[Recueil].

Capitulare ecclesiasticum (1-7v). - Capitula legibus addenda (7v-14v). - Capitula per se scibenda (14v-16v). - Capitulare missorum (16v-20). "Domine Deus omnipotens propitius est omni peccatori..." [Ajout du Xe s.] (20v). - Collectio capitularium Ansegisi (21-40v). - Lex salica (41-83v). Les cahiers des ff. 1-20 et 41-83 faisaient partie du même ms. Ils ont été copiés durant le second quart ou vers le milieu du IXe s., et sont signés de QI à QVI, tandis que les ff. 21-40v ont été copiés plus tardivement, durant la seconde moitié du IXe s. ou la première moitié du Xe s. Les ff. 44-45 ont été rajoutés pour compléter une lacune du texte, mentionnée au f. 43v par une main du XIVe s.: "hic deficiunt II° folia". La portion manquante du texte a été recopiée par deux mains différentes, du XVIIe s. Les mss. lat. 18237 et 18238 ont été consultés par Etienne Baluze (1630-1718), bibliothécaire de Colbert et canoniste, pour son édition des Capitularia regum francorum."

Segmental copy number variation shapes tissue transcriptomes.

Copy number variation (CNV) is a key source of genetic diversity, but a comprehensive understanding of its phenotypic effect is only beginning to emerge. We have generated a CNV map in wild mice and classical inbred strains. Genome-wide expression data from six major organs show not only that expression of genes within CNVs tend to correlate with copy number changes, but also that CNVs influence the expression of genes in their vicinity, an effect that extends up to half a megabase. Genes within CNVs show lower expression and more specific spatial expression patterns than genes mapping elsewhere. Our analyses reveal differential constraint on copy number changes of genes expressed in different tissues. Dosage alterations of brain-expressed genes are less frequent than those of other genes and are buffered by tighter transcriptional regulation. Our study provides initial evidence that CNVs shape tissue transcriptomes on a global scale.

Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.

We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1.

Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Mémoire instructif sur la ville de Navarreins

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

Mémoire sur la fortification de Navarreins et le projet estimatif des ouvrages qu'il conviendroit d'y faire pour mettre la place dans un état proportionné à sa scituation et à son utilité

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

Resumen de los trabajos científicos pesqueros de la segunda expedición del BEC Profesor Mesiatzev en las aguas del Océano Pacífico adyacentes a la costa del Perú, 9 marzo al 27 junio 1973

Presenta las características de los trabajos experimentales desarollados con el fin de determinar la magnitud posible de captura de peces con el equipo hidroacústico, arrastres de comprobación y la pesca a nivel industrial.

Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity.

Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an altered cytokine profile and are more potent than matched control cells in stimulating allogeneic T cell proliferation in mixed lymphocyte reactions. These findings shed new light on the role of osteopontin and its regulation by TRAP in the pathogenesis of common autoimmune disorders.