Showing papers by "University of Valencia published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The clustering of galaxies in the sdss-iii baryon oscillation spectroscopic survey: Baryon acoustic oscillations in the data release 9 spectroscopic galaxy sample

Abstract: We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately $8\,500$ square degrees and the redshift range $0.2

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial

Abstract: Summary Background Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting. Methods In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m 2 , escalating, if tolerated, to 100 mg/m 2 every 3 weeks; group A) or pertuzumab (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint, examined in the intention-to-treat population, was pathological complete response in the breast. Neither patients nor investigators were masked to treatment. This study is registered with ClinicalTrials.gov, number NCT00545688. Findings Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate (49 of 107 patients; 45·8% [95% CI 36·1–55·7]) compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29·0% [20·6–38·5]; p=0·0141). 23 of 96 (24·0% [15·8–33·7]) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16·8% [10·3–25·3]) given pertuzumab and trastuzumab (group C). The most common adverse events of grade 3 or higher were neutropenia (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52 of 94 in group D), febrile neutropenia (eight, nine, none, and seven, respectively), and leucopenia (13, five, none, and seven, respectively). The number of serious adverse events was similar in groups A, B, and D (15–20 serious adverse events per group in 10–17% of patients) but lower in group C (four serious adverse events in 4% of patients). Interpretation Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer. Funding F Hoffmann-La Roche.

The ninth data release of the sloan digital sky survey: First spectroscopic data from the sdss-iii baryon oscillation spectroscopic survey

Abstract: The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z ~ 0.52), 102,100 new quasar spectra (median z ~ 2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T eff -0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SEGUE-2. The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the APOGEE along with another year of data from BOSS, followed by the final SDSS-III data release in 2014 December.

Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation

Abstract: Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.

Optical chemosensors and reagents to detect explosives

Abstract: This critical review is focused on examples reported from 1947 to 2010 related to the design of chromo-fluorogenic chemosensors and reagents for explosives (141 references).

Luminescent ionic transition-metal complexes for light-emitting electrochemical cells.

Abstract: Higher efficiency in the end-use of energy requires substantial progress in lighting concepts. All the technologies under development are based on solid-state electroluminescent materials and belong to the general area of solid-state lighting (SSL). The two main technologies being developed in SSL are light-emitting diodes (LEDs) and organic light-emitting diodes (OLEDs), but in recent years, light-emitting electrochemical cells (LECs) have emerged as an alternative option. The luminescent materials in LECs are either luminescent polymers together with ionic salts or ionic species, such as ionic transition-metal complexes (iTMCs). Cyclometalated complexes of IrIII are by far the most utilized class of iTMCs in LECs. Herein, we show how these complexes can be prepared and discuss their unique electronic, photophysical, and photochemical properties. Finally, the progress in the performance of iTMCs based LECs, in terms of turn-on time, stability, efficiency, and color is presented.

A 14-Item Mediterranean Diet Assessment Tool and Obesity Indexes among High-Risk Subjects: The PREDIMED Trial

Abstract: Objective: Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes.

Warmer climates boost cyanobacterial dominance in shallow lakes

Abstract: Dominance by cyanobacteria hampers human use of lakes and reservoirs worldwide. Previous studies indicate that excessive nutrient loading and warmer conditions promote dominance by cyanobacteria, but evidence from global scale field data has so far been scarce. Our analysis, based on a study of 143 lakes along a latitudinal transect ranging from subarctic Europe to southern South America, shows that although warmer climates do not result in higher overall phytoplankton biomass, the percentage of the total phytoplankton biovolume attributable to cyanobacteria increases steeply with temperature. Our results also reveal that the percent cyanobacteria is greater in lakes with high rates of light absorption. This points to a positive feedback because restriction of light availability is often a consequence of high phytoplankton biovolume, which in turn may be driven by nutrient loading. Our results indicate a synergistic effect of nutrients and climate. The implications are that in a future warmer climate, nutrient concentrations may have to be reduced substantially from present values in many lakes if cyanobacterial dominance is to be controlled.

Evidence for an excess of B̄→D( *)τ -ν ̄τ decays

Abstract: Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.

Magnetic polyoxometalates: from molecular magnetism to molecular spintronics and quantum computing

Abstract: In this review we discuss the relevance of polyoxometalate (POM) chemistry to provide model objects in molecular magnetism. We present several potential applications in nanomagnetism, in particular, in molecular spintronics and quantum computing.

The cost of headache disorders in Europe: the Eurolight project.

Abstract: Background and purpose: Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe. Methods: From November 2008 to August 2009, a cross-sectional survey was conducted in eight countries representing 55% of the adult EU population. Participation rates varied between 11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using bottom-up methodology, we estimated direct (medications, outpatient health care, hospitalization and investigations) and indirect (work absenteeism and reduced productivity at work) annual per-person costs. Prevalence data, simultaneously collected and, for migraine, also derived from a systematic review, were used to impute national costs. Results: Mean per-person annual costs were €1222 for migraine (95% CI 1055–1389; indirect costs 93%), €303 for tension-type headache (TTH, 95% CI 230–376; indirect costs 92%), €3561 for medication-overuse headache (MOH, 95% CI 2487–4635; indirect costs 92%), and €253 for other headaches (95% CI 99–407; indirect costs 82%). In the EU, the total annual cost of headache amongst adults aged 18–65 years was calculated, according to our prevalence estimates, at €173 billion, apportioned to migraine (€111 billion; 64%), TTH (€21 billion; 12%), MOH (€37 billion; 21%) and other headaches (€3 billion; 2%). Using the 15% systematic review prevalence of migraine, calculated costs were somewhat lower (migraine €50 billion, all headache €112 billion annually). Conclusions: Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

Electron performance measurements with the ATLAS detector using the 2010 LHC proton-proton collision data

Abstract: Detailed measurements of the electron performance of the ATLAS detector at the LHC are reported, using decays of the Z, W and J/psi particles. Data collected in 2010 at root s = 7 TeV are used, corresponding to an integrated luminosity of almost 40 pb(-1). The inter-alignment of the inner detector and the electromagnetic calorimeter, the determination of the electron energy scale and resolution, and the performance in terms of response uniformity and linearity are discussed. The electron identification, reconstruction and trigger efficiencies, as well as the charge misidentification probability, are also presented.

Electrical conductive coordination polymers

Abstract: Coordination polymers are currently one of the hottest topics in Inorganic and Supramolecular Chemistry. This critical review summarizes the current state-of-the-art on electrical conductive coordination polymers (CPs), also named metal–organic frameworks (MOFs). The data were collected following two sort criteria of the CPs structure: dimensionality and bridging ligands (151 references).

Recent Advances and Applications of Hyperspectral Imaging for Fruit and Vegetable Quality Assessment

Abstract: Hyperspectral imaging systems are starting to be used as a scientific tool for food quality assessment. A typical hyperspectral image is composed of a set of a relatively wide range of monochromatic images corresponding to continuous wavelengths that normally contain redundant information or may exhibit a high degree of correlation. In addition, computation of the classifiers used to deal with the data obtained from the images can become excessively complex and time-consuming for such high-dimensional datasets, and this makes it difficult to incorporate such systems into an industry that demands standard protocols or high-speed processes. Therefore, recent works have focused on the development of new systems based on this technology that are capable of analysing quality features that cannot be inspected using visible imaging. Many of those studies have also centred on finding new statistical techniques to reduce the hyperspectral images to multispectral ones, which are easier to implement in automatic, non-destructive systems. This article reviews recent works that use hyperspectral imaging for the inspection of fruit and vegetables. It explains the different technologies available to acquire the images and their use for the non-destructive inspection of the internal and external features of these products. Particular attention is paid to the works aimed at reducing the dimensionality of the images, with details of the statistical techniques most commonly used for this task.

Performance of the ATLAS Trigger System in 2010

Abstract: Proton-proton collisions at root s = 7 TeV and heavy ion collisions at root(NN)-N-s = 2.76 TeV were produced by the LHC and recorded using the ATLAS experiment's trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presented.

AGATA - Advanced GAmma Tracking Array

Abstract: The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation gamma-ray spectrometer. AGATA is based on the technique of gamma-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a gamma ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of gamma-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector-response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer.

Progress and Challenges in the Calculation of Electronic Excited States

Abstract: A detailed understanding of the properties of electronic excited states and the reaction mechanisms that molecules undergo after light irradiation is a fundamental ingredient for following light-driven natural processes and for designing novel photonic materials. The aim of this review is to present an overview of the ab initio quantum chemical and time-dependent density functional theory methods that can be used to model spectroscopy and photochemistry in molecular systems. The applicability and limitations of the different methods as well as the main frontiers are discussed. To illustrate the progress achieved by excited-state chemistry in the recent years as well as the main challenges facing computational chemistry, three main applications that reflect the authors' experience are addressed: the UV/Vis spectroscopy of organic molecules, the assignment of absorption and emission bands of organometallic complexes, and finally, the obtainment of non-adiabatic photoinduced pathways mediated by conical intersections. In the latter case, special emphasis is put on the photochemistry of DNA. These applications show that the description of electronically excited states is a rewarding but challenging area of research.

Field-Induced Slow Magnetic Relaxation in a Six-Coordinate Mononuclear Cobalt(II) Complex with a Positive Anisotropy

Abstract: The novel mononuclear Co(II) complex cis-[CoII(dmphen)2(NCS)2]·0.25EtOH (1) (dmphen = 2,9-dimethyl-1,10-phenanthroline) features a highly rhombically distorted octahedral environment that is responsible for the strong positive axial and rhombic magnetic anisotropy of the high-spin CoII ion (D = +98 cm–1 and E = +8.4 cm–1). Slow magnetic relaxation effects were observed for 1 in the presence of a dc magnetic field, constituting the first example of field-induced single-molecule magnet behavior in a mononuclear six-coordinate Co(II) complex with a transverse anisotropy energy barrier.

Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)

Abstract: Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. Patients and Methods Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm. Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Exercise acts as a drug; the pharmacological benefits of exercise

Abstract: The beneficial effects of regular exercise for the promotion of health and cure of diseases have been clearly shown. In this review, we would like to postulate the idea that exercise can be considered as a drug. Exercise causes a myriad of beneficial effects for health, including the promotion of health and lifespan, and these are reviewed in the first section of this paper. Then we deal with the dosing of exercise. As with many drugs, dosing is extremely important to get the beneficial effects of exercise. To this end, the organism adapts to exercise. We review the molecular signalling pathways involved in these adaptations because understanding them is of great importance to be able to prescribe exercise in an appropriate manner. Special attention must be paid to the psychological effects of exercise. These are so powerful that we would like to propose that exercise may be considered as a psychoactive drug. In moderate doses, it causes very pronounced relaxing effects on the majority of the population, but some persons may even become addicted to exercise. Finally, there may be some contraindications to exercise that arise when people are severely ill, and these are described in the final section of the review. Our general conclusion is that exercise is so effective that it should be considered as a drug, but that more attention should be paid to the dosing and to individual variations between patients.

Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis.

Abstract: Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.

Database of diazotrophs in global ocean: abundance, biomass and nitrogen fixation rates

Abstract: . Marine N2 fixing microorganisms, termed diazotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen (N2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR assays targeting the nifH genes) and N2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N2 fixation rate in the global ocean is estimated to be 62 (52–73) Tg N yr−1 and the pelagic diazotrophic biomass in the global ocean is estimated to be 2.1 (1.4–3.1) Tg C from cell counts and to 89 (43–150) Tg C from nifH-based abundances. Reporting the arithmetic mean and one standard error instead, these three global estimates are 140 p 9.2 Tg N yr−1, 18 p 1.8 Tg C and 590 p 70 Tg C, respectively. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about p70%. It was recently established that the most commonly applied method used to measure N2 fixation has underestimated the true rates. As a result, one can expect that future rate measurements will shift the mean N2 fixation rate upward and may result in significantly higher estimates for the global N2 fixation. The evolving database can nevertheless be used to study spatial and temporal distributions and variations of marine N2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models, keeping in mind that future rate measurements may rise in the future. The database is stored in PANGAEA ( doi:10.1594/PANGAEA.774851 ).