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1.
ARTC1-mediated ADP-ribosylation of GRP78/BiP: a new player in endoplasmic-reticulum stress responses
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Francesca Pancotto Filippo Maria Pericoli Marco Pistagnesi 《Journal of forecasting》2014,33(4):243-258
We use survey data on five bilateral exchange rates to provide empirical evidence of the fact that professional forecasters of foreign exchange rates behave irrationally, in the specific sense that they respond inaccurately to available information in the market when forming their predictions. In particular, we find systematic biases in the forecasts resulting in the overreaction of analysts to past information contained in the exchange rate dynamics: forecasters change their prediction more than it would be rational on the basis of past realized changes. In addition, forecasters are heterogeneous in their irrationality: low performers in previous periods show a more pronounced overreaction effect. This can be read as an indication of perpetration of past errors and continued inability to learn from the past. In the second part of the paper, we exploit the novel structure of our dataset, which consists of survey data extracted from the Bloomberg platform and readily available to anyone. This feature allows us to consider their own and others' past forecasts as part of the information set that analysts use in making their predictions. By using past forecasts as proxies for relevant macroeconomic variables, we find evidence that analysts fail to correctly process not only the information contained in the spot rate past dynamics but also the information in this broader set. We see this as confirmation of the existence of inefficiency and heterogeneity between low and high performers also when full information is available. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Maria Pasztoi Agnes Bonifacius Joern Pezoldt Devesha Kulkarni Jana Niemz Juhao Yang René Teich Janina Hajek Fabio Pisano Manfred Rohde Petra Dersch Jochen Huehn 《Cellular and molecular life sciences : CMLS》2017,74(15):2839-2850
Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4+ T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4+ T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3+ regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4+ T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4+ T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3+ Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4+ T cell subsets by altering their TCR downstream signaling. 相似文献
5.
In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism
and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex
macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the
formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively
glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells.
Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed,
sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated
sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in
modulating specific signaling pathways and cell metabolism in mammals. 相似文献
6.
Ahn J Woo HN Ko A Khim M Kim C Park NH Song HY Kim SW Lee H 《Cellular and molecular life sciences : CMLS》2012,69(18):3147-3158
Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents. 相似文献
7.
Zhang Z Lee JC Lin L Olivas V Au V LaFramboise T Abdel-Rahman M Wang X Levine AD Rho JK Choi YJ Choi CM Kim SW Jang SJ Park YS Kim WS Lee DH Lee JS Miller VA Arcila M Ladanyi M Moonsamy P Sawyers C Boggon TJ Ma PC Costa C Taron M Rosell R Halmos B Bivona TG 《Nature genetics》2012,44(8):852-860
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer. 相似文献
8.
Elia J Glessner JT Wang K Takahashi N Shtir CJ Hadley D Sleiman PM Zhang H Kim CE Robison R Lyon GJ Flory JH Bradfield JP Imielinski M Hou C Frackelton EC Chiavacci RM Sakurai T Rabin C Middleton FA Thomas KA Garris M Mentch F Freitag CM Steinhausen HC Todorov AA Reif A Rothenberger A Franke B Mick EO Roeyers H Buitelaar J Lesch KP Banaschewski T Ebstein RP Mulas F Oades RD Sergeant J Sonuga-Barke E Renner TJ Romanos M Romanos J Warnke A Walitza S Meyer J Pálmason H Seitz C Loo SK Smalley SL 《Nature genetics》2012,44(1):78-84
Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts. 相似文献
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10.
Lu W Schneider M Neumann S Jaeger VM Taranum S Munck M Cartwright S Richardson C Carthew J Noh K Goldberg M Noegel AA Karakesisoglou I 《Cellular and molecular life sciences : CMLS》2012,69(20):3493-3509
Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size. 相似文献