Reductionist Approach Research Articles

Identifying Key In Silico Knockout for Enhancement of Limonene Yield Through Dynamic Metabolic Modelling.

Living cells display dynamic and complex behaviors. To understand their response and to infer novel insights not possible with traditional reductionist approaches, over the last few decades various computational modelling methodologies have been developed. In this chapter, we focus on modelling the dynamic metabolic response, using linear and nonlinear ordinary differential equations, of an engineered Escherichia coli MG1655 strain with plasmid pJBEI-6409 that produces limonene. We show the systems biology steps involved from collecting time-series data of living cells, to dynamic model creation and fitting the model with experimental responses using COPASI software.

Flower heterochrony and crop yield.

Crop improvement has focused on enhancing yield, nutrient content, harvestability, and stress resistance using a trait-centered reductionist approach. This has downplayed the fact that plants are developmentally integrated and respond coordinately and predictably to genetic and environmental variation, with potential consequences for food production. Crop yield, including both fruit/seed production and the possibility of generating hybrid crop varieties, is highly dependent on flower morphology and sex, which, in turn, can be profoundly affected by slight shifts in the timing and rate of flower organ development (i.e., flower heterochrony). We argue that understanding the genetic and environmental bases of flower heterochrony and their effect on flower morphology and sex in cultivated plants and in their wild relatives can facilitate crop improvement.

A Novel Platform for Evaluating Dose Rate Effects on Oxidative Damage to Peptides: Toward a High-Throughput Method to Characterize the Mechanisms Underlying the FLASH Effect.

High dose rate radiation has gained considerable interest recently as a possible avenue for increasing the therapeutic window in cancer radiation treatment. The sparing of healthy tissue at high dose rates relative to conventional dose rates, while maintaining tumor control, has been termed the FLASH effect. Although the effect has been validated in animal models using multiple radiation sources, it is not yet well understood. Here, we demonstrate a new experimental platform for quantifying oxidative damage to protein sidechains in solution as a function of radiation dose rate and oxygen availability using liquid chromatography mass spectrometry. Using this reductionist approach, we show that for both X-ray and electron sources, isolated peptides in solution are oxidatively modified to different extents as a function of both dose rate and oxygen availability. Our method provides an experimental platform for exploring the parameter space of the dose rate effect on oxidative changes to proteins in solution.

Identifying a core protein signature of small extracellular vesicles derived from B-cell precursor acute lymphoblastic leukaemia.

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP-ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV-marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP-ALL patients. The EV proteome of primary BCP-ALL cell-derived EVs were compared against EVs from healthy donor B cells and the BCP-ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP-ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP-ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.

Non-neuronal acetylcholine is causal for cardioprotection by hypoxic preconditioning in adult rat cardiomyocytes

Abstract Introduction Brief episodes of non-lethal myocardial ischemia/reperfusion preceding more sustained ischemia and reperfusion reduce lethal ischemia/reperfusion injury. The underlying protective signaling mechanisms of such ischemic preconditioning are unclear in their details. Among other protective mediators, neuronal acetylcholine (ACh) and its signaling through cholinergic receptors is involved in protection by ischemic preconditioning. Recently, a non-neuronal cardiac cholinergic system (NNCCS) has been identified, suggesting that a nervous system-independent, cardiomyocyte-derived acetylcholine signaling with signal amplification by auto- and paracrine cholinergic receptor activation could also participate in ischemic preconditioning. Aim We aimed to examine the role of NNCCS-derived ACh as a mediator of ischemic preconditioning. We therefore, in a reductionist approach, used isolated adult cardiomyocytes with hypoxic preconditioning (HPC). Methods Adult ventricular rat cardiomyocytes were isolated (from n=9 hearts), and HPC was induced by one cycle of 10 min hypoxia / 20 min reoxygenation. Thirty min normoxia served as control. Cardiomyocytes were then exposed to 30 min sustained hypoxia / 5 min reoxygenation (H/R), or a 35 min time control (TC). Cardiomyocyte viability was quantified before and after H/R or TC, respectively, by trypan blue staining. In a subgroup of experiments (cardiomyocytes from n=6 hearts) in the presence of physostigmine (0.2 mmol/L), intracellular ACh was quantified before and after HPC or normoxia and after sustained hypoxia and reoxygenation or TC, respectively, via liquid chromatography-coupled tandem mass spectrometry. Experiments on cardiomyocyte viability (from n=9 hearts) were repeated with the addition of cholinergic receptor antagonists (nicotinic: hexamethonium [1 µmol/L], muscarinic: atropine [0.1 µmol/L]) a) during the first 30 min with HPC or normoxia, b) during H/R or TC (30-65 min), or c) throughout the total 65 min protocol. Results The viability of cardiomyocytes subjected to H/R was better preserved with HPC than without (Figure A), and intracellular ACh was increased during hypoxia after prior HPC (Figure B). Cholinergic receptor antagonists during HPC did not change HPC´s protection (Figure A). However, the combination of both antagonists during sustained hypoxia abrogated HPC´s protection (Figure A), whereas nicotinic or muscarinic cholinergic receptor antagonists alone did not. Cholinergic receptor antagonists throughout the total 65 min also abrogated HPC´s protection (Figure A). Conclusion: The NNCCS is activated by HPC and causal for HPC´s protection. HPC increases intracellular acetylcholine, and cardiomyocyte protection is mediated via both nicotinic and muscarinic cholinergic receptors, suggesting an auto- and paracrine signal amplification on the cardiomyocyte level.Figure

Beyond the Asylum Walls: Tracing the Tapestry of Mental Health Interventions Across Eras and Cultures.

This article offers an extensive review of the changing field of mental health therapies, charting a transformational path from traditional methods to modern breakthroughs and speculating on potential future developments. The story develops by investigating historical viewpoints while reflecting on the present and highlighting the lessons learned and their impact on contemporary practices. We have advanced from the stigmatized constraints of asylums to a paradigm that puts human rights, dignity, and individualized, culturally sensitive treatment first. Modern methods are much more varied and evidence-based, from cutting-edge technical advancements to evidence-based psychotherapies. The ethical considerations arising from the delicate balance of pharmacological therapies underline the responsibility of administering drugs that significantly affect mental health.Cultural factors become a pillar, highlighting how crucial cultural sensitivity is to promoting tolerance. By acknowledging how many facets of the human experience are interrelated, holistic methods help close the gap between the mind and body. Integrative medicine and alternative therapies represent a shift away from reductionist approaches and towarda holistic viewpoint. The delivery of mental health treatment is being reimagined by technological advancements, with virtual and digital environments opening up new access and support channels. These developments cut beyond regional boundaries, reinventing conventional therapy dynamics and paving the way for individualized therapies. Cultural concerns highlight the significance of cultural competency in navigating the complex mental health treatment system and adapting interventions to fit the particular requirements of various cultural contexts. With telepsychiatry, virtual reality, and artificial intelligence among the new technologies that promise to further revolutionize mental health therapies, the essay looks to the future. This review concludes by imagining a day when mental health is prioritized, therapies are available, and the diversity of human experience is valued. The path to a society that values, nurtures, and celebrates mental health continues.

Collaborative narrative coaching in medicine: a case study with a resident physician and a practicing emergency physician

In recent years, many postgraduate medical institutions are transitioning to a competency based medical education (CBME). This paradigm shift offers many advantages but has also been criticized for its potentially reductionist approach of targeting competency as the end goal. In this context, coaching may be an interesting intervention as it has been employed with success in other professional settings to go beyond achieving competency with a focus on continuous development. Currently there is little published data on this intervention in the medical field. Our study aims to describe a coaching intervention between two dyads of a coach and physician as well as exploring the repercussions of the intervention on their professional practice by analyzing interviews conducted per the value creation framework. Results of our study show the unique learning journeys of both dyads as well as the creation of value in each cycle for both participants. In conclusion, coaching in medicine is an interesting intervention with the potential to complement the existing medical training programs in order to achieve optimal professional development.

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine.

As time has come to translate trial results into individualized medical diagnosis and therapy, we analyzed how to minimize residual risk of cardiovascular disease (CVD) by reviewing papers on "residual cardiovascular disease risk". During this review process we found 989 papers that started off with residual CVD risk after initiating statin therapy, continued with papers on residual CVD risk after initiating therapy to increase high-density lipoprotein-cholesterol (HDL-C), followed by papers on residual CVD risk after initiating therapy to decrease triglyceride (TG) levels. Later on, papers dealing with elevated levels of lipoprotein remnants and lipoprotein(a) [Lp(a)] reported new risk factors of residual CVD risk. And as new risk factors are being discovered and new therapies are being tested, residual CVD risk will be reduced further. As we move from CVD risk reduction to improvement of patient management, a paradigm shift from a reductionistic approach towards a holistic approach is required. To that purpose, a personalized treatment dependent on the individual's CVD risk factors including lipid profile abnormalities should be configured, along the line of P5 medicine for each individual patient, i.e., with Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive approaches.

The efficacy of biodiversity and ecosystem assessment approaches for informing a regenerative approach to built development.

The built environment, even at its "greenest," inevitably entails changing ecosystem structure and function. Multiple sustainable development tools and approaches are available to reduce environmental harm from built development. However, the reality that society exists within fully integrated socioecological systems, wholly interdependent on supporting ecosystems, is not yet adequately represented in regulation or supporting tools. Regenerative development seeks to address this interdependence in part by improving the health of supporting socioecological systems through the development process. We demonstrate the relevance of a series of approaches-Local Nature-Related Planning Policy (LNRPP), Biodiversity Net Gain (BNG), the Environmental Benefits from Nature Tool (EBN Tool), Nature Assessment Tool for Urban and Rural Environments (NATURE Tool), and Rapid Assessment of Wetland Ecosystem Services+ (RAWES+)-for their ability to meet their stated aims and objectives and how these relate to wider regenerative themes. A comparative analysis of the five approaches is done by applying them to a practical case study site, resulting in policy- and practice-relevant learning and recommendations. The research reveals current gaps in methodology, which can lead to adverse outcomes for sustainability. This is particularly clear for the spatial and temporal scales across which each approach operates. In addition, this research discusses the inherent limitations of taking a reductionist approach to examining complex systems. Integr Environ Assess Manag 2024;20:248-262. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Non-Abelian Constructivist Lagrangian

A whole Yang-Mills symmetry is proposed. A grouping physics is constituted. It consists in inserting a given Yang-Mills field Aaμ in a fields set {Aa μI } constituted by other fields families, I = 1, . . . , N. Each field becomes part of a whole. A set action physics happens preserving the Yang-Mills symmetry. However the usual properties of an isolated field are extended to antireductionist properties. An associative physics is formed. A Yang-Mills whole quantum system is constituted. A whole Yang-Mills physics isobtained. The quantum corresponding to a specific Aa μI field inserted in a whole develops features depending on thefields set {Aa μI } associativity. Properties established from a so-called constructivist gauge theory are identified. Usual YM interactions are enlarged to YM interrelationships. Classical equations are studied under set action. A Yang-Mills whole unity is constituted by a constructivist Lagrangian. The reductionist approach substituted by constructivism. Physics under set transformations. A cause and effect relationship is expressed based on whole unity. The whole is that moves to future. Minimal action principle, Noether theorem, Bianchi identities are derived. A fields set with diversity, interdependence, nonlinearity, chance is expressed.

Enzyme-mimetic catalyst architectures: the role of second coordination sphere in catalytic activity

Abstract Enzymes with well-defined three-dimensional structure have in-built information for molecular organization in the near vicinity of the active sites—popularly known as enzyme architecture. Over the past few years, molecular assembly has been exploited in creating artificial enzyme or catalyst architectures. Emergent spatiotemporal structure and catalytic activity can be achieved through controlled assembly of suitable molecular building blocks. The programmed molecular assembly governed by the scheme of molecule architectonics can generate enzyme-mimetic catalyst assembly architecture. Apart from the conventional ligand-metal interaction in the first coordination sphere of a catalyst, a second coordination sphere plays a key role in the catalytic activity of enzymes. This review attempts to unravel the balancing act between molecular architectonics and second coordination spheres in catalyst assembly architecture development. Judicious design and exploitation of state-of-the-art biomimetic catalyst architecture derived from small molecules, sugars, nucleic acids, peptides, and proteins are discussed under the above-mentioned framework. Metal-coordinated molecular assembly architectures of specific catalytic properties are considered with respect to the nature of molecular assembly and experimental conditions. The concise and critical discussion provides a holistic view of enzyme-mimetic architectures and their second coordination spheres through a reductionistic approach based on the molecular architectonics of simple and modular molecular building blocks.

Potential of ADAM 17 Signal Peptide To Form Amyloid Aggregates in Vitro.

ADAM 17, a disintegrin and metalloproteinase 17 belonging to the adamalysin protein family, is a Zn2+-dependent type-I transmembrane α-secretase protein. As a major sheddase, ADAM 17 acts as an indispensable regulator of chief cellular events and controls diverse cytokines, adhesion molecules, and growth factors. The signal peptide (residues 1-17) of ADAM 17 targets the protein to the secretory pathway and gets cleaved off afterward. No other function is documented for the ADAM 17 signal peptide (ADAM 17-SP) inside the cells. Here, we have taken a reductionist approach to understand the biophysical properties of ADAM 17-SP. Aiming to understand the possibility of aggregation, we found several aggregation-prone segments in the signal peptide. We performed in vitro experiments to show that the signal peptide forms amyloid-like aggregates in buffered conditions. We also studied its aggregation in the presence of sodium tripolyphosphate and heparin to correlate with the cellular conditions, as these biomolecules are naturally present inside cells. Further, we performed seeding experiments to observe the possibility of ADAM 17-SP aggregate interaction with the Aβ42 peptide. The results suggest that its seeds escalate the aggregation kinetics of the Aβ42 peptide and form heteromeric aggregates with it. We believe this finding could further intensify the aggregation studies on other signal peptides and shed light on the potential role of these segments other than signaling.

Warming indirectly simplifies food webs through effects on apex predators

Warming alters ecosystems through direct physiological effects on organisms and indirect effects via biotic interactions, but their relative impacts in the wild are unknown due to the difficulty in warming natural environments. Here we bridge this gap by embedding manipulative field experiments within a natural stream temperature gradient to test whether warming and apex fish predators have interactive effects on freshwater ecosystems. Fish exerted cascading effects on algal production and microbial decomposition via both green and brown pathways in the food web, but only under warming. Neither temperature nor the presence of fish altered food web structure alone, but connectance and mean trophic level declined as consumer species were lost when both drivers acted together. A mechanistic model indicates that this temperature-induced trophic cascade is determined primarily by altered interactions, which cautions against extrapolating the impacts of warming from reductionist approaches that do not consider the wider food web.

Modeling Human Suboptimal Control: A Review.

This review paper provides an overview of the approaches to model neuromuscular control, focusing on methods to identify nonoptimal control strategies typical of populations with neuromuscular disorders or children. Where possible, the authors tightened the description of the methods to the mechanisms behind the underlying biomechanical and physiological rationale. They start by describing the first and most simplified approach, the reductionist approach, which splits the role of the nervous and musculoskeletal systems. Static optimization and dynamic optimization methods and electromyography-based approaches are summarized to highlight their limitations and understand (the need for) their developments over time. Then, the authors look at the more recent stochastic approach, introduced to explore the space of plausible neural solutions, thus implementing the uncontrolled manifold theory, according to which the central nervous system only controls specific motions and tasks to limit energy consumption while allowing for some degree of adaptability to perturbations. Finally, they explore the literature covering the explicit modeling of the coupling between the nervous system (acting as controller) and the musculoskeletal system (the actuator), which may be employed to overcome the split characterizing the reductionist approach.

The Phenomenology of Tactile Perception for Design

For design, tactile perception is a crucial dimension of the user experience. Design disciplines can find an essential body of knowledge in the tradition of the psychology of perception. This article first introduces the physiological aspects, starting from receptor differences and leading to the tactile representation in the brain. Consistent with the phenomenological perspective, it is argued, however, that the reductionist approach provides an understanding of physiological mediation, useful for knowing the functioning of the organism, but not sufficient to make the user's perceptual-tactile experience immediate. The perceptual-tactile experience extends to the dimension of the self and demonstrates that the bodily self extends beyond the boundaries of the physical body. For the designer, therefore, scientific knowledge of the tactile experience derived from experimental phenomenology, developed from Gestalt psychology, is a priority.

The New Antireductionism: Its Components and Its Significance

Beginning in the 1970s and culminating in the first two decades of the 21st century, there has been a marked shift in the sciences from a predominantly reductionist and mechanistic approach to a broader and more holistic viewpoint. It goes without saying that such a shift in point of view will have significant implications, not only for the sciences but for our concepts of nature and of human beings. The present essay is an attempt to assess the significance of this change in the focus of the sciences and to describe the nature of its components. Originally, it had a far more limited scope, that of comparing two of the parts of the new nonreductionist stance: brain plasticity and biological systems theory. Unfortunately, my understanding of one of these factors (systems theory) turned out to be incorrect, while the section on brain plasticity was incomplete. The result of this dual realization is an essay of far greater scope, taking in both new developments in the sciences far beyond that of plasticity, and reassessing the content and impact of systems theory, which is greater than I had thought. I will begin with a study of systems theory, dealing first with the unexpected mathematics which made its present status possible. Then I will deal with its history, which reaches back over a century. One of the confusions into which we are liable to fall is to fail to distinguish the old systems theory from the new. This is even more likely because the two versions of the theory have many features in common.

A definition for circular bio-based cities based on a reductionist metabolic approach

The 2020 coronavirus pandemic demonstrated that moderation in living and consumption styles can contribute towards a more environmentally sustainable and resilient future. However, such restrained lifestyles are associated with the risk of global economic stagnation. Transitioning from linear to circular economy can potentially provide a framework to decouple environmental benefits from economic stasis. Circular cities are placed in the centre of such efforts to cradle and nurture humanity’s shift towards a sustainable future. However, we investigated the current state of circular cities around the world finding that a bio-based focus is not always prioritised. The lack of emphasis on bio-based solutions could lead to missed economic and environmental opportunities. A symbiosis between “circular”, “regenerative” and “bio-based” is here proposed as the foundation for sustainable societies transitioning to circularity. This Short Communication discusses the vision of circular bio-based cities and proposes a definition based on a reductionist metabolic approach. The aim is to set the basis for an international dialogue on urban development models capable of delivering both human and environmental prosperity beyond the reuse, refurbish and recycle concepts, and towards fully integrated regenerative urban systems which foster symbiotic relationships between urban communities and the natural ecosystem.

Ethically Digital: Contested Cultural Heritage in Digital Context

Over the past century, our understanding of cultural heritage has evolved, and now, heritage is seen more as a process than a product. Although the advancement of digital technologies has significantly aided in the research, protection, management, interpretation, and education of cultural heritage, it also raises the question of how far this technology works in accordance with our current understanding of heritage as a process and is not taking a reductionist approach, in which heritage is cut off from its community and context. Ethical risks are higher for contested heritage, when meaning and values are questioned, or when people's ability to access and enjoy heritage is threatened. This paper discusses potential ethical risks regarding access, control, dissemination, and the digital economy by looking at existing approaches, guidelines, and principles in this field and a few digital heritage projects about contested heritage, and it questions whether the lack of an inclusive ethical framework could lead to a new kind of digital colonisation.
 

Analysing engagement with Indigenous Peoples in the Intergovernmental Panel on Climate Change’s Sixth Assessment Report

Indigenous Peoples’ advocacy and contributions to climate action have drawn international attention, including from the Intergovernmental Panel on Climate Change (IPCC). This article assesses to which degree the IPCC’s Sixth Assessment Report (AR6) recognises the role and knowledge systems of Indigenous Peoples. Through a content analysis of the Working Groups I, II, and III reports and the Synthesis Report, we found an increasing number of references related to Indigenous Peoples and their knowledge systems. However, the IPCC still perpetuates a reductionist approach that reinforces harmful stereotypes. Overcoming this weakness requires greater reflexivity and concrete actions, including consistent recognition of Indigenous Peoples’ rights, refraining from merely portraying Indigenous Peoples as vulnerable and adopting a strengths-based approach, ensuring ethical and equitable application of Indigenous Peoples’ knowledge systems, and involving Indigenous Peoples from the scoping process. By implementing these measures, the IPCC can improve its partnership with Indigenous Peoples in preparation for AR7.

Traits and Behavior Theory of Leadership: Critique from Undistributed Middle

Traits and/or behavior theory of leadership has a long tradition but the popular understanding of it may lead to fallacious positions. The current paper provides a critique, stemming from logic, of a reductionist approach to leadership in popular sources. The reductionist approach is manifested in propositions such as “possession of trait and/or behavior X makes one a leader.” First, the logical fallacy of the undistributed middle is explained. Second, the paper presents the appearance of the fallacy of the undistributed middle in leadership training and popular leadership materials. The paper demonstrates that popular unchecked traits and/or behavioral understandings of leadership generate misleading and logically flawed statements about leadership. The understanding of leadership built on such statements both originates and increases the ambiguity of the term leader and it likely results in ineffective training programs and actual performance on the job.