Sēfer lēv ṭôv

[Isaak Ben-Eljakim aus Posen]

Qerôvēṣ : doś iz ... Qōl rinnā w-îšûaʿ be-ohôlê ṣaddîqîm ; doś iz ṭaiṭš šṭim gizang un heltz in gtzelṭ fun tzadikim ...

Übers. d. Hauptsacht.: Hymnen. Die Stimme der Freude und Erlösung

Sēfer Meleket maḥaševet

še-ḥibbartî anî haq-qaṭ Mōše Zeraḥ Aydlîṣ mip-Prâg

Tôrā ṣiwwā lānû Mōše môrāšā qehillat Yaʿaqōv : gor hipš drinn tzu lezn ... hipš greimṭ ... doz erśṭ (ḥelek) ... oiz den (sefer ha-jašar) ginumn

... ḥibbērô ... Yaʿaqōv Bar-Yiṣḥāq ... de-q"q Riṭlzia

Pirqê āvôt : ir libe laṭ zaiṭ an braiṭ un komṭ tzu loifn dize hipš naie prokim koifn ...

Digitalisat der Ausg. Prag, 1712/13

ʿEśrîm we-arbaʿ oif ṭaiṭš : ein oiṭ enndišr ṭaiṭš oif jedn worṭ ...

Digitalisat der Ausg. Prag, [1764/65]

Hisṭorie : hertzog oiz holendiš flandrn ; fasṭiṭ einnn zelṭ zomin enṭšlus ; noch dem er in šẹhrn zehi kunśṭ iber oiz wohl infermirṭ und oiz glehnṭ war ...

Digitalisat der Ausg. Prag, [1762]

Prehistoric genomes reveal the genetic foundation and cost of horse domestication

The domestication of the horse revolutionized warfare, trade, and the exchange of people and ideas. This at least 5,500-y-long process, which ultimately transformed wild horses into the hundreds of breeds living today, is difficult to reconstruct from archeological data and modern genetics alone. We therefore sequenced two complete horse genomes, predating domestication by thousands of years, to characterize the genetic footprint of domestication. These ancient genomes reveal predomestic population structure and a significant fraction of genetic variation shared with the domestic breeds but absent from Przewalski’s horses. We find positive selection on genes involved in various aspects of locomotion, physiology, and cognition. Finally, we show that modern horse genomes contain an excess of deleterious mutations, likely representing the genetic cost of domestication.

Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Danksagung

Albert Katz

Kineret

Eugen Katz

Komposition [Illustration] : (Ölgemälde)

Leo Katz

Studie [Illustration] : (Tusch-Zeichnung)

Leo Katz