Defective Transport Research Articles

(Invited) Modeling the Defect Chemistry, Transport Properties, and Stability of Anti-Perovskite Materials

Solid-state electrolytes with fast lithium conduction are the core of the all-solid-state Li-battery technology. By substituting the organic electrolyte with a piece of non-flammable ceramic material, we can achieve better safety, higher specific capacity, and a higher energy density. To date, the major bottleneck for this technology is the slow Li diffusion in the solid-state electrolyte and the interfacial incompatibility between the electrolyte and electrodes. To resolve these issues, several families of fast ionic conductors have been developed. Understanding Li diffusion in these materials is essential to the development of novel family fast ionic conductors. To this end, atomistic modeling provides us with a unique tool to obtain comprehensive information on atom motion, which is difficult to access with experimental techniques. In this talk, we showcase our group’s atomistic simulations regarding a novel family of superionic conductors, Li-rich antiperovskites (LiRAPs)LiRAPs are a promising family of solid electrolytes, which exhibit ionic conductivities above 1 mS/cm at room temperature, among the highest reported values to date. Here, we report on the defect chemistry and the associated lithium transport in Li3OCl, a prototypical LiRAP, using DFT calculations and classical MD simulations [1]. We studied these materials’ phase, interfacial, and voltage stability [2,3] with DFT, showing good agreement with experiments, further proposing low-dimensional superionic antiperovskites [3]. In addition, the interfacial properties were studied for both protonated and fluorinated materials [4]. Analogous simulations were also carried out for Na-rich antiperovskites [5]. Acknowledgments Support from the Research Grants Council of Hong Kong is gratefully acknowledged.

Tailoring solvent-mediated ligand exchange for CsPbI3 perovskite quantum dot solar cells with efficiency exceeding 16.5%

<h2>Summary</h2> Inorganic CsPbI₃ perovskite quantum dot (PQD) shows high potential for new-generation photovoltaics due to its outstanding optoelectronic properties. However, the binding-energy-driven ligand exchange of PQDs limits the construction of conductive and stable PQD solids for efficient PQD solar cells (PQDSCs). Herein, protic 2-pentanol with superior ligand solubility is delicately screened from massive solvents to mediate the ligand exchange of PQDs due to its appropriate dielectric constant and acidity, which could maximize the removal of pristine insulating oleylamine ligands from the PQD surface without introducing halogen vacancy defects. Employing tailored short choline ligands and 2-pentanol solvent for the post-treatment of PQD solids, PQDSC yields an efficiency of 16.53%, which is the highest among inorganic PQDSCs. This outstanding performance is attributed to the improved charge carrier transport and surface defect passivation of PQDs. This work provides a feasible platform for tuning the surface properties of PQDs and paves the way for realizing high-performing optoelectronics.

DISTAL RENAL TUBULAR ACIDOSIS WITH SEVERE HYPOKALEMIA – A CASE REPORT

Background: Renal tubular acidosis is a group of transport defects secondary to either reduced distal secretion of hydrogen ion or decreased proximal tubular reabsorption of bicarbonate or both, resulting in impaired acidication of urine with persistent hyperchloremic metabolic acidosis. Our case is that of a 5-year-old female child presenting with failure to thrive and weakness.Clinical description and Investigations: Physical examination revealed skeletal deformities with enamel defects. Subsequent blood tests and arterial blood gas analysis revealed hyperchloremic metabolic acidosis with hypokalemia. Urine analysis revealed a positive urinary anion gap with hypercalciuria and hypocitraturia. Imaging studies revealed skeletal changes secondary to rickets and USG whole abdomen showed bilateral kidney nephrocalcinosis. Oral ammonium chloride loading was given and blood and urine pH were monitored every hour for the next 6 hours but the urine pH failed to fall below 5.3 which led us to a diagnosis of distal renal tubular acidosis. Bicarbonate and potassium citrate supplementation was given alongTreatment: with vitamin D and calcium to this child. Timely diagnosis and initiation of appropriate supplementation can help in improving theConclusion: quality of life of these patients.

Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk ) and prickle-spiny-legs (pksple ) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pkspl e flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.

Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export.

Eukaryotic gene expression requires multiple cellular events, including transcription and RNA processing and transport. Sus1, a common subunit in both the Spt-Ada-Gcn5 acetyltransferase (SAGA) and transcription and export complex-2 (TREX-2) complexes, is a key factor in coupling transcription activation to mRNA nuclear export. Here, we report that the SAGA DUB module and TREX-2 distinctly regulate yeast replicative lifespan in a Sir2-dependent and -independent manner, respectively. The growth and lifespan impaired by SUS1 loss depend on TREX-2 but not on the SAGA DUB module. Notably, an increased dose of the mRNA export factors Mex67 and Dbp5 rescues the growth defect, shortened lifespan, and nuclear accumulation of poly(A)+ RNA in sus1Δ cells, suggesting that boosting the mRNA export process restores the mRNA transport defect and the growth and lifespan damage in sus1Δ cells. Moreover, Sus1 is required for the proper association of Mex67 and Dbp5 with the nuclear rim. Together, these data indicate that Sus1 links transcription and mRNA nuclear export to the lifespan control pathway, suggesting that prevention of an abnormal accumulation of nuclear RNA is necessary for maintenance of a normal lifespan.

Pharyngeal timing and particle transport defects in Caenorhabditis elegans feeding mutants

The nematode Caenorhabditis elegans uses rhythmic muscle contractions (pumps) of the pharynx, a tubular feeding organ, to filter, transport, and crush food particles. A number of feeding mutants have been identified, including those with slow pharyngeal pumping rate, weak muscle contraction, defective muscle relaxation, and defective grinding of bacteria. Many aspects of these pharyngeal behavioral defects and how they affect pharyngeal function are not well understood. For example, the behavioral deficits underlying inefficient particle transport in "slippery" mutants have been unclear. Here we use high-speed video microscopy to describe pharyngeal pumping behaviors and particle transport in wild-type animals and in feeding mutants. Different "slippery" mutants exhibit distinct defects including weak isthmus contraction, failure to trap particles in the anterior isthmus, and abnormal timing of contraction and relaxation in pharyngeal compartments. Our results show that multiple deficits in pharyngeal timing or contraction can cause defects in particle transport. NEW & NOTEWORTHY The nematode C. elegans uses rhythmic contractions of its pharynx (feeding organ) to filter, transport, and crush food bacteria. Genetic analyses have identified mutants with defective pharyngeal motions, but many details of these movements and how they affect feeding are poorly understood. We use high-speed video microscopy to describe pharyngeal pumping behaviors and particle transport in feeding mutants. We find that multiple deficits in pharyngeal timing or contraction can cause defects in particle transport.

The human ATP-binding cassette (ABC) transporter superfamily.

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Mutations in ABC genes cause 21 human disorders or phenotypes with Mendelian inheritance, including cystic fibrosis, adrenoleukodystrophy, retinal degeneration, cholesterol, and bile transport defects. To provide tools to study the function of human ABC transporters we compiled data from multiple genomics databases. We analyzed ABC gene conservation within human populations and across vertebrates and surveyed phenotypes of ABC gene mutations in mice. Most mouse ABC gene disruption mutations have a phenotype that mimics human disease, indicating they are applicable models. Interestingly, several ABCA family genes, whose human function is unknown, have cholesterol level phenotypes in the mouse. Genome-wide association studies confirm and extend ABC traits and suggest several new functions to investigate. Whole-exome sequencing of tumors from diverse cancer types demonstrates that mutations in ABC genes are not common in cancer, but specific genes are overexpressed in select tumor types. Finally, an analysis of the frequency of loss-of-function mutations demonstrates that many human ABC genes are essential with a low level of variants, while others have a higher level of genetic diversity.

Cultured dissociated primary dorsal root ganglion neurons from adult horses enable study of axonal transport.

Neurological disorders are prevalent in horses, but their study is challenging due to anatomic constraints and the large body size; very few host‐specific in vitro models have been established to study these types of diseases, particularly from adult donor tissue. Here we report the generation of primary neuronal dorsal root ganglia (DRG) cultures from adult horses: the mixed, dissociated cultures, containing neurons and glial cells, remained viable for at least 90 days. Similar to DRG neurons in vivo, cultured neurons varied in size, and they developed long neurites. The mitochondrial movement was detected in cultured cells and was significantly slower in glial cells compared to DRG‐derived neurons. In addition, mitochondria were more elongated in glial cells than those in neurons. Our culture model will be a useful tool to study the contribution of axonal transport defects to specific neurodegenerative diseases in horses as well as comparative studies aimed at evaluating species‐specific differences in axonal transport and survival.

Thyroid hormone resistance: Mechanisms and therapeutic development

As an essential primary hormone, thyroid hormone (TH) is indispensable for human growth, development and metabolism. Impairment of TH function in several aspects, including TH synthesis, activation, transportation and receptor-dependent transactivation, can eventually lead to thyroid hormone resistance syndrome (RTH). RTH is a rare syndrome that manifests as a reduced target cell response to TH signaling. The majority of RTH cases are related to thyroid hormone receptor β (TRβ) mutations, and only a few RTH cases are associated with thyroid hormone receptor α (TRα) mutations or other causes. Patients with RTH suffer from goiter, mental retardation, short stature and bradycardia or tachycardia. To date, approximately 170 mutated TRβ variants and more than 20 mutated TRα variants at the amino acid level have been reported in RTH patients. In addition to these mutated proteins, some TR isoforms can also reduce TH function by competing with primary TRs for TRE and RXR binding. Fortunately, different treatments for RTH have been explored with structure-activity relationship (SAR) studies and drug design, and among these treatments. With thyromimetic potency but biochemical properties that differ from those of primary TH (T3 and T4), these TH analogs can bypass specific defective transporters or reactive mutant TRs. However, these compounds must be carefully applied to avoid over activating TRα, which is associated with more severe heart impairment. The structural mechanisms of mutation-induced RTH in the TR ligand-binding domain are summarized in this review. Furthermore, strategies to overcome this resistance for therapeutic development are also discussed.

Urine metabolomics links dysregulation of the tryptophan-kynurenine pathway to inflammation and severity of COVID-19

SARS-CoV-2 causes major disturbances in serum metabolite levels, associated with severity of the immune response. Despite the numerous advantages of urine for biomarker discovery, the potential association between urine metabolites and disease severity has not been investigated in coronavirus disease 2019 (COVID-19). In a proof-of-concept study, we performed quantitative urine metabolomics in patients hospitalized with COVID-19 and controls using LC–MS/MS. We assessed whether metabolites alterations were associated with COVID-19, disease severity, and inflammation. The study included 56 patients hospitalized with COVID-19 (26 non-critical and 30 critical disease); 16 healthy controls; and 3 controls with proximal tubule dysfunction unrelated to SARS-CoV-2. Metabolomic profiling revealed a major urinary increase of tryptophan metabolites kynurenine (P < 0.001), 3-hydroxykynurenine (P < 0.001) and 3-hydroxyanthranilate (P < 0.001) in SARS-CoV-2 infected patients. Urine levels of kynurenines were associated with disease severity and systemic inflammation (kynurenine, r 0.43, P = 0.001; 3-hydroxykynurenine, r 0.44, P < 0.001). Increased urinary levels of neutral amino acids and imino acid proline were also common in COVID-19, suggesting specific transport defects. Urine metabolomics identified major alterations in the tryptophan-kynurenine pathway, consistent with changes in host metabolism during SARS-CoV-2 infection. The association between increased urinary levels of kynurenines, inflammation and COVID-19 severity supports further evaluation of these easily available biomarkers.

PROPOSING A MATHEMATICAL MODEL OF BALANCING THE INVENTORY OF MULTI-ZONE BICYCLE SHARING SYSTEMS WITH MOBILE STATIONS AND APPLYING MAINTENANCE CONSTRAINTS

Regarding the necessity of developing transportation infrastructures and its increasing importance in urban issues, nowadays in different cities, bicycles are considered the main and sustainable vehicle along with walking and drawing more attention day by day. The case considers highly paramount since preservation of the environment, natural resources, and energy is one of the significant pillars of sustainable development, and urban transportation intensively influences it. Thus, Bicycle Sharing System (BSS) is recognized as an innovative urban transportation option that meets the citizens’ demand for commuting during the day. The BSS can highly affect the level of citizens’ health, and it can be counted as one of the leading health programs whether it’s added to the public transportation system, it can help the culture to be created to use bicycles instead of cars in most of the internal trips, and also it can be so influential in decreasing the air pollution and in the following its harmful effects on health issues. The mathematical model of rebalancing multi-zone BSS with mobile stations and applying maintenance constraints in a static status is considered in this research. The objective function of this research is a single-objective one, which is modeled with the aims of reducing the costs of traveled distances by the tracks within and outside the zones, reducing the costs of intact and defective bicycles transportation within and outside the zones, and eventually, reducing the costs of surplus bicycles depot at the stations. This issue is a multi-product one that includes different types of bicycles and balancing tracks. Computational results confirm the model’s efficiency. Also, sensitivity analysis has been done to prove that the model is affected by both parameters of storage costs of surplus bicycles and transportation costs within and outside the zones.

Electronic transport mechanism and defect states for p-InP/i-InGaAs/n-InP photodiodes

We have studied the defect states and electronic transport mechanisms in the mismatched p-InP/i-InGaAs/n-InP photodiode grown by molecular beam epitaxy (MBE) using deep-level transient spectroscopy (DLTS) and current–voltage (I–V) measurements. Two defect states were observed in the p-InP layer, which could have originated from Zn diffusion, and another one detected in i-InGaAs acted as a dislocation defect. The total defect density of the device estimated by DLTS and space-charge limited current (SCLC) was about 4 × 1013, which was much lower than the device grown by other methods. I–V measurements pointed out that the leakage current in this photodiode was caused by the existence of defect states and the small conduction band offset. Therefore, to suppress the leakage current in the devices, it is urgent to reduce the trap density and optimize the thickness of the p-InP layer. The study of defect state and electronic transport mechanism in p-InP/i-InGaAs/n-InP PIN diodes could help to develop a strategy to improve the SWIR sensing technology in the future.

Study the effect of defects on the quantum efficiency of perovskite solar cells

Perovskite solar cells (PSCs) have generated considerable interest in the field of solar energy. With the rapid development of fabrication technology, high efficiency, environmentally friendly perovskite solar cells are becoming more attractive as candidates for power generation. Defects in the absorber and interface layers of mixed lead halide perovskite solar cells reduce the efficiency and stability of the cells. The current study examined the impact of defects density, defect capturing cross-section, defect level, and defect type on the quantum efficiency (QE) of the absorber layer. Furthermore, the impact of defects in the hole transport layer/absorber and electron transport layer/absorber interface layers is also be extensively studied. SCAPS-1D will be used to simulate perovskite solar cells in this work. The perovskite solar cells structure proposed is FTO/ ETM/ absorber/ HTM structure based on TiO2 as ETM layer; Cu2O as HTM layer, and on CH3NH3PbI3 as absorber layer. According to the results, the quantum efficiency QE reduced sharply from 90.2% to 20% with varying the density of the defect Nt and the capture cross-section carriers σ in absorber layer from 1015 cm-3 to 10 18 cm-3 and 2×10-13 cm2 to 2×10-10 cm2, respectively. Additionally, it is discovered that the capture cross-section carriers exhibits behavior similar to that of the absorber layer's defect density.

Lead-free organic inorganic halide perovskite solar cell with over 30% efficiency

In this study, numerical analysis on an Sn-based planner heterojunction perovskite device structure of Glass/ FTO/ ZnO/ CH3NH3SnI3/ CZTS/ Metal, with CH3NH3SnI3 as an absorber layer, was performed by using the solar cell device simulator SCAPS 1D. As an electron transport layer (ETL) and a hole transport layer (HTL), inorganic materials ZnO and CZTS (kesterite) were used. To optimize the device, the thickness of the absorber, electron, and hole transport layers, defect density, and absorber doping concentrations were varied, and their impact on device performance was evaluated. The effect of temperature and work function of various anode materials were also investigated. The optimum absorber layer thickness was found at 750 nm for the proposed structure. The acceptor concentration with a reduced defect density of the absorber layer enhances device performance significantly. For better performance, a higher work function anode material is required. The optimized solar cell achieved a maximum power conversion efficiency of 30.41% with an open-circuit voltage of 1.03 V, a short circuit current density of 34.31 mA/cm2, and a Fill Factor 86.39%. The proposed cell structure also possesses an excellent performance under high operating temperature indicating great promise for eco-friendly, low-cost solar energy harvesting.

METALIC reveals interorganelle lipid flux in live cells by enzymatic mass tagging

The distinct activities of organelles depend on the proper function of their membranes. Coordinated membrane biogenesis of different organelles necessitates lipid transport from their site of synthesis to their destination. Several factors have been proposed to participate in lipid distribution, but despite its basic importance, in vivo evidence linking the absence of putative transport pathways to specific transport defects remains scarce. A reason for this scarcity is the near absence of in vivo lipid trafficking assays. Here we introduce a versatile method named METALIC (Mass tagging-Enabled TrAcking of Lipids In Cells) to track interorganelle lipid flux inside cells. In this strategy, two enzymes, one directed to a ‘donor’ and the other to an ‘acceptor’ organelle, add two distinct mass tags to lipids. Mass-spectrometry-based detection of lipids bearing the two mass tags is then used to quantify exchange between the two organelles. By applying this approach, we show that the ERMES and Vps13–Mcp1 complexes have transport activity in vivo, and unravel their relative contributions to endoplasmic reticulum–mitochondria lipid exchange.

First person – Karin Tuschl

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Karin Tuschl is first author on ‘ Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish’, published in DMM. Karin conducted the research described in this article while an academic clinical lecturer in Prof. Stephen Wilson’s and Prof. Corinne Houart's labs at University College London and King's College London, London, UK, respectively. She is now a MRC Clinician Scientist Fellow and has established her own group at UCL GOS Institute of Child Health, London, investigating the role of manganese in brain physiology and disease – from inherited manganese transporter defects to common neurodegenerative disorders.

Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish.

ABSTRACTManganese neurotoxicity is a hallmark of hypermanganesemia with dystonia 2, an inherited manganese transporter defect caused by mutations in SLC39A14. To identify novel potential targets of manganese neurotoxicity, we performed transcriptome analysis of slc39a14−/− mutant zebrafish that were exposed to MnCl2. Differentially expressed genes mapped to the central nervous system and eye, and pathway analysis suggested that Ca2+ dyshomeostasis and activation of the unfolded protein response are key features of manganese neurotoxicity. Consistent with this interpretation, MnCl2 exposure led to decreased whole-animal Ca2+ levels, locomotor defects and changes in neuronal activity within the telencephalon and optic tectum. In accordance with reduced tectal activity, slc39a14−/− zebrafish showed changes in visual phototransduction gene expression, absence of visual background adaptation and a diminished optokinetic reflex. Finally, numerous differentially expressed genes in mutant larvae normalised upon MnCl2 treatment indicating that, in addition to neurotoxicity, manganese deficiency is present either subcellularly or in specific cells or tissues. Overall, we assembled a comprehensive set of genes that mediate manganese-systemic responses and found a highly correlated and modulated network associated with Ca2+ dyshomeostasis and cellular stress. This article has an associated First Person interview with the first author of the paper.

Unraveling small-scale defects in irradiated ThO2 using kinetic Monte Carlo simulations

Point defects and their clusters generated through irradiation can have significant impact on the physical and mechanical properties of materials. However, direct experimental visualization of these small-scale defects using high-resolution scanning transmission electron microscopy remains a challenging task. Here, using thorium dioxide (ThO2) with the fluorite structure as a model system, we demonstrate the use of ab initio basin-hopping simulations in synergy with object kinetic Monte Carlo simulations as a powerful tool for identifying small defect complexes in irradiated materials. In addition to providing quantitative insights into defect evolution in ThO2 under irradiation, our study reveals an unexpected role of bound anti-Schottky defect clusters in mediating defect transport. Remarkably, despite their poor thermal stability against dissociation at high temperatures, the transient formation of bound anti-Schottky defects under irradiation and their subsequent migration provide the dominant mechanism for the growth of large interstitial loops that have been experimentally observed in ThO2.

Metabolomics-based safety evaluation of acute exposure to electronic cigarettes in mice

IntroductionA growing number of epidemiological evidence reveals that electronic cigarettes (E-cigs) were associated with pneumonia, hypertension and atherosclerosis, but the toxicological evaluation and mechanism of E-cigs were largely unknown. ObjectiveOur study was aimed to explore the adverse effects on organs and metabolomics changes in C57BL/6J mice after acute exposure to E-cigs. Methods and resultsHematoxylin and eosin (H&E) staining found pathological changes in tissues after acute exposure to E-cigs, such as inflammatory cell infiltration, nuclear pyknosis, and intercellular interstitial enlargement. E-cigs could increase apoptosis-positive cells in a time-dependent way using Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Oxidative damage indicators of reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonena (4-HNE) were also elevated after E-cigs exposure. There was an increasing trend of total glycerol and cholesterol in serum, while the glucose and liver enzymes including alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltranspeptidase (γ-GT) had no significant change compared to that of control. Further, Q Exactive high field (HF) mass spectrometer was used to conduct metabolomics, which revealed that differential metabolites including l-carnitine, Capryloyl glycine, etc. Trend analysis showed the type of compounds that change over time. Pathway enrichment analysis indicated that E-cigs affected 24 metabolic pathways, which were mainly regulated amino acid metabolism, further affected the tricarboxylic acid (TCA) cycle. Additionally, metabolites-diseases network analysis found that the type 2 diabetes mellitus, propionic acidemia, defect in long-chain fatty acids transport and lung cancer may be related to E-cigs exposure. ConclusionsOur findings provided important clues for metabolites biomarkers of E-cigs acute exposure and are beneficial for disease prevention.

Selective motor activation in organelle transport along axons.

The active transport of organelles and other cargos along the axon is required to maintain neuronal health and function, but we are just beginning to understand the complex regulatory mechanisms involved. The molecular motors, cytoplasmic dynein and kinesins, transport cargos along microtubules; this transport is tightly regulated by adaptors and effectors. Here we review our current understanding of motor regulation in axonal transport. We discuss the mechanisms by which regulatory proteins induce or repress the activity of dynein or kinesin motors, and explore how this regulation plays out during organelle trafficking in the axon, where motor activity is both cargo specific and dependent on subaxonal location. We survey several well-characterized examples of membranous organelles subject to axonal transport - including autophagosomes, endolysosomes, signalling endosomes, mitochondria and synaptic vesicle precursors - and highlight the specific mechanisms that regulate motor activity to provide localized trafficking within the neuron. Defects in axonal transport have been implicated in conditions ranging from developmental defects in the brain to neurodegenerative disease. Better understanding of the underlying mechanisms will be essential to develop more-effective treatment options.