were reported. Conclusions: In this pilot study, injection with onabotulinumtoxinA was shown to be of possible usefulness to relieve the pain and improve function in Morton neuroma. This finding opens the door to further clinical research. [ABSTRACT FROM AUTHOR]

Rooting space is considered as a resource in plants, but comparative studies on the biomass allocation plasticity in response to rooting volume (RV) are rare. We compared responses in growth, biomass allocation and ontogenetic heteroblasty in nine hard pine species of contrasted ecology. Seedlings were cultivated in containers of 0.2, 0.5, 1.0, 2.8 and 7 L for two growing seasons (425 days). Reduction in RV caused a reduction in plant absolute and relative growth rate and biomass allocated to stems but it increased biomass allocated to roots. RV affected to a lesser extent and in a less consistent direction allocation to leaves. Species that grew faster (higher relative growth rate) had a steeper decrease in growth with the reduction in RV. Ontogenetic heteroblasty, evaluated as the proportion of secondary needles in the needle biomass, showed highly different plasticity patterns in response to RV. Decrease in RV caused negligible or no change either in the most ontogenetically delayed Mediterranean pines or in the most ontogenetically advanced pines, the mesic Pinus sylvestris and P. uncinata. By contrast, ontogenetically intermediate species showed steep reaction norms in response to reduction in RV. While P. pinaster and P. brutia showed marked rejuvenation, P. nigra accelerated the development of adult foliage. [ABSTRACT FROM AUTHOR]

Heteroblastic development in pine seedlings includes extreme morphological changes with still unclear adaptive and evolutionary significance. In particular, Mediterranean and Eurasian pines (section Pinus) living in the Mediterranean basin seem to follow quite distinct developmental trajectories at the seedling stage. Aiming to confirm this ontogenetic differentiation we performed a nursery experiment with seedlings of five Mediterranean pines ( Pinus pinaster, P. brutia, P. halepensis, P. pinea and P. canariensis) and three Eurasian pines ( P. sylvestris, P. uncinata, and P. nigra subsp. salzmannii), also including P. radiata as an outgroup. After destructive analyses at two harvest times (9 and 32 weeks), we found sharp differentiation between Mediterranean and Eurasian pines in a combination of traits linked to shoot heteroblasty. In particular, Mediterranean pines showed a marked delay in the proportion of adult needles to total needles in the shoot compared to Eurasian species, especially at the second harvest. However, two Mediterranean pines, P. pinaster and P. brutia showed a slightly higher proportion of secondary needles, and a higher rate of budset at a more advanced stage (68 weeks) compared to the other three Mediterranean species. Meaningfully, the outgroup P. radiata was the only species combining a high proportion of adult foliage since the first harvest with a delayed formation of the first terminal bud. We discussed the adaptive significance of these findings at the light of species' climatic niches and life histories. [ABSTRACT FROM AUTHOR]

Foliar plasticity in response to ontogeny, location within the plant and environmental changes is widespread among long-lived organisms. To quantify the phenotypic variation in needle morphology and anatomy in response to a climate gradient, we compared contrasted populations of Pinus canariensis grown in five sites inside and outside the natural distribution area of the species. Most needle and growth traits were strongly affected by site. In general, site xericity increased the relative area of the dermal and transfusion tissues and decreased mesophyll and endodermis. Within each site, provenances from less productive locations tended to show longer needles, less relative area of dermal tissues but higher relative area of mesophyll and transfusion tissue than provenances from fertile origins. Although sclerophylly increased with aridity, no genetic differences were found for this trait thus apparently the ontogenetic delay of some provenances in xeric environments was not related with the formation of tougher needles. Several patterns of phenotypic response to different environments were shown. In general, all traits were plastic but the degree of plasticity was higher in traits related with growth than foliar traits. These results, combined with formerly published research, suggest that highly plastic populations rather than narrowly specialized ones have been selected in this species to cope with the complex interaction of environmental factors in its habitat. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that fertilized containerized Pinus canariensis seedlings increases survival when planted in semiarid sites through the improvement of their physiological status during the establishment phase by an increment in root growth. Seedlings were cultured under two different regimes: traditional (in non-fertilized natural soil) and alternative (in fertilized peat). Morphological attributes and nitrogen content were measured before planting. Measurements of survival and growth in the plantation were made periodically for 2 years and physiological plant responses (leaf water potential, gas exchange and chlorophyll fluorescence) during the third summer after planting were tested and finally a set of plants were excavated to measure the same parameters as before planting. Seedlings cultivated using fertilized peat achieved the highest values for all of evaluated parameters. During the third dry season, big seedlings exhibited better physiological status. Therefore, enhanced root growth can result in better water uptake during the dry period thereby increasing survival and growth in the next few years after planting. A feed-back physiological model is proposed to explain P. canariensis establishment in a semiarid environment. [ABSTRACT FROM AUTHOR]

Most human cancers derive from a single cell targeted by genetic and epigenetic alterations that initiate malignant transformation. Progressively, these early cancer cells give rise to different generations of daughter cells that accumulate additional mutations, acting in concert to drive the full neoplastic phenotype1,2. As we have currently deciphered many of the gene pathways disrupted in cancer, our knowledge about the nature of the normal cells susceptible to transformation upon mutation has remained more elusive. Adult stem cells are those that show long-term replicative potential, together with the capacities of self-renewal and multi-lineage differentiation. These stem cell properties are tightly regulated in normal development, yet their alteration may be a critical issue for tumorigenesis. This concept has arisen from the striking degree of similarity noted between somatic stem cells and cancer cells, including the fundamental abilities to self-renew and differentiate. Given these shared attributes, it has been proposed that cancers are caused by transforming mutations occurring in tissue-specific stem cells3–9. This hypothesis has been functionally supported by the observation that among all cancer cells within a particular tumor, only a minute cell fraction has the exclusive potential to regenerate the entire tumor cell population3,10–13; these cells with stem-like properties have been termed cancer stem cells. Cancer stem cells can originate from mutation in normal somatic stem cells that deregulate their physiological programs. Alternatively, mutations may target more committed progenitor cells or even mature cells, which become reprogrammed to acquire stem-like functions14,15 In any case, mutated genes should promote expansion of stem/progenitor cells, thus increasing their predisposition to cancer development by expanding self-renewal and pluripotency over their normal tendency towards relative quiescency and proper differentiation. [ABSTRACT FROM AUTHOR]

The life history of Spanish pines and their relation to fire as the main disturbance factor in their ecosystems was analysed. The primary ecological attributes studied were the canopy seed bank (onset of cone production, percentage and persistence of serotinous cones), seed and cone morphology, sprouting and bark thickness. Four ecological groups were separated using multivariate cluster analysis and their life-history characteristics are discussed. Serotiny and early flowering in Pinus halepensis and P. pinaster reflect their evader strategy in relation to fire as this character is advantageous to survive frequent crown fires and to attain successful post-fire recruitment. Late flowering and absence of serotinous cones in P. nigra, P. sylvestris and P. uncinata indicate that their natural forest did not evolve under frequent crown fires. P. canariensis and P. pinea appeared in two single groups because of their sprouting capability and their seed size respectively. Intraspecific variation in P. pinaster was also analysed using the same criteria and high variability was found in its life history traits. A group of P. pinaster populations showed high levels of serotiny and thin bark as a possible adaptation to frequent stand-replacing crown fires. In contrast, a group of non- or weakly-serotinous populations seems to have evolved under a low-intensity fire regime where the best fitness corresponds to thick-barked individuals capable of surviving ground fires. Intermediate strategies were also evident in this species and were discussed in relation to the effect of different fire regimes caused by the understorey vegetation. [ABSTRACT FROM AUTHOR]

A wide set of phenotypic characteristics related to life history were studied in mature stands of Pinus canariensis throughout its natural range of distribution in the Canary archipelago. Natural forests ranging from those located in xeric areas through to the sub-tropical cloud forests and high mountain stands were classified into eight ecological regions according to their main climatic features. The recent history of forest fires (covering the last 30 years) was taken into account using a categorical factor with three levels. The phenotypic variables studied included those related to seed dispersal (cone size, number of seed scales, seed and wing size and percentage of serotinous trees) and stem growth both on the breast height section (bark thickness, radial growth at various ages and sapwood and heartwood sizes) and on the entire stem (height growth related to age). The average percentage of serotinous trees present in the ecological regions studied varied from 3 to 35%. Average bark thickness in adult trees ranged from 22 to 49 mm and was found to be unrelated to age or diameter. Growth both in height and diameter was found to decline after an average of 25 years, although clear trends in relation to this could not be established across the ecological regions. A high correlation was found to exist between annual rainfall, fire frequency, serotiny and bark thickness at a regional level. Sapwood area per hectare proved to be a valuable indirect site-quality index for the objectives of this paper. Favourable sites (characterised by a high sapwood area per hectare) displayed the highest levels of both bark thickness and serotiny. These particular areas are those, which have suffered more frequent and intense fires over the last decades. The evolutionary implications of this trend and of other general traits of the species, such as vegetative resprouting, are discussed here in relation to the role of understorey vegetation in fire regimes, competition and volcanic history of the islands. [ABSTRACT FROM AUTHOR]