Global organization of neuronal activity only requires unstructured local connectivity

Modern electrophysiological recordings simultaneously capture single-unit spiking activities of hundreds of neurons spread across large cortical distances. Yet, this parallel activity is often confined to relatively low-dimensional manifolds. This implies strong coordination also among neurons that are most likely not even connected. Here, we combine in vivo recordings with network models and theory to characterize the nature of mesoscopic coordination patterns in macaque motor cortex and to expose their origin: We find that heterogeneity in local connectivity supports network states with complex long-range cooperation between neurons that arises from multi-synaptic, short-range connections. Our theory explains the experimentally observed spatial organization of covariances in resting state recordings as well as the behaviorally related modulation of covariance patterns during a reach-to-grasp task. The ubiquity of heterogeneity in local cortical circuits suggests that the brain uses the described mechanism to flexibly adapt neuronal coordination to momentary demands.

Multiple parameters shape the 3D chromatin structure of single nuclei

The spatial organization of chromatin at the scale of topologically associating domains (TADs) and below displays large cell-to-cell variations. Up until now, how this heterogeneity in chromatin conformation is shaped by chromatin condensation, TAD insulation, and transcription has remained mostly elusive. Here, we used Hi-M, a multiplexed DNA-FISH imaging technique providing developmental timing and transcriptional status, to show that the emergence of TADs at the ensemble level partially segregates the conformational space explored by single nuclei during the early development of Drosophila embryos. Surprisingly, a substantial fraction of nuclei displayed strong insulation even before TADs emerged. Moreover, active transcription within a TAD led to minor changes to the local inter- and intra-TAD chromatin conformation in single nuclei and only weakly affected insulation to the neighboring TAD. Overall, our results indicate that multiple parameters contribute to shaping the chromatin architecture of single nuclei at the TAD scale.

Rethinking the Body in the Brain after Spinal Cord Injury

Spinal cord injuries (SCI) are disruptive neurological events that severly affect the body leading to the interruption of sensorimotor and autonomic pathways. Recent research highlighted SCI-related alterations extend beyond than the expected network, involving most of the central nervous system and goes far beyond primary sensorimotor cortices. The present perspective offers an alternative, useful way to interpret conflicting findings by focusing on the deafferented and deefferented body as the central object of interest. After an introduction to the main processes involved in reorganization according to SCI, we will focus separately on the body regions of the head, upper limbs, and lower limbs in complete, incomplete, and deafferent SCI participants. On one hand, the imprinting of the body’s spatial organization is entrenched in the brain such that its representation likely lasts for the entire lifetime of patients, independent of the severity of the SCI. However, neural activity is extremely adaptable, even over short time scales, and is modulated by changing conditions or different compensative strategies. Therefore, a better understanding of both aspects is an invaluable clinical resource for rehabilitation and the successful use of modern robotic technologies.

A connectivity-constrained computational account of topographic organization in primate high-level visual cortex

Inferotemporal (IT) cortex in humans and other primates is topographically organized, containing multiple hierarchically organized areas selective for particular domains, such as faces and scenes. This organization is commonly viewed in terms of evolved domain-specific visual mechanisms. Here, we develop an alternative, domain-general and developmental account of IT cortical organization. The account is instantiated in interactive topographic networks (ITNs), a class of computational models in which a hierarchy of model IT areas, subject to biologically plausible connectivity-based constraints, learns high-level visual representations optimized for multiple domains. We find that minimizing a wiring cost on spatially organized feedforward and lateral connections, alongside realistic constraints on the sign of neuronal connectivity within model IT, results in a hierarchical, topographic organization. This organization replicates a number of key properties of primate IT cortex, including the presence of domain-selective spatial clusters preferentially involved in the representation of faces, objects, and scenes; columnar responses across separate excitatory and inhibitory units; and generic spatial organization whereby the response correlation of pairs of units falls off with their distance. We thus argue that topographic domain selectivity is an emergent property of a visual system optimized to maximize behavioral performance under generic connectivity-based constraints.

Healing Architecture in Healthcare: A Scoping Review

Objectives: The purpose of this scoping review is to identify evidence on how characteristics of healing architecture in clinical contexts impact clinical practice and patient experiences. Based on these insights, we advance a more practice-based approach to the study of how healing architectures work. Background: The notion of “healing architecture” has recently emerged in discussions of the spatial organization of healthcare settings, particularly in the Nordic countries. This scoping review summarizes findings from seven articles which specifically describe how patients and staff experience characteristics of healing architecture. Methods: This scoping review was conducted using the framework developed by Arksey and O’Malley. We referred to the decision tool developed by Pollock et al. to confirm that this approach was the most appropriate evidence synthesis type to identify characteristics related to healing architecture and practice. To ensure the rigor of this review, we referred to the methodological guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Results: There are two main findings of the review. First, there is no common or operative definition of healing architecture used in the selected articles. Secondly, there is limited knowledge of how healing architecture shapes clinical and patient outcomes. Conclusions: We conclude that further research is needed into how healing architectures make a difference in everyday clinical practices, both to better inform the development of evidence-based designs in the future and to further elaborate criteria to guide postoccupancy evaluations of purpose-built sites.

Refugee-led socio-spatial organization in Al Baqa’a camp, Jordan

The increase in refugee numbers is an increasingly important concern globally. Many countries in different regions have been accommodating refugees by providing temporary shelters made from ineffective and inadequate materials to provide thermal comfort for refugees. However, the shelters provided are often inadequate solutions for shelter and neglect the social and cultural diversity of the refugees. Socio-cultural norms, practices and values are rarely considered in the design of shelters and this has an adverse impact on how refugees live in these spaces. Using insights from the Al Baqa’a refugee camp in Jordan as a case study, this paper uses a mixed-method approach to explore how the challenges of inadequate shelter has consequently led refugees to self-organize and create new socio-cultural spaces to adapt to the place. The findings suggest that historically, Al Baqa’a camp has reorganized by users due to social needs and climate challenges. When the camp was created in 1967, the inadequacy of the housing and infrastructure to provide comfort influenced refugees to self-organize and create adaptive spaces of comfort. However, over the decades, these spaces have evolved into spaces of enterprise, belonging and memory of their homeland. Therefore, this paper argues that refugee shelter design should have an integrated consideration of the climatic elements and the social and cultural aspects of refugees. The paper concludes with lessons learned drawn from the evidence to act as guideline for the consideration of official humanitarian organizations in other camps and local communities.

Excavations at the Iron Age Village Site of Fibobe II, Central Zambia

The period from c. AD 900 to AD 1300 in southern Africa is characterized by transitions from small-scale Iron Age mixed economy communities to the beginnings of more intensive food production and eventually the emergence of complex polities. In Zambia, this coincides with the appearance of larger and more permanent agro-pastoralist villages that began participating in Indian Ocean trade networks. Unlike other parts of southern Africa where stone architecture became common, the predominance of wattle-and-daub type construction methods across Zambia have often impeded preservation of Iron Age activity areas. It has therefore been difficult to reconstruct how economic and land-use changes between the Early and Later Iron Ages impacted family and community relationships reflected in intra-site and intra-household spatial organization. Fibobe II, in the Mulungushi River Basin of Central Zambia, is a rare example of an Early-to-Mid Iron Age village site where these spatial patterns may be discernable due to preservation of activity spaces and vitrified remains of wattle-and-daub structures. This paper reports on new investigations following original testing of the site in 1979, confirming preservation of an Iron Age hut with distinct patterning of features, artifacts, and charcoal. These results reaffirm the unique nature of Fibobe II and indicate the potential for programs of household archaeology aimed at studying this important and understudied period in Zambian prehistory.

Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma

Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting.

Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives

The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model.