Materialism as A Cultural Medium Three Projects by Finnish Architects in China

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Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer

Runx1 is a developmentally regulated transcription factor that is essential for haemopoiesis. Runx1 can bind as a monomer to the core consensus sequence TGTGG, but binds more efficiently as a hetero-dimer together with the non-DNA binding protein CBFβ as a complex termed core binding factor (CBF). Here, we demonstrated that CBF can also assemble as a dimeric complex on two overlapping Runx1 sites within the palindromic sequence TGTGGCTGCCCACA in the human granulocyte macrophage colony-stimulating factor enhancer. Furthermore, we demonstrated that binding of Runx1 to the enhancer is rigidly controlled at the level of chromatin accessibility, and is dependent upon prior induction of NFAT and AP-1, which disrupt a positioned nucleosome in this region. We employed in vivo footprinting to demonstrate that, upon activation of the enhancer, both sites are efficiently occupied. In vitro binding assays confirmed that two CBF complexes can bind this site simultaneously, and transfection assays demonstrated that both sites contribute significantly to enhancer function. Computer modelling based on the Runx1/CBFβ/DNA crystal structure further revealed that two molecules of CBF could potentially bind to this class of palindromic sequence as a dimeric complex in a conformation whereby both Runx1 and CBFβ within the two CBF complexes are closely aligned

Micellar Iron Oxide Nanoparticles Coated with Anti-Tumor Glycosides

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.This research was funded by FP7 Marie Curie Pulmonary imaging network (PINET) and Ministerio de Economia y Competitividad MAT2015-65184-C2-2-R; SAF2016-79593-P; SAF2017-84494-C2-1-R). This work was partially funded by Instituto de Salud Carlos III (DTS16/00059), CNIC (Centro Nacional de Investigaciones Cardiovasculares), and Comunidad de Madrid (B2017-BMD3731 and B2017-BMD3875). We thank Ligue contre le cancer, comite Charentes Maritimes which allows to free up some time to complete the redaction of this manuscript during a grant-not dedicated on this work-agreed to LIENSs, UMR CNRS 7266, La Rochelle.S

Predictors Of Positivity Of [F-18]F-Choline PET-CT In Prostate Cancer Recurrence. Preliminary Results

EP-173 Aim/Introduction: To analyze the validity of [18F]F-Choline PET-CT results in prostate cancer recurrence in our daily practice, based on theoretical cut-off points of prostatespecific antigen (PSA), its kinetic, and PSA doubling time (PSADT), to identify predictors of positivity and modify the indication criteria. Materials and Methods: Prior to the validity analysis, a descriptive, prospective analysis of consecutive patients with prostate cancer treated with curative intent by radical prostatectomy (RP) or radiotherapy (RT), who underwent PET-CT scan with recurrence criteria: PSA =1 or PSA 0.4-1 with PSADT Nadir + 2 after RT, was performed. Results: From April to December 2019, 69 patients were included, 40 were treated with RP (58%) and 29 with RT (42%). In 45 patients (65%) PET-CT was able to identify recurrence of the disease (positive PET) and in 24 it was not (negative PET). Of patients treated with RP, 82, 5% (33/40) had PSA>1, and of those, 61% were positive PET. 17, 5% (7/40) had PSA6months (28/69), in 71% if PSADT6 months, in 61% and 92% if PSADT<6 months and in 77% and 100% if PSADT<3 months. Conclusion: Preliminarily and awaiting validation, it seems that PSA>1 after RP or Nadir +2 after RT is an indicator of PET-CT. There seems to be a tendency that shows that PSA<1 after RP is an indicator of PET-CT if PSADT<3 months. PSADT <3 or <6 months could be the best predictor of positivity of PET-CT with [18F]F-Choline in recurrent prostate cancer

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibresDisfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosaDisfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosaIrritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.)

Memoria del segundo simposium sobre historia, sociedad y cultura de México y América Latina

La presente obra reúne 20 ponencias de las 27 que se presentaron en el “Segundo simposium sobre historia, sociedad y cultura de México y América Latina”, realizado el 8 y 9 de noviembre de 2006, en el Centro de Investigación en Ciencias Sociales y Humanidades (CICSyH) de la Universidad Autónoma del Estado de México (UAEM), en Toluca, Estado de México

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Towards a TILLING platform for functional genomics in Piel de Sapo melons

Background The availability of genetic and genomic resources for melon has increased significantly, but functional genomics resources are still limited for this crop. TILLING is a powerful reverse genetics approach that can be utilized to generate novel mutations in candidate genes. A TILLING resource is available for cantalupensis melons, but not for inodorus melons, the other main commercial group. Results A new ethyl methanesulfonate-mutagenized (EMS) melon population was generated for the first time in an andromonoecious non-climacteric inodorus Piel de Sapo genetic background. Diverse mutant phenotypes in seedlings, vines and fruits were observed, some of which were of possible commercial interest. The population was first screened for mutations in three target genes involved in disease resistance and fruit quality (Cm-PDS, Cm-eIF4E and Cm-eIFI(iso)4E). The same genes were also tilled in the available monoecious and climacteric cantalupensis EMS melon population. The overall mutation density in this first Piel de Sapo TILLING platform was estimated to be 1 mutation/1.5 Mb by screening four additional genes (Cm-ACO1, Cm-NOR, Cm-DET1 and Cm-DHS). Thirty-three point mutations were found for the seven gene targets, six of which were predicted to have an impact on the function of the protein. The genotype/phenotype correlation was demonstrated for a loss-of-function mutation in the Phytoene desaturase gene, which is involved in carotenoid biosynthesis. Conclusions The TILLING approach was successful at providing new mutations in the genetic background of Piel de Sapo in most of the analyzed genes, even in genes for which natural variation is extremely low. This new resource will facilitate reverse genetics studies in non-climacteric melons, contributing materially to future genomic and breeding studies.González, M.; Xu, M.; Esteras Gómez, C.; Roig Montaner, MC.; Monforte Gilabert, AJ.; Troadec, C.; Pujol, M.... (2011). Towards a TILLING platform for functional genomics in Piel de sapo melons. BMC Research Notes. 4(289):289-299. doi:10.1186/1756-0500-4-289S2892994289The International Cucurbit Genomics Initiative (ICuGI). [ http://www.icugi.org ]González-Ibeas D, Blanca J, Roig C, González-To M, Picó B, Truniger V, Gómez P, Deleu W, Caño-Delgado A, Arús P, Nuez F, García-Mas J, Puigdomènech P, Aranda MA: MELOGEN: an EST database for melon functional genomics. BMC Genomics. 2007, 8: 306-10.1186/1471-2164-8-306.Fita A, Picó B, Monforte A, Nuez F: Genetics of Root System Architecture Using Near-isogenic Lines of Melon. J Am Soc Hortic Sci. 2008, 133: 448-458.Fernandez-Silva I, Eduardo I, Blanca J, Esteras C, Picó B, Nuez F, Arús P, Garcia-Mas J, Monforte AJ: Bin mapping of genomic and EST-derived SSRs in melon (Cucumis melo L.). Theor Appl Genet. 2008, 118: 139-150. 10.1007/s00122-008-0883-3.Deleu W, Esteras C, Roig C, González-To M, Fernández-Silva I, Blanca J, Aranda MA, Arús P, Nuez F, Monforte AJ, Picó MB, Garcia-Mas J: A set of EST-SNPs for map saturation and cultivar identification in melon. BMC Plant Biol. 2009, 9: 90-10.1186/1471-2229-9-90.Mascarell-Creus A, Cañizares J, Vilarrasa J, Mora-García S, Blanca J, González-Ibeas D, Saladié M, Roig C, Deleu W, Picó B, López-Bigas N, Aranda MA, Garcia-Mas J, Nuez F, Puigdomènech P, Caño-Delgado A: An oligo-based microarray offers novel transcriptomic approaches for the analysis of pathogen resistance and fruit quality traits in melon (Cucumis melo L.). BMC Genomics. 2009, 10: 467-10.1186/1471-2164-10-467.Blanca JM, Cañizares J, Ziarsolo P, Esteras C, Mir G, Nuez F, Garcia-Mas J, Pico B: Melon transcriptome characterization. SSRs and SNPs discovery for high throughput genotyping across the species. Plant Genome. 2011, 4 (2): 118-131. 10.3835/plantgenome2011.01.0003.González VM, Benjak A, Hénaff EM, Mir G, Casacuberta JM, Garcia-Mas J, Puigdomènech P: Sequencing of 6.7 Mb of the melon genome using a BAC pooling strategy. BMC Plant Biology. 2010, 10: 246-10.1186/1471-2229-10-246.Moreno E, Obando JM, Dos-Santos N, Fernández-Trujillo JP, Monforte AJ, Garcia-Mas J: Candidate genes and QTLs for fruit ripening and softening in melon. Theor Appl Genet. 2007, 116: 589-602.Essafi A, Díaz-Pendón JA, Moriones E, Monforte AJ, Garcia-Mas J, Martín-Hernández AM: Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon accession PI 161375. Theor Appl Genet. 2009, 118: 275-284. 10.1007/s00122-008-0897-x.Comai L, Henikoff S: TILLING: practical single-nucleotide mutation discovery. Plant J. 2006, 45: 684-94. 10.1111/j.1365-313X.2006.02670.x.Cooper JL, Till BJ, Laport RG, Darlow MC, Kleffner JM, Jamai A, El-Mellouki T, Liu S, Ritchie R, Nielsen N, et al: TILLING to detect induced mutations in soybean. BMC Plant Biol. 2008, 8 (1): 9-10.1186/1471-2229-8-9.Dalmais M, Schmidt J, Le Signor C, Moussy F, Burstin J, Savois V, Aubert G, de Oliveira Y, Guichard C, Thompson R, Bendahmane A: UTILLdb, a Pisum sativum in silico forward and reverse genetics tool. Genome Biol. 2008, 9: R43-10.1186/gb-2008-9-2-r43.Dierking EC, Bilyeu KD: New sources of soybean meal and oil composition traits identified through TILLING. BMC Plant Biol. 2009, 9: 89-10.1186/1471-2229-9-89.Perry J, Brachmann A, Welham T, Binder A, Charpentier M, Groth M, Haage K, Markmann K, Wang TL, Parniske M: TILLING in Lotus japonicus identified large allelic series for symbiosis genes and revealed a bias in functionally defective ethyl methanesulfonate alleles toward glycine replacements. Plant Physiol. 2009, 151 (3): 1281-1291. 10.1104/pp.109.142190.Caldwell DG, McCallum N, Shaw P, Muehlbauer GJ, Marshall DF, Waugh R: A structured mutant population for forward and reverse genetics in Barley (Hordeum vulgare L.). Plant J. 2004, 40 (1): 143-150. 10.1111/j.1365-313X.2004.02190.x.Henikoff S, Bradley JT, Comai L: TILLING. Traditional mutagenesis meets functional genomics. Plant Physiol. 2004, 135: 630-636. 10.1104/pp.104.041061.Wu JL, Wu C, Lei C, Baraoidan M, Bordeos A, Madamba MR, Ramos-Pamplona M, Mauleon R, Portugal A, Ulat VJ, et al: Chemical- and irradiation-induced mutants of indica rice IR64 for forward and reverse genetics. Plant Mol Biol. 2005, 59 (1): 85-97. 10.1007/s11103-004-5112-0.Slade AJ, Fuerstenberg SI, Loeffler D, Steine MN, Facciotti D: A reverse genetic, nontransgenic approach to wheat crop improvement by TILLING. Nat Biotechnol. 2005, 23: 75-81. 10.1038/nbt1043.Till BJ, Cooper J, Tai TH, Colowit P, Greene EA, Henikoff S, Comai L: Discovery of chemically induced mutations in rice by TILLING. BMC Plant Biol. 2007, 7: 19-10.1186/1471-2229-7-19.Xin Z, Wang ML, Barkley NA, Burow G, Franks C, Pederson G, Burke J: Applying genotyping (TILLING) and phenotyping analyses to elucidate gene function in a chemically induced sorghum mutant population. BMC Plant Biol. 2008, 8: 103-10.1186/1471-2229-8-103.Dong C, Dalton-Morgan J, Vincent K, Sharp P: A modified TILLING method for wheat breeding. Plant Genome. 2009, 2: 39-47. 10.3835/plantgenome2008.10.0012.Sestili F, Botticella E, Bedo Z, Phillips A, Lafiandra D: Production of novel allelic variation for genes involved in starch biosynthesis through mutagenesis. Mol Breeding. 2010, 25: 145-154. 10.1007/s11032-009-9314-7.Watanabe S, Mizoguchi T, Aoki K, Kubo Y, Mori H, Imanishi S, Yamazaki Y, Shibata D, Ezura H: Ethylmethanesulfonate (EMS) mutagenesis of Solanum lycopersicum cv. Micro-Tom for large-scale mutant screens. Plant Biotech. 2007, 24: 33-38. 10.5511/plantbiotechnology.24.33.Elias R, Till BJ, Mba Ch, Al-Safadi B: Optimizing TILLING and Ecotilling techniques for potato (Solanum tuberosum L). BMC Res Notes. 2009, 2: 141-10.1186/1756-0500-2-141.Piron F, Nicolaı M, Minoıa S, Piednoir E, Moretti A, Salgues A, Zamir D, Caranta C, Bendahmane A: An induced mutation in tomato eIF4E leads to immunity to two Potyviruses. PLoS ONE. 2010, 5 (6): e11313-10.1371/journal.pone.0011313.Himelblau E, Gilchrist EJ, Buono K, Bizell C, Mentzer L, Vogelzang R, Osborn T, Amasino RM, Parkin IAP, Haughn : Forward and reverse genetics of papid cycling Brassica oleracea. Theor Appl Genet. 2009, 118: 953-961. 10.1007/s00122-008-0952-7.Stephenson P, Baker D, Girin T, Perez A, Amoah S, King GJ, Østergaard L: A rich TILLING resource for studying gene function in Brassica rapa. BMC Plant Biol. 2010, 10: 62-10.1186/1471-2229-10-62.Pitrat M: Melon (Cucumis melo L.). Handbook of Crop Breeding Vol I. Vegetables. Edited by: Prohens J, Nuez F. 2008, New York:Springer, 283-315.Dahmani-Mardas F, Troadec Ch, Boualem A, Leveque S, Alsadon AA, Aldoss AA, Dogimont C, Bendahman A: Engineering Melon Plants with Improved Fruit Shelf Life Using the TILLING Approach. PLoS ONE. 2010, 5: e15776-10.1371/journal.pone.0015776.Nieto C, Piron F, Dalmais M, Marco CF, Moriones E, Gómez-Guillamón ML, Truniger V, Gómez P, Garcia-Mas J, Aranda MA, Bendahmane A: EcoTILLING for the identification of allelic variants of melon eIF4E, a factor that controls virus susceptibility. BMC Plant Biol. 2007, 7: 34-10.1186/1471-2229-7-34.Qin G, Gu H, Ma L, Peng Y, Deng XW, Chen Z, Qu LJ: Disruption of phytoene desaturase gene results in albino and dwarf phenotypes in Arabidopsis by impairing chlorophyll, carotenoid, and gibberellin biosynthesis. Cell Res. 2007, 17: 471-482. 10.1038/cr.2007.40.Codons Optimized to Deliver Deleterious Lesions (CODDLe). [ http://www.proweb.org/input ]Lasserre E, Bouquin T, Hernández JA, Bull J, Pech JC, Balague C: Structure and expression of three genes encoding ACC oxidase homologs from melon (Cucumis melo L.). Mol Gen Genet. 1996, 251 (1): 81-90.Giovannoni JJ: Fruit ripening mutants yield insights into ripening control. Curr Opin Plant Biol. 2007, 10: 1-7. 10.1016/j.pbi.2006.11.012.Davuluri GR, van Tuinen A, Mustilli AC, Manfredonia A, Newman R, Burgess D, Brummell DA, King SR, Palys J, Uhlig J, Pennings HMJ, Bowler C: Manipulation of DET1 expression in tomato results in photomorphogenic phenotypes caused by post-transcriptional gene silencing. Plant J. 2004, 40: 344-354. 10.1111/j.1365-313X.2004.02218.x.Wei S, Li X, Gruber MI, Li R, Zhou R, Zebarjadi A, Hannoufa A: RNAi-mediated suppression of DET1 alters the levels of carotenoids and sinapate esters in seeds of Brassica napus. J Agric Food Chem. 2009, 57 (12): 5326-5333. 10.1021/jf803983w.Wang TW, Zhang CG, Wu W, Nowack LM, Madey E, Thompson JE: Antisense suppression of deoxyhypusine synthase in tomato delays fruit softening and alters growth and development DHS mediates the first of two sequential enzymatic reactions that activate eukaryotic translation initiation factor-5A. Plant Physiol. 2005, 138: 1372-1382. 10.1104/pp.105.060194.Ng PC, Henikoff S: SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003, 31 (13): 3812-3814. 10.1093/nar/gkg509.Guzman P, Ecker JR: Exploiting the triple response of Arabidopsis to identify ethylene-related mutants. The Plant Cell. 1990, 2: 513-523.Henikoff S, Comai L: Single-nucleotide mutations for plant functional genomics. Ann Rev Plant Biol. 2003, 54: 375-401. 10.1146/annurev.arplant.54.031902.135009.Greene EA, Codomo CA, Taylor NE, Henikoff JG, Till BJ, Reynolds SH, Enns LC, Burtner C, Johnson JE, Odden AR, et al: Spectrum of chemically induced mutations from a large-scale reverse genetic screen in Arabidopsis. Genetics. 2003, 164 (2): 731-740.Britt AB: DNA damage and repair in plants. Annu Rev Plant Physiol Plant Mol Biol. 1996, 47: 75-100. 10.1146/annurev.arplant.47.1.75.Truniger V, Nieto C, González-Ibeas D, Aranda M: Mechanism of plant eIF4E-mediated resistance against a Carmovirus (Tombusviridae): cap-independent translation of a viral RNA controlled in cis by an (a)virulence determinant. Plant J. 2008, 56 (5): 716-727. 10.1111/j.1365-313X.2008.03630.x.Gao Z, Johansen E, Eyers S, Thomas CL, Ellis THN, Maule AJ: The potyvirus recessive resistance gene, sbm1, identifies a novel role for translation initiation factor eIF4E in cell-to-cell trafficking. Plant J. 2004, 40 (3): 376-385. 10.1111/j.1365-313X.2004.02215.x.Kang BC, Yeam I, Frantz JD, Murphy JF, Jahn MM: The pvr1 locus in Capsicum encodes a translation initiation factor eIF4E that interacts with Tobacco etch virus VPg. Plant J. 2005, 42 (3): 392-405. 10.1111/j.1365-313X.2005.02381.x.Ruffel S, Gallois J, Lesage M, Caranta C: The recessive potyvirus resistance gene pot-1 is the tomato orthologue of the pepper pvr2-eiF4 genes. Mol Genet Genom. 2005, 274 (4): 346-353. 10.1007/s00438-005-0003-x.Nicaise V, German-Retana S, Sanjuán R, Dubrana MP, Mazier M, Maisonneuve B, Candresse T, Caranta C, LeGall O: The Eukaryotic Translation Initiation Factor 4E Controls Lettuce Susceptibility to the Potyvirus Lettuce mosaic virus1. Plant Physiol. 2003, 132: 1272-1282. 10.1104/pp.102.017855.Esteras C, Pascual L, Saladie M, Dogimont C, Garcia-Mas J, Nuez F, Picó B: Use of Ecotilling to identify natural allelic variants of melon candidate genes involved in fruit ripening. Proceedings Plant GEM8 Lisbon. 2009Levin I, Frankel P, Gilboa N, Tanny S, Lalazar A: The tomato dark green mutation is a novel allele of the tomato homolog of the DEETIOLATED1 gene. Theor Appl Genet. 2003, 106: 454-460.Kolotilin I, Koltai H, Tadmor Y, Bar-Or C, Reuveni M, Meir A, Nahon S, Shlomo S, Chen L, I Levin: Transcriptional profiling of high pigment-2dg tomato mutant links early fruit plastid biogenesis with its overproduction of phytonutrients. Plant Physiol. 2007, 145: 389-401. 10.1104/pp.107.102962

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p