•Provides an overview of e-scooter operators worldwide.•Analyses media items in ten cities regarding conflicts over e-scooter introductions.•Shows that divisions arise over space, speed, and ...safety.•Cities can address many of these issues by implementing rules and policies.•E-scooters may become a force for transforming automotive systems.
Throughout the world, cities seek to ease transport-related problems of congestion, air pollution, noise, and traffic injuries. Urban transport planners have welcomed e-scooters as an alternative to motorized individual transport, specifically the car. The public has met e-scooters with both enthusiasm and scepticism, as cities have struggled with unforeseen outcomes such as forms of irresponsible riding, cluttering, or vandalism. This paper investigates the challenges associated with the introduction of e-scooters in ten major cities, based on a content analysis of local media reports. News items (n = 173) were identified through Internet searches and include print media, TV and radio websites. Concerns prior to and after the introduction of e-scooters are assessed, analysed, and interpreted in the context of new policies for this transport mode. Results suggest that many cities have moved through trial and error stages in their search for appropriate legislation. The paper concludes that it is prudent for urban planners to introduce policies regarding maximum speeds, mandatory use of bicycle infrastructure, and dedicated parking, as well as to limit the number of licensed operators. Where negative public opinion can be averted, e-scooters stand a chance to become a disruptive niche innovation with the potential to transform urban transport systems.
•A minimal retailer density is needed to achieve positive cost savings.•There is a domain of retailer densities that never produce savings regardless site-parameters.•Emission savings is the most ...restrictive condition to satisfy.•The current monetary values of pollutants make the emission savings negligible.•Consolidation strategies alleviate the negative impact of access restriction policies on carriers.
This paper presents the necessary conditions to ensure a minimal profitability of carrier-led consolidation strategies in urban distribution. These conditions are shown by compact formulas obtained by continuous approximations representing the cost of the stakeholders involved: society, regular carriers, consolidation facility operator and environment. The domain of the retailer density variable that always produces negative effects on each stakeholder has been identified. The envelope of this domain does not depend on vehicle costs and other site-related parameters. On the other hand, there is a critical density of receivers that makes the carrier cost savings higher than the CF operator costs.
This paper has two main parts. The first questions two of the underlying principles of conventional transport planning on travel as a derived demand and on travel cost minimisation. It suggests that ...the existing paradigm ought to be more flexible, particularly if the sustainable mobility agenda is to become a reality. The second part argues that policy measures are available to improve urban sustainability in transport terms but that the main challenges relate to the necessary conditions for change. These conditions are dependent upon high-quality implementation of innovative schemes, and the need to gain public confidence and acceptability to support these measures through active involvement and action. Seven key elements of sustainable mobility are outlined, so that public acceptability can be more effectively promoted.
The sequential action of the Vps27/HRS complex, ESCRT-I, -II, and -III is required to sort ubiquitinated transmembrane proteins to the lumen of lysosomes via the multivesicular body (MVB) pathway. ...While Vps27/HRS, ESCRT-I, and -II are recruited to endosomes as preformed complexes, the ESCRT-III subunits Vps20, Snf7, Vps24, and Vps2 only assemble into a complex on endosomes. We have addressed the pathway and the regulation for ESCRT-III assembly. Our findings indicate the ordered assembly of a transient 450 kDa ESCRT-III complex on endosomes. Despite biochemical and structural similarity, each subunit contributes a specific function. Vps20 nucleates transient oligomerization of Snf7, which appears to sequester MVB cargo. Vps24 terminates Snf7 oligomerization by recruiting Vps2, which subsequently engages the AAA-ATPase Vps4 to dissociate ESCRT-III. We propose that the ordered assembly and disassembly of ESCRT-III delineates an MVB sorting domain to sequester cargo and complete the last steps of MVB sorting.
Cardiomyocytes rely on metabolic substrates, not only to fuel cardiac output, but also for growth and remodelling during stress. Here we show that mitochondrial pyruvate carrier (MPC) abundance ...mediates pathological cardiac hypertrophy. MPC abundance was reduced in failing hypertrophic human hearts, as well as in the myocardium of mice induced to fail by angiotensin II or through transverse aortic constriction. Constitutive knockout of cardiomyocyte MPC1/2 in mice resulted in cardiac hypertrophy and reduced survival, while tamoxifen-induced cardiomyocyte-specific reduction of MPC1/2 to the attenuated levels observed during pressure overload was sufficient to induce hypertrophy with impaired cardiac function. Failing hearts from cardiomyocyte-restricted knockout mice displayed increased abundance of anabolic metabolites, including amino acids and pentose phosphate pathway intermediates and reducing cofactors. These hearts showed a concomitant decrease in carbon flux into mitochondrial tricarboxylic acid cycle intermediates, as corroborated by complementary 1,2-
C
glucose tracer studies. In contrast, inducible cardiomyocyte overexpression of MPC1/2 resulted in increased tricarboxylic acid cycle intermediates, and sustained carrier expression during transverse aortic constriction protected against cardiac hypertrophy and failure. Collectively, our findings demonstrate that loss of the MPC1/2 causally mediates adverse cardiac remodelling.
Zip14 is a member of the SLC39A zinc transporter family, which is involved in zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the hepatic zinc accumulation and ...hypozincemia of inflammation. At least three members of the SLC39A family transport other trace elements, such as iron and manganese, in addition to zinc. We analyzed the capability of Zip14 to mediate non-transferrin-bound iron (NTBI) uptake by overexpressing mouse Zip14 in HEK 293H cells and Sf9 insect cells. Zip14 was found to localize to the plasma membrane, and its overexpression increased the uptake of both$^{65}Zn$and$^{59}Fe$. Addition of bathophenanthroline sulfonate, a cell-impermeant ferrous iron chelator, inhibited Zip14-mediated iron uptake from ferric citrate, suggesting that iron is taken up by HEK cells as Fe²⁺. Iron uptake by HEK and Sf9 cells expressing Zip14 was inhibited by zinc. Suppression of endogenous Zip14 expression by using Zip14 siRNA reduced the uptake of both iron and zinc by AML12 mouse hepatocytes. Zip14 siRNA treatment also decreased metallothionein mRNA levels, suggesting that compensatory mechanisms were not sufficient to restore intracellular zinc. Collectively, these results indicate that Zip14 can mediate the uptake of zinc and NTBI into cells and that it may play a role in zinc and iron metabolism in hepatocytes, where this transporter is abundantly expressed. Because NTBI is commonly found in plasma of patients with hemochromatosis and transfusional iron overload, Zip14-mediated NTBI uptake may contribute to the hepatic iron loading that characterizes these diseases.
The natural resistance-associated macrophage protein (Nramp) family encompasses transition metal and proton cotransporters that are present in many organisms from bacteria to humans. Recent ...structures of Deinococcus radiodurans Nramp (DraNramp) in multiple conformations revealed the intramolecular rearrangements required for alternating access of the metal-binding site to the external or cytosolic environment. Here, using recombinant proteins and metal transport and cysteine accessibility assays, we demonstrate that two parallel cytoplasm-accessible networks of conserved hydrophilic residues in DraNramp, one lining the wide intracellular vestibule for metal release and the other forming a narrow proton transport pathway, are essential for metal transport. We further show that mutagenic or posttranslational modifications of transmembrane helix (TM) 6b, which structurally links these two pathways, impede normal conformational cycling and metal transport. TM6b contains two highly conserved histidines, His232 and His237. We found that different mutagenic perturbations of His232, just below the metal-binding site along the proton exit route, differentially affect DraNramp's conformational state, suggesting that His232 serves as a pivot point for conformational changes. In contrast, any replacement of His237, lining the metal exit route, locked the transporter in a transport-inactive outward-closed state. We conclude that these two histidines, and TM6b more broadly, help trigger the bulk rearrangement of DraNramp to the inward-open state upon metal binding and facilitate return of the empty transporter to an outward-open state upon metal release.
Arabidopsis (Arabidopsis thaliana) absorbs inorganic phosphate (Pi) from the soil through an active transport process mediated by the nine members of the PHOSPHATE TRANSPORTER1 (PHT1) family. These ...proteins share a high level of similarity (greater than 61%), with overlapping expression patterns. The resulting genetic and functional redundancy prevents the analysis of their specific roles. To overcome this difficulty, our approach combined several mutations with gene silencing to inactivate multiple members of the PHT1 family, including a cluster of genes localized on chromosome 5 (PHT1;1, PHT1;2, andPHT1;3). Physiological analyses of these lines established that these three genes, along withPHT1;4, are the main contributors to Pi uptake. Furthermore,PHT1;1plays an important role in translocation from roots to leaves in high phosphate conditions. These genetic tools also revealed that some PHT1 transporters likely exhibit a dual affinity for phosphate, suggesting that their activity is posttranslationally controlled. These lines display significant phosphate deficiency-related phenotypes (e.g. biomass and yield) due to a massive (80%–96%) reduction in phosphate uptake activities. These defects limited the amount of internal Pi pool, inducing compensatory mechanisms triggered by the systemic Pi starvation response. Such reactions have been uncoupled from PHT1 activity, suggesting that systemic Pi sensing is most probably acting downstream of PHT1.
Abstract
A new facile route to fabricate N‐doped graphene‐SnO
2
sandwich papers is developed. The 7,7,8,8‐tetracyanoquinodimethane anion (TCNQ
−
) plays a key role for the formation of such ...structures as it acts as both the nitrogen source and complexing agent. If used in lithium‐ion batteries (LIBs), the material exhibits a large capacity, high rate capability, and excellent cycling stability. The superior electrochemical performance of this novel material is the result from its unique features: excellent electronic conductivity related to the sandwich structure, short transportation length for both lithium ions and electrons, and elastomeric space to accommodate volume changes upon Li insertion/extraction.
The uptake of nutrients, including metals, amino acids and peptides are required for many biological processes. Pathogenic bacteria scavenge these essential nutrients from microenvironments to ...survive within the host. Pathogens must utilize a myriad of mechanisms to acquire these essential nutrients from the host while mediating the effects of toxicity. Bacteria utilize several transport proteins, including ATP-binding cassette (ABC) transporters to import and expel substrates. ABC transporters, conserved across all organisms, are powered by the energy from ATP to move substrates across cellular membranes. In this review, we will focus on nutrient uptake, the role of ABC importers at the host–pathogen interface, and explore emerging therapies to combat pathogenesis. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain.
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