The article is devoted to the study of the phenomenon of ideology in the context of its normative and regulatory function. The author's contribution to the further knowledge of the ideology was the following main conclusions. The emergence of ideology as a regulatory mechanism was primarily due to the transition from a traditional society to a modern one. Ideology is an attribute of modern society, since it acts as an intermediary between a person and social reality, determining (...) and regulating the activities of all people and relations between them in any sphere of society. In the XIX – first half of the XX centuries political ideology in its theoretical form dominated. As a regulatory mechanism, it functioned alongside religion, morality, and law, complementing them. In the second half of the XX – XXI centuries, as a result of the third STR, ideology in an ordinary and practical form became widespread. It began to replace the traditional regulatory mechanisms, surpassing them in the degree of influence on public consciousness and becoming the main mechanism of social regulation. (shrink)

Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light‐induced TIM degradation, (...) the model accounts for damping of oscillations in constant light, entrainment of the rhythm by light‐dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84–93, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

It is argued that once biological systems reach a certain level of complexity, mechanistic explanations provide an inadequate account of many relevant phenomena. In this article, I evaluate such claims with respect to a representative programme in systems biological research: the study of regulatory networks within single-celled organisms. I argue that these networks are amenable to mechanistic philosophy without need to appeal to some alternate form of explanation. In particular, I claim that we can understand the mathematical modelling techniques (...) of systems biologists as part of a broader practice of constructing and evaluating mechanism schemas. This argument is elaborated by considering the case of bacterial chemotactic networks, where some research has been interpreted as explaining phenomena by means of abstract design principles. (shrink)

Autophagy promotes both health and disease, depending on tissue types and genetic contexts, yet the regulatory mechanism remain incompletely understood. Our recent publication has uncovered a coherent FOXO‐SNAI feed‐forward loop in autophagy, which is evolutionarily conserved from Drosophila to human. In addition, it's revealed that DNA binding plays a critical role in intracellular localization of nucleocytoplasmic shuttling proteins. Based on these findings, herein we further integrate mechanistic insights of FOXO‐SNAI regulatory interplay in autophagy and unravel the potential (...) link of FOXO‐induced autophagy with SNAI in diseases. Besides, the generality of DNA‐retention mechanism on transcription factor nuclear localization is illustrated with wide‐ranging discussion, and more functions potentially regulated by FOXO‐SNAI feedforward loop are provided. Elucidation of these unsolved paradigms will expand the understanding of FOXO‐SNAI interplay and facilitate the development of new therapeutics targeting FOXO‐SNAI axis in diseases. (shrink)

U.S. regulations do not afford consistent protections to human research subjects. One complaint is that they focus on federally sponsored research, with private research covered only if it falls under the jurisdiction of the Food and Drug Administration. This paper examines a deeper problem: Even when the regulations do apply, they still do not afford consistent standards of protection. The U.S. Common Rule and related FDA regulations lack a workable regulatory control mechanism.

Whistleblower bounty schemes that pay individuals a cash “bounty” for surfacing information about illegal conduct have rapidly gained public and scholarly attention, fueling calls to install a bounty approach across numerous regulatory areas, from workplace safety, environmental protection, and civil rights to political corruption, immigration, and antitrust. Yet despite the enthusiasm, bounty regimes have remained confined to the fraud context. This Article uses this fact as a jumping off point and, looking across the regulatory state, aims to answer (...) some basic questions about bounty regimes that have thus far eluded sustained scholarly attention: What features of a given regulatory area make it more or less conducive to a bounty approach? Given this, how might existing bounty regimes be revised? And if bounty regimes were to break out of the fraud area, where might they most profitably spread? It offers some initial answers to these questions by constructing a simple framework that shows how two features of the regulatory environment - the directness of the harm to be regulated and the determinacy of the legal mandate to be implemented - structure the choice among competing bounty approaches. These aspects of regulatory context, I argue, map onto the two most vexing challenges facing regulatory architects weighing a bounty mechanism or choosing among competing designs: optimizing the quantity and quality of information revelation and maintaining public control over the elaboration of legal mandates. The framework brings into relief some of the fault-lines in the growing scholarly debate about the optimal use and design of bounty schemes, including the choice between a simple cash-for-information scheme and a more elaborate qui tam scheme in which whistleblowers are vested with independent enforcement authority via a private right of action. It also yields a rough regulatory roadmap showing where existing bounty schemes might be revised and also the areas to which a bounty approach might be usefully exported. (shrink)

Guiding core enterprises to participate in supply chain work safety governance is an innovative mode of work safety control, which has an important impact on improving the work safety level of small and medium-sized enterprises in the supply chain. Through in-depth interviews, the grounded theory is adopted to explore the driving factors of work safety management behaviors of core enterprise. It is found that the work safety management behavior of the core enterprise is driven by both internal and external factors. (...) External driving factors are the main category of institutional pressure composed of regulatory pressure, normative pressure, and cognitive pressure. Internal driving factors are divided into the main category of behavioral awareness and the behavioral capability of the core enterprises. The behavioral awareness is composed of responsibility sense, problem cognition and behavioral effect perception. The behavioral capability is composed of safety management strength and safety coordination capability. Institutional pressure, behavioral awareness, and behavioral capability all influence the work safety management behavior of core enterprise in supply chain significantly, but with different ways and paths. On this basis, the driving mechanism model of the above three main categories on the work safety management behavior in core enterprise supply chain is explored. The research can provide targeted policy ideas and implementation paths for the government to formulate effective guiding policies to promote the work safety management behavior of core enterprise. (shrink)

There is mounting evidence that non-invasive brain stimulation devices - transcranial direct current stimulation and transcranial magnetic stimulation could be used for cognitive enhancement. However, the regulatory environment surrounding such uses of stimulation devices is less clear than for stimulant drugs—a fact that has already been commercially exploited by several companies. In this paper, the mechanism of action, uses and adverse effects of non-invasive neurostimulation devices are reviewed, along with social and ethical challenges pertaining to their use as (...) cognitive enhancements. Two regulatory approaches that could be used to facilitate responsible use of these devices as products and services are outlined. Apart from establishing the urgently needed comprehensive regulatory framework, they might provide a starting point for establishing long term physiological and social effects of enhancement uses of tDCS and TMS. (shrink)

The proteins encoded by the ras proto‐oncogenes play critical roles in normal cellular growth, differentiation and development in addition to their potential for malignant transformation. Several proteins that are involved in the control of the activity of p21ras have now been characterised. p120GAP stimulates the GTPase activity of p21ras and hence acts as a negative regulator of ras proteins. It may be controlled by tyrosine phosphorylation or association with tyrosine phosphorylated proteins. The neurofibromatosis type 1 (NF 1) gene also encodes (...) a potential GTPase activating protein which is likely to be subject to a different control mechanism. Guanosine nucleotide exchange factors for p21ras have now been identified: these may be positive regulators of ras protein function. It appears that p21ras is subject to rapid regulation by several distinct mechanisms which are likely to vary in different cell types; the ras proteins are thereby able to act as very sensitive cellular monitors of the extracellular environment. (shrink)

The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. This (...) review will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation. (shrink)

ABSTRACT:Regulatory focus theory is proposed as offering an explanation for the influence of ethical leadership on organizational citizenship behaviors and employee commitments. The prevention focus mindset of an employee is argued to be the mechanism by which an ethical leader influences extra-role compliance behavior as well as normative commitment, whereas the promotion focus mindset of an employee is argued to be the mechanism by which an ethical leader influences extra-role voice behavior as well as affective commitment. Moreover, (...) leader-member exchange is proposed as a moderator of the relationship of ethical leadership to regulatory focus mindsets and employee behavior and commitments. Using the data collected in two waves from 250 working adults, we tested the proposed relationships with moderated mediation bootstrap procedures. The findings generally support the hypothesized relationships and point toward important implications for ethical leadership in work settings. (shrink)

Explanation in terms of gene regulatory networks has become standard practice in evolutionary developmental biology. In this paper, we argue that GRNs fail to provide a robust, mechanistic, and dynamic understanding of the developmental processes underlying the genotype–phenotype map. Explanations based on GRNs are limited by three main problems: the problem of genetic determinism, the problem of correspondence between network structure and function, and the problem of diachronicity, as in the unfolding of causal interactions over time. Overcoming these problems (...) requires dynamic mechanistic explanations, which rely not only on mechanistic decomposition, but also on dynamic modeling to reconstitute the causal chain of events underlying the process of development. We illustrate the power and potential of this type of explanation with a number of biological case studies that integrate empirical investigations with mathematical modeling and analysis. We conclude with general considerations on the relation between mechanism and process in evo-devo. (shrink)

The regulation of chemicals is undergoing drastic changes with the use of computational models to predict environmental toxicity. This particular issue has not attracted much attention, despite its major impacts on the regulation of chemicals. This raises the problem of causality at the crossroads between data and regulatory sciences, particularly in the case models known as quantitative structure–activity relationship models. This paper shows that models establish correlations and not scientific facts, and it engages anew the way regulators deal with (...) uncertainties. It does so by exploring the tension and problems raised by the possibility of causal explanation afforded by quantitative structure–activity relationship models. It argues that the specificity of predictive modelling promotes rethinking of the regulation of chemicals. (shrink)

Asymmetric cell division generates two cells that contain different regulatory proteins and express different fates. In an example of asymmetric cell division from B. subtilis, a site on the membrane of the dividing cell is chosen to establish the initial asymmetry. Recent results(1,2) show that a key regulatory protein, SpollE, is localized to one side of a sporulating B. subtilis cell, and subsequently functions in an asymmetric manner. SpollE is a phosphatase at the beginning of a regulatory (...) cascade that leads to activation of a cell fate‐determining transcription factor in only one daughter cell. (shrink)

Ferroptosis, a form of regulated cell death triggered by lipid hydroperoxide accumulation, has an important role in a variety of diseases and pathological conditions, such as cancer. Targeting ferroptosis is emerging as a promising means of therapeutic intervention in cancer treatment. Polyunsaturated fatty acids, reactive oxygen species, and labile iron constitute the major underlying triggers for ferroptosis. Other regulators of ferroptosis have also been discovered recently, among them the mechanistic target of rapamycin complex 1 (mTORC1), a central controller of cell (...) growth and metabolism. Inhibitors of mTORC1 have been used in treating diverse diseases, including cancer. In this review, we discuss recent findings linking mTORC1 to ferroptosis, dissect mechanisms underlying the establishment of mTORC1 as a key ferroptosis modulator, and highlight the potential of co‐targeting mTORC1 and ferroptosis in cancer treatment. This review will provide valuable insights for future investigations of ferroptosis and mTORC1 in fundamental biology and cancer therapy. (shrink)

The development and deployment of medical devices, along with most areas of healthcare, has been significantly impacted by the COVID-19 pandemic. This has had variable ethical implications, two of which we will focus on here. First, medical device regulations have been rapidly amended to expedite approvals of devices ranging from face masks to ventilators. Although some regulators have issued cessation dates, there is inadequate discussion of triggers for exiting these crisis standards, and evidence that this may not be feasible. Given (...) the relatively low evidence standards currently required for regulatory approval of devices, this further indefinite reduction in standards raises serious ethical issues. Second, the pandemic has disrupted the usual operations of device representatives in hospitals, providing an opportunity to examine and refine this potentially ethically problematic practice. In this paper we explain and critically analyse the ethical implications of these two pandemic-related impacts on medical devices and propose suggestions for their management. These include an endpoint for pandemic-related adjustments to device regulation or a mechanism for continued refinement over time, together with a review of device research conducted under crisis conditions, support for the removal and replacement of emergency approved devices, and a review of device representative credentialling. (shrink)

The function of meiotic recombination has remained controversial, despite recent inroads into mechanisms. Ideas concerning a possible role of recombination in the elimination or efficient incorporation of mutations have been backed by theoretical studies but have lacked empirical support. Recent investigations into the basis for local variations in recombination frequency in yeast have uncovered a strong association between recombination initiation sites and transcriptional regulatory sequences. Other recent studies indicate a strong correlation between transcription and mutation rates in yeast genes. (...) Taken together, these data imply that distributions of recombination and mutation frequencies may be strongly correlated. This suggests that recombination may be targeted to genomic sites of high mutation frequency; such a ‘mutation‐tracking’ function would clearly aid in the shuffling of mutations to break up unfavorable and create favorable allelic combinations. Moreover, recent insights into the mechanism of gene conversion in yeast reveal a very strong inherent bias in favor of alleles on the non‐initiating homolog. Combined with mutation tracking, these findings suggest a novel and general mechanism by which allelic gene conversion may act to eliminate mutations. (shrink)

Individuals often prefer information that matches their needs. In this study, we aimed to explore the relationship between regulatory focus and information preference. Specifically, we investigated the effects of promotion-focused information and prevention-focused information on explicit and implicit information preferences and choice behavior, and examined the mediating roles of information preference. In Experiment 1, we found that prevention-focused individuals were more likely to choose functional information, whereas promotion-focused people were more likely to choose hedonic information. However, there was no (...) significant relationship between regulatory focus and explicit preference and no mediating effect of explicit information preference. In Experiment 2, we found that promotion-focused individuals had a greater implicit preference for hedonic information than did prevention-focused individuals. Implicit information preference mediated the influence of regulatory focus on information choice. The findings of this study may help us understand the psychological mechanism underlying information preference and have important implications for information dissemination. (shrink)

Hereditary retinal degeneration due to mutations in visual genes may be amenable to therapeutic interventions that modulate, either positively or negatively, the amount of protein product. Some of the proteins involved in phototransduction are rapidly moved by a lightdependent mechanism between the inner segment and the outer segment in rod photoreceptor cells, and this phenomenon is important in phototransduction.

The stable differentiation of cells into other cell types typically involves dramatic reorganization of cellular structures and functions. This often includes remodeling of the cell cycle and the apparatus that controls it. Here we review our understanding of the role and regulation of cell cycle control elements during cell differentiation in the yeast, Saccharomyces cerevisiae. Although the process of differentiation may be more overtly obvious in metazoan organisms, those systems are by nature more difficult to study at a mechanistic level. (...) We consider the relatively well‐understood mechanisms by which mating‐type switching and the pheromone‐induced differentiation of gametes are coupled to the cell cycle as well as the more obscure mechanisms that govern the remodeling of the cell cycle during meiosis and filamentous growth. In some cases, the cell cycle is a primary stimulus for differentiation whereas, in other cases, the signals that promote differentiation alter the cell cycle. Thus, despite relative simplicity of these processes in yeast, the nature of the interplay between the cell cycle and differentiation is diverse. BioEssays 25:856–867, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Synthesizing self‐regulatory theories, we provide new insights into the antecedents of abusive supervision. We, from the perspective of supervisor's self‐regulatory resources depletion or impairment, introduce supervisor hindrance stress as an underlying mechanism of the subordinate deviance–abusive supervision relationship: this mediated relationship will be intensified at the level of high subordinate job performance. In addition, we develop a complex contingency model and propose a three‐way interaction (i.e., subordinate deviance, job performance, supervisor outcome dependence) to obtain the complete understanding (...) of the subordinate deviance–abusive supervision relationship facilitated through the supervisors’ hindrance stress. To test our moderated moderated mediation model, we gathered time‐lagged and multisource data from a large food service company located in southern China. We collected data at two different points (i.e., Time 1 and Time 2) from supervisors and their direct reports (N = 298 responses from 68 supervisors and 298 direct reports), and findings provide support for the hypothesized moderated moderated mediation model of our study. We highlight the implications of our study for theory, research, and practice. (shrink)

During development one mechanism for generating different cell types is asymmetric cell division, by which a cell divides and contributes different factors to each of its daughter cells. Asymmetric cell division occurs through out the eukaryotic kingdom, from yeast to humans. Many asymmetric cell divisions occur in a defined orientation. This implies a cellular mechanism for sensing direction, which must ultimately lead to differences in gene expression between two daughter cells. In this review, we describe two classes of (...) molecules: regulatory factors that are differentially expressed upon asymmetric cell division, and components of a signal transduction pathway that may define cell polarity. The lin‐11 and mec‐3 genes of C. elegans, the Isl‐1 gene of mammals and the HO gene of yeast, encode regulatory factors that determine cell type of one daughter after asymmetric cell division. The CDC24 and CDC42 genes of yeast affect both bud positioning and orientation of mating projections, and thus may define a general cellular polarity. We speculate that molecules such as Cdc24 and Cdc42 may regulate expression of genes such as lin‐11, mec‐3, Isl‐1 and HO upon asymmetric cell division. (shrink)

School enterprise cooperation, as the basic school running form of applied undergraduate education, is an important way to cultivate applied talents. However, at present, the lack of motivation for enterprises to participate in school enterprise cooperation and the resulting problem of “school hot and enterprise cold” seriously limit the talent training quality in China’s application-oriented universities. There is an urgent need to explore the influencing factors and mechanisms of enterprises’ participation in school enterprise cooperation to improve the training quality of (...) applied talents. Taking Ajzen Theory of Planned Behavior as the theoretical framework, this study constructs the influencing factor model of enterprise participation in school enterprise cooperation from four aspects, namely, behavior attitude, subjective norms, perceived behavior control, and behavior intention. In this study, participants completed a questionnaire assessing their participation in school enterprise cooperation, which was analyzed by a structural equation model. The results show that the behavior attitude and perceived behavior control of enterprises have a significant positive impact on their intention to participate in school enterprise cooperation and then have a significant positive impact on the school enterprise cooperation behavior of enterprises. The behavior intention and perceived behavior control of enterprises have a significant positive impact on their participation in school enterprise cooperation. The policy environment has a significant regulatory effect on the relationship between the intention and behavior of enterprises’ participation in school enterprise cooperation. Therefore, from the perspective of enhancing the intention of enterprises to cooperate, colleges and universities should establish the awareness of win-win cooperation and meet the interest demands of enterprises in school enterprise cooperation in order to improve the behavior attitude and intention of enterprises. From the perspective of the formation conditions of school enterprise cooperation, with the help of industry associations, an information service platform for school enterprise cooperation should be built in order to eliminate the information islands between enterprises and universities. From the perspective of the needs of school enterprise cooperation environment, government departments should strengthen the policy support for school enterprise cooperation in order to eliminate the worries of enterprises’ participation in school enterprise cooperation. (shrink)

At the interface of developmental biology and evolutionary biology, the very criteria of scientific knowledge are up for grabs. A central issue is the status of evolutionary genetics models, which some argue cannot coherently be used with complex gene regulatory network (GRN) models to explain the same evolutionary phenomena. Despite those claims, many researchers use evolutionary genetics models jointly with GRN models to study evolutionary phenomena. This dissertation compares two recent research projects in which researchers jointly use the two (...) kinds of models. I use methods from the empirical social sciences, such as digital corpus analysis, content analysis, and structured case analysis. I infer three primary conclusions about projects of the kind studied. First, they employ an implicit concept of gene that enables the joint use of both kinds of models. Second, they pursue more epistemic aims besides mechanistic explanation of phenomena. Third, they don’t work to create and export broad synthesized theories. Rather, they focus on phenomena too complex to be understood by a common general theory, they distinguish parts of the phenomena, and they apply models from different theories to the different parts. For such projects, seemingly incompatible models are synthesized largely through mediated representations of complex phenomena. (shrink)

Although developmental biology is an institutionalized discipline, no unambiguous account of what development is and when it stops has so far been provided. In this article, I focus on two sets of developmental molecular mechanisms, namely those underlying the heterochronic pathway in C. elegans and those involving Hox genes in vertebrates, to suggest a conceptual account of animal development. I point out that, in these animals, the early stages of life exhibit salient mechanistic features, in particular in the way mechanisms (...) of genetic regulation occur in the organism. Indeed, these stages are characterized by sequential and irreversible changes in gene expression taking place throughout the organism. A general definition of animal development based on these distinctive features implies that, at least for some animal species, development does not go on throughout the life of the animal, contrary to what has recently been claimed by some biologists and philosophers. Instead, in such species, development encompasses various events occurring sequentially at the beginning of life. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. I focus (...) on three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)

Cellular events must be executed in a certain sequence during the cell division in order to maintain genome integrity and hence ensure a cell's survival. In M phase, for instance, chromosome segregation always precedes mitotic exit (characterized by mitotic kinase inactivation via cyclin destruction); this is then followed by cytokinesis. How do cells impose this strict order? Recent findings in budding yeast have suggested a mechanism whereby partitioning of chromosomes into the daughter cell is a prerequisite for the activation (...) of mitotic exit network (MEN). So far, however, a regulatory scheme that would temporally link the initiation of cytokinesis to the execution of mitotic exit has not been determined. We propose that the requirement of MEN components for cytokinesis, their translocation to the mother–daughter neck and triggering of this translocation by inactivation of the mitotic kinase may be the three crucial elements that render initiation of cytokinesis dependent on mitotic exit. BioEssays 24: 659–666, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The present study explores the underlying mechanism of the relationship between college students’ social anxiety and mobile phone addiction. Adopting college students’ social anxiety scale, regulatory emotional self-efficacy scale, subjective well-being scale and mobile phone addiction scale, this research tested valid samples of 680 Chinese college students. The results indicated that social anxiety exerted a significant and positive impact on mobile phone addiction. Regulatory emotional self-efficacy played a partial mediating role between social anxiety and mobile phone addiction. (...) Subjective well-being also played a partial mediating role between social anxiety and mobile phone addiction. Moreover, both regulatory emotional self-efficacy and subjective well-being were found to play a chain mediating role between social anxiety and mobile phone addiction. The study provides valuable insights into the impact of college students’ social anxiety on mobile phone addiction. (shrink)

We hypothesize that recent uses of the Internet as a public-participation mechanism in the United States fail to overcome the adversarial culture that characterizes the American regulatory process. Although the Internet has the potential to facilitate deliberative processes that could result in more widespread public involvement, greater transparency in government processes, and a more satisfied citizenry, we argue that efforts to implement Internet-based public participation have overlaid existing problematic government processes without fully harnessing the transformative power of information (...) technologies. Public comments submitted in two United States Department of Agriculture rulemaking processes—the National Organic Program’s organic standard and the Forest Service’s Roadless Area Conservation Rule—compose our data. We conclude that the Internet provides an arena for playing out three types of conflicts that have long plagued environmental decision-making processes: conflicts over trust of federal agencies, the use of science, and the role of public values. (shrink)

Evolutionary biology teaches that all biological complexity is the result of material mechanisms. These include principally the Darwinian mechanism of natural selection and random variation, but also include other mechanisms (symbiosis, gene transfer, genetic drift, the action of regulatory genes in development, self-organizational processes, etc.). These mechanisms are just that: mindless material mechanisms that do what they do irrespective of intelligence. To be sure, mechanisms can be programmed by an intelligence. But any such intelligent programming of evolutionary mechanisms (...) is not properly part of evolutionary biology. (shrink)

Mucoidy and cytotoxicity arise from two independent modifications of the phenotype of the bacterium Pseudomonas aeruginosa that contribute to the mortality and morbidity of cystic fibrosis. We show that, even though the transcriptional regulatory networks controlling both processes are quite different from a molecular or mechanistic point of view, they may be identical from a dynamic point of view: epigenesis may in both cases be the cause of the acquisition of these new phenotypes. This was highlighted by the identity (...) of formal graphs modelling these networks. A mathematical framework based on formal methods from computer science was defined and implemented with a software environment. It allows an easy and rigorous validation and certification of these models and of the experimental methods that can be proposed to falsify or validate the underlying hypothesis. (shrink)

Neurons of organisms with complex and flexible behavior, especially humans, must precisely control protein localization and activity to support higher brain functions such as learning and memory. In contrast, simpler organisms generally have simpler individual neurons, less complex nervous systems and display more limited behaviors. Strikingly, however, many key neuronal proteins are conserved between organisms that have very different degrees of behavioral complexity. Here we discuss a possible mechanism by which conserved neuronal proteins acquired new attributes that were crucial (...) in the evolution of complexity of nervous system structure and function. Specifically, we hypothesize that vertebrate‐specific post‐translational palmitoylation sites and PDZ‐binding protein‐protein interaction motifs act as gain‐of‐function mutations, increasing the regulatory potential of conserved proteins without affecting their core functions. We further hypothesize that the additional regulation of neurotransmitter receptors and other membrane proteins made possible by these sites and motifs is critical for the function of complex nervous systems. (shrink)

This article challenges recent assumptions that physicians may ethically and legally prescribe psychopharmacological enhancement drugs to patients and the counterintuitive notion that in some cases ingesting an enhancement drug constitutes the more ethical choice than forgoing this option. Enhancement proponents have touted modafinil as an ideal mechanism to improve concentration, alertness, and forgo sleep and keep pace with our society's demands. However, patients who use modafinil for these reasons risk potentially severe side effects and addiction, and face unintended consequences (...) related to their cognitive, emotive, and physiological functioning. Importantly, prescribing a controlled substance such as modafinil for performance enhancement and sleep avoidance runs contrary to a physician's ethical duty to the patient and the standard of practice set forth in legal requirements governing the prescription of controlled substances. (shrink)

Reproduction and immunity are energy intensive, intimately linked processes in most organisms. In women, pregnancy is associated with widespread immunological adaptations that alter immunity to many diseases, whereas, immune dysfunction has emerged as a major cause for infertility in both men and women. Deciphering the molecular bases of this dynamic association is inherently challenging in mammals. This relationship has been traditionally studied in fast‐living, invertebrate species, often in the context of resource allocation between life history traits. More recently, these studies (...) have advanced our understanding of the mechanistic underpinnings of the immunity‐fertility dialogue. Here, we review the molecular connections between reproduction and immunity from the perspective of human pregnancy to mechanistic discoveries in laboratory organisms. We focus particularly on recent invertebrate studies identifying conserved signaling pathways and transcription factors that regulate resource allocation and shape the balance between reproductive status and immune health. (shrink)

The integrated stress response (ISR) is a key determinant of tumorigenesis in response to oncogenic forms of stress like genotoxic, proteotoxic and metabolic stress. ISR relies on the phosphorylation of the translation initiation factor eIF2 to promote the translational and transcriptional reprogramming of gene expression in stressed cells. While ISR promotes tumor survival under stress, its hyperactivation above a level of tolerance can also cause tumor death. The tumorigenic function of ISR has been recently demonstrated for lung adenocarcinomas (LUAD) with (...) KRAS mutations. ISR mediates the translational repression of the dual‐specificity phosphatase DUSP6 to stimulate ERK activity and LUAD growth. The significance of this finding is highlighted by the strong anti‐tumor responses of ISR inhibitors in pre‐clinical LUAD models. Elucidation of the mechanisms of ISR action in LUAD progression via cell‐autonomous and immune regulatory mechanisms will provide a better understanding of its tumorigenic role to fully exploit its therapeutic potential in the treatment of a deadly form of cancer. (shrink)

RNAs have emerged as a major target for diagnostics and therapeutics approaches. Regulatory nonprotein‐coding RNAs (ncRNAs) in particular display remarkable versatility. They can fold into complex structures and interact with proteins, DNA, and other RNAs, thus modulating activity, localization, or interactome of multi‐protein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of regulatory control. Interestingly, long noncoding RNAs (lncRNAs) tend to acquire complex secondary and tertiary structures and their function—in many cases—is dependent on structural (...) conservation rather than primary sequence conservation.Whereas for many proteins, structure and its associated function are closely connected, for lncRNAs, the structural domains that determine functionality and its interactome are still not well understood. Numerous approaches for analyzing the structural configuration of lncRNAs have been developed recently. Here, will provide an overview of major experimental approaches used in the field, and discuss the potential benefit of using combinatorial strategies to analyze lncRNA modes of action based on structural information. (shrink)

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy‐related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple (...) class='Hi'>regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. (shrink)

The regulatory mechanism which ensures that eukaryotic chromosomes replicate precisely once per cell cycle is a basic and essential cellular property of eukaryotes. This fundamental aspect of DNA replication is still poorly understood, but recent advances encourage the view that we may soon have a clearer picture of how this regulation is achieved. This review will discuss in particular the role of proteins in the minichromosome maintenance (MCM) family, which may hold the key to understanding how DNA is (...) replicated once, and only once, per cell cycle. (shrink)

In a globalizing world, governments are not always able or willing to regulate the social and environmental externalities of global business activities. Multi-stakeholder initiatives (MSI), defined as global institutions involving mainly corporations and civil society organizations, are one type of regulatory mechanism that tries to fill this gap by issuing soft law regulation. This conceptual paper examines the conditions of a legitimate transfer of regulatory power from traditional democratic nation-state processes to private regulatory schemes, such as (...) MSIs. Democratic legitimacy is typically concerned with input legitimacy (rule credibility, or the extent to which the regulations are perceived as justified) and output legitimacy (rule effectiveness, or the extent to which the rules effectively solve the issues). In this study, we identify MSI input legitimacy criteria (inclusion, procedural fairness, consensual orientation, and transparency) and those of MSI output legitimacy (rule coverage, efficacy, and enforcement), and discuss their implications for MSI democratic legitimacy. (shrink)

In a globalizing world, governments are not always able or willing to regulate the social and environmental externalities of global business activities. Multi-stakeholder initiatives (MSI), defined as global institutions involving mainly corporations and civil society organizations, are one type of regulatory mechanism that tries to fill this gap by issuing soft law regulation. This conceptual paper examines the conditions of a legitimate transfer of regulatory power from traditional democratic nation-state processes to private regulatory schemes, such as (...) MSIs. Democratic legitimacy is typically concerned with input legitimacy (rule credibility, or the extent to which the regulations are perceived as justified) and output legitimacy (rule effectiveness, or the extent to which the rules effectively solve the issues). In this study, we identify MSI input legitimacy criteria (inclusion, procedural fairness, consensual orientation, and transparency) and those of MSI output legitimacy (rule coverage, efficacy, and enforcement), and discuss their implications for MSI democratic legitimacy. (shrink)

Roboethics is a recently developed field of applied ethics which deals with the ethical aspects of technologies such as robots, ambient intelligence, direct neural interfaces and invasive nano-devices and intelligent soft bots. In this article we look specifically at the issue of (moral) responsibility in artificial intelligent systems. We argue for a pragmatic approach, where responsibility is seen as a social regulatory mechanism. We claim that having a system which takes care of certain tasks intelligently, learning from experience (...) and making autonomous decisions gives us reasons to talk about a system (an artifact) as being “responsible” for a task. No doubt, technology is morally significant for humans, so the “responsibility for a task” with moral consequences could be seen as moral responsibility. Intelligent systems can be seen as parts of socio-technological systems with distributed responsibilities, where responsible (moral) agency is a matter of degree. Knowing that all possible abnormal conditions of a system operation can never be predicted, and no system can ever be tested for all possible situations of its use, the responsibility of a producer is to assure proper functioning of a system under reasonably foreseeable circumstances. Additional safety measures must however be in place in order to mitigate the consequences of an accident. The socio-technological system aimed at assuring a beneficial deployment of intelligent systems has several functional responsibility feedback loops which must function properly: the awareness and procedures for handling of risks and responsibilities on the side of designers, producers, implementers and maintenance personnel as well as the understanding of society at large of the values and dangers of intelligent technology. The basic precondition for developing of this socio-technological control system is education of engineers in ethics and keeping alive the democratic debate on the preferences about future society. (shrink)

Since the development of assisted reproductive technologies, infertile individuals have crossed borders to obtain treatments unavailable or unaffordable in their own country. Recent media coverage has focused on the outsourcing of surrogacy to developing countries, where the cost for surrogacy is significantly less than the equivalent cost in a more developed country. This paper discusses the ethical arguments against international surrogacy. The major opposition viewpoints can be broadly divided into arguments about welfare, commodification and exploitation. It is argued that the (...) only valid objection to international surrogacy is that surrogate mothers may be exploited by being given too little compensation. However, the possibility of exploitation is a weak argument for prohibition, as employment alternatives for potential surrogate mothers may be more exploitative or more harmful than surrogacy. It is concluded that international surrogacy must be regulated, and the proposed regulatory mechanism is termed Fair Trade Surrogacy. The guidelines of Fair Trade Surrogacy focus on minimizing potential harms to all parties and ensuring fair compensation for surrogate mothers. (shrink)

The chapter shows how the recognition of reflexivity of emotions is crucial for understanding the role of emotions in reasoning because it highlights the regulatory role of emotion in emotional experience. The chapter begins by showing that to attain a conception of rationality that incorporates feelings, emotions, and sentiments as parts of the reasoning processes requires capturing the emotional landscape in all its complexity, and that integrating the role of meta-emotions is a contribution in that direction. Then introducing the (...) notion of meta-emotions and showing how emotional reflexivity modifies the nature of our emotional world, it is shown how emotions also have a regulatory mechanism that can either be maladaptive or at the center of emotional health. In addition, because meta-emotions provide a test for the more general assumptions of theories of emotions, the chapter ends by showing how adopting a Situated Approach to Emotions is well-suited for explaining the refinement and complexity of emotion regulation. The final reflection of the chapter explains why adopting such theoretical frame of work makes it possible to use the term situation in a technical manner, which then reveals that emotions sometimes are described as causes while other times as reasons in connection to their regulative mechanisms. (shrink)

The principle of informed consent, codified in the Declaration of Helsinki, has been widely seen as fundamental to bio-medical and research ethics. The importance of informed consent is increasing in procedures regulating the acquisition, possession and use of personal information, including genetic and medical information. Informed consent, it is believed, ensures that patients and research subjects can decide autonomously whether to permit or refuse actions that affect them. In response to this assurance, there are numerous guidelines at local, national and (...) international levels that recognise the importance of informed consent, especially in research related to healthcare in developing countries. However, complications arise in applying these guidelines to a particular situation, especially under conditions that are prevalent in developing societies, for instance in India. This article discusses common forms of impediments or hindrances encountered while exercising the principles of informed consent in the context of genetic and genomics related research among the tribal and rural caste communities in India. These hindrances include: illiteracy, poverty, paternalistic attitudes, socio-cultural barriers, ineffective regulatory mechanism and procedural inconsistency among others. The data used in this article is based on an ethnographic study conducted between December 2006 and May 2007 using social-science qualitative research techniques. We observe that three areas require attention: first, the ways in which informed public debate on bioethical issues can be held, and how the application of genetics and genomics in Indian society can be discussed; second, the readiness with which researchers, IRB members and the state appreciate and wish to map the genetic diversity in Indian society; and, third, the risks associated with the application of bioethical principles at a micro-level. (shrink)

In an instant classic paper ; 2002: 179–182) biologist Yuri Lazebnik deplores the poor effectiveness of the approach adopted by biologists to understand and “fix” biological systems. Lazebnik suggests that to remedy this state of things biologist should take inspiration from the approach used by engineers to design, understand, and troubleshoot technological systems. In the present paper I substantiate Lazebnik’s analysis by concretely showing how to apply the engineering approach to biological problems. I use an actual example of electronic circuit (...) troubleshooting to ground the thesis that, in engineering, the crucial phases of any non-trivial troubleshooting process are aimed at generating a mechanistic explanation of the functioning of the system, which makes extensive recourse to problem-driven qualitative reasoning possibly based on cognitive artifacts applied to systems that are known to have been designed for function. To show how to translate these findings into biological practice I consider a concrete example of biological model building and “troubleshooting”, aimed at the identification of a “fix” for the human immune system in presence of progressing cancer, autoimmune disease, and transplant rejection. The result is a novel immune system model—the danger model with regulatory cells— and new, original hypotheses concerning the development, prophylaxis, and therapy of these unwanted biological processes. Based on the manifest efficacy of the proposed approach, I suggest a refocusing of the activity of theoretical biologists along the engineering-inspired lines illustrated in the paper. (shrink)

Background Morality is a fundamental component of nurses’ daily work. Nurses’ cognitive tendencies toward moral disengagement in high-stress work environments can easily lead them to engage in counterproductive work behaviors that are not conducive to the organization. However, there is limited research on how to mitigate the impact of moral disengagement on counterproductive work behavior. Objective The objective was to explore the impact of moral disengagement on counterproductive work behavior, as well as the reverse regulatory mechanism of moral (...) identity on the relationship between moral disengagement and counterproductive work behavior. Research design This was a quantitative, cross-sectional study. Participants and research context From September to October 2023, nurses from emergency departments of major hospitals in Hunan Province were recruited, and 500 questionnaires were distributed and collected using the WeChat app Credamo Seeing Numbers. Ethical consideration All study procedures were approved by the Ethics Committee of Hunan Normal University (No. 2023-388). Findings Moral disengagement had a positive effect on counterproductive work behavior directed at the organization (CWB-O) as well as counterproductive work behavior directed at individuals (CWB-I). Moral identity was not significant in moderating the relationship between moral disengagement and CWB-O. Moral identity had an inverse moderating effect on the mechanism of action between moral disengagement and CWB-I. Conclusion Counterproductive work behavior guided by moral disengagement is detrimental to organizations, and moral identity can inhibit the effect of moral disengagement on CWB-I. Nursing administrators should focus on improving nurses’ moral identity and improving the healthcare workplace environment so that moral identity can better exert its inhibitory effect on counterproductive work behavior among nurses. (shrink)

Life-history-derived models of female sexual development propose menarche timing as a key regulatory mechanism driving subsequent sexual behavior. The current research utilized a twin subsample of the National Longitudinal Study of Adolescent to Adult Health (Add Health; _n_ = 514) to evaluate environmental effects on timings of menarche and sexual debut, as well as address potential confounding of these effects within a genetically informative design. Results show mixed support for each life history model and provide little evidence rearing (...) environment is important in the etiology of individual differences in age at menarche. This research calls into question the underlying assumptions of life-history-derived models of sexual development and highlights the need for more behavior genetic research in this area. (shrink)