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Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1BCSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive webbased survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1BID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., We are grateful for the assistance of Pepijn Cox in setting up the website www.arid1bgene.com. This study has made use of data generated by the Human Disease Genes website series, www.humandiseasegenes.com. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (917-86-319 to B.B.A.d.V., 912-12-109 to B.B.A.d.V.)

Introduction Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immuneviral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. Methods We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. Results We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Discussion Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population., This work was financed through ABAMI (Balearic Association of Infectious Diseases).The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naive-HIV-infected patients. Methods We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). Results All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). Conclusions DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naive HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection., This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Accion Estrategica en Salud, Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdireccion General de Evaluacion) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 Cancer Nanomedicine from the Bench to the Bedside supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by Instituto de Salud Carlos III [grant number CP14/0010 and CP17CIII/00007, respectivelly].

Introduction: CHARGE syndrome is a multisystem disorder that, in addition to Kallmann syndrome/isolated hypogonadotrophic hypogonadism, has been associated with anterior pituitary hypoplasia (APH). However, structural abnormalities such as an ectopic posterior pituitary (EPP) have not yet been described in such patients. Objective: The aims of the study were: 1) to describe the association between CHARGE syndrome and a structurally abnormal pituitary gland; and 2) to investigate whether CHD7 variants, which are identified in 65% of CHARGE patients, are common in septo-optic dysplasia/hypopituitarism. Methods: We describe 2 patients with features of CHARGE and EPP. CHD7 was sequenced in these and other patients with septo-optic dysplasia/hypopituitarism. Results: EPP, APH, and GH, TSH, and probable LH/FSH deficiency were present in 1 patient, and EPP and APH with GH, TSH, LH/FSH, and ACTH deficiency were present in another patient, both of whom had features of CHARGE syndrome. Both had variations in CHD7 that were novel and undetected in control cohorts or in the international database of CHARGE patients, but were also present in their unaffected mothers. No CHD7 variants were detected in the patients with septo-optic dysplasia/hypopituitarism without additional CHARGE features. Conclusion: We report a novel association between CHARGE syndrome and structural abnormalities of the pituitary gland in 2 patients with variations in CHD7 that are of unknown significance. However, CHD7 mutations are an uncommon cause of septo-optic dysplasia or hypopituitarism. Our data suggest the need for evaluation of pituitary function/anatomy in patients with CHARGE syndrome. (J Clin Endocrinol Metab 98: E737-E743, 2013), This work was supported by a project grant from Birth Defects Foundation-Newlife (08-09/29 to M.J.M. and M. T. D.); in part by a grant from the British Society for Pediatric Endocrinology and Diabetes (to M. T. D.); and the Wellcome Trust (Grants 084361 and 086545; to M. T. D. and L. C. G.). M. T. D. is also funded by Great Ormond Street Hospital Children's Charity.

L’objectiu d’aquesta tesi doctoral és explorar la utilització de proteïnes d’unió al ADN en la generació i amplificació de senyal en biosensors. L’alta especificitat i afinitat d’aquestes proteïnes per les seves respectives seqüencies específiques de ADN de doble cadena (ADNdc) ha sigut utilitzada per desenvolupar un sistema d’immobilització que permet la co-immobilització de forma controlada de múltiples proteïnes. El sistema proposat està basat en la utilització d’aquestes proteïnes d’unió al ADN com a etiquetes de fusió de les proteïnes a immobilitzar i amb l’ús conjunt d’una molècula de ADNdc que fa la funció de plantilla per a la co-immobilització degut al posicionament de les seqüències de ADN que reconeixen específicament aquestes proteïnes d’unió al ADN. Aquest treball descriu la preparació i caracterització de dos conjugats universals d’enzim-proteïna d’unió al ADN i demostra el seu ús en la generació i amplificació de senyal en biosensors per a la detecció d’àcids nucleics i proteïnes. A més, també es mostra la idoneïtat d’aquestes proteïnes d’unió al ADN per immobilitzar directament molècules de ADN. El objetivo de esta tesis doctoral es explorar la utilización de proteínas de unión al ADN en la generación y amplificación de señal en bionsensores. La alta especificidad y afinidad de estas proteínas por sus respectivas secuencias específicas de ADN de doble cadena (ADNdc) ha sido utilizada par a desarrollar un sistema de inmovilización que permite la co-inmovilización de forma controlada de múltiples proteínas. El sistema propuesto está basado en la utilización de estas proteínas de unión al ADN como etiquetas de fusión de las proteínas a inmovilizar y con el uso conjunto de una molécula de ADNdc que hace la función de plantilla para la co-inmovilización debido al posicionamiento de las secuencias de ADN que reconocen específicamente estas proteínas de unión al ADN. Este trabajo describe la preparación y caracterización de dos conjugados universales de enzima-proteína de unión al ADN y demuestra su uso en la generación y amplificación de señal en biosensores para la detección de ácidos nucleicos y proteínas. Además, también se muestra la idoneidad de estas proteínas de unión al ADN para inmovilizar directamente moléculas de ADN. The objective of this doctoral thesis is to explore the use of DNA binding proteins in biosensors for signal generation and amplification. The specificity and high affinity that these proteins exhibit for their respective double stranded DNA (dsDNA) sequence was thus exploited in order to develop a protein immobilization technique that allows the controlled co-immobilization of several proteins. The proposed system is based on the utilization of these DNA binding proteins as fusion tags for the target proteins to be immobilized and the use of dsDNA as the template to direct the protein co-immobilization by specific positioning of the target DNA sequences recognized by the DNA binding proteins. The preparation and characterization of two novel universal enzyme-DNA binding protein conjugates is described and their use for signal generation and amplification in biosensors for the detection of nucleic acid and protein targets is demonstrated. In addition, the suitability of these DNA binding proteins to directly immobilize DNA molecules is also shown.

Los telómeros son estructuras complejas de ADN y proteína localizadas en el extremo de los cromosomas eucariotes. Su principal función es proteger el extremo cromosomal de ser reconocido y procesado como ADNs fracturado, evitando así eventos de recombinación y fusión que conducen a inestabilidad cromosomal. El ADN telomérico consta de secuencias cortas, repetidas una tras otra, ricas en guanina; la cadena rica en guanina se extiende formando una región de cadena sencilla denominada extremo 3´ protuberante. Las proteínas por su parte, se pueden clasificar en: dsBPs, o proteínas de unión a la cadena doble, GBPs aquellas que reconocen específicamente el extremo protuberante y, proteínas que las interconectan mediante interacciones proteína-proteína. El gen PF3D7_1006800 de Plasmodium falciparum codifica para una proteína putativa similar a una GBP de Criptosporidium parvum, con el fin de establecer si esta proteína de P. falciparum presenta la capacidad de unión al ADN telomérico del parásito, se produjo una proteína recombinante a partir de la región codificante del gen, se purificó y se utilizó en ensayos de unión a ADN, y en la generación de anticuerpos policlonales específicos contra PfGBP. Nuestros resultados indican que la proteína de P. falciparum es una proteína nuclear con capacidad de unión al ADN telomérico in vitro, por lo que podría ser parte del complejo proteico encargado de proteger y/o mantener el telómero in vivo. Telomeres are specialized structures at the end of chromosomes that consist of repetitive DNA sequences and associated proteins. The primary role of telomeres is to protect the end of linear chromosomes from recombination, fusion, and recognition as broken DNA ends. This protective function can be achieved through association with specific telomere binding proteins. Telomeric DNA consists of G-rich double-stranded arrays followed by a single-stranded G-rich overhang. The telomeric proteins can be classified in dsBPs, which bind double-stranded DNA, GBPs those that bind specifically to G-rich overhang, and proteins that interact with telomeric factors. Plasmodium falciparum gene PF3D7_1006800 codifies for a protein highly similar to Cryptosporidium parvum GBP. In order to investigate whether the P. falciparum protein binds telomeric DNA, a recombinant protein was produced, purified and DNA binding assays were performed. Polyclonal antibodies against rPfGBP were produced and tested in western blot. Our results indicate that PfGBP is a nuclear protein that binds telomeric DNA in vitro, which could be part of the protein complex responsible for protecting and/or maintaining the telomere in vivo.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al., [Background]: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. [Methods]: CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn's post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. [Results]: EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. [Conclusions]: Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing., ISCIII PI11/00873; Fundación Asociación Española Contra el Cancer (AECC), Grupos Estables 2011; InveNNta (Innovation in Nanomedicine), co-financed by the European Union (EU) through the Operational Programme for Cross-border Cooperation, Spain-Portugal (POCTEP 2007-2013), European Regional Development Fund (ERDF); Helse Vest, Research Council of Norway, Norwegian Cancer Society and Harald Andersens legat (H.B.S.); L. Alonso-Alconada is recipient of fellowship from the Basque Government (Spain).

Journal Article; Research Support, Non-U.S. Gov't; Review; The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation. Yes

DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIV-infection by an overexpression of DING proteins., This study was supported by grants from the Instituto de Salud Carlos III (PI 05/1607, 08/1032 and 08/1175), Madrid, Spain. M. E. is a fellow supported by the IEF Marie Curie program (grant No. 252836). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10-13; odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10-15; OR = 1.50). Instituto de Salud Carlos III/Programa Grupos Emergentes

In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is the first report to show that the cooperative binding of transcription factors to DNA promotes the "all-or-none" phenomenon observed in eukaryotic systems. In addition, we confirm that gene expression fluctuation levels associated with one of two cooperative binding mechanism never exceed the fluctuation levels of the other., Facultad de Ciencias Exactas

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24. METHODS: CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24. RESULTS: None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk. CONCLUSIONS: TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts. British Journal of Cancer (2011) 105, 870-875. doi: 10.1038/bjc.2011.296 www.bjcancer.com Published online 2 August 2011, We are sincerely grateful to all patients participating in this study who were recruited in 25 (EPICOLON 1) and 14 (EPICOLON 2) Spanish hospitals as part of the EPICOLON project. We are also grateful to the Spanish National Genotyping Center (CEGEN-ISCIII)-USC and UPF nodes, and the Genome Analysis Platform of the CIC-BioGUNE. The work was carried out (in part) at the Esther Koplowitz Centre, Barcelona. SC-B, CF-R and MDG are supported by contracts from the Fondo de Investigacion Sanitaria (CP 03-0070 to SC-B, CM10/00084 to MDG, and PS09/02368 to CF-R). JM is supported by a contract from the CIBERehd. Both CIBERehd and CIBERER are funded by the Instituto de Salud Carlos III. This work was supported by grants from the Fondo de Investigacion Sanitaria/FEDER (06/1384, 08/0024, 08/1276, PS09/02368, 10/00918), Instituto de Salud Carlos III (Accion Transversal de Cancer), Xunta de Galicia (07PXIB9101209PR), Ministerio de Ciencia e Innovacion (SAF2010-19273), Asociacion Espanola contra el Cancer (Fundacion Cientifica y Junta de Barcelona), Fundacio Olga Torres (SCB and CRP) and FP7 CHIBCHA Consortium (LC-C, ACar and SC-B).

This article is available from: http://www.biomedcentral.com/1471-2199/8/29, ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after γ-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATMkinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ H2AX foci accumulation, in an ATMdependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase., This work has been supported by grants SAF 2003-01217, RNIHG c03/02, PI050972, SAF2006- 01089 and FIS G03/152 to FJO, grants CICYT SAF:2001–3533 and SAF2004-00889 to JMRdA; grant FIS c03/02 to RQP.