Entre le four et la cour. Quelques documents sur une famille de Pampelune au XlVème siècle, les Moza de la Población

A short study of documents of the municipal and cathedral Archives of Pamplona, allow us to know the economic basis of a family of burghers in the district of the Población in Navarrese main town, the family Moza. Owners of a furnace, lands, mills, around Pamplona and houses in the town, the Mozas in the XIVth century manage the chancery and the tressury of the realm of Navarre, allied with the most influential families.A short study of documents of the municipal and cathedral Archives of Pamplona, allow us to know the economic basis of a family of burghers in the district of the Población in Navarrese main town, the family Moza. Owners of a furnace, lands, mills, around Pamplona and houses in the town, the Mozas in the XIVth century manage the chancery and the tressury of the realm of Navarre, allied with the most influential families

De 1390 a 1420, le roi Charles III de Navarre protecteur des juifs étrangers a son royaume

As a manifestation of his independent frame of mind and individualistic policy, Charles III, King of Navarre used to welcome Jewish foreigners in bis kingdom. In 1401-1402 he received Hasdai Crescas, of Zaragoza, in Sangüesa, to talk about the settlement in Tudela of some Zaragozan Jewish families. The King also invited Maestre Ezdra Alazar, a physician of Zaragoza, keeping in his service doctor Josef ben Wakkar of Castilla as well. This fact is explained through Charles III's general policy of protecting the aljamas and promoting the élite of the Jews to higher responsibilities, while leading them into conversion.El rey de Navarra Carlos III, como manifestación de su independencia y de su política individual, acogía en su reino a judíos extranjeros. En los años 1401-1402 recibió en Sangüesa a Hasdai Crescas, de Zaragoza, para tratar del asentamiento en Tudela de varias familias judías procedentes de aquella ciudad. El rey invitó también al Maestre Ezdra Alazar, físico de Zaragoza, manteniendo a su servicio al médico Josef ben Wakkar de Castilla. Este hecho se explica por la política de Carlos III de proteger las aljamas y dar cargos de responsabilidad a la elite de los judíos, al mismo tiempo que les invitaba a convertirse

Le traité des armes de Diego de Valera, vers 1455-1460

Diego de Valera, maître d’Armes de la cour de Castille, a offert vers 1455-1460 un Traité des Armes au roi du Portugal. Il y rappelle d’abord la législation en vigueur en Espagne, en France, ailleurs en Europe, concernant les défis et les « emprises d’armes » où s’affrontent les nobles en combats singuliers soutenus devant les cours. Il évoque les cas de trahison qui suscitent ces défis. Puis, il détaille les principes de l’héraldique.Diego de Valera, Mestre de Armas de Castilla, ofrece hacia 1455-1460 un Tratado de las Armas al rey de Portugal. Recuerda la legislación de España y Francia relativa a los retos y « empresas de armas » sostenidos por los nobles en torneos delante de las cortes reales. Menciona los casos de traición, causa de esos desafíos, describiendo además las normas de la heráldica.Diego de Valera, Fencing-Master in the royal court of Castile, wrote for the king of Portugal, towards 1455-1460, a Treaty of Arms. He examines the laws of Spain, France, Europe on duels and the « Emprises of Arms » where noblemen were engaged in single combats before royal courts. He evokes the various treasons which lead to those duels. Then, he enumerates the rudiments of Heraldry

Molecular profiling of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1, based on large-scale real-time RT-PCR

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a complex range of clinical symptoms. The hallmark of NF1 is the onset of heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas can give rise to malignant peripheral nerve sheath tumors (MPNSTs), and the underlying molecular mechanisms are largely unknown. RESULTS: To obtain further insight into the molecular pathogenesis of MPNSTs, we used real-time quantitative RT-PCR to quantify the mRNA expression of 489 selected genes in MPNSTs, in comparison with plexiform neurofibromas. The expression of 28 (5.7%) of the 489 genes was significantly different between MPNSTs and plexiform neurofibromas; 16 genes were upregulated and 12 were downregulated in MPNSTs. The altered genes were mainly involved in cell proliferation (MKI67, TOP2A, CCNE2), senescence (TERT, TERC), apoptosis (BIRC5/Survivin, TP73) and extracellular matrix remodeling (MMP13, MMP9, TIMP4, ITGB4). More interestingly, other genes were involved in the Ras signaling pathway (RASSF2, HMMR/RHAMM) and the Hedgehog-Gli signaling pathway (DHH, PTCH2). Several of the down-regulated genes were Schwann cell-specific (L1CAM, MPZ, S100B, SOX10, ERBB3) or mast cell-specific (CMA1, TPSB), pointing to a depletion and/or dedifferentiation of Schwann cells and mast cells during malignant transformation of plexiform neurofibromas. CONCLUSION: These data suggest that a limited number of signaling pathways, and particularly the Hedgehog-Gli signaling pathway, may be involved in malignant transformation of plexiform neurofibromas. Some of the relevant genes or their products warrant further investigation as potential therapeutic targets in NF1

Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia

Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early‐onset cone photoreceptor dysfunction. PDE6C encodes the catalytic α′‐subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically preselected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach. We were able to identify potentially pathogenic biallelic variants in 15 index cases. The mutation spectrum comprises 18 different alleles, 15 of which are novel. Our study significantly contributes to the mutation spectrum of PDE6C and allows for a realistic estimate of the prevalence of PDE6C mutations in ACHM since our entire ACHM cohort comprises 1,074 independent families.In a cohort of 176 genetically undiagnosed achromatopsia patients, we performed screening of the PDE6C gene and identified potentially pathogenic biallelic variants in 15 cases. Taking into account a previous screening approach, we calculate a prevalence of 2.4% for PDE6C mutations in our cohort, which is most probably representative for the Western population. As achromatopsia is in the focus of retinal gene therapy with four clinical trials ongoing, our study provides a valuable resource for putative gene therapy trials targeting PDE6C.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146275/1/humu23606-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146275/2/humu23606_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146275/3/humu23606.pd

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since &gt;280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.</p

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.This study received funding from Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This work was supported by grants from Foundation Fighting Blindness Career Development Award CDGE-0621-0809-RAD (SR), Foundation Fighting Blindness project program award PPA-0123-0841-UCL (SR and SdB), Retinitis Pigmentosa Fighting Blindness, Fight for Sight UK (RP Genome Project GR586), Ghent University Special Research Fund (BOF20/GOA/023) (EDB and BL); EJP RD Solve-RET EJPRD19-234 (EDB, BL, SB, CR, FC, and SR). EDB (1802220N) and BL (1803816N) are FWO Senior Clinical Investigators of the Research Foundation Flanders (FWO). EDB, BL, SB, FC, and SR are members of ERN-EYE (Framework Partnership Agreement No. 739534)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Les grands chantiers publics en Navarre sous la dynastie d'Evreux (1328- 1430)

Leroy Béatrice. Les grands chantiers publics en Navarre sous la dynastie d'Evreux (1328- 1430). In: Cahiers de la Méditerranée, n°31, 1, 1985. La construction dans la péninsule ibérique (XIe-XVIe) sous la direction de Denis Menjot et Adeline Rucquoi. pp. 55-71