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Parkinson disease is a progressive neurodegenerative disease that affects, among other neurotransmitter systems, the nigrostriatal dopaminergic projection. Palliative treatment with levodopa and/or dopamine agonists improves motor symptoms even though patients continue to get clinically worse by the neurodegenerative process that continues to act as the major factor of physiological aging. Studies (in vitro and in vivo) with experimental models have shown that dopamine agonists have neuroprotective effects, directly or indirectly mediated by their ability to stabilize mitochondria, antioxidant effects, synthesis of growth factors, stabilization of the ubiquitin-proteasome system, activation of autophagy, antiapoptotic induction of Bcl2 family, or enhancement of neurogenesis (proliferation and migration) in the subventricular zone. Clinical studies have not completely confirmed these effects. Analysis in better characterized groups of patients with similar clinical symptoms, identical treatments, and the same evolution time are required. Technological advances which enable the learning of the etiology and the pathogenesis (genetic and environmental) of the disease, together with clinical assessment methods, bring hope to the development of new molecules in the symptomatic treatment of Parkinson disease. These molecules must display neuroprotective potential (prophylactic and/or therapeutic) which must be able to maintain the brain's physiological function and to modify or slow the natural course of the disease.

Loquat (Eriobotrya japonica Lindl.; Pyrinae, Rosaceae) is an evergreen fruit tree which is acquiring increasing importance as an alternative crop in warm-temperate and subtropical regions. Recent pollination studies suggest that crop intensification has resulted in a reduction of fruit productivity in different locations. Loquat exhibits gametophytic self-incompatibility (GSI) and, consequently, fruit set strongly depends on cross-pollination between intercompatible cultivars. S-genotyping and incompatibility group assignment is therefore essential for adequate loquat orchard design. This study reports the molecular characterization of the S-RNase allele composition of 31 loquat cultivars grown in Spain. PCR with primers developed from loquat S-RNase sequences was used in combination with high-performance capillary polyacrilamide electrophoresis for the fine-evaluation of length polymorphisms at the S-RNase gene. This approach allowed to uncover a new S-RNase allele (S 5), whose sequence is reported and to characterize the first six S-RNase-based incompatibility groups (I–VI) in loquat, resulting from the combination of five S-alleles (S 1–S 5). The large number of cultivars that could be assigned to only six groups suggests a narrow genetic base for this crop in Spain and stresses the need for careful determination of the S-genotype of cultivars in an attempt to overcome production problems associated with inadequate pollination.

The ubiquitin-proteasome system (UPS) functions as a major degradation pathway for misfolded and damaged proteins with an important neuroprotective role in the CNS against a variety of cellular stresses. Parkin and ubiquitin C-terminal hydrolase L1 (UCH-L1) are two relevant components of the UPS associated with a number of neurodegenerative disorders. We here address the expression profile of parkin and UCH-L1 in the mammalian retina, with special emphasis on primates. We describe for the first time the presence of parkin in the retina of mammals, including humans. Parkin and UCH-L1 genes were expressed at the mRNA and protein levels in the retina of all species examined. The immunolocalization pattern of parkin was quite widespread, being expressed by most retinal neuronal types, including photoreceptors. UCH-L1 was localized to horizontal cells and specific subtypes of bipolar and amacrine cells, as well as to ganglion cells and their axons forming the nerve fiber layer. In rodents no UCH-L1 immunoreactivity was found in cone or rod photoreceptors, whereas this protein was present along the whole length of cones in all other mammals. Remarkably, UCH-L1 was expressed by dopaminergic amacrine cells of primates. The ample distribution of parkin and UCH-L1 in the mammalian retina, together with the crucial role played by the UPS in normal neuronal physiology in the brain, points to a participation of these two proteins in the ubiquitin-proteasomal pathway of protein degradation in most retinal cell types, where they could exert a protective function against neuronal stress. This research was supported by grants from the Spanish Instituto de Salud Carlos III (ISCIII; PI09/1623) to J.M.-N., Ministerio de Ciencia e Innovación (MICINN; SAF2007-62262), Fundación Séneca (FS/05662/PI/07) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) to M.-T.H.; and MICINN (BFU2009-07793/BFI), ISCIII (RETICS RD07/0062/0012), Generalitat Valenciana (ACOMP/2009/139), Organización Nacional de Ciegos de España (ONCE) and Fundación Lucha contra la Ceguera (FUNDALUCE) to N.C. J.E.-R. and L.C. are recipients of predoctoral contracts from the Universidad de Alicante.

Low fruit set in fruit trees has been traditionally related to weather conditions. In apricot, flowering takes place in winter or early spring, when adverse meteorological conditions can influence the pollination process and subsequent fruit set. The blooming period usually lasts one to two weeks in most cultivars and locations. Thus, external conditions can strongly vary over this period, and flowers in the same tree could have different conditions during their development depending on the time of anthesis. In order to evaluate whether the capacity of flowers to set fruits is affected by the time of anthesis, in this work flower development and fruit drop have been characterised in early and late flowers of the cv. Moniqui. Flowers from both populations were hand-pollinated with compatible pollen. A set of flowers were weekly counted in marked branches from anthesis to harvest. Another set of flowers were collected at anthesis, weighed and anatomically characterized. Fruit set in early flowers was considerably higher than in late flowers. These differences in the capacity of flowers to set fruits between early and late flowers were associated with differences in the size of different floral structures. Results are discussed in terms of the implications of floral differences at anthesis in the subsequent fruit set.

Objective To find factors associated with the development of renal colic during uricosuric therapy. Methods We performed a prospective cohort followup study of patients with gout and no previous history of kidney stones who had been treated with uricosurics. Clearance of creatinine and urate, 24-hour urinary uric acid (UA), undissociated urinary UA concentration, 24-hour undissociated urinary UA, and pH and urine sediment were obtained. Cox proportional hazards regression analysis was used to identify variables associated with renal colic as the outcome. The rate of renal colic was compared with that of control patients receiving allopurinol who had no previous history of renal stones. Results We analyzed a 784 patient-year exposure from 216 patients: 206 with renal underexcretion of UA and 10 with normal excretion. There were 21 clinical events. Two variables showed increased risk hazard for developing lithiasis: clearance of UA at baseline and undissociated urinary UA concentration during followup. When only patients with underexcretion of UA were included in the analysis, undissociated urinary UA during followup remained the only statistically significant variable. Patients who showed an undissociated UA concentration

[EN] The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min¿1). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 °C; (3) substantial errors (larger than 15 °C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 °C)., This work was supported by the 'Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica del Ministerio de Educacion y Ciencia' of Spain (TEC200801369/ TEC) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd and the Spanish National Research Council (CSIC). The English revision and correction of this paper was funded by the Universidad Politecnica de Valencia, Spain. We thank L Melecio for his invaluable technical support in conducting the experiments.

Seedlessness is an important trait in the evaluation of commercial mandarin for fresh consumption. However, in the last decade, the presence of seeds in fruit of cultivars considered as seedless has become a problem in different citrus-growing areas because the commercial value is depreciated. Seeds have appeared concomitantly with the introduction of new cultivars that appear to be cross-compatible. To overcome this problem, different strategies have been explored, but a definitive answer is still elusive. The search for alternatives contrasts with how little is known about the basis of the problem: the pollen-pistil incompatibility reaction in mandarin, and the intercompatibility relationship between different cultivars. In this work, we characterized the pollen-pistil incompatibility in the two commonly grown mandarin cultivars Fortune and Nova, and evaluated the intercompatibility relationship between six cultivars with different genetic origins; these cultivars included Fortune (Citrus clementina Hort. ex Tan. × Citrus reticulata Blanco), Nova [(Citrus paradisi Macf. × C. reticulata) × C. clementina), Comune Clementine (C. clementina), Avana apireno (C. reticulata), Primosole (Citrus unshiu Marcov. × C. reticulata), and Simeto (C. unshiu × Citrus deliciosa Ten.). Following the controlled hand pollination in the field, we evaluated pollen tube performance after self- and cross-pollination, as well as intercultivar compatibility by observing pollen tube growth. The results show the self-incompatibility of these cultivars with the pollen tube having been arrested in the style, which explains their seedless condition when planted in solid blocks. The study of intercompatibility indicates a different pollen tube behavior depending on the genotype, as well as on the cross combinations. These results provide a basis to evaluate self- and intercompatibility in citrus, and the effect of close planting of some cultivars., Financial support for this research was provided by the Italian Ministry of Agriculture and Forestry, Project RAVAGRU (Advanced research in citriculture), publication no. 32; by the Italian Ministry of the University, Project PRIN ‘‘The productive process in fruit tree species: molecular, physiological, and agronomical aspects of floral incompatibility and strategies for its control’’; by the Minister of Science and Innovation, EU Feder (Project grant CICYT AGL-2006-13529-CO2-01/AGR); and by the Grupo de Excelencia del Gobierno de Aragón A-43.

The involvement of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus (CuN), known as the mesencephalic locomotor area, in the pathophysiology of parkinsonian symptoms is receiving increasing attention. Taking into account the role of dopamine (DA) in motor control and its degeneration in Parkinson's disease, this neurotransmitter could induce dysfunction in the PPN and CuN through a direct dopaminergic innervation of these brainstem structures. This study provides the first demonstration that the PPN and CuN are innervated by dopamine transporter-bearing fibres in normal monkeys, which points to a novel dopaminergic system that targets the lower brainstem. Intoxication with MPTP induced a significant loss of dopamine transporter-positive fibres in the PPN and CuN of young (3-5 years old) acutely or chronically intoxicated monkeys compared with control animals. The more severe DA depletion found after chronic intoxication may explain, at least in part, deficits that appear late in the evolution of Parkinson's disease. A drastic loss of DA fibres was also observed in aged acutely intoxicated monkeys (about 30 years old) suggesting that age- and disease-related loss of dopaminergic fibres might be responsible for symptoms, such as gait disorders, that are more severe in elderly parkinsonian patients.

The recent knowledge that 10 years after transplantation surviving human fetal neurons adopt the histopathology of Parkinson's disease suggests that Lewy body formation takes a decade to achieve. To determine whether similar histopathology occurs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-primate models over a similar timeframe, the brains of two adult monkeys made parkinsonian in their youth with intermittent injections of MPTP were studied. Despite substantial nigral degeneration and increased alpha-synuclein immunoreactivity within surviving neurons, there was no evidence of Lewy body formation. This suggests that MPTP-induced oxidative stress and inflammation per se are not sufficient for Lewy body formation, or Lewy bodies are human specific.

33 Pag., 3 Tabl., 6 Fig. The definitive version is available at www.blackwell-synergy.com, Although pollination is essential for both seed and fruit set in most angiosperms, even after an adequate pollination, only a fraction of the flowers develop into fruits. The role played by floral traits on reproductive success is well known, but the possible influence of pistil traits has been overlooked, probably because of the difficulty of non-destructive pistil examination. The aim of this work was to examine the influence of several pistil traits on reproductive success in apricot (Prunus armeniaca). For this purpose, in a population of individually labelled flowers, the styles were cut off once the pollen tubes had reached the ovary but prior to the achievement of fertilisation. This approach allowed relating several morphological and physiological pistil parameters in the dissected styles and stigmas to the subsequent set or abscission of the corresponding ovary that remained in the plant. Under the same pollination conditions, the flowers that finally set a fruit show a larger stigmatic area and a higher number of pollen grains, pollen tubes growing along the style and xylem vessels surrounding the transmitting tissue than flowers that abscise before the establishment of fruit set. Furthermore, starch is present in the transmitting tissue of the style in all the flowers that develop into fruits but only in half of the flowers that abscise. The examined pistil traits established prior to fertilisation are related to flower fate, suggesting that the capacity of a flower to become a fruit could be preconditioned at anthesis., Financial support for this research was provided by Ministerio de Ciencia e Innovación-FEDER (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, project grants: AGL2006-13529-C02-00/AGR and AGL2007-60130/AGR) and by Grupo de Excelencia A-43 (Gobierno de Aragón).

Most angiosperms release bicellular pollen. However, in about one-third of extant angiosperms, the second pollen mitosis occurs before anthesis such that pollen is tricellular upon release. The shift from bicellular to tricellular development has occurred several times independently, but its causes are largely unknown. In this work, we observed the coexistence of both kinds of pollen at anther dehiscence in Annona cherimola, a species that belongs to the basal angiosperm family Annonaceae. Examination of pollen cell number during anther development showed that this coexistence was due to a late mitosis starting shortly before pollen shedding. Both types of pollen germinated equally well over the course of development. Because variable proportions of bicellular and tricellular pollen were observed at different sampling times, we tested the role of temperature by performing field and growth chamber experiments, which showed that higher temperatures near anthesis advanced the time of pollen mitosis II. The results show that selection could favor the production of tricellular pollen under certain environmental circumstances that prime rapid pollen germination and provide evidence of a system in which developmental variation persists, but that can be modified by external factors such as temperature., Financial support for this work was provided by the Spanish Ministry of Education (Project grants AGL2004-02290/AGR, AGL2006-13529 and AGL2007-60130/AGR), GIC-Aragón 43, Junta de Andalucía (AGR2742), and the European Union under the INCO-DEV program (Contract 015100). J.L. was supported by a grant from Junta de Andalucía.

Financial support was provided by FEDER-CICYT (AGL2003-05318-C02-00 and AGL-2006-13529-CO2-00/AGR) and by Grupo Consolidado de Aragon A-43 (DGA). C.J. was supported by a fellowship of INIA.

Cherimoya (Annona cherimola Mill) belongs to the Annonaceae, a basal Angiosperm family that includes a number of tropical and subtropical fruit tree species. Cherimoya shows protogynous dichogamy, a common characteristic in Annonaceae, where female and male structures do not mature simultaneously. Moreover, flowers of the same genotype usually open synchronously and, consequently, transfer of pollen between different flowers of the same genotype is difficult. This mechanism has been assumed to prevent self-fertilization and to encourage cross-pollination and has clear implications both from a plant breeding perspective and in an agronomic context. Inadequate pollination is one of the most important factors that limit commercial production of cherimoya resulting in low fruit set and in the production of misshapen fruits. This is due to the lack of overlap between the male and female stages and the expansion of the crop to areas outside its native range in absence of its natural pollinating insects. As a consequence, hand pollination is a common practice for commercial production. In spite of the implications of this isolating mechanism, its efficiency has not been previously evaluated. In this work, we evaluate stigmatic receptivity under the microscope and natural outcrossing rate using molecular markers to test the paternity of the seeds. The results obtained show that stigmas can still be receptive when the flowers pass to the male stage and that a surprisingly high proportion of the seeds produced are the result of self-fertilization. The results are discussed in terms of the implications of these results both in plant breeding and in an adequate crop handling.

Loquat (Eriobotrya japonica Lindl.) is a fruit tree species of the Pyrinae subtribe of the Rosaceae that behaves as self incompatible. Since self-incompatibility in the Rosaceae is of the gametophytic type where a stylar ribonuclease (S-RNase) controls the female function of pollen–pistil recognition, consensus primers derived from the alignment of S-RNase sequences from other Pyrinae species were used to search for S-RNases in loquat. As a result, the first four S-RNases were sequenced for this species. The genomic sequences obtained showed the structural features of Pyrinae S-RNases. Moreover, microscopic observations of pollen tube growth in the style confirmed the inter-(in)compatibility relationships predicted from the molecular analyses. Phylogenetic analysis of the deduced amino acid sequences with other Pyrinae S-RNases confirmed that divergence of S-alleles in loquat and the Pyrinae predated speciation. This study reports for the first time the genomic characterization of S-RNases in loquat, providing a sound basis for an appropriate selection of pollinator cultivars and an adequate design of breeding programs.

The clearance of virally infected cells from the brain is mediated by T cells that engage antigen-presenting cells to form supramolecular activation clusters at the immunological synapse. However, after clearance, the T cells persist at the infection site and remain activated locally. In the present work the long-term interactions of immune cells in brains of monkeys were imaged in situ 9 months after the viral inoculation. After viral immunity, the persistent infiltration of T cells and B cells was observed at the infection sites. T cells showed evidence of T-cell receptor signaling as a result of contacts with B cells. Three-dimensional analysis of B-cell-T-cell synapses showed clusters of CD3 in T cells and the segregation of CD20 in B cells, involving the recruitment of CD40 ligand at the interface. These results demonstrate that immunological synapses between B cells and T cells forming three-dimensional microclusters occur in vivo in the central nervous system and suggest that these interactions may be involved in the lymphocyte activation after viral immunity at the original infection site.

Most pear (Pyrus communis L.) cultivars are impaired to set fruit under self-pollination, because self-fertilization is prevented by a gametophytic self-incompatibility system. However, accumulated information in this species shows that often for a same cultivar, after self-pollination, a variable response in fruit set can be obtained in different years or growing conditions. In this work, we characterize self-incompatibility and self-fruitfulness in ‘Agua de Aranjuez’, the main Spanish pear cultivar, which also shows a variable response to self-pollination. Two years with a different fruit setting response after self-pollination, one with no fruit set and the other with a moderate fruit set, were compared for parthenocarpic fruit development and for pollen tube performance. Results show that in both years, this cultivar behaves as self-incompatible with absence of parthenocarpy. In selfed flowers, most pollen tubes are arrested in the upper half of the style, although in a small proportion of the styles, a pollen tube can reach the base of the style and eventually effect fertilization. Self-fertilization, although occurring at a low level, can explain the fruit set levels obtained under self-pollination given that flowers with just one fertilized ovule are able to set fruit. This behavior could explain confusing results about self-fruitfulness in ‘Agua de Aranjuez’ and other pear cultivars.

12 Pags.- 1 Tabl.- 4 Figs., Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S-alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S-allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post-pollination, prezygotic sexual selection, with male–male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S-haplotype frequencies., This work was supported by Ministerio de Economía y Competitividad–European Regional Development Fund, European Union (AGL2012-40239, AGL2013-43732-R, RTA2012-00103, and Recupera2020), and Gob. Aragón A-43. AH is also supported by ERC Advanced Grant Medea 250358. Ö.K. acknowledges financial support from ‪SystemsX.ch initiative, evaluated by the Swiss National Science Foundation.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and localized neuroinflammation occurring in the midbrain several years before the actual onset of symptoms. Neuroinflammation leads to microglia activation and release of a large number of proinflammatory mediators. The kynurenine pathway (KP) of tryptophan catabolism is one of the major regulators of the immune response and is also likely to be implicated in the inflammatory and neurotoxic events in Parkinsonism. Several neuroactive compounds are produced through the KP that can be either a neurotoxic, neuroprotective or immunomodulator. Among these metabolites kynurenic acid (KYNA), produced by astrocytes, is considered as neuroprotective whereas quinolinic acid (QUIN), released by activated microglia, can activate the N-methyl-d-aspartate (NMDA) receptor-signalling pathway, leading to excitotoxicity and amplify the inflammatory response. Previous studies have shown that NMDA antagonists can ease symptoms and exert a neuroprotective effect in PD both in vivo and in vitro. There are to date several lines of evidence linking some of the KP intermediates and the neuropathogenesis of PD. Moreover, it is likely that some of the KP metabolites could be used as prognostic biomarkers and that pharmacological modulators of the KP enzymes could represent a new therapeutic strategy for PD.

Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

The retina is sensitive to age-dependent degeneration. To find suitable animal models to understand and map this process has particular importance. The degu (Octodon degus) is a diurnal rodent with dichromatic color vision. Its retinal structure is similar to that in humans in many respects, therefore, it is well suited to study retinal aging. Histological, cell type-specific and ultrastructural alterations were examined in 6-, 12- and 36-months old degus. The characteristic layers of the retina were present at all ages, but slightly loosened tissue structure could be observed in 36-month-old animals both at light and electron microscopic levels. Elevated Glial fibrillary acidic protein (GFAP) expression was observed in Müller glial cells in aging retinas. The number of rod bipolar cells and the ganglion cells was reduced in the aging specimens, while that of cone bipolar cells remained unchanged. Other age-related differences were detected at ultrastructural level: alteration of the retinal pigment epithelium and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and often differed in morphology from those in the young animals. These results support our hypothesis that (i) the rod pathway seems to be more sensitive than the cone pathway to age-related cell loss; (ii) structural changes in the basement membrane of pigment epithelial cells can be one of the early signs of degenerative processes; (iii) the loss of synaptic proteins especially from those of the ribbon synapses are characteristic; and (iv) the degu retina may be a suitable model for studying retinal aging.

22 Pags.- 1 Tabl.- 4 Figs. The definitive version is available at: http://www.sciencedirect.com/science/journal/03044238, Longan (Dimocarpus longan) is an important evergreen fruit crop grown in tropical and subtropical climates, with a clear expanding potential, but with a poorly described phenology. In this work, the different phenological growth stages of longan are characterized according to the BBCH (Biologische Bundesanstalt, Bundessortenamt und Chemische industrie) scale. From vegetative bud dormancy to fruit harvest, seven main growth stages are described for bud, leaf and shoot development, inflorescence emergence, flowering, fruit development and fruit maturity. Within them 41 secondary growth stages are described. The BBCH code will be an important tool to assist the development and implementation of longan management protocols and to standardize observations made in different edaphoclimatic and experimental conditions., This work was supported by the Spanish Ministerio de Economía y Competitividad—European Regional Development Fund, European Union (no. AGL2013-43732-R, and AGL2012-40239), Gobierno de Aragon A-43, and Junta de Andalucía (no. FEDERP08-AGR-3694). VTP was supported by a PhD scholarship in the frame of an agreement between the Consejo Superior de Investigaciones Científicas (CSIC), Spain and the Vietnamese Academy of Science and Technology (VAST).

25 Pags. 1 Tabl. 5 Figs. The definitive version is available at: http://www.sciencedirect.com/science/journal/03044238, In recent years, a growing interest to widen the cherry (Prunus avium L.) production calendar results in cultivation out of the traditional cultivation areas. Since cherry has high chilling requirements, this often causes erratic cropping related to phenological alterations. However, appropriate phenological characterisation and comparison is hampered, due to the lack of a consensus phenological scale for this species. In this work, we have characterised flower development in sweet cherry, framing it in the BBCH scale. For this purpose, the phenology of two cherry cultivars has been characterized over 2 consecutive years and adapted to the BBCH code, and flower development has been framed within the principal growth stages of this code. This provides a unified standardised approach for phenological comparative studies., This work was supported by Ministerio de Economía y Competitividad (MINECO) – European Regional Development Fund, European Union (Project grants: AGL2009-12621-C02-00, AGL2012-40239-C02, INIA RF2011-00029-C03 and INIA RFP2012-00017-C03) and Gobierno de Aragón (Grupo Consolidado A-43). E. Fadón was supported by a FPI fellowship of MINECO [BES-2010-037992].

6 Pags.- 5 Figs., Longan (Dimocarpus longan) is a subtropical fruit tree with a long cultivation tradition in South East Asia, and also with a clear potential in other areas of the world. In other plant species, the reproductive phase is most vulnerable to temperature conditions, but information on the effect of temperature on pollen germination and tube growth in longan is still lacking. In order to fill this gap, in this work the effect of temperature on longan pollen germination was assessed both in vivo and in vitro. For this purpose first pollen germination was evaluated in vivo at three temperature regimes, showing the best performance at 23/24 °C. Then an in vitro pollen germination medium was optimized for longan and pollen storage conditions were evaluated, showing good pollen germination in vitro after storage for one year at −20 °C. Finally, the effect of temperature was evaluated in vitro in four cultivars and for two male flower types M1 and M2, differing on the degree of pistil differentiation. Both pollen types behave similarly in all conditions, and all the cultivars studied had good pollen germination in vitro at 30 °C, a temperature higher than that reported as optimum in vivo reflecting a higher sensitivity of the stigma than pollen to high temperatures. However, clear differences between cultivars in their performance at 20 °C and 40 °C were recorded. These results set the basis for reproductive biology studies and breeding in longan, opening a window to select the best cultivars for different temperature conditions., This work was supported by the Spanish Ministerio de Economía y Competitividad—European Regional Development Fund, European Union (AGL2013-43732-R, and AGL2012-40239 and Recupera2020) and Gobierno de Aragón A-43. VTP was supported by a Ph.D. scholarship from the Consejo Superior de Investigaciones Científicas (CSIC), Spaings and Vietnam Academy of Science and Technology (VAST).

In Prunus species, developing flower buds survive winter by entering a dormant stage. However, dormancy is not just a survival strategy, but also a prerequisite for proper flowering and fruiting. In spite of its importance and the fact that cold requirements are empirically known for a number of cultivars, what occurs during dormancy at the cellular and molecular level remains somewhat of a mystery. Here we review the information available on the genetic control and the possible physiological mechanisms involved in flower bud dormancy in Prunus species. Genes involved in flower regulation appear to play some role, but the interactions between these genes is still being determined, as well as the possible epigenetic control of this process. From a physiological perspective, dormancy in vegetative buds appears to be associated with isolation both at the cell and at the organ level, and this could also be the case in developing flower buds, but this remains to be studied. Finally, characterization of biological factors impacting these processes will clearly contribute to our understanding of dormancy.

We have examined whether degeneration of nigrostriatal dopaminergic neurons causes dysfunction of both the basal ganglia-thalamic and cerebello-thalamic pathways. Changes in the activity of thalamic neurons receiving input from the basal ganglia or the cerebellum were examined in two models of Parkinson's disease, 6-hydroxydopamine (6-OHDA)-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Metabolic activity of the neurons was evaluated at the cellular level by quantitative in situ hybridization, using the expression of messenger RNA for subunit I of cytochrome oxidase (COI), encoded by the mitochondrial genome, as the marker. COI mRNA expression decreased significantly in thalamocortical neurons receiving input from the substantia nigra (-50.6%) or the cerebellum (-45%) in 6-OHDA-lesioned rats compared with controls. The decrease was observed in all thalamic neurons whether or not they were retrogradely labelled with a tracer injected into the motor cortex. Similarly, COI mRNA expression decreased in projection neurons and interneurons of the thalamus receiving input from the substantia nigra (-39 and -38%, respectively), the internal pallidum (-20 and -42.4%, respectively) and the cerebellum (-36.2 and -50%, respectively) of MPTP-treated monkeys compared with controls. These decreases in COI mRNA levels show that nigrostriatal denervation results in a decrease in the metabolic activity of thalamic neurons in the territories innervated by the substantia nigra, pallidum and cerebellum, which in turn is indicative of a decrease in their neuronal activity. The decrease did not concern the entire thalamus, however, since metabolic activity was unchanged in two thalamic nuclei considered to be limbic structures, the laterodorsal nucleus in 6-OHDA-lesioned rats and the anterior nucleus in MPTP-treated monkeys. Hypoactivity of both the basal ganglia-thalamic and cerebellar-thalamic pathways might therefore be implicated in the development of parkinsonian symptoms.

Transcranial magnetic stimulation (TMS) is a non-invasive method that can be used as an interventional technique to investigate causality in the brain-behavior relationship, through depolarization or hyperpolarization in the neurons of the brain. Different techniques of TMS can be used to investigate causality in the brain-behavior relationship. The behavioral effects induced by TMS are complex since it has been shown that the performance in the same cognitive task can be either facilitated or inhibited depending on the area being stimulated. To date, most studies involving TMS are focused mainly on the facilitation properties of this technique. It is used to treat a wide-range of neurological and psychiatric conditions such as depression, ischemia, Alzheimer's disease, or motor impairment. Interestingly, TMS can be used to induce a virtual lesion that could provide a valuable and much needed model of cognitive impairments in early preclinical development. This review describes the existing TMS paradigms in rodents and the major challenges that were encountered by the researchers as the method was translated from clinical to preclinical applications. In summary, the existing knowledge gained in animal research emphasizes the necessity to investigate new TMS paradigms in the preclinical setting and its effects.

Memory loss is one of the key features of cognitive impairment in either aging, Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for memory loss are today focused on addressing symptomatology. One of these approved compounds is memantine, a partial NMDA receptor antagonist that has proved its beneficial effects in cognition. The Octodon degus (O. degus) has been recently proposed as a potential model relevant for neurodegenerative diseases. However, there are no previous studies investigating the effect of pharmacological treatments for age-related cognitive impairment in this rodent. In this work we aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced memory impairment in young and old O. degus. Young and old animals were trained in different behavioral paradigms validated for memory evaluation, and randomly assigned to a control (CTL, n = 14) or an SD (n = 14) condition, and treated with vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that SD impairs memory in both young and old animals, although the effect in the old group was significantly more severe (P < 0.05). Memantine pretreatment was able to prevent the cognitive impairment caused by SD in both age groups, while it had no negative effect on CTL animals. The positive effect of memantine in counteracting the negative effect of SD on the retrieval process even in the aged O. degus further supports the translational potential of both the challenge and the species, and will enable a better understanding of the behavioral features of memantine effects, especially related with reference and working memories.

Pollen competition and selection have significant evolutionary consequences, but very little is known about how they can be modulated. We have examined in cherry (Prunus avium L.) how pollen performance is affected by the genotype of the pollen and by the environmental conditions under which it grows, namely the pistilar tissue and temperature. The different pollen donor genotypes tested in this work differed in their behaviour both in vitro and in vivo and this behaviour was modulated depending on the female recipient they grew on. Furthermore, there was a significant temperature-genotype interaction that affected the pollen tube population census that succeeded in reaching the base of the style. The combination of these three factors, while enabling a capacity of response to variations in environmental pressures, could maintain variability in pollen performance avoiding the fixation of the genes that control pollen tube growth rate.

The definitive version is available at: http://www.thieme.de/fz/plantbiology/, Temperature is a major climatic factor that limits geographical distribution of plant species, and the reproductive phase has proven to be one of the most temperature-vulnerable stages. Here, we have used peach to evaluate the effect of temperature on some processes of the progamic phase, from pollination to the arrival of pollen tubes in the ovary. Within the range of temperatures studied, 20 °C in the laboratory and, on average, 5.7 °C in the field, the results show an accelerating effect of increasing temperature on pollen germination and pollen tube growth kinetics, as well as an increase in the number of pollen tubes that reach the style base. For the last two parameters, although the range of temperature registered in the field was much lower, the results obtained in the laboratory paralleled those obtained in the field. Increasing temperatures drastically reduced stigmatic receptivity. Reduction was sequential, with stigmas first losing the capacity to sustain pollen tube penetration to the transmitting tissue, then their capacity to offer support for pollen germination and, finally, their capacity to support pollen grain adhesion. Within a species-specific range of temperature, this apparent opposite effect of temperature on the male and female side could provide plants with the plasticity to withstand changing environmental effects, ensuring a good level of fertilization., A. H. was supported by an AECI, SIA-DGA, and a CSIC fellowship. Financial support for this work was provided by project grants INIA-RTA 01-103, CICYT AGL2003-05318-C02-01 and by the “Grupo de Investigación Consolidado de Aragón: A-02, A-43”.

Inflammatory changes have been found in Parkinson's disease, in humans intoxicated with the parkinsonian toxin MPTP, and in animal models of the disease. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or if they have a protective role against neurodegeneration. In this study, we analyzed the glial reaction in the substantia nigra pars compacta (SNpc) and the striatum of monkeys rendered parkinsosian by chronic MPTP injections. At postmortem examination 1 year after the last MPTP injection, the density of astroglial cells and activated microglial cells in the SNpc, but not in the striatum, of MPTP-intoxicated animals was significantly higher than in the two control animals. These data suggest that neurodegeneration was still active despite the absence of the agent triggering cell death and that the glial reaction is associated with long-term neurodegeneration.

Plant reproduction is highly vulnerable to environmental conditions such as temperature and, consequently, planet warming may have significant consequences on the reproductive phase with serious implication in agricultural crops. Although pollen tube growth is clearly affected by temperature, little information is available on its effect on the female side and on flower receptivity. In this work, the effect of temperature has been evaluated on stigmatic receptivity of sweet cherry in vivo, in the laboratory, and in planta, in the field. Results herein show that temperature has a clear effect on the duration of stigmatic receptivity. Thus, whereas high temperature reduced stigmatic receptivity, low temperature enlarged it. The stigma lost the capacity to offer support first for pollen penetration, second for pollen germination and, finally, for pollen adhesion. The effect of temperature was more pronounced on pollen germination and penetration than on pollen adhesion. High temperature reduced the germination capacity of the pollen as early as the first day after anthesis, a time when no apparent signs of stigma degeneration are apparent. This clear effect of temperature on stigmatic receptivity and pollen performance may have clear implication in crop performance and in establishing screening criteria of best-adapted genotypes.

Apples and pears are fruit crops particularly susceptible to cropping irregularities. A strong relationship has been observed between the effective pollination period (EPP) and the general cropping of the orchard. The EPP concept has also been proven to be a useful parameter to establish a relationship between the variation in the reproductive process and cropping behaviors. For apples and pears, a slow pollen tube growth has been shown to be the main limiting factor of the EPP in the traditional cooler temperate cultivation regions. However, while higher temperatures speed up the pollen tube growth, the expansion of these crops into warmer areas often results in failures of fruit set. Thus, with the aim to ascertain the main limiting factor responsible for fruit set failures in Mediterranean conditions we have evaluated the EPP for two consecutive years in 'Agua de Aranjuez' pear, the main Spanish cultivar, by studying the stigmatic receptivity, pollen tube kinetics, and ovule development. Complete flower fertility was maintained for just 2 days after anthesis in both years. Pollen tube kinetics and ovule degeneration do not appear to limit flower receptivity. However, the stigmatic receptivity expressed as flowers with at least one receptive stigma, closely matches the duration of the EPP evaluated from fruit set experiments. This was consistent over the 2 years of experiments, in spite of the differences recorded in the EPP, suggesting that stigmatic receptivity is clearly the limiting factor of flower receptivity. This is the first report for stigmatic receptivity limiting the EPP in pears and suggests that stigmatic receptivity could be an important factor limiting pear flower receptivity and hence cropping performance under warmer conditions.

Background. Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients. Methods. We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for > 12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions. Results. Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of > 75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups. Conclusions. Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses > 75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

In 1988 McGeer and colleagues (Neurology 38, 1285-91) observed an activation of the microglia in substantia nigra pars compacta (SNpc) and striatum of brains from patients with Parkinson's disease. In the years that followed several studies performed in the cerebrospinal fluid and during post-mortem analysis in parkinsonian patients revealed increased levels of cytokines, suggesting the activation of a proinflammatory response. Moreover, Langston and his group described the presence of active microglia in the SNpc of three patients who had been exposed to MPTP several years before death. These results suggested that the inflammatory response may increase negative feed-back into the damaged area of the cerebral parenchyma, inducing an imbalance that could perpetuate and/or accelerate neuronal death over a period of years. Similar results have been obtained in parkinsonian monkeys, rats and mice. For these reasons, several groups have treated parkinsonian animals with different anti-inflammatory drugs and obtained promising results. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or whether they play a protective role in neurodegeneration. These changes are putatively related to neuronal loss and suggest that anti-inflammatory treatment for parkinsonian patients could have beneficial effects in the progression of the disease by slowing down the process of neuronal loss.

We have tested the idea that oxidative metabolism of dopamine may be involved in MPTP toxicity using the RCSN-3 cell line derived from the substantia nigra of an adult rat. Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (10 microM), MPTP combined with 40 microM dicoumarol (an inhibitor of DT-diaphorase) and dicoumarol alone, did not induce toxicity in RCSN-3 cells after 72 h incubation. The lack of toxicity in MPTP-treated RCSN-3 cells may be explained by the fact that they are unable to metabolize MPTP to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion (MPP+ as determined by HPLC. Incubation for 72 h with 100 microM MPP+ induced a 6.6 +/- 1.4% cell death of RCSN-3 cells compared to 3.5 +/- 0.4 observed in control cells. However, when the cells were treated with 100 microM MPP+ and 40 microM dicoumarol, cell death increased 4-fold compared to that of cells treated solely with MPP+ (27 +/- 2%; P

Objective To compare renal handling of uric acid in patients with primary gout with that of a control group. Methods A case–control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. Results Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. Conclusions Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.

THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a single thalamic nucleus and send back information to different thalamic nuclei. The corticofugal projection provides positive feedback to the "correct" input, while at the same time suppressing irrelevant information. Topographical organisation of the thalamic afferents and efferents is contralateral, and the lateralisation of the thalamic functions affects both sensory and motoric aspects. Symptoms of lesions located in the thalamus are closely related to the function of the areas involved. An infarction or haemorrhage thalamic lesion can develop somatosensory disturbances and/or central pain in the opposite hemibody, analgesic or purely algesic thalamic syndrome characterised by contralateral anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often, persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in the complex extrapyramidal motor system, as opposed to the pyramidal motor system (corticobulbar and corticospinal pathways). Basal ganglia are involved in many neuronal pathways having emotional, motivational, associative and cognitive functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens) receive inputs from all cortical areas and, throughout the thalamus, project principally to frontal lobe areas (prefrontal, premotor and supplementary motor areas) which are concerned with motor planning. These circuits: (i) have an important regulatory influence on cortex, providing information for both automatic and voluntary motor responses to the pyramidal system; (ii) play a role in predicting future events, reinforcing wanted behaviour and suppressing unwanted behaviour, and (iii) are involved in shifting attentional sets and in both high-order processes of movement initiation and spatial working memory. Basal ganglia-thalamo-cortical circuits maintain somatotopic organisation of movement-related neurons throughout the circuit. These circuits reveal functional subdivisions of the oculomotor, prefrontal and cingulate circuits, which play an important role in attention, learning and potentiating behaviour-guiding rules. Involvement of the basal ganglia is related to involuntary and stereotyped movements or paucity of movements without involvement of voluntary motor functions, as in Parkinson's disease, Wilson's disease, progressive supranuclear palsy or Huntington's disease. The symptoms differ with the location of the lesion. The commonest disturbances in basal ganglia lesions are abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) and dystonia, which become manifest as behavioural and motor disturbances, respectively.

Self and cross-incompatibility determination by means of fruit and seed set experiments or pollen tube growth observations in the style has been frequently reported to be unclear in pear (Pyrus communis L.). Thus,in order to develop a reliable in vivo method to test pollen-pistil incompatibility in pear, pollen tube performance has been studied along the pistil following self and cross-pollinations. Results show that, while pollen tube growth in the style may be an unclear test, ovule observation at the microscope for the presence of pollen tube in the nucellus is a proper method to test incompatibility in this crop. With this analysis we could identify S-alleles of ‘Williams’ (S1S2) and ‘Coscia’(S3S4), and three of the four possible S-genotypes resulting from the ‘Williams’ × ‘Coscia’ cross, as represented by ‘Butirra Precoz Morettini’ (S1S3), ‘Santa Maria Morettini’ (S2S3)and ‘Tosca’ (S1S4). This result demonstrates that ‘Williams’ and ‘Coscia’ cultivars do not share any allele in common. We also established two new inter-incompatibility groups in pear. Furthermore, the presence of a common allele between ‘Williams’ and ‘Agua de Aranjuez’,and ‘Coscia’ and ‘Agua de Aranjuez’, three apparently unrelated old cultivars, may indicate a narrower genetic base than expected for European pear. This finding together with the fact that 40% of new released cultivars have direct or indirect parental relationship with the cultivars ‘Coscia’ and/or ‘Williams’, anticipates the possibility of new cases of cross-incompatibility for this crop in the future. Both the method described and the determination of the S-genotypes will facilitate the characterisation of self and cross-incompatibility relationships in this species.

Pags.- Figs.- Tabls. The definitive version is available at: http://www.amjbot.org/, • Premise of the study: Permanent tetrads are the most common form of pollen aggregation in flowering plants. The production of pollen in monads is plesiomorphic in angiosperms, but the aggregation into tetrads has arisen independently different times during the evolution of flowering plants. The causes behind the recurrent evolution of pollen aggregation from monads remain elusive. Permanent tetrad pollen is quite common in the Annonaceae, the largest family in the early-divergent order Magnoliales. In some genera, such as Annona, both tetrad- and monad-producing species can be found. • Methods: In this comparative study of pollen development, we use immunolocalization, cytological characterization, and enzymatic assays of four species in the genus Annona and one species in its closely related genus Asimina that release pollen in tetrads and two species in the genus Annona that release pollen in monads. • Key results: The main difference between species with tetrad and monad pollen is a delayed digestion of callose and cellulose at the pollen aperture sites that resulted in nonlayering of the exine in these areas, followed by a rotation and binding of the young microspores at the aperture sites. • Conclusions: Small changes in development resulted in clear morphological changes on pollen dispersal time and open a window on the possible selective advantage of the production of aggregated pollen., This work was supported by Ministerio de Economía y Competitividad–European Regional Development Fund, European Union (AGL2010-15140, AGL2012-40239, and AGL2013-43732-R), the BBVA Foundation (BIOCON 08-184/09), INIA (RF2012-00010 and RFP2012-00016), and Gob. Aragón A-43. J.L. was supported by a Juan de la Cierva postdoctoral grant of the Spanish Ministry of Science and Innovation.

Gout has been academically considered to be a step-up disease consisting of different stages: acute gout, intercritical gout, and chronic gout. This simple approach may lead to misinterpretation and misdiagnosis. In clinical practice, we should consider gout as a single disease with either or both acute (most commonly, episodes of acute inflammation) and persistent clinical manifestations, but not restricted to chronic synovitis. In this article, an innovative, practical, and rational approach to the clinical manifestations and diagnosis of gout is presented, which may be supportive for clinicians involved in everyday care and management of patients with gout.

27 pag., 3 fig., 2 suppl. fig., 1 tabl. Available online 14 December 2013. The definitive version is available at: http://www.sciencedirect.com/science/journal/00988472, In temperate woody plants, flowering time is adjusted to the environmental temperature, and survival to cold winter temperatures is achieved through dormancy. But also chilling temperatures during dormancy are required for proper flower bud development and flowering. The time the flower bud remains dormant is both genetically and environmentally controlled, and is a major factor determining the adaptation of species and cultivars to particular ecological conditions because chilling requirements vary greatly among genotypes. Recently this adaptation is jeopardised with climate changing conditions. However, little is known on the biological milestones underpinning these events, and when differences in flowering time are established. In this work we evaluate the hypothesis that anther meiosis time is related to winter cold temperatures, and that differences in flowering time are set up by differences in the time when pollen meiosis occurs. For this purpose, anther development has been characterised in five apricot cultivars with different chilling requirements. The work was done over two years with different weather conditions, a cold and a mild winter. The sporogenous tissues differentiated prior to dormancy and remained in this apparently quiescent stage during the winter. Once chilling requirements were fulfilled, meiosis closely followed and was highly correlated to breaking of endodormancy. Meiosis was completed within one week and was followed by a change in the colour of the anthers from green to yellowish, which could be a useful visual indicator to know that breaking of endodormancy had already occurred. The fact that this sequence of events was consistent in all the cultivars, and different climatic years analysed, supports the hypothesis that winter cold temperatures are related to the time of pollen meiosis, which in turn reflects in different flowering times., Financial support for this research was provided by Ministerio de Economía y Competitividad - European Regional Development Fund, European Union (AGL2009-12621-C02, AGL2012-40239) and 24 Gobierno de Aragón - European Social Fund, European Union (Grupo de Investigación de Aragón A-43). C. J. was supported by a fellowship of INIA (Instituto Nacional de Investigación y Tecnología Agroalimentaria)

[Background] The characteristics of pollen tube growth are not constant, but display distinct patterns of growth within the different tissues of the pistil. In the stigma, the growth rate is slow and autotrophic, whereas in the style, it is rapid and heterotrophic. Very little is known about the interactions between these distinct maternal tissues and the traversing pollen tube and the role of this interaction on the observed metabolism. In this work we characterise pollen tube growth in the apple flower and look for differences in glycoprotein epitope localization between two different maternal tissues, the stigma and the style., [Results] While immunocytochemically-detected arabinogalactan proteins were present at high levels in the stigma, they were not detected in the transmitting tissue of the style, where extensins were abundant. Whereas extensins remained at high levels in unpollinated pistils, they were no longer present in the style following pollen tube passage. Similarily, while abundant in unpollinated styles, insoluble polysaccharides such as β-glucans, were depleted in pollinated pistils., [Conclusions] The switch from autotropic to heterotrophic pollen tube growth correlates spatially with a change of glycoprotein epitopes between the stigma and the style. The depletion of extensins and polysaccharides following pollen tube passage in the style suggest a possible contribution to the acceleration of heterotrophic pollen tube growth, which would imply an active contribution of female tissues on prezygotic male–female crosstalk., This work was supported by Ministerio de Ciencia e Innovación (MICINN)-FEDER [AGL2006-13529-C02-01, AGL 12621-C02-01, AGL 2012–40239], and Gobierno de Aragón [group A43].

39 Pags., Figs. The definitive version is available at: http://www.amjbot.org/, • Premise of the study: Factors affecting floral receptivity in angiosperms remain opaque, but recent studies suggest that the acquisition of stigmatic receptivity associated with cell-wall-related arabinogalactan proteins (AGPs) may be a widespread feature of flowering plants. Here, the time during which a stigma is receptive is evaluated and related to the secretion of AGPs in Magnolia virginiana, a protogynous member of an early-divergent angiosperm clade (magnoliids) with a clearly discernible female receptive phase. • Methods: Magnolia virginiana flower phenology was documented, and histochemical changes in the stigma before and after pollination were examined. Stigmatic receptivity was evaluated in relation to the secretion of AGPs detected in whole mounts and immunolocalized in sectioned stigmas. • Key results: Protogynous Magnolia flowers had a precise window of stigmatic receptivity, which is concomitant with the secretion of two AGPs labeled for different epitopes. After pollen germination and tube growth, these two AGPs could no longer be detected in the stigmas, suggesting that these AGPs interact with the growing male gametophytes and could be markers of stigmatic receptivity. • Conclusions: These results show that the period of stigmatic receptivity is finely coordinated with the secretion of two arabinogalactan proteins on stigmas of flowers of M. virginiana. This first report of AGP presence in stigmatic tissues in a member of the magnoliids, together with recently described similar patterns in eudicots, monocots, and members of early-divergent lineages of flowering plants, suggests an ancient and widespread role for AGPs on stigmatic receptivity in angiosperms., J.M.L. has been supported by an FPI fellowship from the Spanish Ministry of Science and Innovation, a Deland Award for student research and a Putnam Scholar Award, both from the Arnold Arboretum of Harvard University. Research was supported in part by NSF grants to W.E.F. (IOS-0919986) and by grants from the Spanish Ministerio de Economía y Competitividad to M.H. (AGL2012-40239) and J.I.H. (AGL2013-43732-R).

El desarrollo de metodologías didácticas apoyadas en las Tecnologías de la Información y la Comunicación (TIC), y que además den respuesta a la implantación del Espacio Europeo de Educación Superior supone un reto tanto para los docentes responsables de sus diseños, como para el discente principal protagonista del aprendizaje. Esta investigación, realizada con una metodología cualitativa, basada en el estudio de casos, a través de las opiniones recabadas del alumnado de Educación Primaria del Centro de Magisterio Sagrado Corazón, revela que el uso de recursos tecnológicos por parte del profesorado, incide de manera positiva en la formación por competencias. The development of teaching methodologies, which are supported by the Information and Communication Technologies, and which also fit into the European Higher Education Area, is a challenge not only for the teachers, who are accountable for their designs, but also for the learners, who are the main learning characters. This research work has been conducted with a qualitative methodology and is based on a case study. The opinions of students of the Degree in Elementary Education in the Teacher Training Centre Sagrado Corazón has been gathered and reveal that the use of technological resources by teachers has a positive impact in the students' training of skills.

Gout can be defined as the presence of monosodium urate crystals (MSUCs) in tissues. These MSUCs may induce acute inflammation when shed into the synovial fluid or cause aggregate-inducing chronic tissue inflammation. The nucleation and formation of MSUCs is related to the presence of longstanding hyperuricemia, which is an essential factor in the development of gout. Other factors, such as level of hyperuricemia, time exposed to hyperuricemia, and genetic or acquired tissue predisposition for the nucleation of MSUCs, may explain why not all patients with hyperuricemia develop gout, or why some patients develop early or rapidly progressive symptoms associated with gout.

The treatment of gout with chronic clinical manifestations comprises three aspects, in the following order of clinical importance: (1) reducing serum urate to the therapeutic range to dissolve monosodium urate crystals (MSUCs) formed in tissues, using urate-lowering therapy (ULT); (2) preventing or reducing the risk of episodes of acute inflammation (EAIs) that appear and even increase in frequency during the initiation of ULT (prophylaxis); (3) promptly, safely, and effectively treating any EAIs that may appear until proper and stable serum urate levels are achieved.