Mutations in PCSK9 cause autosomal dominant hypercholesterolemia

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.     

ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells

Induction of cytotoxic T-cell immunity requires the phagocytosis of pathogens, virus-infected or dead tumour cells by dendritic cells. Peptides derived from phagocytosed antigens are then presented to CD8+ T lymphocytes on major histocompatibility complex (MHC) class I molecules, a process called "cross-presentation". After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex "loading machinery" (which includes tapasin, calreticulin and Erp57). Here we show that soon after or during formation, phagosomes fuse with the ER. After antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. Therefore, cross-presentation in dendritic cells occurs in a specialized, self-sufficient, ER-phagosome mix compartment.     

La relativité générale à l'étiage: 1925–1955

Sans résumé     

De l'influence de la gravitation sur la propagation de la lumière en théorie newtonienne. L'archéologie des trous noirs

Sans résumé Présenté par J. D. North     

Thrombocytes et thrombopathies

Summary Preliminary results of a statistical survey of electron micrographs of thrombocytes from 15 patients with haemorrhagic diathesis are reported. The possible significance of ultrastructural changes in relation to factor 3 activity and metabolism deficiency are discussed.     

Large selenium isotopic variations and its implication in the Yutangba Se deposit, Hubei Province, China

The selenium isotopic ratios have been measured in the Yutangba Se deposit, Hubei Province, China. The results show that the δ 82/76SeNIST values vary from -12.77‰ to 4.93‰, which is the largest Se iso- topic variation found so far in natural terrestrial samples. The sample Ytb-5 of high-selenium carbona-ceous shale has the lightest Se isotopic composition with a δ 82/76SeNIST value of -12.77‰. On the basis of variations of Se isotope in the deposit along with other geological and geochemical evidence, the "redox model" is suggested to favor the explanation of the occurrence of native Se in the deposit. The application to the Yutangba Se deposit with the discovery of large Se isotopic fractionation for natural samples indicates the potential of Se isotope as a new geochemical tracer.     

Model–proxy comparison for overshoot phenomenon of Atlantic thermohaline circulation at Bφlling–Allerφd

The overshoot phenomenon of the Atlantic thermohaline circulation （THC） is a transient climate response to meltwater forcing and could induce intense climate change by increasing the magnitudes of Atlantic THC changes at the end of meltwater discharges. This phenomenon was formally presented with the successfully simulated Bolling-Allerod （BA） event in the first transient simulation of the last deglaciation with fully coupled model NCAR-CCSM3 （TraCE-21K）. Currently, not all proxy records of Atlantic THC support the occurrence of the THC overshoot at BA. Commonly used THC proxy from Bermuda Rise （GGC5） does not exhibit THC overshoot at BA but other proxies such as TTR-451 at Eirik Drift do. How to interpret this regional discrepancy of proxy records is a key question for the validation of the Atlantic THC overshoot at BA. Here, we show that the vigor of deep circulation varies regionally during the Atlantic THC overshoot at BA in TraCE-21K simulation, and this regional discrepancy in the simulation is consistent with that in the marine sediment records in North Atlantic. The consistent model-proxy evidence supports the occurrence of Atlantic THC overshoot at BA.