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1.
The role of water coordination in the pH-dependent gating of hAQP10.
Truelsen, SF, Missel, JW, Gotfryd, K, Pedersen, PA, Gourdon, P, Lindorff-Larsen, K, Hélix-Nielsen, C
Biochimica et biophysica acta. Biomembranes. 2022;(1):183809
Abstract
Human aquaporin 10 (hAQP10) is an aquaglyceroporin that assists in maintaining glycerol flux in adipocytes during lipolysis at low pH. Hence, a molecular understanding of the pH-sensitive glycerol conductance may open up for drug development in obesity and metabolically related disorders. Control of hAQP10-mediated glycerol flux has been linked to the cytoplasmic end of the channel, where a unique loop is regulated by the protonation status of histidine 80 (H80). Here, we performed unbiased molecular dynamics simulations of three protonation states of H80 to unravel channel gating. Strikingly, at neutral pH, we identified a water coordination pattern with an inverted orientation of the water molecules in vicinity of the loop. Protonation of H80 results in a more hydrophobic loop conformation, causing loss of water coordination and leaving the pore often dehydrated. Our results indicate that the loss of such water interaction network may be integral for the destabilization of the loop in the closed configuration at low pH. Additionally, a residue unique to hAQP10 (F85) reveals structural importance by flipping into the channel in correlation with loop movements, indicating a loop-stabilizing role in the closed configuration. Taken together, our simulations suggest a unique gating mechanism combining complex interaction networks between water molecules and protein residues at the loop interface. Considering the role of hAQP10 in adipocytes, the detailed molecular insights of pH-regulation presented here will help to understand glycerol pathways in these cells and may assist in drug discovery for better management of human adiposity and obesity.
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2.
Dynamics and energetics of water transport through aquaporin mutants causing nephrogenic diabetes insipidus (NDI): A molecular dynamics study.
Hadidi, H, Kamali, R, Binesh, A
Journal of biomolecular structure & dynamics. 2022;(3):1273-1284
Abstract
Human aquaporin-2 (AQP2) is the principal water channel in the human kidney. Any alteration of its physiological functioning may lead to the water imbalance and consequently diseases in humans, especially nephrogenic diabetes insipidus (NDI). Although many of the mutations associated with NDI are experimentally discovered and examined, a molecular level characterization of the structure and transport mechanism is still missing. In this paper, the gating effects of selectivity filter (SF) as wide/narrow states on the mechanism and dynamics of water permeation within the wild-type AQP2 and two NDI causing mutants as AQP2-V168M and AQP2-G64R are studied for the first time. The analysis of the 200 ns trajectory shows that the SF region in AQP2 is not only a selectivity filter, as previously reported but also it performs as a gating site depending on the side-chain conformation of His172. The assignment of the wide/narrow states of SF is supported by computing the free energy and permeability through the AQP2. Moreover, by exploring the effects of V168M and G64R mutants on the AQP2 structure during 200 ns trajectories, remarkable increases of energy barriers are observed in the middle and cytoplasmic side of the pore, respectively. Interestingly, it is found that due to the variable conformations of the SF region as wide/narrow, the effect of the NDI causing mutants on the average water permeability can be revealed with notably better accuracy by finding the wide states in the wild-type and mutated types of AQP2 and comparing the osmotic permeabilities for this state.Communicated by Ramaswamy H. Sarma.
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3.
Breeding rice for a changing climate by improving adaptations to water saving technologies.
Heredia, MC, Kant, J, Prodhan, MA, Dixit, S, Wissuwa, M
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2022;(1):17-33
Abstract
Climate change is expected to increasingly affect rice production through rising temperatures and decreasing water availability. Unlike other crops, rice is a main contributor to greenhouse gas emissions due to methane emissions from flooded paddy fields. Climate change can therefore be addressed in two ways in rice: through making the crop more climate resilient and through changes in management practices that reduce methane emissions and thereby slow global warming. In this review, we focus on two water saving technologies that reduce the periods lowland rice will be grown under fully flooded conditions, thereby improving water use efficiency and reducing methane emissions. Rice breeding over the past decades has mostly focused on developing high-yielding varieties adapted to continuously flooded conditions where seedlings were raised in a nursery and transplanted into a puddled flooded soil. Shifting cultivation to direct-seeded rice or to introducing non-flooded periods as in alternate wetting and drying gives rise to new challenges which need to be addressed in rice breeding. New adaptive traits such as rapid uniform germination even under anaerobic conditions, seedling vigor, weed competitiveness, root plasticity, and moderate drought tolerance need to be bred into the current elite germplasm and to what extent this is being addressed through trait discovery, marker-assisted selection and population improvement are reviewed.
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4.
Normal mode calculation and infrared spectroscopy of proteins in water solution: Relationship between amide I transition dipole strength and secondary structure.
Ripanti, F, Luchetti, N, Nucara, A, Minicozzi, V, Venere, AD, Filabozzi, A, Carbonaro, M
International journal of biological macromolecules. 2021;:369-376
Abstract
Dipole Strength (DS) of the amides has gained a renewed interest in chemical physics since it provides an important tool to disclose the on-site vibrational energy distributions. Apart from earlier experimental efforts on polypeptides, little is still known about DS in complex proteins. We accurately measured the Fourier Transform Infrared absorption spectra of nine proteins in water solution obtaining their Molar Extinction Coefficient in the amide I and II spectral region. Our results show that the amide I DS value depends on the protein secondary structure, being that of the α-rich and unstructured proteins lower by a factor of 2 than that of the β-rich proteins. The average DS for amino acids in α and β secondary structures confirms this finding. Normal Mode calculation and Molecular Dynamics were performed and used as tools for data analysis and interpretation. The present outcomes corroborate the hypothesis that antiparallel β-sheet environment is more prone to delocalize the on-site CO stretching vibration through coupling mechanisms between carbonyl groups, whereas α-helix structures are energetically less stable to permit vibrational mode delocalization.
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5.
Rheological stability of carbomer in hydroalcoholic gels: Influence of alcohol type.
Kolman, M, Smith, C, Chakrabarty, D, Amin, S
International journal of cosmetic science. 2021;(6):748-763
Abstract
OBJECTIVE The main objective of this paper is to analyse and attempt to understand the nature of rheological changes observed and the dynamics of Carbopol NF 980 hydroalcoholic gels neutralized specifically by triethanol amine (TEA), both as a function of time and alcohol type to probe time stabilities and ageing effects in such carbopol gel systems. The rheological changes and dynamics of 3 carbopol gel systems were observed; the gels included a water-based, ethanol-based, and isopropyl alcohol-based gel. It is hoped that this study shall shed light on the dynamical nature and the microstructural evolution of such networked gel systems, which were maintained under closed isothermal conditions and left completely unperturbed. The experimental results can provide the information necessary to understand and proposes plausible mechanisms guiding this dynamical behaviour in hydroalcoholic carbopol gels. METHODS A TA instrument mechanical rheometer was used to measure the viscosity and storage and loss modulus, and a pH meter was utilized to determine the changes in each sample over the period. RESULTS Studying the differences in the gel structures upon initial preparation illustrated that the ethanol and isopropyl alcohol (IPA) gels differed from the water-based gel in terms of viscosity, G', and G″, with the IPA gel displaying the lowest viscosity and moduli values across all shear rates. All the three gel systems exhibited strong shear thinning characteristics and were reminiscent of yield stress type found in colloidal gels. The water-based gel compared to the hydroalcoholic gels was strongly G' dominated, with the magnitude of the difference between G' and G″ observed to be much higher. This reflects that initial formation of the water-based gel structure possesses a much more rigid structure with a high elastic modulus component dominating. This also suggests that the water-based gel structure displayed stronger interactions between the carbopol particles when compared to those of the hydroalcoholic gels. Over the 30-day period, it was observed that the ethanol and water-based gels did not reveal any appreciable viscosity changes, with only an approximate 12% and 7% change from day 1 to 30, respectively. It was observed that the IPA systems' viscosity drastically increased over the period, with an approximately 77% change from day 1 to 30. The water and ethanol-based gels also exhibited very similar rheological behaviour over the entire time period with G' dominating G″. The G″ values of the water and ethanol-based gels decreased slightly at the end of day 30 by 10% and 16%, respectively, while the G' values for each sample remained essentially unchanged, increasing only 0.06% for the water-based gel, and increasing 1.4% for the ethanol-based gel. This further confirms the relatively stable gel structures attained. For the isopropyl gel system, the storage modulus of the system exhibited an average percent increase of approximately 16% from day 1 to day 30, but interestingly the loss modulus varied the least amongst all the gel systems, with only a 3% increase. The increase in G' reflects upon the evolution of a more rigid structure by day 30 for the IPA gel. This observation is clearly consistent with the corresponding increase in viscosity observed in the IPA gel. None of the gels tested displayed a consistent pH over the period. The pH of the hydroalcoholic gels was higher than that of the water-based gel for a majority of the period. The greatest fluctuations in pH were observed for the water and IPA gels, even though the water-based gel had one of the most stable rheological profiles out of the samples tested. The water, ethanol, and IPA gels' pH increased approximately 25%, 6%, and 5%, respectively, from day 1 to day 30. CONCLUSION The rheological and pH study of the 3 hand sanitizer systems over a 30-day period allowed for rational insights into the plausible reasons responsible for driving the observed rheological changes in these unperturbed systems. For the water-based gel, we hypothesize that the changes observed are due to physical ageing, where the gel structure has evolved over time to eventually progress towards a more stabilized framework structure. The pH of the gel upon formation was on the lower side. Such a lower pH influences the formation of a gel, which is comparatively less swollen and occupies a slightly lesser volume, and thereby points to a much less compacted gel network structure or alternatively, a more fluid structure. If the particles moved around more, the system was not initially in a state of low energy, causing increased particle movement, and in turn, physical ageing. This could be responsible for the development of a physically altered structure over time. The gel structure dynamically attempts to minimize its free energy by becoming more rigid, which has been observed as being manifested in the decrease of both the viscosity and the G″. For the hydroalcoholic gels, we conjecture that ageing observed was a result of chemical ageing, and the alcohol type employed in the preparation is primarily responsible for exhibiting this effect. The polarities of ethyl alcohol and isopropyl alcohol are key to the stabilization of such resultant network structures which get formed because of neutralization. It has been observed in previous studies that with decreasing polarity, there was an increase in the neutralization needed to obtain the development of a structure half as well developed as the final resultant structure. Isopropyl alcohol is a much less polar solvent compared to ethanol and water, and therefore required higher levels of TEA as the base to neutralize the system. We conjecture that the charged TEA cationic species had a greater propensity to get exchanged with bulk solution in the vicinity of the polymer into the bulk solution, and that the pH fluctuation observed indicated a kinetic exchange process over time, causing the viscosity and moduli profiles to increase along with the pH. At this time though, further investigations need to be carried out to truly understand the underlying instability, and thus dynamics for gel systems of this type.
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6.
Application of Monolayer Graphene and Its Derivative in Cryo-EM Sample Preparation.
Wu, K, Wu, D, Zhu, L, Wu, Y
International journal of molecular sciences. 2021;(16)
Abstract
Cryo-electron microscopy (Cryo-EM) has become a routine technology for resolving the structure of biological macromolecules due to the resolution revolution in recent years. The specimens are typically prepared in a very thin layer of vitrified ice suspending in the holes of the perforated amorphous carbon film. However, the samples prepared by directly applying to the conventional support membranes may suffer from partial or complete denaturation caused by sticking to the air-water interface (AWI). With the application in materials, graphene has also been used recently to improve frozen sample preparation instead of a suspended conventional amorphous thin carbon. It has been proven that graphene or graphene oxide and various chemical modifications on its surface can effectively prevent particles from adsorbing to the AWI, which improves the dispersion, adsorbed number, and orientation preference of frozen particles in the ice layer. Their excellent properties and thinner thickness can significantly reduce the background noise, allowing high-resolution three-dimensional reconstructions using a minimum data set.
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7.
Artificial Water Channels: Towards Biomimetic Membranes for Desalination.
Huang, LB, Di Vincenzo, M, Li, Y, Barboiu, M
Chemistry (Weinheim an der Bergstrasse, Germany). 2021;(7):2224-2239
Abstract
Natural Aquaporin (AQP) channels are efficient water translocating proteins, rejecting ions. Inspired by this masterpiece of nature, Artificial Water Channels (AWCs) with controlled functional structures, can be potentially used to mimic the AQPs to a certain extent, offering flexible avenues toward biomimetic membranes for water purification. The objective of this paper is to trace the historical development and significant advancements of current reported AWCs. Meanwhile, we attempt to reveal important structural insights and supramolecular self-assembly principles governing the selective water transport mechanisms, toward innovative AWC-based biomimetic membranes for desalination.
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8.
Hormonal and environmental signaling pathways target membrane water transport.
Maurel, C, Tournaire-Roux, C, Verdoucq, L, Santoni, V
Plant physiology. 2021;(4):2056-2070
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Abstract
Plant water transport and its molecular components including aquaporins are responsive, across diverse time scales, to an extremely wide array of environmental and hormonal signals. These include water deficit and abscisic acid (ABA) but also more recently identified stimuli such as peptide hormones or bacterial elicitors. The present review makes an inventory of corresponding signalling pathways. It identifies some main principles, such as the central signalling role of ROS, with a dual function of aquaporins in water and hydrogen peroxide transport, the importance of aquaporin phosphorylation that is targeted by multiple classes of protein kinases, and the emerging role of lipid signalling. More studies including systems biology approaches are now needed to comprehend how plant water transport can be adjusted in response to combined stresses.
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9.
[Solid State NMR Investigation for Molecular States of Specialized Formulation to Improve the Water Solubility of Poorly Water-soluble Drugs].
Higashi, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2021;(9):1063-1069
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Abstract
70-90% of recently developed new drug candidates are poorly soluble in water, which creates a series of thorny challenges in developing its oral dosage forms, resulting in low bioavailability. In pre-formulation study, various specialized formulations have been developed to improve drug solubility. Intermolecular interactions between drug and excipients in the formulations can modify the drug state and achieve the improvement of drug solubility. Therefore, the understanding of intermolecular interaction is essential to design formulations with higher quality and to assure the quality as a pharmaceutical product. Solid-state NMR has attracted much attention as a promising method to evaluate the molecular state of a drug and the interaction between a drug and excipient in its formulation. I have applied solid-state NMR and its characteristic technique, namely magic-angle spinning (MAS), for various specialized formulations including amorphous solid dispersion, supersaturated solution, drug-loaded organic nanotube, and drug nanosuspension. The intermolecular interactions of drug and excipient in amorphous solid dispersion have been identified by 13C and 15N solid-state NMR. High-resolution MAS determined the interaction modes of drug and excipient in a supersaturated solution. The two-step dissolution profile of drug from organic nanotube was understood, based on the molecular states revealed by the combination of various solid-state NMR techniques. A suspended-state NMR clarified the nanostructure of drug nanoparticles dispersed in water. It is expected that more qualified pharmaceutical formulations with improved drug solubility can be designed based on the remarkable development of recent solid-state NMR technology.
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10.
A microscopic study on scattering in tissue section of Alternanthera philoxeroides under polarized light.
Roy, S, Bhattacharya, B, Bal, B, Ghosh, K
Journal of biosciences. 2021
Abstract
Like any other biological tissue, plant tissue also exhibits optical properties like refraction, transmission, absorption, coloration, scattering and so on. Several studies have been conducted using different parts of plants such as leaves, seedlings, roots, stems and so on, and their optical properties have been analyzed to study plant physiology, influence of environmental cues on plant metabolism, light propagation through plant parts and the like. Thus, it is essential to study in detail the optical properties of several plant parts to determine their structural relationship. In this backdrop, an experimental study was conducted to observe and analyze the optical properties of node and inter-nodal tissue cross-sections of the plant Alternanthera philoxeroides under a polarizing microscope constructed and standardized in the laboratory. The observed optical properties of the microscopic tissue sections have been then studied to determine a significant structural relationship between nodal and inter-nodal tissue arrangement patterns as a whole. Tissue sections that have undergone a sort of biological perturbation like loss of water (dried in air for 15 min) have also been studied to study the change in the pattern of tissue optical property when compared with that of normal plant-tissue cross-sections under a polarizing microscope. This type of biological perturbation was chosen for the study because water plays an important role in maintenance of the normal physiological processes in plants and most other forms of life.