Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in ...neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.
Heptahelical receptors (HHRs) are generally thought to function as monomeric entities. Several HHRs such as somatostatin receptors (SSTRs), however, form homo- and heterooligomers when activated by ...ligand binding. By using dual fluorescent ligands simultaneously applied to live cells monotransfected with SSTR5 (R5) or SSTR1 (R1), or cotransfected with R5 and R1, we have analyzed the ligand receptor stoichiometry and aggregation states for the three receptor systems by fluorescence resonance energy transfer and fluorescence correlation spectroscopy. Both homo- and heterooligomeric receptors are occupied by two ligand molecules. We find that monomeric, homooligomeric, and heterooligomeric receptor species occur in the same cell cotransfected with two SSTRs, and that oligomerization of SSTRs is regulated by ligand binding by a selective process that is restricted to some (R5) but not other (R1) SSTR subtypes. We propose that induction by ligand of different oligomeric states of SSTRs represents a unique mechanism for generating signaling specificity not only within the SSTR family but more generally in the HHR family.
The behavioral agency model suggests that to preserve socioemotional wealth, loss-averse family firms usually invest less in R&D than nonfamily firms. However, behavioral agency model predictions are ...inconsistent with the well-accepted premise that family firms have a long-term investment orientation. We reconcile these seemingly incompatible predictions by adding insights from the myopic loss aversion framework, which deals with the impact of decision-making time horizons. The combination of these two prospect theory derivatives led us to hypothesize that family firms usually invest less in R&D than nonfamily firms but the variability of their investments will be greater owing to differences in the compatibility of long- and short-term family goals with the economic goals of a firm. However, when performance is below aspiration levels, we theorize that family goals and economic goals tend to converge. In this situation, the R&D investments of family firms are expected to increase and the variability of those investments decrease, relative to nonfamily firms. Analysis of 964 publicly held family and nonfamily firms from the Standard & Poor's 1500 between 1998 and 2007 support our hypotheses, confirming a need to take the heterogeneity of family firms more fully into account.
•Digitalization without servitization capabilities can lead to negative returns, i.e., the digitalization paradox.•Digital servitization explains profiting from digitalization requires servitization ...in manufacturing firms.•Emphasizing value of servitization in driving financial performance from digitalization, a call for digital servitization.•The results also emphasize the need for high investments in digitalization.•Further studies are needed on the complex relationship between digitalization, servitization and company performance.
The present study investigates the effect of the interaction between digitalization and servitization on the financial performance of manufacturing companies. We challenge the simple linear assumption between digitalization and financial performance with a sample of 131 manufacturing firms and hypothesize a nonlinear U-shaped interaction effect between digitalization and servitization on financial performance. From low to moderate levels of digitalization, the interaction effect between digitalization and high servitization on company financial performance is negative and significant. From moderate to high levels of digitalization, the interplay between digitalization and high servitization becomes positive and significant, improving companies’ financial performance. The results demonstrate the need for an effective interplay between digitalization and servitization, the digital servitization. Without this interplay, a manufacturing company may face the paradox of digitalization. For managers of manufacturing companies, the study provides insights into the complex relationship between digitalization and financial performance, emphasizing the value of servitization in driving financial performance from digitalization. Thus, the study demonstrates how manufacturing companies can become data-driven by advancing servitization.
Over the past decade, the rise of blockchain technology has led to the emergence of a growing number of decentralized platforms that are governed less by platform owners and more through community ...efforts. The emergence of blockchain platforms offers a unique opportunity to examine alternative structures for platform governance and to develop a theory around the value of centralized, semi-decentralized, and decentralized governance. Drawing on mechanism design theory, we evaluate the tradeoffs between centralization and decentralization and hypothesize semi-decentralization as a higher performing governance structure. Empirical evidence from the blockchain industry shows that decentralization has an inverted U-shaped relationship with platforms’ market capitalization, developer attention, and development activity. We further examine factors driving the decentralization of platform governance and find that digital platforms of the infrastructure layer—relative to those of the application layer—have a tendency to become more decentralized. This tendency, nevertheless, can be offset by experienced leaders to achieve semi-decentralization. Overall, this study contributes new insights on the characteristics, antecedents, and consequences of effective platform governance.
Although more generalist CEOs command a significant pay premium and are known for initiating a variety of strategic changes, whether their sought-after experience is associated with higher firm ...performance remains unexplored. Drawing on instrumental leadership and domain expertise frameworks, we propose a negative association between more generalist CEO experience (across different industries or firms) and firm performance, but one that is alleviated by longer tenure. Based on a sample of 16,158 CEO-firm-year observations from 2243 firms, we find support for a negative association between more generalist CEO experience and firm performance, which is alleviated with longer CEO tenure. These preliminary results have implications for the increasingly common practice of seeking to hire more generalist CEOs in an effort to improve firm performance.
Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and ...inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.
During the early 2020 COVID-19 pandemic, several US states had implemented stay-in-place orders (SIPOs) with varying degrees of stringency which resulted in inter-state differences in mobility (i.e., ...longer presence at home). We test whether the inter-state differences in mobility influenced changes in reported psychological distress. Our study is not on the surge in COVID-19 in the later part of 2020.
To identify whether the change in state-level mobility is associated with the change in individuals’ reported psychological distress during the early COVID-19 pandemic and whether the intensity of the association varies by older individuals, females, and nonwhites.
We use differences in state-level mobility and change in reported psychological distress between the two dates of interviews of 5,132 individuals who participated in March and April 2020 waves of Understanding America Study (UAS).
We find support for modest effects, i.e., a one standard deviation decline in mobility was associated with a 3.02% higher psychological distress 95% CI: 0.4%–5.64%, and the effects are robust to controlling for reported changes in exercise intensity, alcohol consumption, cannabis use, recreational drug use, and meditation intensity. We also find support for a stronger association for females, but not for older individuals or non-whites. Further, we do not find support for the mediation effects from change in chance of running out of money or change in chance of getting COVID-19.
Our findings show that reduced mobility from lockdowns during the early COVID-19 wave in the US is associated with a modest increase in reported psychological distress, especially for females. However, these conclusions should not be construed as a small increase in psychological distress in general, as a variety of non-mobility related factors associated with COVID-19 could have exacerbated psychological distress during the early COVID-19 wave in the US.
•Did reduced mobility early in 2020 COVID-19 pandemic affect psychological distress?•Used two waves of Understanding America Study individual survey for analysis.•Found that decline in mobility is associated with modest increase in distress.•Found evidence of stronger association especially among females.
The upper echelons of publicly traded family firms can comprise family members and non-family members. Due to ownership and control factors, family members often wield significant influence in the ...upper echelons. If non-family members lack sources of influence, they may exhibit lower participation. Limited participation by non-family members lowers access to and integration of knowledge from non-family members, thus lowering the ability to devise strategic actions that increase performance. Drawing on the structural basis of power, we set out that greater equality in structural power (or compensation, status, and representation) across family and non-family top management team members increases performance in family firms. Moreover, we posit that this relationship is stronger under increasing environmental dynamism and higher governance performance, but weaker under the presence of a founder CEO. Using a sample of 231 publicly traded family firms, representing 1,934 firm-year observations from 2001 to 2010 and controlling for endogeneity, we find support for these proposed relationships.
Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the ...time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.
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