Research on social equity pertaining to transportation typically addresses how residents in a region have access to desirable destinations. Nonetheless, little is known about how public transit fare structures relate to social equity concerns. Some transit agencies charge more for fewer rides weekly fares often cost more per ride than unlimited monthly fares, though monthly fares cost more upfront. For some social groups, in particular low-income earners, purchasing monthly passes may place a burden on their budget, and influence them to buy weekly passes instead. In this study, we analyze transit fare purchases of total monthly, weekly, and three or more weekly passes during the month of September 2014 in Montreal, Canada. We discovered that fare vendors in neighborhoods with low median household income and/or with a high proportion of unemployed residents are predicted to sell more weekly fares than vendors in neighborhoods with high household income and low rates of unemployment. Monthly fare purchases were not dependent on income or unemployed residents. Moreover, using smartcard data to track individual fare cards, we found that recurring purchases of three or more weekly passes depend on income and unemployment, so neighborhoods with socially vulnerable individuals are predicted to have more riders purchasing multiple weekly fares than socially secure neighborhoods. Our findings indicate that individuals residing in marginalized neighborhoods are likely to spend more money on transit fares over the course of a month compared to those residing in wealthy neighborhoods. These findings raise concerns regarding the financial burden that the existing fare structure in the city of Montreal imposes, especially on low-income groups. The methodology and findings from this study provide insight for transport planners, particularly those concerned with providing an equitable public transit system. (C) 2016 Elsevier Ltd. All rights reserved.

We present a rapid assessment – using simple metrics based on publicly available data– of how effectively public transit agencies achieve key outcomes, and reconcile trade-offs among these outcomes, from the perspective of transit users, society and the agencies, in the largest 14 cities in North America with a population greater than three million. We assess the trade-offs among service quality, incorporating accessibility, service frequency, and comfort (which are important for transit users); transit ridership per capita (reflecting the society perspective); financial viability from the agency perspective; and affordability of fares for minimum-wage earners. We also assess the overall performance of transit in these cities, considering these perspectives in an integrated manner. Agencies vary widely in achieving and reconciling the above outcomes and trade-offs. Generally speaking, however, agencies that perform well (or badly) on one of these objectives and trade-offs also perform well (or badly) on the others, and in terms of overall transit performance. Finally, we discuss how our assessment may be improved upon, including in terms of better and more nuanced measures, in future work. We suggest that metrics be assessed uniformly and reported regularly across transit agencies, to track and reliably compare their performance over time; and that it would be desirable to understand how transit users and decision makers weigh the relative importance of key objectives, and to incorporate this understanding in assessments of transit performance.

If transit agencies wish to retain and attract riders, they need to provide reliable and efficient services. Transit agencies tend to run high-frequency bus routes during peak hours, and in many cities, different routes can also overlap along major corridors. In some instances, consecutive buses can arrive at a shared stop simultaneously or one bus may arrive while another bus is currently servicing the stop. This phenomenon, known as bus bunching, can delay buses and passengers, and is usually inefficient. In this study, we attempt to understand how bus bunching from the same or different routes can impact bus operations, specifically dwell and running times. This research uses stop-level records obtained from automatic vehicle location (AVL) and automatic passenger counter (APC) systems from TriMet, Portland, OR. Using linear modeling, we find that bus bunching increases both dwell and running times. Specifically, when different routes bunch or are scheduled to arrive at a bus stop within a short time frame, or when buses from the same route arrive with a short time frame, dwell times increase by ~10 s. Similarly, bus bunching from the same route or different route prolongs running times by ~40 s. Our findings suggest that bus schedulers and operators should consider adding more time between consecutive buses from different routes at shared stops to minimize the negative impacts that we observed from bus bunching.

To retain and grow ridership, transit agencies continuously survey riders to learn how to improve services and understand what leads to rider satisfaction. Nevertheless, transit riders are not a homogeneous entity and understanding the distinctions between transit riders can help transit agencies in their efforts to provide satisfactory service to retain existing riders and attract new ones. To uncover how diverse aspects of bus services can differentially impact satisfaction of different riders, we use data from a large-scale, multiyear bus satisfaction survey from London, UK. Specifically, we model satisfaction using logistic regressions to learn how encumbered riders and riders with physical disabilities value different features of bus services compared to other types of riders. For riders traveling with large items, shopping bags, or children, we find that satisfaction depends on the presence and condition of a bus shelter and the availability of a seat. Satisfaction of riders with disabilities depends on information availability at the bus stop, as well as trip speed and reliability. Our findings indicate that improving waiting area conditions and providing information at the stop can increase the satisfaction of riders with encumbrances and disabilities, respectively. Findings from this paper can be of benefit to transit planners and policy makers as it offers new insights about the determinants of satisfaction of two groups of bus riders not often considered in the public transport literature.

Social equity is increasingly incorporated as a long-term objective into urban transportation plans. Researchers use accessibility measures to assess equity issues, such as determining the amount of jobs reachable by marginalized groups within a defined travel time threshold and compare these measures across socioeconomic categories. However, allocating public transit resources in an equitable manner is not only related to travel time, but also related to the out-of-pocket cost of transit, which can represent a major barrier to accessibility for many disadvantaged groups. Therefore, this research proposes a set of new accessibility measures that incorporates both travel time and transit fares. It then applies those measures to determine whether people residing in socially disadvantaged neighborhoods in Montreal, Canada experience the same levels of transit accessibility as those living in other neighborhoods. Results are presented in terms of regional accessibility and trends by social indicator decile. Travel time accessibility measures estimate a higher number of jobs that can be reached compared to combined travel time and cost measures. However, the degree and impact of these measures varies across the social deciles. Compared to other groups in the region, residents of socially disadvantaged areas have more equitable accessibility to jobs using transit; this is reflected in smaller decreases in accessibility when fare costs are included. Generating new measures of accessibility combining travel time and transit fares provides more accurate measures that can be easily communicated by transportation planners and engineers to policy makers and the public since it translates accessibility measures to a dollar value. (C) 2016 Elsevier Ltd. All rights reserved.

To retain and grow ridership, transit agencies continuously survey riders to learn how to improve services and understand what leads to rider satisfaction. Nevertheless, transit riders are not a homogeneous entity and understanding the distinctions between transit riders can help transit agencies in their efforts to provide satisfactory service to retain existing riders and attract new ones. To uncover how diverse aspects of bus services can differentially impact satisfaction of different riders, the authors use data from a large-scale, multiyear bus satisfaction survey from London, UK. Specifically, they model satisfaction using logistic regressions to learn how encumbered riders and riders with physical disabilities value different features of bus services compared to other types of riders. For riders traveling with large items, shopping bags, or children, the authors find that satisfaction depends on the presence and condition of a bus shelter and the availability of a seat. Satisfaction of riders with disabilities depends on information availability at the bus stop, as well as trip speed and reliability. The findings indicate that improving waiting area conditions can specifically increase the satisfaction of riders with disabilities and encumbrances. Findings from this paper can be of benefit to transit planners and policy makers as it offers new insights about the determinants of satisfaction of two groups of bus riders that were previously overlooked in the public transport literature.

Neurological diseases associated with neuronal death are also accompanied by axonal denervation of connected brain regions. In these areas, denervation leads to a decrease in afferent drive, which may in turn trigger active central nervous system (CNS) circuitry rearrangement. This rewiring process is important therapeutically, since it can partially recover functions and can be further enhanced using modern rehabilitation strategies. Nevertheless, the cellular mechanisms of brain rewiring are not fully understood. We recently reported a mechanism by which neurons remodel their local connectivity under conditions of network-perturbance: hippocampal pyramidal cells can extend spine head protrusions (SHPs), which reach out toward neighboring terminals and form new synapses. Since this form of activity-dependent rewiring is observed only on some spines, we investigated the required conditions. We speculated, that the actin-associated protein synaptopodin, which is involved in several synaptic plasticity mechanisms, could play a role in the formation and/or stabilization of SHPs. Using hippocampal slice cultures, we found that ~70 % of spines with protrusions in CA1 pyramidal neurons contained synaptopodin. Analysis of synaptopodin-deficient neurons revealed that synaptopodin is required for the stability but not the formation of SHPs. The effects of synaptopodin could be linked to its role in Ca2+ homeostasis, since spines with protrusions often contained ryanodine receptors and synaptopodin. Furthermore, disrupting Ca2+ signaling shortened protrusion lifetime. By transgenically reintroducing synaptopodin on a synaptopodin-deficient background, SHP stability could be rescued. Overall, we show that synaptopodin increases the stability of SHPs, and could potentially modulate the rewiring of microcircuitries by making synaptic reorganization more efficient.

CX 546, an allosteric positive modulator of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid‐type ionotropic glutamate receptors (AMPARs), belongs to a drug class called ampakines. These compounds have been shown to enhance long‐term potentiation (LTP), a cellular model of learning and memory, and improve animal learning task performance, and have augmented cognition in neurodegenerative patients. However, the chronic effect of CX546 on synaptic structures has not been examined. The structure and integrity of dendritic spines are thought to play a role in learning and memory, and their abnormalities have been implicated in cognitive disorders. In addition, their structural plasticity has been shown to be important for cognitive function, such that dendritic spine remodeling has been proposed as the morphological correlate for LTP. Here, we tested the effect of CX546 on dendritic spine remodeling following long‐term treatment. We found that, with prolonged CX546 treatment, organotypic hippocampal slice cultures showed a significant reduction in CA3–CA1 excitatory synapse and spine density. Electrophysiological approaches revealed that the CA3–CA1 circuitry compensates for this synapse loss by increasing synaptic efficacy through enhancement of presynaptic release probability. CX546‐treated slices showed prolonged and enhanced potentiation upon LTP induction. Furthermore, structural plasticity, namely spine head enlargement, was also more pronounced after CX546 treatment. Our results suggest a concordance of functional and structural changes that is enhanced with prolonged CX546 exposure. Thus, the improved cognitive ability of patients receiving ampakine treatment may result from the priming of synapses through increases in the structural plasticity and functional reliability of hippocampal synapses.

Most excitatory transmission in the brain is mediated by the AMPA receptor subtype of the ionotropic glutamate receptors. In many neurological diseases, synapse structure and AMPA receptor function are altered, thus making AMPA receptors potential therapeutic targets for clinical intervention. The work summarized in this review suggests a link between AMPA receptor function and debilitating neuropathologies, and discusses the current state of therapies targeting AMPA receptors in four diseases. In amyotrophic lateral sclerosis, AMPA receptors allow cytotoxic levels of calcium into neurons, leading to motor neuron death. Likewise, in some epilepsies, overactivation of AMPA receptors leads to neuron damage. The same is true for ischemia, where oxygen deprivation leads to excitotoxicity. Conversely, Alzheimer's disease is characterized by decreased AMPA activation and synapse loss. Unfortunately, many clinical studies have had limited success by directly targeting AMPA receptors in these diseases. We also discuss how the use of AMPA receptor modulators, commonly known as ampakines, in neurological diseases initially seemed promising in animal studies, but mostly ineffective in clinical trials. We propose that indirectly affecting AMPA receptors, such as by modulating transmembrane AMPA receptor regulatory proteins or, more generally, by regulating glutamatergic transmission, may provide new therapeutic potential for neurological disorders.

Accumulating evidence supports the idea that synapses are tripartite, whereby perisynaptic astrocytes modulate both pre‐ and postsynaptic function. Although some of these features have been uncovered by using electrophysiological methods, less is known about the structural interplay between synapses and glial processes. Here, we investigated how astrocytes govern the plasticity of individual hippocampal dendritic spines. Recently, we uncovered that a subgroup of innervated dendritic spines is able to undergo remodeling by extending spine head protrusions (SHPs) toward neighboring functional presynaptic boutons, resulting in new synapses. Although glutamate serves as a trigger, how this behavior is regulated is unknown. As astrocytes control extracellular glutamate levels through their high‐affinity uptake transporters, together with their privileged access to synapses, we investigated a role for astrocytes in SHP formation. Using time‐lapse confocal microscopy, we found that the volume overlap between spines and astrocytic processes decreased during the formation of SHPs. Focal application of glutamate also reduced spine‐astrocyte overlap and induced SHPs. Importantly, SHP formation was prevented by blocking glial glutamate transporters, suggesting that glial control of extracellular glutamate is important for SHP‐mediated plasticity of spines. Hence, the dynamic changes of both spines and astrocytes can rapidly modify synaptic connectivity. © 2012 Wiley Periodicals, Inc.

The pH milieu of the central and peripheral nervous systems is an important determinant of neuronal excitability, function, and survival. In mammals, neural acid-base homeostasis is coordinately regulated by ion transporters belonging to the Na(+)/H(+) exchanger (NHE) and bicarbonate transporter gene families. However, the relative contributions of individual isoforms within the respective families are not fully understood. This report focuses on the NHE family, specifically the plasma membrane-type NHE5 which is preferentially transcribed in brain, but the distribution of the native protein has not been extensively characterized. To this end, we generated a rabbit polyclonal antibody that specifically recognizes NHE5. In both central (cortex, hippocampus) and peripheral (superior cervical ganglia, SCG) nervous tissue of mice, NHE5 immunostaining was punctate and highly concentrated in the somas and to lesser amounts in the dendrites of neurons. Very little signal was detected in axons. Similarly, in primary cultures of differentiated SCG neurons, NHE5 localized predominantly to vesicles in the somatodendritic compartment, though some immunostaining was also evident in punctate vesicles along the axons. NHE5 was also detected predominantly in intracellular vesicles of cultured SCG glial cells. Dual immunolabeling of SCG neurons showed that NHE5 did not colocalize with markers for early endosomes (EEA1) or synaptic vesicles (synaptophysin), but did partially colocalize with the transferrin receptor, a marker of recycling endosomes. Collectively, these data suggest that NHE5 partitions into a unique vesicular pool in neurons that shares some characteristics of recycling endosomes where it may serve as an important regulated store of functional transporters required to maintain cytoplasmic pH homeostasis.

A key feature at excitatory synapses is the remodelling of dendritic spines, which in conjunction with receptor trafficking modifies the efficacy of neurotransmission. Here we investigated whether activation of cholinergic receptors, which can modulate synaptic plasticity, also mediates changes in dendritic spine structure. Using confocal time-lapse microscopy in mouse slice cultures we found that brief activation of muscarinic receptors induced the emergence of fine filopodia from spine heads in all CA1 pyramidal cells examined. This response was widespread occurring in 48% of imaged spines, appeared within minutes, was reversible, and was blocked by atropine. Electron microscopic analyses showed that the spine head filopodia (SHFs) extend along the presynaptic bouton. In addition, the decay time of miniature EPSCs was longer after application of the muscarinic acetylcholine receptor agonist methacholine (MCh). Both morphological and electrophysiological changes were reduced by preventing microtubule polymerization with nocodazole. This extension of SHFs during cholinergic receptor activation represents a novel structural form of subspine plasticity that may regulate synaptic properties by fine-tuning interactions between presynaptic boutons and dendritic spines.

Intersectin-short (intersectin-s) is a multimodule scaffolding protein functioning in constitutive and regulated forms of endocytosis in non-neuronal cells and in synaptic vesicle (SV) recycling at the neuromuscular junction of Drosophila and Caenorhabditis elegans. In vertebrates, alternative splicing generates a second isoform, intersectin-long (intersectin-l), that contains additional modular domains providing a guanine nucleotide exchange factor activity for Cdc42. In mammals, intersectin-s is expressed in multiple tissues and cells, including glia, but excluded from neurons, whereas intersectin-l is a neuron-specific isoform. Thus, intersectin-I may regulate multiple forms of endocytosis in mammalian neurons, including SV endocytosis. We now report, however, that intersectin-l is localized to somatodendritic regions of cultured hippocampal neurons, with some juxtanuclear accumulation, but is excluded from synaptophysin-labeled axon terminals. Consistently, intersectin-l knockdown (KD) does not affect SV recycling. Instead intersectin-l co-localizes with clathrin heavy chain and adaptor protein 2 in the somatodendritic region of neurons, and its KD reduces the rate of transferrin endocytosis. The protein also co-localizes with F-actin at dendritic spines, and intersectin-l KD disrupts spine maturation during development. Our data indicate that intersectin-l is indeed an important regulator of constitutive endocytosis and neuronal development but that it is not a prominent player in the regulated endocytosis of SVs.

Rabs and Arfs/Arls are Ras-related small GTPases of particular relevance to membrane trafficking. It is thought that these proteins regulate specific pathways through interactions with coat, motor, tether and SNARE proteins. We screened a comprehensive list of Arf/Arl/Rab proteins, previously identified on purified Golgi membranes by a proteomics approach (37 in total), for Golgi or intra-Golgi localization, dominant-negative and overexpression phenotypes. Further analysis of two of these proteins, Rab18 and Rab43, strongly indicated roles in ER-Golgi trafficking. Rab43-T32N redistributed Golgi elements to ER exit sites without blocking trafficking of the secretory marker VSVG-GFP from ER to cell surface. Wild-type Rab43 redistributes the p150Glued subunit of dynactin, consistent with a specific role in regulating association of pre-Golgi intermediates with microtubules. Overexpression of wild-type GFP-Rab18 or incubation with any of three siRNAs directed against Rab18 severely disrupts the Golgi complex and reduces secretion of VSVG. Rab18 mutants specifically enhance retrograde Golgi-ER transport of the COPI-independent cargo β-1,4-galactosyltransferase (Galtase)-YFP but not the COPI-dependent cargo p58-YFP from the Golgi to ER in a photobleach assay. Rab18-S22N also potentiated brefeldin-A-induced ER-Golgi fusion. This study is the first comprehensive application of large-scale proteomics to the cell biology of small GTPases of the secretory pathway.