The calmodulin fraction responsible for contraction in an intestinal smooth muscle

AbstractFreeze-dried fibers of smooth muscle from Taenia coli were used to determine the concentration of calmodulin responsible for contraction. About 10% of the total intracellular calmodulin (12.6 μmol/kg wet wt) is directly involved in initiation of smooth muscle contraction

The Foreign Direct Investment Location Decision: A Contingency Model of the Foreign Direct Investment Location Decision-Making Process

Despite considerable prior research into foreign direct investment (FDI) location decisions, our understanding of the processes underlying such decisions is still limited. Findings from work based in the economics and behavioral theories of the multinational enterprise (MNE) both acknowledge that FDI is not a point-of-time decision but a gradual process that yields important changes over its duration. However, these competing traditions both fall short when attempting to portray the actual process by which FDI location decisions are made by managers in MNEs. This gap has been recently attributed to two interrelated limitations. Firstly, level of analysis concerns have artificially separated managerial decision-making processes from the organizational and environmental structures within which they are made. Secondly, because of the complexity inherent in the FDI location decision environment, the study of these decisions has not taken contextual factors into consideration. This study addresses three important questions in order to build our understanding of the FDI location decision-making processes: (1) What are the decision-making processes that lead to FDI location choice? (2) What is the impact of contextual variables on FDI location decision-making processes at different levels of analysis, and are there any patterns of variation in decision processes under different decision conditions? (3) What factors drive final FDI location choice, and can a useful framework or theory be developed that links FDI location decision-making processes and context to drivers of FDI location choice? In order to address level of analysis concerns, the study places the manager at the center of the FDI location decision in modeling and in research, a strategy recommended by an emerging stream of behavioral-focused international business research (Aharoni, 2010; Buckley et al., 2007; Devinney, 2011). By examining FDI location decisions from the perspective of the managers who implement them, it is possible to clarify the nature of processes that lead to FDI location choice, and identify the impact of different elements of decision maker, firm and environmental context on such processes. The conceptual framework builds on Aharoni’s (1966) pivotal research while incorporating findings from broader behavioral managerial decision models and international business research. The framework is based on the assumption that FDI location decision-making processes and final choice are contingent upon interactions between the environmental, firm and decision maker context under which the decision is made. The research was undertaken in three phases. Phase 1 included a literature review that covered research on the MNE, internationalization, and decision making. The findings of the review identified key aspects of FDI location decision context and led to the development of an initial contingency framework of strategic decision making. Phase 2 consisted of an exploratory case study of twenty four FDI location decisions. The initial contingency framework developed during the literature review was used during this stage to identify the relationship between decision-making processes and contextual variables at the case decisions. By drawing on results from the exploratory research, an initial conceptual model and a set of propositions were developed. In Phase 3, twenty case studies were theoretically sampled from a pool of MNEs of varying size and parent-country nationality within the knowledge-based industries. The data collection and analysis followed a process, event-driven approach to case study research involving the mapping of key sequences of events as well as within- and cross-case analysis. The results identify the key elements of the decision process that explain FDI location behavior and develop a framework that links them together and makes them sensible. The four key elements of the FDI location decision that comprise the framework include: (i) the process, (ii) the context, (iii) patterns, and (iv) location. Research findings show the FDI location decision process as comprising of five broad stages, the content of each driven by a dynamic and evolving interpretation of maximum subjective expected utility. Utility preferences are identified as the consequence of shifting and opaque goals, founded upon imperfect information, operating in an environment marked by uncertainty. Five variations in the overall orientation of utility at case decisions, classified in the study as ‘decision rules,’ proved to be more useful predictors of decision-making behavior than traditional notions of bounded rationality seeking rent extraction and profitability. Decision processes were found to vary in five prototypical patterns, according to clusters of contextual variables that together moderated the level of decision-maker autonomy, hierarchical centralization, rule formalization, commitment to strategy, and politicization of the decision. Patterns are described as FDI location decision-making models, and proposed as an initial step towards the development of a taxonomy of FDI location decision-making processes. Because of the dynamic and staged nature of the process, findings showed that factors that were important at one stage of the decision were not as important at the next. As such, the task of identifying universal drivers of FDI location was deemed an unfeasible one. In place of universal drivers, the initiating force of the investment, the purpose of investment and information sources and networks are identified as the key context-specific determinants of location in FDI decisions. Bounded by uncertainty, chance, the dynamics of the process and decision-maker effects, each of these aspects of the decision served to limit the possible consideration set for investment, and formed the value basis and measures from which to select the most attractive location choice. Despite the contextual differences in these drivers, however, the study revealed a strong pattern that showed that the importance of specific location considerations differed in much the same way across case decisions. During the first stage of case decisions primarily strategic aspects of locations were considered; during the second, considerations relating to the system; operational concerns in the third; implementation concerns in the fourth; and added value factors in the final choice. How each of these concerns was interpreted to reach final location choice differed according to the drivers mentioned previously, although the patterns were the same. This study develops a contingency framework for examining the FDI location decision-making processes of MNEs under different operating conditions. By identifying the four key components of the FDI location decision, their interrelationships and many sources of variance, this thesis shows that despite its complexity, the FDI location decision is amenable to useful conceptual structuring. From an academic standpoint, the framework answers Aharoni’s most recent call to action in ‘Behavioral Elements in Foreign Direct Investment’ (2010) by developing a replicable structure within which to think about incorporating managerial decision models and context into the theory of the MNE. These findings enhance understandings of decision making at MNEs, reconcile a number of inconsistencies between opposing perspectives of MNE theory, and thereby update extant theory so that it has greater relevance in today’s diverse international business environment. From a managerial standpoint, the thesis helps managers to recognize the opportunities and limitations posed by different aspects of decision context so that they are able to tailor their FDI location decision strategies to best suit their needs. Finally, from the perspective of policy markers, research findings provide great support for the use of investment attraction schemes through the use of targeted location marketing and investment incentives.

Capture of farmed Nile crocodiles (Crocodylus niloticus) : comparison of physiological parameters after manual capture and after capture with electrical stunning

The electric stunner (e-stunner) is commonly used to handle Nile crocodiles (Crocodylus niloticus) on commercial farms in South Africa, but while it seems to improve handling and safety for the keepers, no information regarding physiological reactions to e-stunning is currently available. The aim of this study was therefore to compare various physiological parameters in farmed Nile crocodiles captured either manually (noosing) or by using an e-stunner. A total of 45 crocodiles were captured at a South African farm by either e-stunning or noosing, and blood samples were taken immediately as well as four hours after capture. Parameters monitored were serum corticosterone, lactate, glucose, as well as alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, and creatinine kinase. Lactate concentrations were significantly higher in noosed compared to e-stunned animals (P < 0.001). No other blood parameter differed significantly between the two capture methods. In addition, recorded capture time confirmed that noosing takes significantly longer compared to e-stunning (P < 0.001), overall indicating that e-stunning seems the better option for restraint of especially large numbers of crocodiles in a commercial setup because it is quicker, safer, and did not cause a significant increase in any of the parameters measured.http://veterinaryrecord.bmj.com/hb201

Dynamics of intracellular mannan and cell wall folding in the drought responses of succulent <i>Aloe</i> species

Plants have evolved a multitude of adaptations to survive extreme conditions. Succulent plants have the capacity to tolerate periodically dry environments, due to their ability to retain water in a specialized tissue, termed hydrenchyma. Cell wall polysaccharides are important components of water storage in hydrenchyma cells. However, the role of the cell wall and its polysaccharide composition in relation to drought resistance of succulent plants are unknown. We investigate the drought response of leaf-succulent Aloe (Asphodelaceae) species using a combination of histological microscopy, quantification of water content, and comprehensive microarray polymer profiling. We observed a previously unreported mode of polysaccharide and cell wall structural dynamics triggered by water shortage. Microscopical analysis of the hydrenchyma cell walls revealed highly regular folding patterns indicative of predetermined cell wall mechanics in the remobilization of stored water and the possible role of homogalacturonan in this process. The in situ distribution of mannans in distinct intracellular compartments during drought, for storage, and apparent upregulation of pectins, imparting flexibility to the cell wall, facilitate elaborate cell wall folding during drought stress. We conclude that cell wall polysaccharide composition plays an important role in water storage and drought response in Aloe

Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction

BACKGROUND: In guinea pigs, we have previously demonstrated that the contribution of Rho-kinase to airway responsiveness in vivo and ex vivo is enhanced after active sensitization with ovalbumin (OA). Using conscious, unrestrained OA-sensitized guina pigs, we now investigated the role of Rho-kinase in the development of airway hyperresponsiveness (AHR) after the allergen-induced early (EAR) and late asthmatic reaction (LAR) in vivo. METHODS: Histamine and PGF(2α )PC(100)-values (provocation concentrations causing 100% increase in pleural pressure) were assessed before OA-challenge (basal airway responsiveness) and after the OA-induced EAR (5 h after challenge) and LAR (23 h after challenge). Thirty minutes later, saline or the specific Rho-kinase inhibitor Y-27632 (5 mM, nebulizer concentration) were nebulized, after which PC(100)-values were reassessed. RESULTS: In contrast to saline, Y-27632 inhalation significantly decreased the basal responsiveness toward histamine and PGF(2α )before OA-challenge, as indicated by increased PC(100 )-values. Both after the allergen-induced EAR and LAR, AHR to histamine and PGF(2α )was present, which was reversed by Y-27632 inhalation. Moreover, there was an increased effectiveness of Y-27632 to reduce airway responsiveness to histamine and PGF(2α )after the EAR and LAR as compared to pre-challenge conditions. Saline inhalations did not affect histamine or PGF(2α )PC(100)-values at all. Interestingly, under all conditions Y-27632 was significantly more effective in reducing airway responsiveness to PGF(2α )as compared to histamine. Also, there was a clear tendency (P = 0.08) to a more pronounced degree of AHR after the EAR for PGF(2α )than for histamine. CONCLUSION: The results indicate that inhalation of the Rho-kinase inhibitor Y-27632 causes a considerable bronchoprotection to both histamine and PGF(2α). Moreover, the results are indicative of a differential involvement of Rho-kinase in the agonist-induced airway obstruction in vivo. Increased Rho-kinase activity contributes to the allergen-induced AHR to histamine and PGF(2α )after both the EAR and the LAR, which is effectively reversed by inhalation of Y-27632. Therefore, Rho-kinase can be considered as a potential pharmacotherapeutical target in allergic asthma

Airway smooth muscle relaxation results from a reduction in the frequency of Ca(2+ )oscillations induced by a cAMP-mediated inhibition of the IP(3 )receptor

BACKGROUND: It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca(2+ )oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca(2+ )oscillations. METHODS: The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca(2+ )signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy. RESULTS: All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca(2+ )oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca(2+ )oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca(2+ )oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca(2+ )stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca(2+ )available to stimulate contraction because an elevation of intracellular Ca(2+ )concentration induced by exposure to a Ca(2+ )ionophore (ionomycin) or by photolysis of caged-Ca(2+ )did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca(2+)-activated K(+ )channels, which would be expected to increase Ca(2+ )influx and contraction. By contrast, the photolysis of caged-IP(3 )in the presence of agonist, to further elevate the intracellular IP(3 )concentration, reversed the slowing of the frequency of the Ca(2+ )oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP(3)R to IP(3 )was reduced by FSK and this was supported by the reduced ability of IP(3 )to release Ca(2+ )in SMCs in the presence of FSK. CONCLUSION: These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca(2+ )oscillation frequency by reducing internal Ca(2+ )release through IP(3 )receptors