Key Organizational Principles Research Articles

Neuronal firing rate diversity lowers the dimension of population covariability.

Populations of neurons produce activity with two central features. First, neuronal responses are very diverse - specific stimuli or behaviors prompt some neurons to emit many action potentials, while other neurons remain relatively silent. Second, the trial-to-trial fluctuations of neuronal response occupy a low dimensional space, owing to significant correlations between the activity of neurons. These two features define the quality of neuronal representation. We link these two aspects of population response using a recurrent circuit model and derive the following relation: the more diverse the firing rates of neurons in a population, the lower the effective dimension of population trial-to-trial covariability. This surprising prediction is tested and validated using simultaneously recorded neuronal populations from numerous brain areas in mice, non-human primates, and in the motor cortex of human participants. Using our relation we present a theory where a more diverse neuronal code leads to better fine discrimination performance from population activity. In line with this theory, we show that neuronal populations across the brain exhibit both more diverse mean responses and lower-dimensional fluctuations when the brain is in more heightened states of information processing. In sum, we present a key organizational principle of neuronal population response that is widely observed across the nervous system and acts to synergistically improve population representation.

Convolutional neural networks develop major organizational principles of early visual cortex when enhanced with retinal sampling.

Primate visual cortex exhibits key organizational principles: cortical magnification, eccentricity-dependent receptive field size and spatial frequency tuning as well as radial bias. We provide compelling evidence that these principles arise from the interplay of the non-uniform distribution of retinal ganglion cells, and a quasi-uniform convergence rate from the retina to the cortex. We show that convolutional neural networks outfitted with a retinal sampling layer, which resamples images according to retinal ganglion cell density, develop these organizational principles. Surprisingly, our results indicate that radial bias is spatial-frequency dependent and only manifests for high spatial frequencies. For low spatial frequencies, the bias shifts towards orthogonal orientations. These findings introduce a novel hypothesis about the origin of radial bias. Quasi-uniform convergence limits the range of spatial frequencies (in retinal space) that can be resolved, while retinal sampling determines the spatial frequency content throughout the retina.

The curious case of the disassembling ATP synthase studied using molecular dynamics simulations.

Cellular bioenergetic processes responsible for providing energy to most lifeforms, photosynthesis and respiration, involve cooperative networks of proteins integrated into membrane domains. Exascale computational approaches, hand-in-hand with experiments, are necessary to learn how these processes are achieved. In particular, computations will reveal key organizational principles that underlie the efficient energy harvesting of protein networks. Application of these principles will aid the design of better man-made biohybrid devices in order to harness renewable energy for the world's future energy needs. The universal process of ATP synthesis, a component of the photosynthetic energy harvesting and respiration can now be investigated at atomic detail through the molecular dynamics of a complex biological motor, ATP synthase, that transforms an ion gradient existing across the cell membrane into the synthesis of ATP from ADP. The reversibility of this biomotor is essential for energy-transcending processes in all living systems, yet, the mechanism of its action remains fragmentary. To investigate this mechanism, we performed simulations on full bacterial and bovine F-type ATPase models utilizing Nanoscale Molecular Dynamics software. First, we monitored a water channel located near key acidic residues in the bacterial ATPase c-ring to observe its behavior both before and after proton transfer occurred in this region, and we discovered what we hypothesize to be a mechanism that prevents the back-transport of protons. Second, we designed models for the bovine ATPase to examine its overall stability, degree of water leakage in the membrane-inserted region, and “hook” (subunit e) behavior in the presence of varying voltages. We have preliminarily highlighted the instability of the catalytic stock and significant unfolding of the hook in all models, as well as increased water leakage in models that did not contain a lipid plug inserted into the c-ring.

Organizational model of municipal housing stock management in the contracting system–A case study of Poland

Social housing management across Europe is evolving towards a more market-oriented approach in response to the progressing decentralization of public services and privatization of public housing. In Poland, these trends are particularly related to changes in the organization of municipal housing stock management. One recommended option for such changes has become the evolution from an indirect system based on municipal units into a contracting system based on private entities.This paper presents the organizational model of municipal housing stock management in Poland in the contracting system. The model was designed as an organizational management standard for a typical urban municipality. The model was developed by integrating theoretical solutions and the results of empirical research conducted in Polish cities in view of the key organizational principles. The methodology for developing the model was based on the diagnostic-functional approach to designing organizational systems with the use of the Hijmans competence tables technique. This model strives to enhance the quality and efficiency of municipal housing management services by improving their organization in line with the New Public Management concept. The proposed model could be of interest to other countries where the management of social housing is subjected to restructuring and privatization pressure.

6 - ‘From Cradle to Grave’: Transforming South Africa’s Learning Ecologies

This article examines key organizational principles that underpin responsive transformation strategies that have the potential to create spaces for critical engagement with South Africa’s basic education post the 1994 democratic elections. The article deploys various metaphors like the ‘ants, ecology, London Tube and bridge construction’ to unravel the deeper elements for transforming schools into sustainable learning ecologies. It concludes with an articulation of plausible interventions that the country may deploy to improve educational quality and the system’s efficacy.

Single-cell profiling for advancing birth defects research and prevention.

Cellular analysis of developmental processes and toxicities has traditionally entailed bulk methods (e.g., transcriptomics) that lack single cell resolution or tissue localization methods (e.g., immunostaining) that allow only a few genes to be monitored in each experiment. Recent technological advances have enabled interrogation of genomic function at the single-cell level, providing new opportunities to unravel developmental pathways and processes with unprecedented resolution. Here, we review emerging technologies of single-cell RNA-sequencing (scRNA-seq) to globally characterize the gene expression sets of different cell types and how different cell types emerge from earlier cell states in development. Cell atlases of experimental embryology and human embryogenesis at single-cell resolution will provide an encyclopedia of genes that define key stages from gastrulation to organogenesis. This technology, combined with computational models to discover key organizational principles, was recognized by Science magazine as the "Breakthrough of the year" for 2018 due to transformative potential on the way we study how human cells mature over a lifetime, how tissues regenerate, and how cells change in diseases (e.g., patient-derived organoids to screen disease-specific targets and design precision therapy). Profiling transcriptomes at the single-cell level can fulfill the need for greater detail in the molecular progression of all cell lineages, from pluripotency to adulthood and how cell-cell signaling pathways control progression at every step. Translational opportunities emerge for elucidating pathogenesis of genetic birth defects with cellular precision and improvements for predictive toxicology of chemical teratogenesis.

The natural axis of transmitter receptor distribution in the human cerebral cortex

Transmitter receptors constitute a key component of the molecular machinery for intercellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distill these observations into key organizational principles. We demonstrate that receptor densities form a natural axis in the human cerebral cortex, reflecting decreases in differentiation at the level of laminar organization and a sensory-to-association axis at the functional level. Along this natural axis, key organizational principles are discerned: progressive molecular diversity (increase of the diversity of receptor density); excitation/inhibition (increase of the ratio of excitatory-to-inhibitory receptor density); and mirrored, orderly changes of the density of ionotropic and metabotropic receptors. The uncovered natural axis formed by the distribution of receptors aligns with the axis that is formed by other dimensions of cortical organization, such as the myelo- and cytoarchitectonic levels. Therefore, the uncovered natural axis constitutes a unifying organizational feature linking multiple dimensions of the cerebral cortex, thus bringing order to the heterogeneity of cortical organization.

Образование будущего: репродуктивно-продуктивный переход

Education of the future is a fundamental challenge of the present time that de­fines a horizon of thinking of society and about society. The knowledge society stepping into the role of a horizon brings the substance of the matter to the ability of education to cultivate the creative function of thinking. From the ontological point of view, this article deals with the problem of the education transformation from reproductive to productive forms of working with knowledge (the repro­ductive-productive transition). The prevailing reproductive model of modern ed­ucation is a class-and-lesson (or lecture-seminar) system. Institutionalization of class-and-lesson education in the Reformation years in the XVI c. is ana­lyzed, and key didactic and organizational principles laid down in its basis by Ph. Melanchton are identified. Arguments are presented against qualification of educators in the age of Reformation as humanists. The concept of epistemic dominant is introduced for the purpose of explaining the education transforma­tion process. It is shown that the reproductive-productive transition belongs to the essence of our time. The stability of the class-and-lesson system can be ex­plained by resting on an essential part of educational universals that are timeless in nature. Based on the theory of non-Kuhn’s paradigms, the relationship be­tween the reproductive-productive transition and a shift in the ontological foun­dations of the education phenomenon as to its forms, ways, functions, and gener­alization of its being is shown.

Mechanisms for Active Regulation of Biomolecular Condensates.

Liquid-liquid phase separation is a key organizational principle in eukaryotic cells, on par with intracellular membranes. It allows cells to concentrate specific proteins into condensates, increasing reaction rates and achieving switch-like regulation. We propose two active mechanisms that can explain how cells regulate condensate formation and size. In both, the cell regulates the activity of an enzyme, often a kinase, that adds post-translational modifications to condensate proteins. In enrichment inhibition, the enzyme enriches in the condensate and weakens interactions, as seen in stress granules (SGs), Cajal bodies, and P granules. In localization-induction, condensates form around immobilized enzymes that strengthen interactions, as observed in DNA repair, transmembrane signaling, and microtubule assembly. These models can guide studies into the many emerging roles of biomolecular condensates.

A cross-disorder connectome landscape of brain dysconnectivity.

Many human brain disorders are associated with characteristic alterations in the structural and functional connectivity of the brain. In this article, we explore how commonalities and differences in connectome alterations can reveal relationships across disorders. We survey recent literature on connectivity changes in neurological and psychiatric disorders in the context of key organizational principles of the human connectome and observe that several disturbances to network properties of the human brain have a common role in a wide range of brain disorders and point towards potentially shared network mechanisms underpinning disorders. We hypothesize that the distinct dimensions along which connectome networks are organized (for example, 'modularity' and 'integration') provide a general coordinate system that allows description and categorization of relationships between seemingly disparate disorders. We outline a cross-disorder 'connectome landscape of dysconnectivity' along these principal dimensions of network organization that may place shared connectome alterations between brain disorders in a common framework.

Modular reconfiguration of an auditory control brain network supports adaptive listening behavior

Speech comprehension in noisy, multitalker situations poses a challenge. Successful behavioral adaptation to a listening challenge often requires stronger engagement of auditory spatial attention and context-dependent semantic predictions. Human listeners differ substantially in the degree to which they adapt behaviorally and can listen successfully under such circumstances. How cortical networks embody this adaptation, particularly at the individual level, is currently unknown. We here explain this adaptation from reconfiguration of brain networks for a challenging listening task (i.e., a linguistic variant of the Posner paradigm with concurrent speech) in an age-varying sample of n = 49 healthy adults undergoing resting-state and task fMRI. We here provide evidence for the hypothesis that more successful listeners exhibit stronger task-specific reconfiguration (hence, better adaptation) of brain networks. From rest to task, brain networks become reconfigured toward more localized cortical processing characterized by higher topological segregation. This reconfiguration is dominated by the functional division of an auditory and a cingulo-opercular module and the emergence of a conjoined auditory and ventral attention module along bilateral middle and posterior temporal cortices. Supporting our hypothesis, the degree to which modularity of this frontotemporal auditory control network is increased relative to resting state predicts individuals' listening success in states of divided and selective attention. Our findings elucidate how fine-tuned cortical communication dynamics shape selection and comprehension of speech. Our results highlight modularity of the auditory control network as a key organizational principle in cortical implementation of auditory spatial attention in challenging listening situations.

Capturing protein communities by structural proteomics in a thermophilic eukaryote

The arrangement of proteins into complexes is a key organizational principle for many cellular functions. Although the topology of many complexes has been systematically analyzed in isolation, their molecular sociology in situ remains elusive. Here, we show that crude cellular extracts of a eukaryotic thermophile, Chaetomium thermophilum, retain basic principles of cellular organization. Using a structural proteomics approach, we simultaneously characterized the abundance, interactions, and structure of a third of the C. thermophilum proteome within these extracts. We identified 27 distinct protein communities that include 108 interconnected complexes, which dynamically associate with each other and functionally benefit from being in close proximity in the cell. Furthermore, we investigated the structure of fatty acid synthase within these extracts by cryoEM and this revealed multiple, flexible states of the enzyme in adaptation to its association with other complexes, thus exemplifying the need for in situ studies. As the components of the captured protein communities are known—at both the protein and complex levels—this study constitutes another step forward toward a molecular understanding of subcellular organization.

Ligand-Induced Growth of CD36-Fyn Clusters Induces Signaling

Nanoclustering is emerging as a key organizational principle of membrane proteins. Using superresolution imaging, we investigated the molecular organization of the clustering-responsive receptor CD36 and its downstream effector Fyn in response to thrombospondin-1 (TSP-1), an anti-angiogenic ligand that promotes endothelial cells apoptosis. At steady state, CD36 receptors pre-exist in nanoclusters (diameter of about 100 nm). Fyn is already present in these clusters, and its N-terminal membrane targeting domain is sufficient for this association. Even if already associated, we found that Fyn only becomes activated activated upon TSP-1 binding through an enhancement of CD36-Fyn clustering, forming larger and denser clusters. These enhancements are supported by the actin cytoskeleton and the presence of plasma membrane cholesterol as their perturbation abolishes signaling. Our data demonstrate cooperation between cholesterol-dependent domains and the cortical actin cytoskeleton in the reorganization of the receptor-effector pair CD36-Fyn that enables signaling during TSP-1 stimulation.

Neuronal networks in mental diseases and neuropathic pain: Beyond brain derived neurotrophic factor and collapsin response mediator proteins.

The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.

Editorial: Modularity in motor control: from muscle synergies to cognitive action representation.

Mastering a rich repertoire of motor behaviors, as humans and other animals do, is a surprising and still a poorly understood outcome of evolution, development, and learning. Many degrees-of-freedom, non-linear dynamics, and sensory delays provide formidable challenges for controlling even simple actions. Modularity as a functional element, both structural and computational, of a control architecture might be the key organizational principle that the central nervous system employs for achieving versatility and adaptability in motor control. Recent investigations of muscle synergies, motor primitives, compositionality, basic action concepts, and related work in machine learning have contributed, at different levels, to advance our understanding of the modular architecture underlying rich motor behaviors. However, the existence and nature of the modules comprising the control architecture is far from settled. For instance, regularity and low-dimensionality of the motor output are often taken as an indication of modularity but they could simply be a byproduct of optimization and task constraints. Moreover, what are the relationships between modules at different levels, such as muscle synergies, kinematic invariants, and basic action concepts? One important reason for the new interest in understanding modularity in motor control from different perspectives is the impressive development in cognitive robotics. In comparison to animals and humans, the motor skills of today's best robots are limited and inflexible. However, robot technology is maturing to the point at which it can start approximating a reasonable spectrum of different perceptual, cognitive, and motor capabilities. These advances allow researchers to explore how these motor, sensory, and cognitive functions might be integrated into meaningful architectures and to test their functional limits. Such systems provide a new test bed to explore different concepts of modularity and to experimentally investigate possible interactions between motor and cognitive processes. Thus, the goal of this Research Topic is to review, compare, and debate theoretical and experimental studies of the modular organization of the motor control system at different levels. By bringing together researchers seeking to understand the building blocks of coordinating many muscles, planning endpoint and joint trajectories, and representing motor and behavioral actions in memory we aim at promoting new interactions between often disconnected research areas and approaches and providing a broad perspective on the notion of modularity in motor control.

Anatomical Brain Networks on the Prediction of Abnormal Brain States

Graph-based brain anatomical network analysis models the brain as a graph whose nodes represent structural/functional regions, whereas the links between them represent nervous fiber connections. Initial studies of brain anatomical networks using this approach were devoted to describe the key organizational principles of the normal brain, while current trends seem to be more focused on detecting network alterations associated to specific brain disorders. Anatomical networks reconstructed using diffusion-weighed magnetic resonance-imaging techniques can be particularly useful in predicting abnormal brain states in which the white matter structure and, subsequently, the interconnections between gray matter regions are altered (e.g., due to the presence of diseases such as schizophrenia, stroke, multiple sclerosis, and dementia). This article offers an overview from early gross connectional anatomy explorations until more recent advances on anatomical brain network reconstruction approaches, with a specific focus on how the latter move toward the prediction of abnormal brain states. While anatomical graph-based predictor approaches are still at an early stage, they bear promising implications for individualized clinical diagnosis of neurological and psychiatric disorders, as well as for neurodevelopmental evaluations and subsequent assisted creation of educational strategies related to specific cognitive disorders.

Deadly Fever: Racism, Disease, and a Media Panic by Charles T. Adeyanju (review)

Reviewed by: Deadly Fever: Racism, Disease, and a Media Panic by Charles T. Adeyanju Augie Fleras Charles T. Adeyanju . Deadly Fever: Racism, Disease, and a Media Panic. Halifax-Winnipeg: Fernwood Publishing, 2010. 132 pp. $17.95 sc. There are several things the audience should know before reading this book. First, a commitment to critical race theory provides a key reminder: References to race may not be real in the empirical/objective sense of the concept; nevertheless, the race concept is real because people act as if it was real, with sometimes catastrophic consequences, thus confirming W. I. Thomas's prescient notion that "unreal' ("symbolic") phenomena can yield real ("objective") effects. Second, mainstream newsmedia are racialized—not because of systematic ("deliberate") racism—but because this coverage is systemically ("unintended consequences") biasing, thanks to the predominantly negative framing of diversities and difference implicit in a prevailing media gaze. Third, the centrality of framing as a process for organizing information. [End Page 241] Framing as persuasion draws attention to some aspect of reality as normal and acceptable, yet away from other dimensions of reality as irrelevant and inferior, in the process encouraging a preferred reading without reader/viewer awareness of their complicity or of the biases at play ("hegemony"). Fourth, the concept of media hype and moral panic. Newsmedia are prone to exaggerate and sensationalize incidents or events because it's in their institutional nature to do so, often for self-serving reasons. This amplification of scare stories is not without consequences for "spooking" the general public into panic mode and politicians into hasty decisions. Once equipped with this knowledge, Deadly Fever begins to take shape as an empirically informed and theoretically valuable book. Much of the content and argument can be gleaned from perusing the backcover and preface. In early February 2001, the Hamilton Spectator published an article linking (erroneously as it turns out) a hospitalized Congolese woman with the possibility of importing into Canada a deadly infectious disease known as Ebola. As the author and others note, there is a long history of associating disease with race and nationality (SARS or "bird flu" as Chinese diseases, HIV/AIDS with Haiti), in effect demonstrating the subtle and not-so-subtle ways in which the intersection of race, nationality, and gender are played out in those contemporary societies espousing a code of "racism without race." Although the subsequent media frenzy was seemingly disproportionate to the threat, the author concludes, excessive media coverage of the "nonEbola" panic served as a proxy ("subtext") for expressing white Canadian anxieties over the growing presence (and perceived menace) of racialized minorities. Clearly, then, race remains a key organizational principle in framing reality along the lines of what is normal, acceptable, and desirable. After all, over-the-top reaction to the nonEbola case could resonate meaningfully only with a racialized audience already inured to/by race-logic for making sense of the world (13). The implications of this subliminal yet racialized coverage are consistent with what Frances Henry and Carole Tator call "democratic racism"—a uniquely Canadian racism that thrives on exploiting the contradiction between Canada's ideals of inequality and the reality of racialized inequality. In terms of an explanatory framework, the author's methodology is qualitative in relying on the primacy of peoples' lived experiences in socially constructing reality. With respect to methods for a data base, the author synthesizes content/critical discourse analysis of four major papers, alongside interviews with journalists and medical practitioners. As well, Deadly Fever incorporates the voices of those usually silenced in decisions over newsworthiness. In contrast to media coverage which ignored Black voices because they lack institutional authority or oppose dominant frames, the book explores the experiences and reactions of the Black community in Hamilton, Ontario. Conversations with members of the Black community yield insights into the collective anguish and disruptive impact of coverage that conflated race and (anti-)immigration. [End Page 242] Media insensitivity—however inadvertent—proved pivotal in perpetuating racism and the othering of Blacks as troublesome constituents who have problems or who create problems. Moves by the Black/Congolese community to counteract this negativity are also discussed, followed by a plea to improve newsmedia coverage of racialized communities...

Prosody and Syntax in Sign Languages.

Prosody and Syntax in Sign Languages.

Governance through corporate social responsibility as a key organizational principle

This article addresses Governance through Corporate Social Responsibility as a Key Organizational Principle. The notion of etic and emic depicts the definitional status of CSR. Etic represents the universal recognition of CSR and emic represents the unique implementation of CSR in an organization. This article proposes that organizations behave like complex adaptive systems with complex interactions needing socially responsible strategies. This article describes French based SUEZ’s emic responses to achieve responsible Governance in terms of CSR. A recipe or menu approach to Governance through CSR is inappropriate. SUEZ has acted as a model for recognizing etic and emic differentiation, using CSR as the Key Organizing Principle that allows adaptability in a socially responsible way and developed specific guidelines incorporating the needs of diverse stakeholders.

From a theory of local processes in aquatic ecosystems to a theory at the ecosystem scale

In aquatic ecology, a deterministic theory has been developed of the complex physical, chemical and biological processes at the scale of limnological measurements (i.e. 10 −2–10 2 m, 10 −3–10 2 days). The theory results from non-linear thermodynamics of irreversible processes by introducing biological state characteristics and processes into the balances of mass, energy, momentum and entropy. Additional principles are assumed to govern the biological phenomena at this scale. Basic hypotheses and some of the conclusions are discussed by the present paper, since this ‘local theory’ offers the basis for the derivation of theoretical tools characterizing the ‘ecosystem scale’ (⩾ 100 m, > 10 days). Looking for key variables and organizational principles at the ecosystem scale, local quantities (e.g. energy, entropy production, etc.) are integrated over the ecosystem during a finite time interval in order to aggregate the physical, chemical, and biological processes observed below the ecosystem level. Dissipation of energy (or, more precisely, entropy production) and entropy export are considered to belong to the most important controlling factors of ecosystems. By mathematical methods used also in statistical thermodynamics, the most probable state of the ecosystem can be determined with regard to entropy export. Conclusions can be drawn about equations between key variables which may become the basis for aggregated ecosystem models.