Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels in the (...) cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

We advocate for an integrative long-term perspective on time, noting that culture changes on timescales amenable to behavioral genetic study with appropriate design and modeling extensions. We note the need for replications of behavioral genetic studies to examine model invariance across long-term timescales, which would afford examination of specified as well as unspecified cultural moderators of behavioral genetic effects.

Volume 20, Issue 4, May 2020, Page 35-37.

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult structures (...) solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

Abstract:Sustainable development and built heritage are oft-naturalized hegemonic discourses of the dominant social class. However, under the lens of critical sociomateriality, these categories destabilize—and in Brexit-era London, epicenter of a financial and technological capitalist circulatory space, “all that is solid melts” into the scopal regime of London's View Management Framework (LVMF). Analyzing multiple discourses of Southwark's Strata SE1— billed London's first “sustainable tower”—and adaptive reuse of the historically preserved Lambeth Water Tower, I argue that these structures constitute ‘interface objects’ in (...) a broader relational geography imbricating physical material, social objects, gentrification and the naturalized epistemologies of hegemonic development within London's skyline itself. I offer a reading of critical sociomateriality which illuminates rhythms of daily life within spatial-technological systems of energy provision, urban metabolic processes, as well as “hegemonic premiums,” what Richard Barras terms expected return on symbolic capital vis-à-vis the dominant panopticism of the LVMF. This paper contributes a theorization of critical sociomateriality, operating across a diversity of scales, tactics, and disciplines, analyzing discourses and practices which insinuate politics, artifacts, and technologies across contested issues. Critical sociomateriality is presented as a methodology for deconstructing tactics for inhabiting and interfacing with ‘sustainability’ through London's skyline in an unequal capitalist system marked by dissensus over runaway development, social precarity, and inequality in lived experiences of the urban environment. (shrink)

Background To describe the preferences for disclosure of individual biomarker results among mothers participating in a longitudinal birth cohort. Methods We surveyed 343 mothers that participated in the Health Outcomes and Measures of the Environment Study about their biomarker disclosure preferences. Participants were told that the study was measuring pesticide metabolites in their biological specimens, and that the health effects of these low levels of exposure are unknown. Participants were asked whether they wanted to receive their results and their child's (...) results. In addition, they were asked about their preferred method (letter vs in person) and format (more complex vs less complex) for disclosure of results. Results Almost all of the study participants wanted to receive their individual results (340/343) as well as their child's results (342/343). However, preferences for receiving results differed by education level. Mothers with less than a college degree preferred in-person disclosure of results more often than mothers with some college education or a college degree (34.3% vs 17.4% vs 7.9%, p<0.001). Similarly, mothers with less than a college education preferred a less complex disclosure format than mothers with some college education or a college degree (59.7% vs 79.1% vs 86.3%, p<0.0001). Conclusion While almost all study participants preferred to receive results of their individual biomarker tests, level of education was a key factor in predicting preferences for disclosure of biomarker results. To ensure effective communication of this information, disclosure of biomarker results should be tailored to the education level of the study participants. (shrink)

Beginning in 2002, Wells Fargo began opening fraudulent accounts for unsuspecting customers. Stakeholders at every level either participated in, ignored, or tolerated the bank’s behavior that defrauded consumers on a massive scale. These unethical and well-documented schemes spanned more than a decade. Using public sources, this case recounts the events and ethical lapses that unfolded over the multiyear investigation of the Wells Fargo fraudulent accounts scandal and illuminates the general systemic failures of corporate culture and governance, public regulation, and market (...) responses to promote ethical business practices. This case provides the opportunity to consider what means for fostering ethical conduct might exist if a corporation can be big enough and rich enough that civil, criminal, regulatory, and market forces cannot deter unethical corporate practices, and if the market does not punish the corporation for a culture that promotes fraud. (shrink)

A community's abilities to promote health and maximize its response to public health threats require fulfillment of one of the four elements of public health legal preparedness, the capacity to effectively coordinate law-based efforts across different governmental jurisdictions, as well as across multiple sectors and disciplines. Government jurisdictions can be viewed “vertically” in that response efforts may entail coordination in the application of laws across multiple levels, including local, state, tribal, and federal governments, and even with international organizations. Coordination of (...) legal responses to public health emergencies also may involve a horizontal dimension comprising numerous and diverse sectors, such as public health, public and private health care, emergency management, education, law enforcement, the judiciary, and the military.Although responses to many acute health threats can implicate multiple jurisdictions and sectors, the jurisdictional and sectoral dimensions of legal preparedness are complex and may vary substantially by the nature of a threat, its geographic and geopolitical extent, and the operational response demanded. (shrink)

A community's abilities to promote health and maximize its response to public health threats require fulfillment of one of the four elements of public health legal preparedness, the capacity to effectively coordinate law-based efforts across different governmental jurisdictions, as well as across multiple sectors and disciplines. Government jurisdictions can be viewed “vertically” in that response efforts may entail coordination in the application of laws across multiple levels, including local, state, tribal, and federal governments, and even with international organizations. Coordination of (...) legal responses to public health emergencies also may involve a horizontal dimension comprising numerous and diverse sectors, such as public health, public and private health care, emergency management, education, law enforcement, the judiciary, and the military.Although responses to many acute health threats can implicate multiple jurisdictions and sectors, the jurisdictional and sectoral dimensions of legal preparedness are complex and may vary substantially by the nature of a threat, its geographic and geopolitical extent, and the operational response demanded. (shrink)

Cramer et al. articulate a novel perspective on comorbidity. However, their network models must be compared with more parsimonious latent variable models before conclusions can be drawn about network models as plausible accounts of comorbidity. Latent variable models have proven generative in studying psychopathology and its external correlates, and we doubt network models will prove as useful for psychopathology research.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Caesarean delivery is a common and life-saving intervention. However, it involves an overall increased risk for short-term and long-term complications for both mother and child compared with vaginal delivery. From a medical point of view, healthcare professionals should, therefore, not recommend caesarean sections without any anticipated medical benefit. Consequently, caesarean sections requested by women for maternal reasons can cause conflict between professional recommendations and maternal autonomy. How can we assure ethically justified decisions in the case of caesarean sections on maternal (...) request in healthcare systems that also respect patients’ autonomy and aspire for shared decisions? In the maternal–professional relationship, which can be characterised in terms of reciprocal obligations and rights, women may not be entitled to demand a C-section. Nevertheless, women have a right to respect for their deliberative capacity in the decision-making process. How should we deal with a situation of non-agreement between a woman and healthcare professional when the woman requests a caesarean section in the absence of obvious medical indications? In this paper, we illustrate how the maternal–professional relationship is embedded in a nexus of power, trust and risk that reinforces a structural inferiority for women. To accommodate for beneficial use of power, these decision processes need to be trustworthy. We propose a framework, inspired by Lukes’ three-dimensional notion of power, which serves to facilitate trust and allows for beneficial power in shared processes of decision-making about the delivery mode for women requesting planned C-sections. (shrink)

Cappelen et al. (2015) open their paper, “Fairness is intuitive,” with the observation, “A key question in the social sciences is whether it is intuitive to behave in a fair manner or whether fair behavior requires active self-control” (p. 2). They purport to offer “evidence showing that fair behavior is intuitive to most people” (p. 1). Their premise is that deciding by intuition is faster than deciding by deliberation. While this premise in and on itself is rather uncontroversial—the conclusion that (...) they draw from it is not: “Since a decision that relies on intuition is typically made faster than a decision that relies on deliberation, the response time of a fair decision relative to a selfish decision provides an important indication of the intuitiveness of fair behavior” (p. 2). This reasoning, in fact, amounts to a reverse inference fallacy. ‘Intuitive’ may mean ‘fast’, but this would not imply that ‘fast’ means ‘intuitive’. However, we may ask, under which empirical conditions might we be allowed to draw the inference of ‘intuitive’ from ‘fast’? Naturally, these conditions would require that ‘fast’ rule out ‘deliberative’. To achieve this, we would need information beyond relative response speed alone—such as absolute decision times. And this begs the question, which range of decision times would rule out ‘deliberative’—or at the very least, render it improbable? Although the precise cut-off for deliberative decisions may be difficult to establish (see e.g., Schnei... (shrink)

Counterfactual causal interpretations of family genetic effects are appropriate, but neglect an important feature: Provision of unique information about expected outcomes following an independent decision, such as a decision to intervene. Counterfactual causality criteria are unlikely to resolve controversies about behavioral genetic findings; such controversies are likely to continue until counterfactual inferences are translated into interventional hypotheses and designs.

This article addresses three interrelated concerns: the pervasive nature of technologically induced impatience, a theological understanding of divine patience, and, finally, a suitable response to techno-impatience by way of engagement with the art and practice of holy habit. As we have experienced faster flows of information, and larger amounts of information through which we must sort, we have become less patient people. This loss of patience continues to produce a new kind of personal and communal disquiet on an impressive scale. (...) To address concerns with techno-impatience, arguments will be drawn from scriptural and theological concepts of divine patience. These concepts prompt us to rediscover, and reinvent, a richer understanding of patience as an individuated spiritual virtue. Accordingly, a corrective to the exacerbating effects of technologically induced impatience will be offered: namely, the explicit spiritual discipline of practicing holy patience. (shrink)

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and sex steroids (...) influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

We investigated people's ability to infer others’ mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents’ desires throughout. When the agent observed, but did not cause the outcome, participants’ ability to recover the agent's beliefs depended on the evidence they got. When the agent caused the event, participants’ judgments also depended on the probability of the action ; when actions were improbable given the mental states, people failed to recover the agent's (...) beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout, consistent with the proposal that people rationally integrate information about others’ actions and emotional reactions to infer their unobservable mental states. (shrink)

In 1995, the eyeless (ey) gene was dubbed the “master‐regulator” of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other diverse (...) tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Abstract11β‐hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17β‐hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11β‐hydroxysteroid dehydrogenases and four mammalian 17β‐hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11β‐ and 17β‐hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with β‐hydroxybutyrate dehydrogenase, 11‐cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17β‐hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional enzyme (...) on a fourth branch. Pig 17β‐hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17β‐hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17β‐hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11β‐ and 17β‐hydroxysteroid dehydrogenases. (shrink)

We consider three accepted truths about iris biometrics, involving pupil dilation, contact lenses and template aging. We also consider a relatively ignored issue that may arise in system interoperability. Experimental results from our laboratory demonstrate that the three accepted truths are not entirely true, and also that interoperability can involve subtle performance degradation. All four of these problems affect primarily the stability of the match, or authentic, distribution of template comparison scores rather than the non-match, or imposter, distribution of scores. (...) In this sense, these results confirm the security of iris biometrics in an identity verification scenario. We consider how these problems affect the usability and security of iris biometrics in large-scale applications, and suggest possible remedies. (shrink)

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband’s duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen’s 'joint (...) account model', we adapt Kilbride’s application of the rule of rescue and balance it against the relative’s right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband’s objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband’s privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)