Beyond variegation: the territorialisation of states, communities and developers in large-scale developments in Johannesburg, Shanghai and London

Large-scale urban development projects are a significant format of urban expansion and renewal across the globe. As generators of governance innovation and indicators of the future city in each urban context, large-scale development projects have been interpreted within frameworks of “variegations” of wider circulating processes, such as neoliberalisation or financialisation. However, such projects often entail significant state support and investment, are strongly linked to a wide variety of transnational investors and developers and are frequently highly contested in their local environments. Thus, each project comes to fruition in a distinctive regulatory context, often as an exception to the norm, and each emerges through complex interactions over a long period of time amongst an array of actors. We therefore seek to broaden the discussion from an analytical focus on variegated globalised processes to consider three large-scale urban development projects (in Shanghai, Johannesburg and London) as distinctive (transcalar) territorialisations. Using an innovative comparative approach we outline the grounds for a systematic analytical conversation across mega-urban development projects in very different contexts. Initially, comparability rests on the shared features of large-scale developments – that they are multi-jurisdictional, involve long time scales, and bring significant financing challenges. Comparing three development projects we are able to interrogate, rather than take for granted, how wider processes, circulating practices, transcalar actors, and territorial regulatory formations composed specific urban outcomes in each case. Thinking across these diverse cases provides grounds for rebuilding understandings of urban development politics

Selective herbicide safening in dicot plants: a case study in <em>Arabidopsis</em>

Copyright \ua9 2024 Pingarron-Cardenas, Onkokesung, Goldberg-Cavalleri, Lange, Dittgen and Edwards.Safeners are agrochemicals co-applied with herbicides that facilitate selective control of weeds by protecting monocot crops from chemical injury through enhancing the expression of detoxifying enzymes such as glutathione transferases (GSTs). Even though the application of safeners causes the induction of genes encoding GSTs in model dicots such as Arabidopsis thaliana, safeners do not protect broadleaf crops from herbicide injury. In this study, we proposed that the localized induction of Arabidopsis GSTs and the fundamental differences in their detoxifying activity between dicot and monocot species, underpin the failure of safeners to protect Arabidopsis from herbicide toxicity. Using the herbicide safener, isoxadifen-ethyl, we showed that three tau (U) family GSTs namely AtGSTU7, AtGSTU19 and AtGSTU24 were induced with different magnitude by isoxadifen treatment in root and rosette tissues. The higher magnitude of inducibility of these AtGSTUs in the root tissues coincided with the enhanced metabolism of flufenacet, a herbicide that is active in root tissue, protecting Arabidopsis plants from chemical injury. Assay of the recombinant enzyme activities and the significant reduction in flufenacet metabolism determined in the T-DNA insertion mutant of AtGSTU7 (gstu7) in Arabidopsis plants identified an important function for AtGSTU7 protein in flufenacet detoxification. In-silico structural modeling of AtGSTU7, suggested the unique high activity of this enzyme toward flufenacet was due to a less constrained active site compared to AtGSTU19 and AtGSTU24. We demonstrate here that it is possible to induce herbicide detoxification in dicotyledonous plants by safener treatment, albeit with this activity being restricted to very specific combinations of herbicide chemistry, and the localized induction of enzymes with specific detoxifying activities

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations

Robotic Automation of In Vivo Two-Photon Targeted Whole-Cell Patch-Clamp Electrophysiology

Whole-cell patch-clamp electrophysiological recording is a powerful technique for studying cellular function. While in vivo patch-clamp recording has recently benefited from automation, it is normally performed “blind,” meaning that throughput for sampling some genetically or morphologically defined cell types is unacceptably low. One solution to this problem is to use two-photon microscopy to target fluorescently labeled neurons. Combining this with robotic automation is difficult, however, as micropipette penetration induces tissue deformation, moving target cells from their initial location. Here we describe a platform for automated two-photon targeted patch-clamp recording, which solves this problem by making use of a closed loop visual servo algorithm. Our system keeps the target cell in focus while iteratively adjusting the pipette approach trajectory to compensate for tissue motion. We demonstrate platform validation with patch-clamp recordings from a variety of cells in the mouse neocortex and cerebellum

China’s Dam Builders: their role in transboundary river management in Southeast Asia

This article investigates China’s role as the world’s largest builder of and investor in large dams, focussing on the Greater Mekong Sub-Region in South-East Asia. It addresses the role Chinese actors play in dam-building as well as the environmental, social, economic and political implications by drawing on case studies from Cambodia and Vietnam. The article finds that China’s dam-building is perceived very differently in different countries of South-East Asia. In Cambodia, the dams in the Greater Mekong Sub-Region are considered instruments of economic growth and development, whereas downstream in Vietnam the dams are seen as potentially undermining national growth, development and security

Granulocyte-Colony Stimulating Factor (G-CSF) Improves Motor Recovery in the Rat Impactor Model for Spinal Cord Injury

Granulocyte-colony stimulating factor (G-CSF) improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function

In Vivo Analysis of MEF2 Transcription Factors in Synapse Regulation and Neuronal Survival

MEF2 (A–D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations

Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution

The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells