Transport Mechanism Research Articles

Oxaluria in inflammatory bowel diseases (review)

AIM: to analyse and synthesize Russian and foreign literature, to get acquainted with the concept of oxaluria, its types, transport mechanisms of oxalate transport in the intestine and the relationship between hyperoxaluria and inflammatory bowel diseases in order to identify possible options for therapeutic action on the mechanisms of development of these pathologies. MATERIALS AND METHODS: the literature review was based on the Internet data, including bibliographic directories, books, journals, and original articles. The literature sources used for the article reflect the essence of the described problem to the fullest extent possible and can be useful for both practicing physicians and students of medical universities. RESULTS: the gastrointestinal tract through epithelial transport of oxalate plays an exclusive role in oxalate homeostasis and hyperoxaluria. Metabolism of dietary oxalate and the formation of endogenous oxalate, its secretion, absorption, transport and biodegradation by intestinal microflora may influence the excretion of this compound by the kidneys. Knowledge of the interrelated relationships of the gut-kidney axis, mechanisms of transport, transport and biodegradation of oxalate, especially in inflammatory bowel disease, is of great importance for understanding the pathophysiology of hyperoxaluria as a risk factor for urinary stone formation with a point of pharmacological action in the gut. This literature review introduces the concept and forms of oxaluria, shows the classification of oxaluria, describes each form, and broadly explains the metabolism and mechanisms of oxalate transport in the human body. Special attention is given to intestinal hyperoxaluria and anion exchangers belonging to the large multifunctional SLC26 gene family, most of which are expressed throughout the gastrointestinal tract. The authors emphasise their current role in intestinal oxalate transport, as well as methods of possible drug action on the mechanisms of hyperoxaluria. CONCLUSION: a multidisciplinary approach is needed to address the problems of intestinal hyperoxaluria and, consequently, the treatment of urolithiasis. The role of newly identified intestinal and renal anion exchangers is not fully understood, hence the targets and mechanisms of action on these types of exchangers with the possibility of preventing the development of urolithiasis are not fully understood. Further randomised studies on the problem under investigation are needed.

Differences in the physiology of Pichia pastoris grown on glycerol/glucose using polyurethane foam slabs as solid support

AbstractBACKGROUNDGrowth physiology and metabolic flux of Pichia pastoris were analyzed using glass columns containing slabs of polyurethane foam as a solid support and culture medium with glycerol or glucose as a carbon source.RESULTSMedia with glycerol produced an average of 30.91% more biomass than media where glucose was used. However, the specific growth rate registered higher values for media with glucose than those with glycerol at low substrate concentrations: 0.46 versus 0.22 h−1. Media with glycerol produced a large amount of d‐arabitol, whereas ethanol and citrate were the predominant metabolites in media with glucose. Both types of culture systems generated biphasic curves in terms of the respiratory quotient value, whose inflection point coincided with the transition from aerobic metabolism to a mixed one.CONCLUSIONAdequate oxygen transfer occurred in both culture systems; therefore, the differences found in growth physiology can be explained by the transport mechanism that internalizes glycerol, the access point to primary metabolism, and the degree of glycerol oxidation. The arrangement of cells in the polyurethane matrix allowed an attenuation of the repression phenomenon due to excess substrate for both carbon sources. This is the first work to study metabolic flux comparisons using this system. © 2024 Society of Chemical Industry (SCI).

Drying–Wetting Correlation Analysis of Chloride Transport Behavior and Mechanism in Calcium Sulphoaluminate Cement Concrete

In response to rising CO2 emissions in the cement industry and the growing demand for durable offshore engineering materials, calcium sulphoaluminate (CSA) cement concrete, known for its lower carbon footprint and enhanced corrosion resistance compared to Ordinary Portland Cement (OPC), is increasingly important. However, the chloride transport behavior of CSA concrete in both laboratory and marine environments remains underexplored and controversial. Accordingly, the chloride ion transport behaviors and mechanisms of CSA concrete in laboratory-accelerated drying-wetting cyclic environments using NaCl solution and seawater, as well as in marine tidal environments, were characterized using the rapid chloride test (RCT), X-ray diffraction (XRD), mercury infiltration porosimetry (MIP), and thermogravimetric analysis (TGA). The results reveal that CSA concrete accumulates more chloride ions in NaCl solution than in seawater, with concentrations 2–3.5 times higher at the same water–cement ratio. Microscopic analysis indicates that calcium and sulfate ions present in seawater facilitate the regeneration of ettringite, thereby increasing the density of the surface pore structure. The hydration and repair mechanisms of CSA concrete under laboratory conditions closely resemble those in marine tidal conditions when exposed to seawater. Additionally, this study found that lower chloride ion concentrations and pH levels inhibit the formation of Friedel’s salt. Therefore, laboratory experiments with seawater can effectively simulate CSA concrete’s chloride transport properties in marine tidal environments, whereas NaCl solution does not accurately reflect actual marine conditions.

Large-scale floating polyacrylonitrile hybrid micro-/nanofiber membrane achieves efficient H/D isotope separation via photocatalytic proton transport

Advancements in isotope separation are both essential and challenging. The separation of water isotopes is vital in industrial production, biopharmaceuticals, and healthcare applications. This process is energy-intensive and complex due to the similarity of the isotopes. Pure polyacrylonitrile (PAN) is resistant to proton permeability, but neutral hydrogen radicals are capable of penetration. In this study, we report a novel approach using PAN macroscopic hybrid micro-/nanofibers in combination with a photocatalyst to separate hydrogen ion isotopes. Application of photocatalytic water splitting to generate protons results in significantly slower deuteron permeation in these fibers relative to protons, resulting in a separation factor of approximately 15 at room temperature. The composite PAN fibers exhibit a conductivity of 17.5 mS cm−1 at 25 °C and 95 % relative humidity. Our approach not only converts sunlight directly into storable hydrogen, but also enriches heavy water from H₂O/D₂O by H/D isotope separation. This study provides new insights into proton transport mechanisms in acidic media and demonstrates the significant potential of high molecular weight polymers for hydrogen isotope separation.

Qualitative Identification of the Spin‐to‐Orbital Conversion Mechanism Modulated by Rare‐Earth Nd, Gd, and Ho Metals via Terahertz Emission Measurements

AbstractIt is crucial to study the materials that could effectively facilitate the inter‐conversion between charge, spin, and orbital degrees of freedom. In this work, the conversion among these three types of degrees of freedom in Pt/CoFeB/rare‐earth (RE, represents Nd, Gd, and Ho)/Ti multilayers is manipulated. Through terahertz (THz) emission measurements, it is found that the spin current induced by a femtosecond laser is converted into an orbital current via the spin‐orbit coupling of the RE layer. Notably, the light RE (Nd) and heavy RE (Gd and Ho) induce the orbital current with opposite polarization directions, ultimately leading to a weakening or enhancement of the THz emission intensity, respectively. Moreover, the fast Fourier transform reveals that Gd exerts the most significant influence on increasing the whole THz spectrum within the Pt/CoFeB/RE/Ti structure. The findings of RE‐modulated spin‐to‐orbital conversion provide valuable insights into the fundamental transport mechanism of the orbital current.

Inhibitor binding and disruption of coupled motions in MmpL3 protein: Unraveling the mechanism of trehalose monomycolate transport.

Mycobacterial membrane protein Large 3 (MmpL3) of Mycobacterium tuberculosis (Mtb) is crucial for the translocation of trehalose monomycolate (TMM) across the inner bacterial cell membrane, making it a promising target for anti-tuberculosis (TB) drug development. While several structural, microbiological, and in vitro studies have provided significant insights, the precise mechanisms underlying TMM transport by MmpL3 and its inhibition remain incompletely understood at the atomic level. In this study, molecular dynamic (MD) simulations for the apo form and seven inhibitor-bound forms of Mtb MmpL3 were carried out to obtain a thorough comprehension of the protein's dynamics and function. MD simulations revealed that the seven inhibitors in this work stably bind to the central channel of the transmembrane domain and primarily forming hydrogen bonds with ASP251, ASP640, or both residues. Through dynamical cross-correlation matrix and principal component analysis analyses, several types of coupled motions between different domains were observed in the apo state, and distinct conformational states were identified using Markov state model analysis. These coupled motions and varied conformational states likely contribute to the transport of TMM. However, simulations of inhibitor-bound MmpL3 showed an enlargement of the proton channel, potentially disrupting coupled motions. This indicates that inhibitors may impair MmpL3's transport function by directly blocking the proton channel, thereby hindering coordinated domain movements and indirectly affecting TMM translocation.

Thermal Transport at the AlN-SiC Interface and Grain Boundary of AlN.

AlN is deposited on silicon carbide (SiC) for high-power electronics; in these devices, AlN acts as both a buffer layer for the growth of the active device and a thermal conductor. However, the mechanism of thermal transport through the AlN-SiC interfaces and through grain boundaries of AlN has not been clearly analyzed, even though AlN forms grain boundaries during the deposition process. The thermal properties of the AlN-SiC interface and the inversion domain boundaries (IDBs) of AlN were examined by a phonon transport model based on a nonequilibrium Green function formalism and first-principles calculations. The interface and grain boundary models were designed, and the thermal resistances (TRs) and origins of TR were examined. The TRs of the AlN-SiC interface and the IDB of AlN are much higher than the TRs of AlN and SiC of relevant thickness. Elemental intermixing and vacancy formation were modeled. The formation of charge-balanced defect of VAl + 3ON is thermodynamically favorable compared to other defects, indicating that ON induces formation of VAl. The charge-balanced defect combining VAl and ON increases the TRs of both AlN-SiC interfaces and AlN grain boundaries because vacancy defects induce larger changes in mass than all other defects, and TRs are proportional to changes in mass. In addition, VAl defects are increased by excess ON, resulting in a continuous increase in TR, and then, the calculated thermal boundary resistance (TBR) of the AlN-SiC interface with increased density of VAl by excess ON reaches the experimental TBR. Therefore, it is expected that the large increase in TR by the formation of VAl + ON would be suppressed by controlling the low O density during synthesis.

Current Transport Mechanisms and Electrophysical Characteristics of the 4H-SiC p-n Junctions Formed by Aluminum Diffusion

In this paper, the electrophysical characteristics of the 4H-SiC p-n junction created by low-temperature diffusion of aluminum were studied. Current-voltage (I-V) characteristics are analysed, and the current transport mechanisms in 4H-SiC p-n junctions are discussed. It is shown that at low forward bias voltages, the generation–recombination mechanism dominates, and the I-V characteristics at voltages U > 3.0 V obey the linear law. At reverse biases, the dominant mechanism of current transfer is limited by the space charge.

Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs.

While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material's slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.

Large‐Scale Climate Features Control Fire Emissions and Transport in Africa

AbstractRecent increase in extreme wildfire events has led to major health and environmental consequences across the globe. These adverse impacts underlined the need for better understanding of this phenomenon and to formulate mitigating actions. While previous research has focused on local weather drivers of wildfires, our knowledge about their large‐scale climatic controls remains limited, especially in tropical Africa, which stands out as a global hotspot for fire emissions. Here, we show that interannual variability of carbon emission due to fires in the southern Congo Basin is strongly linked to low‐level winds that are controlled by the Indian Ocean subtropical high. The interhemispheric transport of these emissions to West Africa relies on the intensity and position of both Indian and South Atlantic subtropical highs. Combined effects of this transport mechanism and carbon production in the source region explain a majority of the interannual variability of black carbon in West Africa.

Real-time two-dimensional visualization reveals the transport mechanisms of biochar colloids in the presence of DOM in porous media

Biochar colloids (BCs) have attracted much attention globally, and their fate and transport in the subsurface are significantly influenced by soil-dissolved organic matter (DOM) in soil. This study utilized a real-time and non-invasive visualization system to reveal the transport and retention behavior of BCs in the presence of DOM in two-dimensional porous media. Results indicated that the presence of DOM enhanced the transport of BCs, due to its increased negative charge density and increased repulsion between BCs. The change in the particle size of the porous medium was also shown to affect the BCs transport in the porous media. Additionally, the negative charge of BCs shielded by high IS, the mobility of BCs decreased by 30.37 % from 1 mM to 50 mM. When the pH was increased from 5 to 9, the oxygen-containing functional groups of BCs and DOM were dissociated, and the mobility of BCs increased by 32.41 %. Through a simplified Double-Monod model, we fitted the breakthrough curves for BCs transport in porous media (R2 > 0.94). Moreover, the mechanism of different conditions on colloid clogging behavior was further elucidated through the DLVO theory. These findings extend the understanding of the environmental behavior of BCs in the presence of DOM derived from soil, enabling us to assess better and predict their environmental risks.

Atomic-Level Free Energy Landscape Reveals Cooperative Symport Mechanism of Melibiose Transporter.

The Major Facilitator Superfamily (MFS) transporters are an essential class of secondary active transporters involved in various physiological and pathological processes. The melibiose permease (MelB), which catalyzes the stoichiometric symport of the disaccharide melibiose and monovalent cations (e.g., Na+, H+, or Li+), is a key model for understanding the cation-coupled symport mechanisms. Extensive experimental data has established that positive cooperativity between the cargo melibiose and the coupling cation is central to the symport mechanism. However, the structural and energetic origins of this cooperativity remain unclear at the atomistic level for MelB and most other coupled transporters. Here, leveraging recently resolved structures in inward- and outward-facing conformations, we employed the string method and replica-exchange umbrella sampling simulation techniques to comprehensively map the all-atom free energy landscapes of the Na+-coupled melibiose translocation across the MelB in Salmonella enterica serovar Typhimurium (MelBSt), in comparison with the facilitated melibiose transport in a uniporter mutant. The simulation results unravel asymmetrical free energy profiles of melibiose translocation, which is tightly coupled to protein conformational changes in both the N- and C-terminal domains. Notably, the cytoplasmic release of the melibiose induces the simultaneous opening of an inner gate, resulting in a high-energy state of the system. Periplasmic sugar binding and cytoplasmic melibiose released are dynamically coupled with changes in the internal gating elements along the translocation pathway. The outward-facing sugar-bound state is thermodynamically most stable, while the occluded state is a transient state. The binding of Na+ facilitates melibiose translocation by increasing the melibiose-binding affinity and decreasing the overall free energy barrier and change. The cooperative binding of the two substrates results from the allosteric coupling between their binding sites instead of direct electrostatic interaction. These findings add substantial new atomic-level details into how Na+ binding facilitates melibiose translocation and deepen the fundamental understanding of the molecular basis underlying the symport mechanism of cation-coupled transporters.

A comprehensive mathematical model considering multiple mechanisms for CO2 displacement of methane in shale nanopores

With the rise in energy demand, shale gas exploitation has gained prominence, particularly through the use of carbon dioxide (CO2) injection for enhanced gas recovery. However, the intricate gas flow mechanisms within this process in shale nano-pores remain poorly understood, which greatly limited the accurate numerical simulation of shale gas production by CO2 injection. This study investigates the flow mechanisms of CH4 and CO2 gases in shale nano-pores, developing an improved apparent relative permeability model for the two-component CH4–CO2 gas, incorporating multiple transport mechanisms. Sensitivity analysis includes factors such as pressure, pore radius, viscosity correction effects, flow mechanisms, and composition fractions. Key findings from this study are as follows: (1) Increasing pore radius or decreasing pressure enhances the apparent permeability of CH4–CO2 gas, with pressure effects becoming negligible above 20 MPa. (2) The impact of viscosity correction on gas permeability diminishes with higher pressure or larger pore radius, becoming negligible for pore radii over 10 nm. (3) Larger pore radii increase slip flow and Knudsen diffusion, while molecular and surface diffusion proportions decrease; surface diffusion and slip flow dominate at high pressures. (4) A higher CH4–CO2 component ratio increases CH4 permeability and decreases CO2 permeability, with minimal influence from pressure and pore radius. These results can improve numerical simulations for shale gas production by using CO2 injection.

Two-phase closed thermosiphon with grooved the evaporator section applied for low-grade energy recovery: Thermo-hydrodynamic performance and potentials

High thermal conductivity and simple structure of two-phase closed thermosyphons (TPCTs) facilitate it extensively applied in low-grade thermal recovery, such like geothermal and solar energy exploitation. In present work, by incorporating threaded grooves into the evaporator section of the TPCTs, heat transfer performance could be significantly enhanced. Thermal transport mechanism of thermosyphons with various threaded groove structures was comprehensively investigated, and corresponding thermo-hydrodynamic performance was modelled through CFD/VOF simulations. Numerical procedures were validated well after comparison with experimental ones felled within 5.0 %. Under various heating power levels and filling ratios, heat transfer performance of thermosyphons with threaded grooves evidently surpassed that of smooth thermosyphons. Depending on delicate numerical results, critical point at 33 % filling ratio and 90 W heating power were confirmed that total thermal resistance of the grooved thermosyphon decreased almost close to 4.6 %. Furthermore, deviating from that critical point, higher heating power and lower filling ratio instead confined heat transfer performance of the threaded TPCT, which was primarily due to the rate of bubble generation and growth being significantly was slower than its detachment rate from the wall. In addition, heat and mass transfer performance of thermosyphons with threaded grooves of various pitches and apex angles were further analyzed under various conditions. Our results indicated that, when the groove apex angle turned to 90°, overall thermal transportation capability of the TPCT achieved optimal, with a decline in thermal resistance of up to 6.5 % compared to thermosyphons with smaller apex angles. Apex angle primarily affected the number of nucleation sites and the bubble detachment rate. Additionally, as the screw pitch decreased, boiling heat transfer enhancement, leading to more robust boiling heat transfer of TPCTs. Under high heating power, thermosyphons with larger screw pitch exhibited superior heat transfer performance. Overall, this innovative TPCTs with threaded grooves could be well applied in low-grade energy exploitation, particularly like as geothermal and solar energy fields.

Erosion and transport mechanisms of granular flow: insights from a flume experiment and block energy model

Erosion and transport mechanisms of granular flow: insights from a flume experiment and block energy model

Modeling bacterial transport and fate: Insight into the cascading consequences of soil water repellency and contrasting hydraulic conditions

The mechanisms governing bacteria transport and fate rely on their hydrophobicity and the wettability of porous media across a wide range of soil moisture conditions, extending from extreme dryness to highly saturated states. However, it largely remains unknown how transport, retention, and release mechanisms change in natural soil systems in such conditions. We thus optimized our previously published unique transport data for hydrophilic Escherichia coli (E. coli) and hydrophobic Rhodococcus erythropolis (R. erythropolis) bacteria, and bromide (Br−) in two distinct wettable and water-repellent soils at column scale. The soils were initially dry, followed by injecting influents in two pulses followed by a flushing step under saturated flow conditions for six pore volumes. We conducted simulations for each pulse separately and simultaneously for soils. There were differences in hydraulic properties of the soils due to their contrasting wetting characteristic in separate and simultaneously modeling of each pulse affecting Br− and bacteria transport fate. Bacteria attachment was the dominant retention mechanism in both soils in these conditions. Notably, the 82.4 min−1 attachment rate in wettable soil was almost 10× greater than in the water-repellent soil and it governed optimization of bacteria die-off. Physicochemical detachment and physical release unraveled the effect of bacteria size and hydrophobicity interacting with soil wettability. The smaller and hydrophobic R. erythropolis detached more easily while hydrophilic E. coli released; the rates were enhanced by soil water repellency. Further research is needed to reveal the effects of surface wettability properties on bacteria survival especially at the nanoscale.

Enhancement of tunneling electroresistance in metal/two-dimensional ferroelectric tunnel junctions: Route for polarization-modulated interface transport.

In fabricating ferroelectric tunnel junction (FTJ) devices, it is essential to employ low-resistance metals as electrodes interfacing with two-dimensional (2D) ferroelectric materials. For FTJs with a top contact configuration, two interfaces for charge transport are present, namely the vertical interface between the metal electrode and the 2D ferroelectric material, and the lateral interface between the
electrode and the central scattering region. These interfaces significantly influence the tunneling electroresistance (TER) of FTJs. However, there exists a notable deficiency
in comprehension concerning the physics of charge transport at the interface. In this
work, we explore the interface transport properties in FTJs featuring a top contact configuration between metal and the typical α-In2Se3 monolayer. By employing the non-equilibrium Green's function method, we observe a TER ratio of 1.15 × 105% for
the Pd top contact interfacing with an α-In2Se3 monolayer. The significant TER effect is attributed to polarization-controlled interface transport, which is further
elucidated through an analysis of the transport mechanisms influenced by the out of-plane polarization of α-In2Se3 at the vertical interface and the in-plane polarization at the lateral interface. This investigation of the fundamental physical mechanisms
of polarization-controlled interface transport demonstrates significant potential for enhancing non-volatile memory devices.

322 Nutrient transport across gastrointestinal tissues using Ussing chambers

Abstract One of the principal roles of the gut is the absorption of nutrients to meet animal needs. While in vivo measures such as total tract digestibility indicate the totality of the nutrients that disappear, these methods provide no information on the digestion, site, flux, and mechanism of nutrient absorption. Nutrient absorption is a complex set of transport pathways including passive diffusion, facilitated transport, ion exchange, active transport, and secondary active transport that is driven by electrochemical gradients. To tease apart the complexities of nutrient transport at different sites along the gastrointestinal tract, Ussing chambers have been a useful tool. Two ex vivo chambers, filled with oxygenated physiological buffer, and separated by epithelial tissue allow for the detection of nutrient flux, transepithelial currents, and/or membrane permeability. Historically, detection of the nutrient of interest was achieved using radio-labelled or fluorescent tracers. Beyond detecting flux (uptake, efflux, net flux), Ussing chambers can also tease apart the complex network of transport pathways that govern nutrient absorption. Isolating specific transport pathways can be broad spectrum inhibitors, and alterations to the physiological buffers to target transport pathways of interest. Altering the electrical gradient using a voltage clamp for instance, can be used to neutralize, inhibit, or promote, the electrical gradient; such alterations can be especially useful for charged nutrients. Inhibitors, meanwhile, inhibit the activity of entire families of proteins, useful for when the role of specific protein transporters is of interest. Alterations to buffer composition, such as bicarbonate-free buffer solutions or the inclusion and exclusion of compounds with similar size and charge, can isolate transport solely dependent on that solute or provide knowledge on the solutes that may share a common transport mechanism. Together, these modulations allow for a powerful tool to study the presence or absence of nutrient transport and has been crucial in establishing absorption kinetics of ionic nutrients (e.g., Na+, Cl-), small organic nutrients (e.g., short chain fatty acids, glucose), and macromolecules (e.g., immunoglobulins). Done in conjunction with other techniques, Ussing chambers can offer strong insight to improve our understanding of nutrient absorption and epithelial physiology of the gut. This presentation will discuss the methods key to successful use of Ussing chambers, alongside with their limitations and ways to augment data generated by Ussing chambers.

Presence of pesticide-tolerant microorganisms in high-altitude pristine lakes within Singalila Ridge of the Himalayas.

This is the first report on high pesticide tolerance displayed by the microbiota isolated from the sediments of two high-altitude lakes, located in the Singalila National Park, Singalila Ridge of the Himalayas. Given the remote location of these lakes, direct exposure to chemical pesticides is highly unlikely. However, the high tolerance to commonly used pesticides exhibited, i.e. up to 250mg/ml, suggests repeated exposure and contamination of the lakes. Microbial growth in the presence of varying concentrations of the pesticides, namely, emamectin benzoate, thiamethoxam, quinalphos, deltamethrin, spiromesifen, flubendiamide, monocrotophos, fipronil, fenazaquin and phorate, was tested. Results showed resistance to all pesticides except fenazaquin and fipronil, up to 250mg/ml. For the latter two, tolerance was displayed up to a concentration of 40mg/ml. Tolerance may potentially result from the transport and deposition of pesticides from nearby locations, particularly the tea plantations of Darjeeling and Eastern Nepal. This may create great ecological risks as these lakes are an important water source for endemic wildlife of this protected area. They also hold great significance to the religious sentiment of the local tribes who worship these lakes as sacred. The study highlights the need for monitoring pesticide contamination in such pristine high-altitude environments and the mechanisms of long-range pollutant transport.

Structure and mechanism of a phosphotransferase system glucose transporter

Glucose is the primary source of energy for many organisms and is efficiently taken up by bacteria through a dedicated transport system that exhibits high specificity. In Escherichia coli, the glucose-specific transporter IICBGlc serves as the major glucose transporter and functions as a component of the phosphoenolpyruvate-dependent phosphotransferase system. Here, we report cryo-electron microscopy (cryo-EM) structures of the glucose-bound IICBGlc protein. The dimeric transporter embedded in lipid nanodiscs was captured in the occluded, inward- and occluded, outward-facing conformations. Together with biochemical and biophysical analyses, and molecular dynamics (MD) simulations, we provide insights into the molecular basis and dynamics for substrate recognition and binding, including the gates regulating the binding sites and their accessibility. By combination of these findings, we present a mechanism for glucose transport across the plasma membrane. Overall, this work provides molecular insights into the structure, dynamics, and mechanism of the IICBGlc transporter in a native-like lipid environment.