Transient Connections Research Articles

Restoring transient connectivity during development improves dysfunctions in fragile X mice.

Early-generated circuits are critical for the maturation of cortical network activity and the formation of excitation/inhibition (E/I) balance. This process involves the maturation of specific populations of inhibitory neurons. While parvalbumin (PV)-expressing neurons have been associated with E/I impairments observed in neurodevelopmental disorders, somatostatin-expressing (SST) neurons have recently been shown to regulate PV neuron maturation by controlling neural dynamics in the developing cortex. SST neurons receive transient connections from the sensory thalamus, yet the implications of transient connectivity in neurodevelopmental disorders remain unknown. Here, we show that thalamocortical connectivity to SST neurons is persistent rather than transient in a mouse model of Fragile X syndrome. We were able to restore the transient dynamics using chemogenetics, which led to the recovery of fragile X-associated dysfunctions in circuit maturation and sensory-dependent behavior. Overall, our findings unveil the role of early transient dynamics in controlling downstream maturation of sensory functions.

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

Dynamic Analysis of Common Rail Injection System for Diesel Engine based on AMESim/Simulink Co-Simulation

In common rail diesel engine, the characteristics of fuel injection is concerned both the structure parameters of injector and control strategy of control system (ECU). Thus, fuel injection system, engine performance system and ECU constitute an interactive feedback system. In this paper, first of all, using the AMESim/Simulink co-model for the common rail diesel engine prepared in the previous work, simulation and verification are performed in the AMESim/Simulink co-model based on the initial values of the diesel engine used in the case. Then it is done Simulation and Validation on the AMESim/Simulink co-mode. The engine dynamometer and injection rate test rig makes it possible to take measurements of the engine performance and injection rate in order to compare with the modelling results. This allows the obtained co-model to be validated. Validated model is very effective in describing and analyzing the transient behavior connections among injectors, high-pressure pump, and controller and engine parameters. This co-model was then used to analyze the effects of various structural parameters of injector on the response characteristics of the fuel injection system and engine operation.

Public Libraries and Spaces of Micro Connection in the Intercultural City

Everyday spaces represent central platforms that provide opportunities for encounters marked by ethnic and cultural diversity, where transformations can be negotiated that rethink living together. The significance of these ‘third places’ has been extensively researched. Yet, some spaces such as public libraries continue to be largely overlooked by geographers. Public libraries also remain under-appreciated within wider society despite their obvious social functions. Central here is that public libraries can be understood as dynamic and ‘lived spaces’ that enable the emergence of transient connections and relationships. Such spaces are increasingly sparse within modern cities. This paper explores the potential of everyday spaces of encounter, specifically public libraries, to facilitate the unfolding of ‘light’ connections and relationships, nurturing more inclusive forms of urban togetherness and belonging in multi-ethnic societies and the significance that people attribute to these often mundane encounters and micro connections. In so doing, this paper combines findings from two research projects that investigate mixed or intercultural encounters in public libraries in Bremen (Germany) and Glasgow (Scotland).

Spaces of the maybe: fragments as new urban possibilities in Cairo’s extended urbanisation

ABSTRACT Urban “fragments” play a key role in healing megacities and carving new relationships of civic connectivity. At the edge of a gated community in Cairo, AlRehab, the open market or souq serves as an urban fragment, creating different experiences that unsettle the normative assumptions of the separation between the private and public spheres. Using a Lefebvrian analysis to examine the souq of AlRehab, a two-phase longitudinal study was conducted between 2008–2012 and 2018–2022. Within the geopolitical context of the Arab Spring and the New Administrative Capital, the narratives of the souq’s developer, urban planner, residents, activists and shop workers reveal the power of agency and activism in the provision of “multiple publics” as a civic-common space. This allows the creation of transient connections, sites for political expression, as well as a base of operations for expanding job opportunities and social networks. Based on urban design theories and literature on Global South urbanism, this article poses the nuanced possibilities of re-imagining the edge as a “space of the maybe,” given its capacity to create new public spheres and a new urban grammar of entangled livelihoods, able to adapt to an urbanity of movement and growth.

Chlamydia trachomatis Cell-to-Cell Spread through Tunneling Nanotubes.

Tunneling nanotubes (TNTs) are transient cellular connections that consist of dynamic membrane protrusions. They play an important role in cell-to-cell communication and mediate the intercellular exchanges of molecules and organelles. TNTs can form between different cell types and may contribute to the spread of pathogens by serving as cytoplasmic corridors. We demonstrate that Chlamydia (C.) trachomatis-infected human embryonic kidney (HEK) 293 cells and other cells form TNT-like structures through which reticulate bodies (RBs) pass into uninfected cells. Observed TNTs have a life span of 1 to 5 h and contain microtubules, which are essential for chlamydial transfer. They can bridge distances of up to 50 μm between connecting neighboring cells. Consistent with the biological role for TNTs, we show that C. trachomatis spread also occurs under conditions in which the extracellular route of chlamydial entry into host cells is blocked. Based on our findings, we propose that TNTs play a critical role in the direct, cell-to-cell transmission of chlamydia. IMPORTANCE Intracellular bacterial pathogens often undergo a life cycle in which they parasitize infected host cells in membranous vacuoles. Two pathways have been described by which chlamydia can exit infected host cells: lytic cell destruction or exit via extrusion formation. Whether direct, cell-to-cell contact may also play a role in the spread of infection is unknown. Tunneling nanotubes (TNTs) interconnect the cytoplasm of adjacent cells to mediate efficient communication and the exchange of material between them. We used Chlamydia trachomatis and immortalized cells to analyze whether TNTs mediate bacterial transmission from an infected donor to uninfected acceptor cells. We show that chlamydia-infected cells build TNTs through which the intracellular reticulate bodies (RBs) of the chlamydia can pass into uninfected neighboring cells. Our study contributes to the understanding of the function of TNTs in the cell-to-cell transmission of intracellular pathogens and provides new insights into the strategies by which chlamydia spreads among multicellular tissues.

Effects of lake‐groundwater interaction on the thermal regime of a sub‐alpine headwater stream

AbstractStream thermal regimes are critical to the stability of freshwater habitats. There is growing concern that climate change will result in stream warming due to rising air temperatures, decreased shading in forested areas due to wildfires, and changes in streamflow. Groundwater plays an important role in controlling stream temperatures in mountain headwaters, where it makes up a considerable portion of discharge. This study investigated the controls on the thermal regime of a headwater stream, and the surrounding groundwater processes, in a catchment on the eastern slopes of the Canadian Rocky Mountains. Groundwater discharge to the headwater spring is partially sourced by a seasonal lake. Spring, stream and lake temperature, water level, discharge and chemistry data were used to build a conceptual model of the system. Meteorological data was used to set up a stream temperature model. This study presents a unique example of an indirectly lake‐headed stream, that is, a lake that only has transient subsurface hydrologic connections to the stream and no surface connections. The interaction of groundwater and lake water, and the subsurface connectivity between the lake and the headwater spring determine the resulting stream temperature. Radiation dominated the non‐advective fluxes in the stream energy balance. Sensible and latent heat fluxes play a secondary role, but their effects generally cancel out. During snowfall events, the latent heat associated with melting of direct snowfall onto the water surface was responsible for rapid stream cooling. An increase in advective inputs from groundwater and hillslope pathways did not result in observed cooling of stream water during rainfall events. The results from this study will assist water resource and fisheries managers in adapting to stream temperature changes under a warming climate.

Temporal Course of Transient Direct Corticomotoneuronal Connections during Development in Rodents

We previously observed in rodents that during the 2nd postnatal week corticospinal axons make monosynaptic connections with motoneurons. Prior to that finding, it had been believed that such contacts only occur in higher primates. Although an in vitro electrophysiological study is prerequisite for studying the developmental time course of synaptic connections, the technical difficulty of reliably recording synaptic responses from spinal motoneurons in animals over 2 weeks old hampered the study. Instead, we used retrograde transsynaptic labeling with a genetically modified rabies virus to confirm the presence of direct corticomotoneuronal connections at an early developmental stage and to show that these connections were subsequently eliminated. However, determination of an accurate elimination time course and quantitative evaluation of synaptic connectivity cannot be achieved through viral-tracing experiments.For the present study, we improved the slice preparation procedure and maintenance of slice viability, which enabled us to record postsynaptic responses using the whole cell patch-clamp technique from retrogradely labeled forearm motoneurons up until postnatal week 7. We examined the extent of corticomotoneuronal monosynaptic connections and studied the time course of their accumulation and loss. Positive ratios of monosynaptic corticomotoneuronal EPSCs increased from P6 to P8 and then plateaued (P8–P13: 65%). Thereafter, the monosynaptic connections declined until P21, at which time they were no longer detected. The time course of the falling phase and elimination was confirmed by experiments using optogenetic stimulation. The timing of the elimination fell within the same range (P18-22) estimated in our earlier study using retrograde transsynaptic labeling.

Interactions Between Gas Slug Ascent and Exchange Flow in the Conduit of Persistently Active Volcanoes

AbstractMany volcanoes around the world are persistently active with continuous degassing for years or even centuries, sometimes exceeding historic records. Such long‐term stability contrasts with short‐term instability, reflected in eruptive episodes that punctuate passive degassing. These two aspects of persistent activity, long‐term stability as opposed to short‐term instability, are often conceptualized through two distinct model frameworks: Exchange‐flow in volcanic conduits is commonly invoked to explain the long‐term thermal balance and sustained passive degassing, while the ascent of large gas slugs is called upon to understand explosive eruptions. While typically considered separately, we propose here that both flow processes could occur jointly in the conduits of persistently active volcanoes and in transient connections between subvolcanic melt lenses. To understand the dynamic interplay between exchange flow and slug ascent, we link analogue laboratory experiments with direct numerical simulations. We find that the two flows superimpose without creating major disruptions when only considering the ascent of a single gas slug. However, the sequential ascent of multiple gas slugs is disruptive to the ambient exchange flow, because it may entail continual buildup of buoyant magma at depth. While our study focuses on the laboratory scale, we propose that the dependence of exchange‐flow stability on sequential slug ascent is relevant for understanding why explosive sequences are sometimes followed by effusive eruptions. Taken together, our work suggests that integrating exchange flow and slug ascent could provide a more complete understanding of persistently active volcanoes than either model framework offers in isolation.

Interphase microtubules in nuclear organization and genome maintenance.

Microtubules are major cytoskeletal components mediating fundamental cellular processes, including cell division. Recent evidence suggests that microtubules also regulate the nucleus during the cell cycle's interphase stage. Deciphering such roles of microtubules should uncover direct crosstalk between the nucleus and cytoplasm, impacting genome function and organismal health. Here, we review emerging roles for microtubules in interphase genome regulation. We explore how microtubules exert cytoplasmic forces on the nucleus or transport molecular cargo, including DNA, into or within the nucleus. We also describe how microtubules perform these functions by establishing transient or stable connections with nuclear envelope elements. Lastly, we discuss how the regulation of the nucleus by microtubules impacts genome organization and repair. Together, the literature indicates that interphase microtubules are critical regulators of nuclear structure and genome stability.

RabX1 Organizes a Late Endosomal Compartment that Forms Tubular Connections to Lysosomes Consistent with a "Kiss and Run" Mechanism.

Degradation of endocytosed proteins involves the formation of transient connections between late endosomes and lysosomes in a process called "kiss and run." Genes and proteins controlling this mechanism are unknown. Here, we identify the small guanosine triphosphatase (GTPase) RabX1 as an organizer of a late endosomal compartment that forms dynamic tubular connections to lysosomes. By analyzing trafficking of the adhesion protein Fasciclin2 in the Drosophila follicular epithelium, we show that a reduction of RabX1 function leads to defects in Fasciclin2 degradation. RabX1 mutants fail to form normal lysosomes and accumulate Fasciclin2 in a swelling late-endosomal compartment. RabX1 protein localizes to late endosomes, where it induces the formation of tubular connections to lysosomes. We propose that these tubules facilitate influx of lysosomal content into late endosomes and that this influx leads to the formation of endolysosomes, in which Fasciclin2 is degraded. We show that the formation of RabX1 tubules is dependent on the V-ATPase proton pump. Moreover, we provide evidence that V-ATPase activity is upregulated during epithelial differentiation. This upregulation intensifies RabX1 tubulation and thereby boosts the capacity of the endolysosomal pathway. Enhanced endolysosomal capacity is required for the removal of Fasciclin2 from the epithelium, which is part of a developmental program promoting epithelial morphogenesis.

The Wnt/Ca2+ pathway is involved in interneuronal communication mediated by tunneling nanotubes.

Tunneling nanotubes (TNTs) are actin-based transient tubular connections that allow direct communication between distant cells. TNTs play an important role in several physiological (development, immunity, and tissue regeneration) and pathological (cancer, neurodegeneration, and pathogens transmission) processes. Here, we report that the Wnt/Ca2+ pathway, an intracellular cascade that is involved in actin cytoskeleton remodeling, has a role in TNT formation and TNT-mediated transfer of cargoes. Specifically, we found that Ca2+ /calmodulin-dependent protein kinase II (CaMKII), a transducer of the Wnt/Ca2+ pathway, regulates TNTs in a neuronal cell line and in primary neurons. We identified the β isoform of CaMKII as a key molecule in modulating TNT formation and transfer, showing that this depends on the actin-binding activity of the protein. Finally, we found that the transfer of vesicles and aggregated α-synuclein between primary neurons can be regulated by the activation of the Wnt/Ca2+ pathway. Our findings suggest that Wnt/Ca2+ pathway could be a novel promising target for therapies designed to impair TNT-mediated propagation of pathogens.

Robust spatial memory maps encoded by networks with transient connections.

The spiking activity of principal cells in mammalian hippocampus encodes an internalized neuronal representation of the ambient space—a cognitive map. Once learned, such a map enables the animal to navigate a given environment for a long period. However, the neuronal substrate that produces this map is transient: the synaptic connections in the hippocampus and in the downstream neuronal networks never cease to form and to deteriorate at a rapid rate. How can the brain maintain a robust, reliable representation of space using a network that constantly changes its architecture? We address this question using a computational framework that allows evaluating the effect produced by the decaying connections between simulated hippocampal neurons on the properties of the cognitive map. Using novel Algebraic Topology techniques, we demonstrate that emergence of stable cognitive maps produced by networks with transient architectures is a generic phenomenon. The model also points out that deterioration of the cognitive map caused by weakening or lost connections between neurons may be compensated by simulating the neuronal activity. Lastly, the model explicates the importance of the complementary learning systems for processing spatial information at different levels of spatiotemporal granularity.

Edge-Based Compartmental Modelling of an SIR Epidemic on a Dual-Layer Static\u2013Dynamic Multiplex Network with Tunable Clustering

The duration, type and structure of connections between individuals in real-world populations play a crucial role in how diseases invade and spread. Here, we incorporate the aforementioned heterogeneities into a model by considering a dual-layer static–dynamic multiplex network. The static network layer affords tunable clustering and describes an individual’s permanent community structure. The dynamic network layer describes the transient connections an individual makes with members of the wider population by imposing constant edge rewiring. We follow the edge-based compartmental modelling approach to derive equations describing the evolution of a susceptible–infected–recovered epidemic spreading through this multiplex network of individuals. We derive the basic reproduction number, measuring the expected number of new infectious cases caused by a single infectious individual in an otherwise susceptible population. We validate model equations by showing convergence to pre-existing edge-based compartmental model equations in limiting cases and by comparison with stochastically simulated epidemics. We explore the effects of altering model parameters and multiplex network attributes on resultant epidemic dynamics. We validate the basic reproduction number by plotting its value against associated final epidemic sizes measured from simulation and predicted by model equations for a number of set-ups. Further, we explore the effect of varying individual model parameters on the basic reproduction number. We conclude with a discussion of the significance and interpretation of the model and its relation to existing research literature. We highlight intrinsic limitations and potential extensions of the present model and outline future research considerations, both experimental and theoretical.

Live cell superresolution-structured illumination microscopy imaging analysis of the intercellular transport of microvesicles and costimulatory proteins via nanotubes between immune cells

Membrane nanotubes are transient long-distance connections between cells that can facilitate intercellular communication. These tethers can form spontaneously between many cell types, including cells of the immune and nervous systems. Traffic of viral proteins, vesicles, calcium ions, mRNA, miRNA, mitochondria, lysosomes and membrane proteins/raft domains have all been reported so far via the open ended tunneling nanotubes (TNTs). Recently we reported on existence of plasma membrane derived GM1/GM3 ganglioside enriched microvesicles and costimulatory proteins in nanotubes connecting B lymphocytes, the way they are formed and transported across TNTs, however, still remained unclear. Here, using live cell confocal and Structured Illumination (SR-SIM) superresolution imaging, we show that B cells respond to bacterial (Cholera) toxin challenge by their subsequent internalization followed by rapid formation of intracellular microvesicles (MVs). These MVs are then transported between adjacent B cells via nanotubes. Selective transport-inhibition analysis of two abundant motor proteins in these cell types demonstrated that actin-based non-muscle myosin 2A dominantly mediates intercellular MV-transport via TNTs, in contrast to the microtubule-based dynein, as shown by the unchanged transport after inhibition of the latter. As suggested by SR-SIM images of GFP-CD86 transfected macrophages, these costimulatory molecules may be transferred by unusually shaped MVs through thick TNTs connecting macrophages. In contrast, in B cell cultures the same GFP-CD86 is dominantly transported along the membrane wall of TNTs. Such intercellular molecule-exchange can consequently improve the efficiency of antigen-dependent T cell activation, especially in macrophages with weak costimulator expression and T cell activation capacity. Such improved T cell activating potential of these two cell types may result in a more efficient cellular immune response and formation of immunological memory. The results also highlight the power of superresolution microscopy to uncover so far hidden structural details of biological processes, such as microvesicle formation and transport.

NP-Completeness in the gossip monoid

Gossip monoids form an algebraic model of networks with exclusive, transient connections in which nodes, when they form a connection, exchange all known information. They also arise naturally in pure mathematics, as the monoids generated by the set of all equivalence relations on a given finite set under relational composition. We prove that a number of important decision problems for these monoids (including the membership problem, and hence the problem of deciding whether a given state of knowledge can arise in a network of the kind under consideration) are NP-complete. As well as being of interest in their own right, these results shed light on the apparent difficulty of establishing the cardinalities of the gossip monoids: a problem which has attracted some attention in the last few years.

Cinephilic retreats and transient connections in Hispanic cinemas

Cinephilic retreats and transient connections in Hispanic cinemas

Toward an alternative dialogue between the social and natural sciences

Interdisciplinary research within the field of sustainability studies often faces incompatible ontological assumptions deriving from natural and social sciences. The importance of this fact is often underrated and sometimes leads to the wrong strategies. We distinguish between two broad approaches in interdisciplinarity: unificationism and pluralism. Unificationism seeks unification and perceives disciplinary boundaries as conventional, representing no long-term obstacle to progress, whereas pluralism emphasizes more ephemeral and transient interdisciplinary connections and underscores the autonomy of the disciplines with respect to one another. Both approaches have their merits and pitfalls. Unification runs the risk of scientific imperialism, while pluralism can result in insurmountable barriers between disciplines. We made a comparison of eight distinct interdisciplinary attempts at integration of knowledge across social and natural sciences. The comparison was carried out as four pairwise comparisons: environmental economics versus ecological economics, environmental history versus historical ecology, resilience theory versus political ecology, and socio-biology versus actor-network theory. We conclude by showing that none of these prominent eight interdisciplinary fields in and of itself manages to provide, in a satisfactory way, such an integrated understanding of sustainability. We argue for pluralism and advocate complex ways of articulating divergent ontological assumptions. This is not equivalent to pursuing knowledge unification either through scientific imperialism or by catering to the requirements of narrow practical utility. It means prioritizing interdisciplinary integration by simultaneously acknowledging the role of societal and natural factors in accounting for sustainability issues.

Human-like distal-dominant gradient in the target muscles of transient corticomotoneuronal direct connections in juvenile rodents

Background: It has long been believed that the monosynaptic corticomotoneuronal (CM) connections linking motor cortex directly to spinal motoneurons are the privilege of higher primates that plays an important role in the cortical control of skilled hand movement. CM-connections had been considered to be sparse or absent in non-primates however we recently reported a functional direct connection between motor cortex and the cervical motoneurons in infant rats. It is further known in higher primates that the direct CM-connections were most pronounced for distal arm muscles and especially finger muscles easily linked to the ability to perform skilled movements of fingers.

Control of species-dependent cortico-motoneuronal connections underlying manual dexterity.

Superior manual dexterity in higher primates emerged together with the appearance of cortico-motoneuronal (CM) connections during the evolution of the mammalian corticospinal (CS) system. Previously thought to be specific to higher primates, we identified transient CM connections in early postnatal mice, which are eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM connections into adulthood and exhibit superior manual dexterity as compared with that of controls. Last, differing PlexA1 expression in layer 5 of the motor cortex, which is strong in wild-type mice but weak in humans, may be explained by FEZF2-mediated cis-regulatory elements that are found only in higher primates. Thus, species-dependent regulation of PlexA1 expression may have been crucial in the evolution of mammalian CS systems that improved fine motor control in higher primates.