Altered activity–rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the β2 nicotinic receptor

High-affinity nicotinic receptors containing β2 subunits (β2^*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer's disease, Parkinson's disease and epilepsy. Mutations in both the α4 and β2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In this study, we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation β2V287L. β2^(V287L) mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not show an overt seizure phenotype; however, homozygous mice did show significant alterations in their activity–rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that β2^(V287L) mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of β2^* nicotinic receptors in complex biological processes including the activity–rest cycle, natural reward and anxiety

Lactation and neonatal nutrition: defining and refining the critical questions.

This paper resulted from a conference entitled "Lactation and Milk: Defining and refining the critical questions" held at the University of Colorado School of Medicine from January 18-20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond

The Effect of Affirmative Action on Workers’ Outcomes

Fifty-six years after the introduction of affirmative action in employment in the U.S., there is a lack of consensus regarding the effect of this policy on workers’ careers (Holzer and Neumark, 2000). This paper contributes to fill this gap by building and analyzing a dataset that allows us to quantify the effects of affirmative action in employment on workers’ labor market outcomes. This paper circumvents prior data restrictions by constructing the first administrative database containing worker-level information (from the Longitudinal Employment Household Dynamics) as well as the federal contractor status of workers’ employers (from the Equal Employment Opportunity Commission Data and Federal Procurement Data). We estimate the causal effects of affirmative action on workers’ outcomes exploiting different features specified by the legal obligations of the regulation in a regression discontinuity setting

Identity asymmetries:An experimental investigation of social identity and information exchange in multiteam systems

Many complex organizational tasks are performed by networks of teams, or “multiteam systems.” A critical challenge in multiteam systems is how to promote information exchange across teams. In three studies, we investigate how identity “asymmetries”—differences between teams in terms of whether the team or overarching system constitutes their primary focus of identification—affect interteam information sharing and performance. In Study 1, we manipulate teams’ foci of identification (team vs. system focused) in a sample of 84 five-member teams working in one of 21 four-team multiteam systems performing a computer strategy simulation. We find that, while system-focused teams shared information equally with all teams, team-focused teams shared less information with system-focused teams than they did with other team-focused teams. Interteam information sharing positively predicted interteam performance. In Study 2, we test the assumptions underlying our theory in a vignette experiment, demonstrating that team-focused individuals adopt instrumental motives toward interteam interaction. Finally, in Study 3, we investigate the implications of system composition in terms of team identity foci by means of a simulation study based on the empirical results of Study 1. The results of the simulation yield novel propositions about the nonlinear effects of social identity in multiteam systems

Research on Markets for Inventions and Implications for R&D Allocation Strategies

Several streams of literature have examined the phenomenon of “markets for inventions”, that is, the trade of elements of knowledge which are “disembodied” from individuals, organizations, and products. The aims of this paper are to bring together the various streams of research in this area and discuss their major assumptions and limitations, in order to provide a comprehensive framework for understanding the phenomenon, and identify promising paths for future research. We start our review by identifying the object of market exchange—that is, an invention whose knowledge has been codified and disembodied from individuals, organizations, or artifacts. We then identify those factors that enable firms to trade inventions, distinguishing between institutional-, firm-, and industry-level factors. We close our analysis of the extant literature by discussing the implications of markets for inventions for firm behavior and performance. Against this background, we highlight an important avenue for future research. A neglected implication of the development of invention markets is that firms are confronted with a wide variety of technological paths from which to choose, because the opportunity to acquire technologies on the market offers them a greater variety that can their internal R&D departments. However, the streams of research on markets for inventions and on R&D allocation strategies have been surprisingly disconnected so far. Hence, in the final section, we start to establish and explore the link between these literatures, and to identify a research agenda in this domain

Assessing the stability of ego-centered networks over time using the digital participant-aided sociogram tool Network Canvas

This paper examines the stability of ego-centered networks as reported over time using a novel touchscreen-based participant-aided sociogram. Past work has noted the instability of nominated network alters, with a large proportion leaving and reappearing between network interview observations. To explain this instability of networks over time, researchers often look to structural embeddedness, namely the notion that alters are connected to other alters within personal networks. Recent research has also asked whether the interview situation itself may have a role to play in conditioning respondents to what might be the appropriate size and shape of a social network, and thereby which alters ought to be nominated or not. We report on change in these networks across three waves and assess whether this change appears to be the result of natural churn in the network or whether it might be the result of factors in the interview itself. Our results indicate that there is little change in the average network size across waves, particularly for indirect tie nominations. Where there is change, we speculate on whether it is related to instrument bias, anchoring or natural change in networks. Data come from three waves of a longitudinal panel study of young men who have sex with men in Chicago

Photoactivatable drugs for nicotinic optopharmacology

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales

We All Know How, Don’t We? On the Role of Scrum in IT-Offshoring

Part 2: Creating Value through Software DevelopmentInternational audienceOffshoring in the IT-industry involves dual interactions between a mother company and an external supplier, often viewed with an implicit perspective from the mother company. This article review general off shoring and IT offshoring literature, focusing on the proliferation of a globally available set of routines; Scrum and Agile. Two cases are studied; a small company and short process and a large mother company with a long process. The interactions of the set ups shows that global concepts like Scrum and Agile are far from a common platform. The “well known” concepts are locally shaped and the enterprises have mixed experiences

Acceleration and Deceleration in the Internationalization Process of the Firm

By adopting a processual and dynamic view on internationalization, we develop the concepts of acceleration and deceleration, providing analytical tools to enhance our understanding of the non-linearity and multidimensionality of internationalization. We argue that acceleration and deceleration are embedded in the internationalization process and are a consequence of the firm’s capability to absorb and integrate acquired knowledge, and to find and exploit opportunities. In addition, we advance the idea that changes in speed are further influenced by how the firm integrates and coordinates the resources it has deployed within and across various internationalization dimensions. Thus, it emerges that the overall evolution of commitment to internationalization is more complex than received theories tend to present; therefore, empirical studies should aim to include a wide set of international activities and processes embedded in time

Externalizing, internalizing and fostering commitment: the case of born-global firms in emerging economies

This paper examines the HR practices of mature born-global firms from twenty-nine emerging economies. Through an examination of large scale survey data the paper questions the extent to which firm size impacts the employment of temporary workers, the employment of skilled workers and the extent of employee training. Findings suggest that as firm size increases the use of temporary workers decreases, the number of skilled workers increases and the number of employees receiving training also increases. The paper highlights how born-global firms are able to shift away from externalized, market-based approaches towards more internalized, commitment-based approaches in order to survive, adapt and grow