15,001 research outputs found

    Modulation of the slow/common gating of CLC channels by intracellular cadmium.

    Get PDF
    Members of the CLC family of Cl(-) channels and transporters are homodimeric integral membrane proteins. Two gating mechanisms control the opening and closing of Cl(-) channels in this family: fast gating, which regulates opening and closing of the individual pores in each subunit, and slow (or common) gating, which simultaneously controls gating of both subunits. Here, we found that intracellularly applied Cd(2+) reduces the current of CLC-0 because of its inhibition on the slow gating. We identified CLC-0 residues C229 and H231, located at the intracellular end of the transmembrane domain near the dimer interface, as the Cd(2+)-coordinating residues. The inhibition of the current of CLC-0 by Cd(2+) was greatly enhanced by mutation of I225W and V490W at the dimer interface. Biochemical experiments revealed that formation of a disulfide bond within this Cd(2+)-binding site is also affected by mutation of I225W and V490W, indicating that these two mutations alter the structure of the Cd(2+)-binding site. Kinetic studies showed that Cd(2+) inhibition appears to be state dependent, suggesting that structural rearrangements may occur in the CLC dimer interface during Cd(2+) modulation. Mutations of I290 and I556 of CLC-1, which correspond to I225 and V490 of CLC-0, respectively, have been shown previously to cause malfunction of CLC-1 Cl(-) channel by altering the common gating. Our experimental results suggest that mutations of the corresponding residues in CLC-0 change the subunit interaction and alter the slow gating of CLC-0. The effect of these mutations on modulations of slow gating of CLC channels by intracellular Cd(2+) likely depends on their alteration of subunit interactions

    A Macro-Finance Approach to Exchange Rate Determination

    Get PDF
    The nominal exchange rate is both a macroeconomic variable equilibrating international markets and a financial asset that embodies expectations and prices risks associated with cross border currency holdings. Recognizing this, we adopt a joint macro-finance strategy to model the exchange rate. We incorporate into a monetary exchange rate model macroeconomic stabilization through Taylor-rule monetary policy on one hand, and on the other, market expectations and perceived risks embodied in the cross-country yield curves. Using monthly data between 1985 and 2005 for Canada, Japan, the UK and the US, we employ a state-space system to model the relative yield curves between country-pairs using the Nelson and Siegel (1987) latent factors, and combine them with monetary policy targets (output gap and inflation) into a vector autoregression (VAR) for bilateral exchange rate changes. We find strong evidence that both the financial and macro variables are important for explaining exchange rate dynamics and excess currency returns, especially for the yen and the pound rates relative to the dollar. Moreover, by decomposing the yield curves into expected future yields and bond market term premiums, we show that both expectations about future macroeconomic conditions and perceived risks are priced into the currencies. These findings provide support for the view that the nominal exchange rate is determined by both macroeconomic as well as financial forces.

    What Does the Yield Curve Tell Us About Exchange Rate Predictability?

    Get PDF
    This paper uses information contained in the cross-country yield curves to test the asset-pricing approach to exchange rate determination, which models the nominal exchange rate as the discounted present value of its expected future fundamentals. Research on the term structure of interest rates has long argued that the yield curve contains information about future economic activity such as GDP growth and inflation. Bringing this lesson to the international context, we extract the Nelson-Siegel (1987) factors of relative level, slope, and curvature from cross-country yield differences to proxy expected movements in future exchange rate fundamentals. Using monthly data between 1985-2005 for the United Kingdom, Canada, Japan and the US, we show that the yield curve factors indeed can explain and predict bilateral exchange rate movements and excess currency returns one month to two years ahead. Out-of-sample analysis also shows the yield curve factors to outperform a random walk in forecasting short-term exchange rate returns.

    A Three-Stage Process Model of Self-Initiated Expatriate Career Transitions: A Self-Determination Theory Perspective

    Get PDF
    With more than 31 percent of employers worldwide having difficulty filling positions due to the lack of suitable talent available in their home markets (Manpower, 2010), talent shortage has become a global problem. Thus, many employers are seeking and recruiting skilled employees worldwide. Echoing this trend is the emergence of self-initiated expatriates (SIEs), a growing breed of expatriates that is responding to global talent shortages. Unlike corporate expatriates who are sponsored by organizations to take an international assignment, SIEs independently choose to expatriate and their expatriation experiences are riskier and more unpredictable. Thus, SIEs\u27 motivations pertaining to their decisions to expatriate may play a critical role in sustaining their self-directed transition. Therefore, the purpose of this dissertation is to develop and test a theoretically driven model of SIEs\u27 career transitions and the nested motivational processes. In this dissertation, I first develop an abstract theoretical model of SIEs\u27 career transition processes through the lens of self-determination theory (SDT) (Deci & Ryan, 2002). The proposed model identifies the influences of relational factors, personal factors, and contextual factors on SIEs\u27 psychological need satisfaction, their autonomous motivation, and their well-being at each stage (exploration, establishment, and embeddedness) of their career transitions. The linking mechanism between each career transition stage is also discussed. In this dissertation, I also empirically examine SIEs\u27 career transition experience at the establishment stage using a sample of 245 SIE academics originally from 37 nations/regions and now working and living in 9 different countries. I use structural equation modeling to analyze the data. Results indicate that relational support (e.g., perceived organizational support), personal resources (e.g., proactive personality, prior international work experience, universal language spoken fluency), and supportive contextual factor (host country diversity climate) positively influence SIE academics\u27 expatriate adjustment through the satisfaction of psychological competency need and the increase of autonomous motivation. Overall, this dissertation contributes to SIE, career transition, and SDT scholarship by investigating the nexus of these three literatures. Specifically, this dissertation contributes to the SIE literature by applying SDT to explain SIEs\u27 career transition processes which moves beyond mainstream studies that only explain what but not how and why SIEs are motivated. My dissertation also theoretically advances existing SIE research by considering different stages of SIE career transition and the interplay between stages. Empirical examination of SIE academics\u27 career transition experience at the establishment stage generally supports the proposed motivational processes underlying SIEs\u27 career transition
    • …
    corecore