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Context: Although drought is generally considered the main environmental constraint in Mediterranean environments, the ability to acclimate to and tolerate frost in early developmental stages can be a determinant for seedling survival of many Mediterranean tree species like stone pine ( Pinus pinea L.). Aims: The aim of this study was to assess the impact of the developmental stage of naturally regenerated stone pine individuals on tolerance to low temperature (LT) from summer to late autumn and in spring, at a highly continental site in central Spain. Specifically, we tested to what extent the differences in tolerance are related to shoot heteroblasty. Methods: We assessed LT tolerance of needles from individuals at three age classes (class C1: seedlings, class C2: 4- to 8-year-old saplings and class C3: >9-year-old saplings) over nine dates from summer to spring. Results: LT tolerance displayed severe seasonal trends and differed between age classes. It usually increased with sapling age. Such differences were tightly related to heteroblasty of the shoots. Our results point to a higher LT tolerance associated with larger leaf dry mass per unit area (LMA) values. No impact of late frosts on shoot growth rates was detected during this study. Conclusions: Developmental changes during early plant growth seem to play a role in frost tolerance of stone pine seedlings, a finding which furthers our understanding of regeneration dynamics in this species in areas with continental influence. [ABSTRACT FROM AUTHOR]

Highlights: [•] Using Bayesian tree reconstruction methods, we establish the Mediterranean pine phylogeny using 21 low-copy nuclear genes. [•] Based on this phylogeny we look for signals of selection and adaptation in candidate genes and phenotypic traits of interest. [•] Two genes involved in defense and stress responses show selection signals. [•] Few life-history traits show historical or evolutionary adaptive convergence. [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]

Abstract: We consider the following problem: given a bounded domain and a vector field , find a solution to in , on , where is the 1-homogeneous infinity Laplace operator that is formally given by and a Lipschitz boundary datum. If we assume that is a continuous gradient vector field then we obtain the existence and uniqueness of a viscosity solution by an -approximation procedure. Also we prove the stability of the unique solution with respect to . In addition when is more regular (Lipschitz continuous) but not necessarily a gradient, using tug-of-war games we prove that this problem has a solution. [Copyright &y& Elsevier]

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]

The article discusses a research which tested niche segregation in the habitat between abundant carnivores using presence-only data. Results show that the presence of genets and stone martens were both detectable by tracks and signs but genets were more detectable by live trapping. It was observed that genets had broader niche and used more habitat variables than stone martens. A large overlap between the two species was also observed. Logistic regression analyses revealed that meadows, altitude and structure 3 at the home range scale were the important variables differentiating the niches of the two species. The presence areas of genet and stone marten at the local landscape scale was differentiated mainly by the proportion of structure 3, rocky outcrops and relief.

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]

Age and size at the first reproduction and the reproductive allocation of plants are linked to different life history strategies. Aleppo pine only reproduces through seed, and, as such, early female reproduction confers high fitness in its infertile highly fire- prone habitats along the Mediterranean coast because life expectancy is short. We investigated the extent of ecotypic differentiation in female reproductive allocation and examined the relation between early female reproduction and vegetative growth. In a common-garden experiment, the threshold age and size at first female reproduction and female reproductive allocation at age seven differed significantly among Aleppo pine provenances of ecologically distinct origin. Significant correlations among reproductive features of the provenances and the ecological traits of origin were found using different analytical tools. In nonlinear models of cone counts vs. stem volume, medium-sized trees (not the largest trees) produced the highest cone yield, confirming that, at the individual level, early female reproduction is incompatible with fast vegetative growth. The contribution of founder effects and adaptation to contrasting fire regimes may be confounding factors. But considering all traits analyzed, the geographical patterns of resource allocation by Aleppo pine suggest ecotypic specialization for either resource-poor (favoring early reproduction) or resource-rich (favoring vegetative growth) habitats. [ABSTRACT FROM AUTHOR]

Two strategies have evolved in understory trees in relation to light availability: maximization of light capture and shade tolerance. In the genus Acer, light capture is favored by a suite of traits maximizing twig thickness and leaf size and minimizing the density of branching in the crown. In contrast, shade tolerance is enhanced by minimizing crown area, crown volume, and total leaf area per unit height. Maples with polycyclic shoot growth (i.e., successive flushes of shoot growth separated by a resting phase within the same vegetative period) may benefit from the prolonged growth by growing more and increasing total leaf area; thus we hypothesize that polycyclism is evolutionarily correlated with the suite of traits related to light capture. We tested this hypothesis using different phylogenetic trees to explore correlations between polycyclism and both suites of traits. Polycyclism was correlated with the suite of traits maximizing light capture, suggesting that polycyclic maples are ‘optimists’ (i.e., they make vigorous vertical extensions in rich light) and monocyclic maples are ‘pessimists’ (i.e., they wait in the dark understory until a gap is opened). Both strategies have been described for different floras, and interestingly, polycyclic species recruit over a wider range of environments than the monocyclic species. [ABSTRACT FROM AUTHOR]

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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]

Summary. Imatinib mesylate (STI571) is a highly effective and well-tolerated treatment for patients with chronic-phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty-three chronic-phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6–19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1–4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3–4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non-haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic-phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic-phase CML patients with a previous history of intensive treatment. [ABSTRACT FROM AUTHOR]