Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis

The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.     

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.     

A fractionally integrated exponential model for UK unemployment

Fractionally integrated models with the disturbances following a Bloomfield ( 1973 ) exponential spectral model are proposed in this article for modelling UK unemployment. This gives us a better understanding of the low‐frequency dynamics affecting the series without relying on any particular ARMA specification for its short‐run components which, in general, require many more parameters to estimate. The results indicate that this exponential model, confounded with fractional integration, may be a feasible way of modelling unemployment. It also shows that its order of integration is much higher than one and thus leads to the conclusion that the standard practice of taking first differences may lead to erroneous results. Copyright © 2001 John Wiley & Sons, Ltd.     

Do professional forecasters believe in the Phillips curve? evidence from the G7 countries

This paper uses monthly survey data for the G7 countries for the time period 1989–2007 to explore the link between expectations on nominal wages, prices and unemployment rates as suggested by the wage and price Phillips curves. Four major findings stand out. First, we find that survey participants trust in both types of Phillips curve relationships. Second, we find evidence in favor of nonlinearities in the price Phillips curve. Third, we take into account a kink in the price Phillips curve to indicate that the slope of the Phillips curve differs during the business cycle. We find strong evidence of this feature in the data which confirms recent theoretical discussions. Fourth, we employ our data to the expectations‐augmented Phillips curve model. The results suggest that professional forecasters adopt this model when forecasting macroeconomic variables. Copyright © 2010 John Wiley & Sons, Ltd.     

Functional modifications of cytotoxic T-lymphocyte T200 glycoprotein recognized by monoclonal antibodies

Plasma membrane glycoproteins of cytotoxic T lymphocytes (CTLs) are involved in the binding to and subsequent destruction of appropriate target cells. The electrophoretic profile of surface proteins of mature CTLs, particularly those of high relative molecular mass (Mr), is markedly different from that of naive peripheral T cells or non-cytolytic T cells, suggesting the possible involvement of these molecules in the activation of CTLs and/or in the lytic process itself. By generating monoclonal antibodies to cell-surface proteins of CTL clones, we have now detected CTL-specific modifications in one of these high-Mr membrane proteins, T200. Although forms of T200 are found on a wide variety of cell types, the neoantigenic determinants recognized by our antibodies are present exclusively on activated T cells and in high concentrations only on CTLs. Furthermore, the expression of the modifications recognized by our antibodies is influenced by soluble factors and also seems to have functional significance, as monoclonal antibodies specific for these novel epitopes block cytolytic activity.     

Tourism in the Canary Islands: forecasting using several seasonal time series models

This paper deals with the analysis of the number of tourists travelling to the Canary Islands by means of using different seasonal statistical models. Deterministic and stochastic seasonality is considered. For the latter case, we employ seasonal unit roots and seasonally fractionally integrated models. As a final approach, we also employ a model with possibly different orders of integration at zero and the seasonal frequencies. All these models are compared in terms of their forecasting ability in an out‐of‐sample experiment. The results in the paper show that a simple deterministic model with seasonal dummy variables and AR(1) disturbances produce better results than other approaches based on seasonal fractional and integer differentiation over short horizons. However, increasing the time horizon, the results cannot distinguish between the model based on seasonal dummies and another using fractional integration at zero and the seasonal frequencies. Copyright © 2008 John Wiley & Sons, Ltd.     

Mathematical Arguments in Context

Except in very poor mathematical contexts, mathematical arguments do not stand in isolation of other mathematical arguments. Rather, they form trains of formal and informal arguments, adding up to interconnected theorems, theories and eventually entire fields. This paper critically comments on some common views on the relation between formal and informal mathematical arguments, most particularly applications of Toulmin’s argumentation model, and launches a number of alternative ideas of presentation inviting the contextualization of pieces of mathematical reasoning within encompassing bodies of explicit and implicit, formal and informal background knowledge.     

Pro-Latour

In this comment I want to clarify five topics. The first topic concerns the importance of looking back at the very principles of the foundations of Western society. The second comment argues for the original position of Latour within the field of (social) constructivism. In the third comment, I argue that Haraway adds to the science-politics discussion by elaborating her philosophy beyond dichotomy. In the fourth comment, I argue that the terms ‘objective’ and ‘rational’ are central philosophical concepts which should be retained. Finally I will make the connection between ‘what’ is represented and ‘how’ to represent it.