Functional characterization of CP148, a novel key component for centrosome integrity in Dictyostelium

The Dictyostelium centrosome consists of a layered core structure surrounded by a microtubule-nucleating corona. A tight linkage through the nuclear envelope connects the cytosolic centrosome with the clustered centromeres within the nuclear matrix. At G2/M the corona dissociates, and the core structure duplicates, yielding two spindle poles. CP148 is a novel coiled coil protein of the centrosomal corona. GFP-CP148 exhibited cell cycle-dependent presence and absence at the centrosome, which correlates with dissociation of the corona in prophase and its reformation in late telophase. During telophase, GFP-CP148 formed cytosolic foci, which coalesced and joined the centrosome. This explains the hypertrophic appearance of the corona upon strong overexpression of GFP-CP148. Depletion of CP148 by RNAi caused virtual loss of the corona and disorganization of interphase microtubules. Surprisingly, formation of the mitotic spindle and astral microtubules was unaffected. Thus, microtubule nucleation complexes associate with centrosomal core components through different means during interphase and mitosis. Furthermore, CP148 RNAi caused dispersal of centromeres and altered Sun1 distribution at the nuclear envelope, suggesting a role of CP148 in the linkage between centrosomes and centromeres. Taken together, CP148 is an essential factor for the formation of the centrosomal corona, which in turn is required for centrosome/centromere linkage.     

Occurrence of anisakid larvae (Nematoda: Ascardidia) in fishes from Alaska and Idaho

All 25 sablefish ( Anoplopoma fimbria ) examined from two bays near Sitka, Alaska, were infected with anisakid larvae. There were 1 to 11 larvae per infected fish, with worms encysted in the musculature of the body wall of 5 fish and in the liver of 4 fish. For the other hosts the viscera was the site of infection. Chinook salmon ( Onchorhynchus tshawytscha ) from Barrow, Alaska, and Obsidian, Idaho, were also infected with anisakid larvae. These data extend the known northern distribution of the anisakids along the Pacific Coast for sablefish and chinook salmon. The pathogenesis of the migratory pathway of anisakid larvae is described, and comments on human health implications are presented.     

A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis

Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.     

Predicting crypto‐currencies using sparse non‐Gaussian state space models

In this paper we forecast daily returns of crypto‐currencies using a wide variety of different econometric models. To capture salient features commonly observed in financial time series like rapid changes in the conditional variance, non‐normality of the measurement errors and sharply increasing trends, we develop a time‐varying parameter VAR with t‐distributed measurement errors and stochastic volatility. To control for overparametrization, we rely on the Bayesian literature on shrinkage priors, which enables us to shrink coefficients associated with irrelevant predictors and/or perform model specification in a flexible manner. Using around one year of daily data, we perform a real‐time forecasting exercise and investigate whether any of the proposed models is able to outperform the naive random walk benchmark. To assess the economic relevance of the forecasting gains produced by the proposed models we, moreover, run a simple trading exercise.     

Über die Menschenformen des Jüngeren Paläolithikums in Europa

Summary The humanity of the Upper Palæolithic is represented exclusively byHomo sapiens; already at that time a remarkable diversity in human species was evident. Only by an intensive study of present and future discoveries of skeletons the question can be solved whether the remarkable variety is an individual variability of a homogeneous population or whether it corresponds to different races (up to six).     

Die Biochemie der Chinone

Ohne Zusammenfassung     

Über induzierte Abwehrreaktionen bei Pflanzen

Ohne Zusammenfassung     

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.     

多晶硅电阻中晶粒数、晶粒平均长度及激活能的确定

提出了一种基于实测伏安特性确定多晶硅电阻中晶粒数及晶粒平均长度的方法。用该法得出的结果同透射电子显微镜的实测统计结果符合较好，平均偏差小于１５％，给出了基于多晶硅电阻电流温度关系实测曲线得出的晶粒边界激活能。结果显示：经Ｈ２气氛４５０℃３０ｍｉｎ退火的样品，其激活能高于未退火的。