In recent years, the genetic testing and selection of IVF embryos, known as preimplantation genetic testing (PGT), has gained much traction in clinical assisted reproduction for preventing transmission of genetic defects. However, a more recent ethically and morally controversial development in PGT is its possible use in selecting IVF embryos for optimal intelligence quotient (IQ) and other non–disease-related socially desirable traits, such as tallness, fair complexion, athletic ability, and eye and hair colour, based on polygenic risk scores (PRS), in what (...) is referred to as PGT-P. Artificial intelligence (AI) and machine learning–based analysis of big data sets collated from genome sequencing of specific human ethnic populations can be used to estimate an individual embryo’s likelihood of developing such multifactorial traits by analysing the combination of specific genetic variants within its genome. Superficially, this technique appears compliant with Islamic principles and ethics. Because there is no modification of the human genome, there is no tampering with Allah’s creation (_taghyīr khalq Allah_). Nevertheless, a more critical analysis based on the five maxims of Islamic jurisprudence (_qawa'id fiqhiyyah_) that are often utilized in discourses on Islamic bioethics, namely _qaṣd_ (intention), _yaqın̄_ (certainty), _ḍarar_ (injury), _ḍarūra_ (necessity), and _`urf_ (custom), would instead reveal some major ethical and moral flaws of this new medical technology in the selection of non–disease-related socially desirable traits, and its non-compliance with the spirit and essence of Islamic law (shariah). Muslim scholars, jurists, doctors, and biomedical scientists should debate this further and issue a fatwa on this new medical technology platform. (shrink)

Research on unethical leadership has predominantly focused on interpersonal and high-intensity forms of harmful leader behavior such as abusive supervision. Other forms of harmful leader behavior such as excessively pressuring subordinates or acting in self-centered ways have received less attention, despite being harmful and potentially occurring more frequently. We propose a model of four types of harmful leader behavior varying in intensity and orientation : Intimidation, Lack of Care, Self-Centeredness, and Excessive Pressure for Results. We map out how these relate (...) to other constructs in the unethical leader behavior field in order to integrate the existing work on how leaders can cause harm to followers. Next, in five studies, we develop and test a new survey instrument measuring the four proposed types of perceived HLB. We provide initial validity evidence for this new measure, establish its psychometric properties, and examine its nomological network by linking the four types of HLB to related leadership constructs and soft and hard outcome correlates at the individual and team level. We find that HLB is negatively related to constructive forms of leadership and positively to unethical ones. HLB is also related in the expected direction to job satisfaction, engagement, psychological safety, knowledge sharing, knowledge hiding, deviance, and objectively recorded team-level stress-related absenteeism. (shrink)

Most research on ethical leadership to date investigates the consequences of ethical leadership rather than its antecedents. Here, we aim to contribute to this field by studying leader personality as a potential antecedent of ethical leader behavior. In two multisource studies, we investigated the relationships between personality traits and ethical leader behavior. Leader personality was measured through self-ratings using the five-factor personality framework. Two subordinates rated their leaders' ethical behavior. Study 1 used a unidimensional Ethical Leadership Scale (ELS). In study (...) 2 we used this scale as well as an instrument distinguishing three different ethical leader behaviors, namely, fairness, role clarification, and power sharing. Further, in study 2 we controlled for the influence of the relationship between leader and followers (LMX). As expected, conscientiousness and agreeableness were most consistently related to ethical leadership. In study 1, after controlling for the other personality traits, conscientiousness related positively with ethical leadership. In study 2, after controlling for other traits and LMX, conscientiousness related positively with ethical leadership and the behavior role clarification, and agreeableness with power sharing and fairness. Also, emotional stability related positively with ethical leadership and role clarification after controlling for LMX. As expected, openness to experience and extraversion were unrelated to ethical leader behaviors. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

Burnout has important ramifications for employees and organizations and preventing burnout forms an ethical issue for managers. However, the role of the leader and especially the role of ethical aspects of leadership have received relatively little attention in relation to burnout to date. We conducted a survey among employees (N = 386) of a Dutch retail organization, nested in 122 teams with a leader. Our first contribution is that we empirically show the hypothesized opposing relationships of ethical and passive leadership (...) behavior with follower burnout. Furthermore, we examined two job characteristics as mechanisms that link these forms of leadership and burnout. Lastly, we show that the positive relationship of ethical leadership with burnout via role clarity (but not overload) is dependent on the degree of passive leadership the leader is perceived to display. Our results suggest that organizations should promote ethical leadership behaviors and limit passive leadership behaviors by stimulating leaders to be active in their role and use their social influence to promote ethical conduct. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Through the process of domestication the genetic make-up of farm animals can be changed by means of either selective breeding or genetic engineering. This paper is about the ethical limits to such genetic changes. It is suggested that the ethical significance of domestication has become clear recently in the light of genetic engineering, but that the problem has been there all along. Two ethical approaches to domestication are presented, genetic integrity and animal welfare. It is argued that the welfare approach (...) is superior. Finally, five ethical hypotheses based on the welfare approach are presented. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

We report specific heat and μSR measurements on Th and/or B substituted UBe13. The specific heat data show that either Th or B substitution reduces the Kondo temperature TK and increases the entropy at the superconducting transition by almost 20%, indicating an enhanced density of states. However, whereas μSR shows clear evidence for magnetic correlations for Th substitutions, no magnetism is observed for B substitutions. The enhanced specific heat jump in the B-substituted material is associated with a change in the (...) superconducting properties as TK is reduced. (shrink)

Although narcissists often emerge as leaders, the relationship between leader narcissism and follower performance is ambiguous and often even found to be negative. For women, narcissism seems especially likely to lead to negative evaluations. Since narcissists have the tendency to be impulsive and change their minds on a whim, they may come across as inconsistent. We propose “inconsistent leader behavior” as a new mechanism in the relationship between leader narcissism and follower performance and argue that leader gender plays an important (...) role in whether narcissistic leaders are perceived as inconsistent. Specifically, we expect leader narcissism to have a negative relationship with follower performance through perceived inconsistent leader behavior, especially for female leaders. Thus, we examine leader gender as a personal factor moderating the relationship between narcissism and perceived inconsistent behavior. Also, as perceived inconsistency is likely less problematic when a good relationship exists, we examine leader–member exchange as a contextual condition moderating the relationship between leader behavior and follower performance. We test our moderated mediation model in a multi-source study with 165 unique leader–follower dyads. As expected, leader narcissism was positively related to perceived inconsistent leader behavior, and this relationship was stronger for female leaders. Inconsistent leader behavior was negatively related to follower performance, but only when LMX was low. Our research highlights that perceived behavioral inconsistency can be problematic and—for female leaders—provides an explanation of the negative relation of leader narcissism with follower performance and of the inconsistencies in evaluations of narcissistic leaders’ effectiveness. (shrink)

The social, educational and political writings of Jean-Jacques Rousseau have become enormously influential in the 200 years since his death. But the breadth as well as the depth of Rousseau's achievement - he was amongst other things a creative writer and musical composer as well as a philosopher - is not always appreciated. In around 100 articles, alphabetically arranged and fully cross-referenced, N. J. H. Dent explores all facets of Rousseau's work and thoughts, while his subject's remarkable life is summarized (...) in a biographical introduction. Details of works by and about Rousseau are listed in an extensive bibliography. For students or general readers seeking an introduction to Rousseau's work, and for those already familiar with the material who require a convenient reference source, this dictionary is essential reading. (shrink)