Dependent Transport Research Articles

In silico prediction and expression analysis of vaccine candidate genes of Campylobacter jejuni

Campylobacter jejuni (C. jejuni) is the most common food-borne pathogen that causes human gastroenteritis in the United States. Consumption of contaminated poultry products is considered as the major source of human Campylobacter infection. An effective vaccine would be a promising alternative to antibiotic supplements to curb C. jejuni colonization in poultry gastrointestinal (GI) tract. However, the genetic diversity among the C. jejuni isolates makes vaccine production more challenging. Despite many attempts, an effective Campylobacter vaccine is not yet available. This study aimed to identify suitable candidates to develop a subunit vaccine against C. jejuni, which could reduce colonization in the GI tract of the poultry. In the current study, 4 C. jejuni strains were isolated from retail chicken meat and poultry litter samples and their genomes were sequenced utilizing next-generation sequencing technology. The genomic sequences of C. jejuni strains were screened to identify potential antigens utilizing the reverse vaccinology approach. In silico genome analysis predicted 3 conserved potential vaccine candidates (phospholipase A [PldA], TonB dependent vitamin B12 transporter [BtuB], and cytolethal distending toxin subunit B [CdtB]) suitable for the development of a vaccine. Furthermore, the expression of predicted genes during host-pathogen interaction was analyzed by an infection study using an avian macrophage-like immortalized cell line (HD11). The HD11 was infected with C. jejuni strains, and the RT-qPCR assay was performed to determine the expression of the predicted genes. The expression difference was analyzed using ΔΔCt methods. The results indicate that all 3 predicted genes, PldA, BtuB, and CdtB, were upregulated in 4 tested C. jejuni strains irrespective of their sources of isolation. In conclusion, in silico prediction and gene expression analysis during host-pathogen interactions identified 3 potential vaccine candidates for C. jejuni.

The Contribution of Phytate-Degrading Enzymes to Chicken-Meat Production.

The contribution that exogenous phytases have made towards sustainable chicken-meat production over the past two decades has been unequivocally immense. Initially, their acceptance by the global industry was negligible, but today, exogenous phytases are routine additions to broiler diets, very often at elevated inclusion levels. The genesis of this remarkable development is based on the capacity of phytases to enhance phosphorus (P) utilization, thereby reducing P excretion. This was amplified by an expanding appreciation of the powerful anti-nutritive properties of the substrate, phytate (myo-inositol hexaphosphate; IP6), which is invariably present in all plant-sourced feedstuffs and practical broiler diets. The surprisingly broad spectra of anti-nutritive properties harbored by dietary phytate are counteracted by exogenous phytases via the hydrolysis of phytate and the positive consequences of phytate degradation. Phytases enhance the utilization of minerals, including phosphorus, sodium, and calcium, the protein digestion, and the intestinal uptakes of amino acids and glucose to varying extents. The liberation of phytate-bound phosphorus (P) by phytase is fundamental; however, the impacts of phytase on protein digestion, the intestinal uptakes of amino acids, and the apparent amino acid digestibility coefficients are intriguing and important. Numerous factors are involved, but it appears that phytases have positive impacts on the initiation of protein digestion by pepsin. This extends to promoting the intestinal uptakes of amino acids stemming from the enhanced uptakes of monomeric amino acids via Na+-dependent transporters and, arguably more importantly, from the enhanced uptakes of oligopeptides via PepT-1, which is functionally dependent on the Na+/H+ exchanger, NHE. Our comprehension of the phytate-phytase axis in poultry nutrition has expanded over the past 30 years; this has promoted the extraordinary surge in acceptance of exogenous phytases, coupled with the development of more efficacious preparations in combination with the deflating inclusion costs for exogenous phytases. The purpose of this paper is to review the progress that has been made with phytate-degrading enzymes since their introduction in 1991 and the underlying mechanisms driving their positive contribution to chicken-meat production now and into the future.

Defect assisted magneto-tunable photoresponse in ZnO-rGO/La0.7Sr0.3MnO3/ITO heterojunctions

We have investigated light and magnetic field dependent electrical transport response of (100−x)%ZnO-x%rGO/La0.7Sr0.3MnO3 (LSMO)/ITO (x= 0, 100, 0.6, 0.8) heterostructure devices at room temperature. Negative and positive magnetoresistance(MR) response, respectively for bare (x= 0, 100) and composite devices (x= 0.6, 0.8) is associated with spin dependent scattering at eg2↑ and t2g↓ band of LSMO space charge region. Positive bias current, for bare devices, is supposed to have a defect induced suppression with light leading to an overall decrease of device current at low field. However, the bias current may have started increasing with light at high fields thereby reversing photosensitivity sign from negative (NPS) to positive (PPS). Such reversal from NPS to PPS has been attributed to high defect induced carrier transport through depinning of electrons from weak pinning centers with magnetic field. (100−x)%ZnO-x%rGO/LSMO barrier widths that are directly proportional with defect state population seem to support field induced change of photosensitivity behavior with light illumination.

Impact of dietary glutamate and glycine on growth and nutrient utilization in rainbow trout (Oncorhynchus mykiss)

A feeding trial was conducted to test the effect of dietary glutamate and glycine supplementation on growth potential, nutritional utilization and digestion, and energy metabolism of rainbow trout (Oncorhynchus mykiss). Four isonitrogenous and isolipidic diets (2 × 2 factorial design) were formulated with glutamate (Glu) and glycine (Gly) as the main factors. The protein source consisted mainly of black soldier fly larvae meal (40% inclusion in all diets) for its low-level content of glutamate and glycine. Triplicate groups of rainbow trout (30 fish/tank with mean initial body weight of 87.5 g ± 0.9) were restrictively fed by hand twice a day for 6 weeks. Dietary Glu and Gly supplementation did not affect feed intake, specific growth rate, or the feed conversion ratio. Whole body protein, lipid, amino acid and fatty acid composition were also unaffected by the supplementation of Glu and Gly in the diets. Dietary Gly supplementation increased the apparent digestibility of amino acids. Furthermore, supplementation with Gly, increased the concentration of serine, glycine, tryptophane, tyrosine and citrulline, while supplementation with Glu in the diets increased the concentration of hydroxy-proline and β-alanine in the serum of rainbow trout. Both dietary Glu and Gly supplementation improved the digestibility of the fatty acids. The expression of genes involved in the hepatic bile acid synthesis (e.g., apical sodium dependent bile acid transporter and organic solute transporter) were affected by supplementation of Gly in the diets. In general, this study showed that dietary supplementation with Gly and Glu improved the nutrient digestibility in rainbow trout.

Crystallographic Characterization of Sodium Ions in a Bacterial Leucine/Sodium Symporter

Na+ is the most abundant ion in living organisms and plays essential roles in regulating nutrient uptake, muscle contraction, and neurotransmission. The identification of Na+ in protein structures is crucial for gaining a deeper understanding of protein function in a physiological context. LeuT, a bacterial homolog of the neurotransmitter:sodium symporter family, uses the Na+ gradient to power the uptake of amino acids into cells and has been used as a paradigm for the study of Na+-dependent transport systems. We have devised a low-energy multi-crystal approach for characterizing low-Z (Z ≤ 20) anomalous scattering ions such as Na+, Mg2+, K+, and Ca2+ by combining Bijvoet-difference Fourier syntheses for ion detection and f” refinements for ion speciation. Using the approach, we experimentally identify two Na+ bound near the central leucine binding site in LeuT. Using LeuT microcrystals, we also demonstrate that Na+ may be depleted to study conformational changes in the LeuT transport cycle.

Diminished motor neuron activity driven by abnormal astrocytic EAAT1 glutamate transporter activity in spinal muscular atrophy is not fully restored after lentiviral SMN delivery.

Spinal muscular atrophy (SMA) is characterized by the loss of the lower spinal motor neurons due to survival motor neuron (SMN) deficiency. The motor neuron cell autonomous and non-cell autonomous disease mechanisms driving early glutamatergic dysfunction, a therapeutically targetable phenotype prior to motor neuron cell loss, remain unclear. Using microelectrode array analysis, we demonstrate that the secretome and cell surface proteins needed for proper synaptic modulation are likely disrupted in human SMA astrocytes and lead to diminished motor neuron activity. While healthy astrocyte conditioned media did not improve SMA motor neuron activity, SMA motor neurons robustly responded to healthy astrocyte neuromodulation in direct contact cultures. This suggests an important role of astrocyte synaptic-associated plasma membrane proteins and contact-mediated cellular interactions for proper motor neuron function in SMA. Specifically, we identified a significant reduction of the glutamate Na+ dependent excitatory amino acid transporter EAAT1 within human SMA astrocytes and SMA lumbar spinal cord tissue. The selective inhibition of EAAT1 in healthy co-cultures phenocopied the diminished neural activity observed in SMA astrocyte co-cultures. Caveolin-1, an SMN-interacting protein previously associated with local translation at the plasma membrane, was abnormally elevated in human SMA astrocytes. Although lentiviral SMN delivery to SMA astrocytes partially rescued EAAT1 expression, limited activity of healthy motor neurons was still observed in SMN-transduced SMA astrocyte co-cultures. Together, these data highlight the detrimental impact of astrocyte-mediated disease mechanisms on motor neuron function in SMA and that SMN delivery may be insufficient to fully restore astrocyte function at the synapse.

ABC superfamily transporter Rv1273c of Mycobacterium tuberculosis acts as a multidrug efflux pump.

Efflux pump-mediated drug resistance in bacteria is a common occurrence effective for the general survival of the organism. The Mycobacterium tuberculosis genome has an abundance of adenosine triphosphate (ATP) dependent cassette transporter genes but only a handful of them are documented for their contribution to drug resistance. In this study, we inspected the potential of an ABC transporter Rv1273c from M. tuberculosis as a multidrug efflux pump and a contributor to intrinsic drug resistance. Expression of Rv1273c in Escherichia coli and Mycobacterium smegmatis conferred tolerance to various structurally unrelated antibiotics. Lower accumulation of fluoroquinolones in intact E. coli and M. smegmatis cells expressing the transporter implied its active efflux activity. Energy-dependent efflux by Rv1273c was observed in real-time using the lipophilic dye Nile Red. Expression of Rv1273c also resulted in an increase in biofilm formation by E. coli and M. smegmatis cells. Overall, the results indicate the possibility that Rv1273c might be a multidrug transporter with a wide substrate range and a probable contributor to biofilm formation.

First-principles investigations for the electronic and transport properties of zigzag SiC nanoribbons with Fluorine passivation/adsorption

Nanoribbons with different edge functionalization display interesting electronic properties for various device applications. It requires the necessity of exploring the novel passivating elements commensurate to various technological applications. In this direction, here we have compared the effect of H and F-passivation on the edges of zigzag SiC nanoribbons (ZSiCNR) using density functional theory based calculations. Remarkably, present study reveals that F could be used as an effective passivating element for ZSiCNR similar to widely explored H-passivations. Various possible combinations of F/H are found to have stable structural integrity for practical applications. The effect of F-adatom adsorption is also discussed which present peculiar electronic properties. The half-metallic behavior is observed to be realized via F-adsoprtion which is further confirmed with the transport calculations. The obtained negative differential resistance along the spin dependent electron transport pledges towards wide spread applications of considered ZSiCNR interacting with F.

Green Hybrid Flow Shop Scheduling Problem Considering Sequence Dependent Setup Times and Transportation Times

For the green hybrid flow shop scheduling problem considering sequence dependent setup times (SDST) and transportation times, a mixed integer programming model is established with the objectives of minimizing the maximum completion time (makespan) and total energy consumption simultaneously, and an improved memetic algorithm is proposed with the problem characteristics. First of all, an encoding method combining the jobs sequence code at the first stage with the machine allocation code is designed to ensure that the algorithm can search the entire solution space to the greatest extent; then, a mixed population initialization method is designed to improve the quality of the initial population solution; Thirdly, the crossover and mutation operators, and four neighborhood search strategies are designed to balance the global search and local search capabilities of the algorithm; Finally, the effectiveness of the algorithm is verified by numerical experiments.

Phononic thermal conduction and thermal regulation in low-dimensional micro-nano scale systems: Nonequilibrium statistical physics problems from chip heat dissipation

“Heat death”, namely, overheating, which will deteriorate the function of chips and eventually burn the device and has become an obstacle in the roadmap of the semiconductor industry. Therefore, heat dissipation becomes a key issue in further developing semiconductor. Heat conduction in chips encompasses the intricate dynamics of phonon conduction within one-dimensional, two-dimensional materials, as well as the intricate phonon transport through interfaces. In this paper, the research progress of the complexities of phonon transport on a nano and nanoscale in recent three years, especially the size dependent phonon thermal transport and the relationship between anomalous heat conduction and anomalous diffusion are summarized. Further discussed in this paper is the fundamental question within non-equilibrium statistical physics, particularly the necessary and sufficient condition for a given Hamiltonian whose macroscopic transport behavior obeys Fourier’s law. On the other hand, the methods of engineering the thermal conduction, encompassing nanophononic crystals, nanometamaterials, interfacial phenomena, and phonon condensation are also introduced. In order to comprehensively understand the phononic thermal conduction, a succinct overview of phonon heat transport phenomena, spanning from thermal quantization and the phonon Hall effect to the chiral phonons and their intricate interactions with other carriers is presented. Finally, the challenges and opportunities, and the potential application of phonons in quantum information are also discussed.

Hydraulic Model Prediction of the Total Load of Sediment Transport in The Euphrates River at The Upstream Ramadi Barrage

Examining river engineering properties and bed erosion is one of the most challenging but crucial issues in river engineering and sediment hydraulics, so preventing erosion and sedimentation is one of the primary goals of river management and prediction of river behavior. This research aims to give hydraulic engineers and decision-makers an accurate and dependable sediment transport equation that could be utilized to govern river engineering and modify river morphology. This study evaluated the carried sediments and their estimated quantity upstream of the Ramadi Barrage on the Euphrates River in the Anbar area of western Iraq. Six formulas, including Yang, Shen, Hung, Ackers and White, Engelund and Hansen, and Bagnold's and Toffaleti's, were used to evaluate the applicability of sediment transport in the study area. The performance of these models was assessed based on the precision of the actual sediment load relative to a specified deviation ratio. The analyses indicated that the Engelund-Hansen formula is the most applicable for this section of the river; that concludes, field data indicated an annual total sediment flow of roughly 1, 536, 337 tons.

Pharmacology of Mammalian Na+-Dependent Transporters of Inorganic Phosphate.

Inorganic phosphate (Pi) is an essential component of many biologically important molecules such as DNA, RNA, ATP, phospholipids, or apatite. It is required for intracellular phosphorylation signaling events and acts as pH buffer in intra- and extracellular compartments. Intestinal absorption, uptake into cells, and renal reabsorption depend on a set of different phosphate transporters from the SLC20 (PiT transporters) and SLC34 (NaPi transporters) gene families. The physiological relevance of these transporters is evident from rare monogenic disorders in humans affecting SLC20A2 (Fahr's disease, basal ganglia calcification), SLC34A1 (idiopathic infantile hypercalcemia), SLC34A2 (pulmonary alveolar microlithiasis), and SLC34A3 (hereditary hypophosphatemic rickets with hypercalciuria). SLC34 transporters are inhibited by millimolar concentrations of phosphonoformic acid or arsenate while SLC20 are relatively resistant to these compounds. More recently, a series of more specific and potent drugs have been developed to target SLC34A2 to reduce intestinal Pi absorption and to inhibit SLC34A1 and/or SLC34A3 to increase renal Pi excretion in patients with renal disease and incipient hyperphosphatemia. Also, SLC20 inhibitors have been developed with the same intention. Some of these substances are currently undergoing preclinical and clinical testing. Tenapanor, a non-absorbable Na+/H+-exchanger isoform 3 inhibitor, reduces intestinal Pi absorption likely by indirectly acting on the paracellular pathway for Pi and has been tested in several phase III trials for reducing Pi overload in patients with renal insufficiency and dialysis.

Astrocytic Glutamate Transporters and Migraine.

Glutamate levels and lifetime in the brain extracellular space are dinamically regulated by a family of Na+- and K+-dependent glutamate transporters, which thereby control numerous brain functions and play a role in numerous neurological and psychiatric diseases. Migraine is a neurological disorder characterized by recurrent attacks of typically throbbing and unilateral headache and by a global dysfunction in multisensory processing. Familial hemiplegic migraine type 2 (FHM2) is a rare monogenic form of migraine with aura caused by loss-of-function mutations in the α2 Na/K ATPase (α2NKA). In the adult brain, this pump is expressed almost exclusively in astrocytes where it is colocalized with glutamate transporters. Knockin mouse models of FHM2 (FHM2 mice) show a reduced density of glutamate transporters in perisynaptic astrocytic processes (mirroring the reduced expression of α2NKA) and a reduced rate of glutamate clearance at cortical synapses during neuronal activity and sensory stimulation. Here we review the migraine-relevant alterations produced by the astrocytic glutamate transport dysfunction in FHM2 mice and their underlying mechanisms, in particular regarding the enhanced brain susceptibility to cortical spreading depression (the phenomenon that underlies migraine aura and can also initiate the headache mechanisms) and the enhanced algesic response to a migraine trigger.

IMPACT OF TRANSPORTATION RELIABILITY ON ECONOMIC GROWTH AT UAE’S MARITIME INDUSTRY

A dependable transportation system continuously provides clients with a range of predictable journey times. The reliability of the transportation system is one of the key performance objectives of various management and operating systems that have a huge impact on nation’s economy. In order to evaluate the transportation reliability and its impact on economic growth, time should be taken into account when planning for crises and calamity recovery. This research helps to find out the UAE’s economic growth rate and impact of transportation reliability through prior literature, research articles, journals and latest research reports.

Ganymede's Radiation Cavity and Radiation Belts

AbstractWhile planetary radiation belts are all embedded within the low energy solar wind, Ganymede is in the unique situation of being surrounded by the energetic particles of Jupiter's magnetosphere. Here we study Ganymede's environment based the recent flyby of Juno, as well as through reanalysis of past measurements from the Galileo spacecraft. We find that Ganymede is surrounded by a radiation cavity with intensities that are lower compared to Jupiter. Particles are lost in the cavity due to absorption by Ganymede that is likely enhanced by scattering. In the core of the cavity we find radiation belts. Their intensities are comparable to Jupiter for ions but lower for electrons. The radiation belts form peaks in phase space density, which indicates that they cannot be produced through steady inward influx and accumulation of Jupiter particles. Other processes are needed such as local acceleration, or time dependent transport and loss processes.

Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized.

Temperature dependent charge transport in electrostatically doped poly[benzimidazobenzophenanthroline] thin films

AbstractCharge transport in electrostatically doped poly[benzimidazobenzophenanthroline]‐BBL thin films in a field‐effect transistor geometry were investigated in the temperature range 150 K < T < 370 K. At low temperatures activation and hopping transport mechanisms dominated, while phonon scattering dominated at high temperatures. The activation energies (EA) were found to lie in the range 140 meV < EA < 400 meV implying the existence of deep traps within the polymer bandgap of 1.8 eV. Two quasi‐linear dependencies of EA on the gate voltage (Vg) were observed with EA decreasing as Vg increased. An unexpected “metallic‐like” transport characteristic appeared for T > 335 K which depended on Vg. Enhanced electron delocalization combined with increased carrier density could be responsible for this “metallic‐like” behavior. Our results show that the existence of deep traps with multiple energy distributions, combined with increased carrier density led to the unusual temperature dependence of charge transport observed in BBL.

Accelerated Deterministic Phonon Transport With Consistent Material Temperature and Intensities

Abstract We present a method for deterministically solving the frequency and temperature dependent phonon radiative transport (PRT) equation in the single-mode relaxation time (SMRT) approximation in the self-adjoint angular flux (SAAF) form. To handle the nonlinear coupling between the phonon intensities and the material temperature, we apply a linearization approach that is similar to one in thermal radiative transport. This procedure leads to the PRT equation with pseudo-scattering. The method presented includes acceleration of both the inner pseudo-scattering source iterations and outer temperature iteration with a gray diffusion synthetic acceleration (DSA) and Anderson acceleration, respectively. We use the finite-element method to discretize the PRT equation in space and the method of discrete ordinates (SN) for angular discretization. The proposed method is verified by a gray method of manufactured solutions problem and demonstrated on a problem using temperature and direction dependent multigroup data from lithium aluminate (LiAlO2). The iterative performance of the acceleration method in each test is then compared to the unaccelerated method.

Novel nitroxide-bile acid conjugates inform substrate requirements for human bile acid transporters

Transport of bile acids within the enterohepatic circulation from the liver to the intestines via the gallbladder and back to the liver via the portal vein plays a critical role in bile acid regulation and homeostasis. Deficiency of fibroblast growth factor 19 (FGF19), a hormone whose role is to suppress de novo hepatic bile acid synthesis to maintain homeostatic levels, results in bile acid diarrhea (BAD). FGF19 also modulates gallbladder motility so that bile acids are concentrated in the gallbladder until postprandial contraction. To assess bile acid transport and diagnose ailments like BAD that are associated with altered bile acid synthesis and transport, we created bile acid conjugates with nitroxide radicals. Because nitroxides are paramagnetic and can promote proton relaxation, we reasoned that these paramagnetic conjugates should act as contrast agents in in vivo magnetic resonance imaging (MRI). We tested substrate capability by assessing the inhibitory potential of these novel agents against taurocholate uptake by the apical sodium dependent bile acid transporter (ASBT) and the Na+/taurocholate cotransporting polypeptide (NTCP). Surprisingly, neither the paramagnetic compounds CA-Px-1 and CA-Px-2, nor their reduced forms, CA-Px-1H and CA-Px-2H, inhibited hASBT- or hNTCP-mediated taurocholate uptake. Therefore, the new conjugates cannot serve as contrast agents for MRI in vivo. However, our findings identify important structural constraints of transportable bile acid conjugates and suggest potential modifications to overcome these limitations.

Modelling of p-tyramine transport across human intestinal epithelial cells predicts the presence of additional transporters.

p-Tyramine (TYR) is an endogenous trace amine, which can also be synthesized by intestinal microbiota, and is present in commonly consumed diets. TYR is an agonist for the intracellular trace amine-associated receptor 1, which has been implicated in psychiatric, metabolic, and immune-related disorders. We have previously demonstrated TYR readily diffuses across lipid bilayers, while transport across Caco-2 cell membranes involves Organic Cation Transporter 2 (OCT2) and a Na+-dependent active transporter. Here we developed mathematical models to determine whether known kinetics for these processes are sufficient to explain observed transcellular TYR passage. Ordinary differential equations were developed for known TYR transport processes to predict concentration-time relationships. Michaelis-Menten kinetics were assumed for all transporter-mediated processes and a one phase exponential function used for simple diffusion. Modelled concentration-time plots were compared to published experimental results. Additional transporter functions were sequentially added to models to improve consistency, and a least squares error minimization approach utilized to determine added transporter kinetics. Finally, possible TYR compartmentalization was also modelled. Following apical loading, transport across the apical, but not the basolateral, membrane was modelled without additional transporters, suggesting a basolateral transporter was missing. Consistent with this, models of basolateral compartment loading did not match experimental observations, indicating missing basolateral transporters were bidirectional. Addition of a transporter with the kinetic characteristics of OCT2 did not improve models. Varying the kinetic parameters of the added transporter improved models of basolateral, but worsened apical, loading models, suggesting the need for either a directional preference in transporters, or intracellular TYR compartmentalization. Experimental parameters were recapitulated by introducing asymmetry into the apical OCT2 (Kt_OCT2_apicaltocell = 110.4 nM, Kt_OCT2_celltoapical = 1,227.9nM), and a symmetric basolateral facilitated diffusion transporter (Vmax = 6.0nM/s, Kt = 628.3nM). The apparent directionality of OCT2 may reflect altered TYR ionization due to known pH differences between compartments. Models for asymmetry and compartmentalization were compared by root mean square deviation from experimental data, and it was found that TYR compartmentalization could only partially replace the need for asymmetry of OCT2. In conclusion, modelling indicates that known TYR transport processes are insufficient to explain experimental concentration-time profiles and that asymmetry of the apical membrane OCT2 combined with additional, low affinity, basolateral membrane facilitated diffusion transporters are required.