Long-range Mechanism Research Articles

An Osteoporosis Susceptibility Allele at 11p15 Regulates SOX6 Expression by Modulating TCF4 Chromatin Binding.

Osteoporosis is an age-related complex disease clinically diagnosed with bone mineral density (BMD). Although several genomewide association studies (GWASs) have discovered multiple noncoding genetic variants at 11p15 influencing osteoporosis risk, the functional mechanisms of these variants remain unknown. Through integrating bioinformatics and functional experiments, a potential functional single-nucleotide polymorphism (SNP; rs1440702) located in an enhancer element was identified and the A allele of rs1440702 acted as an allelic specificities enhancer to increase its distal target gene SOX6 (~600 Kb upstream) expression, which plays a key role in bone formation. We also validated this long-range regulation via conducting chromosome conformation capture (3C) assay. Furthermore, we demonstrated that SNP rs1440702 with a risk allele (rs1440702-A) could increase the activity of the enhancer element by altering the binding affinity of the transcription factor TCF4, resulting in the upregulation expression of SOX6 gene. Collectively, our integrated analyses revealed how the noncoding genetic variants (rs1440702) affect osteoporosis predisposition via long-range gene regulatory mechanisms and identified its target gene SOX6 for downstream biomarker and drug development. © 2022 American Society for Bone and Mineral Research (ASBMR).

Smart Coatings for Corrosion Protection: On the Need for New Coating Concepts

Ideally smart coatings for corrosion protection have to be able to protect the underlying metal from corrosion by providing excellent barrier properties, at the same time showing a fast and efficient self-healing in case a defect down to the metal is inflicted into them, while being as delamination resistant as possible.These seem to be basically incompatible properties, as either mobility of species is high or the coating is highly impermeable, i.e. it is difficult to envisage a coating that can be both at the same time. In fact, in recent works we have shown that for excellent self-healing performance especially the resistance against cathodic delamination of a coating should be significantly weakened [1, 2]. Using conductive polymer additions to non-conductive coatings, both high self-healing activity [1-3] as well as high resistance against cathodic delamination [4, 5] can be controlled in a wide range.Based on an in-depth understanding of the underlying mechanisms we are currently working on strategies for developing coatings that show excellent active as well as passive protection properties. Latest progress of the research on this topic well be presented and the implication will be discussed.[1] M. Uebel, L. Exbrayat, M. rabe, T.H. Tran, D. Crespy, M. Rohwerder, On the Role of Trigger Signal Spreading Velocity for Efficient Self-Healing Coatings for Corrosion Protection, Electrochem. Soc. 165 (2018) C1017-C1027[2] H. Tran , A. Vimalanandan , G.Genchev , J. Fickert , K. Landfester, D. Crespy , M.Rohwerder, Regenerative Nano-Hybrid Coating Tailored for Autonomous Corrosion Protection, Advanced Materials 27(25) (2015) 3825-3830[3] A. Vimalanandan, L.P. Lv, T.H. Tran, K. Landfester, D. Crespy, M. Rohwerder, Redox-Responsive Self-Healing for Corrosion Protection, Advanced Materials 25(48) (2013) 6980-6984[4] Anna Merz, Matthias Uebel, Michael Rohwerder, The Protection Zone: A Long-Range Corrosion Protection Mechanism around Conducting Polymer Particles in Composite Coatings: Part I. Polyaniline and Polypyrrole, Electrochem. Soc. 166 (2019) C304-C313[5] Anna Merz, Michael Rohwerder, The Protection Zone: A Long-Range Corrosion Protection Mechanism around Conducting Polymer Particles in Composite Coatings: Part II. PEDOT:PSS, Electrochem. Soc. 166 (2019) C314-C320

(Invited) New Ionic Liquids (ILs) for Secondary Batteries: Interplay between Structure, Electrical Response and Conductivity Mechanism

The main bottleneck towards the development of high-performing “beyond Lithium ion” batteries in the portable electronic, electric automotive, and stationary applications [1] is the lack of electrolytes that are safe, electrochemically stable, and compatible with the electrode materials [2-3].Recently published papers demonstrated that halo-aluminate ionic liquids (ILs) can provide an appealing alternative to conventional ethereal solvent-based electrolytes due to their low volatility, negligible flammability, and excellent electrochemical performance [4-7].Following this, an overview on recent advancements on electrolytes for secondary batteries is presented, with a particular reference to imidazolium- and pyrrolidinium-based ILs. Insights on the interplay between thermal properties, structure and conductivity of BF4 -, Cl-/AlCl3, Cl-/TiCl4, and I-/AlI3-based systems are given, thus providing an in-depth understanding of the relation existing between ion speciation, long-range charge transfer mechanism, conductivity mechanisms and electrochemical performance of this very promising class of materials.

A New Glass Forming Electrolyte Based on Lithium Glycerolate

The study of the interplay between structure and conductivity in lithium-conducting electrolytes is a pivotal point for the development of future secondary batteries [1]. The use of Glycerol as a low molecular weight component in electrolytes is particularly interesting due to its glass-forming behavior and low glass transition temperature (-78.5°C). In addition, a high flexibility of the alkyl backbone chain and the well-known capability of oxygen functionalities to coordinate lithium cations make Glycerol very appealing as ion-conducting media as well as building block to obtain hybrid polymer electrolytes [2].On this basis a family of eleven electrolytes based on Lithium Glycerolate with general formula C3H8-xO3Lix, where 0 ≤ x ≤ 1, is prepared and investigated [3]. In these electrolytes the Glycerolate (C3H8-xO3 x-) component acts as a large and flexible macro-anion which is able to provide a high single-ion conductivity to the material (8.36∙10-5 S∙cm-1 at 20°C and 1.55∙10-2 S∙cm-1 at 150°C for x = 0.25).Finally, the Glycerol∙∙∙Li+ interactions in these electrolytes are studied on T and x, with a particular reference to the detection of: a) macro-anion coordination sites; and b) the secondary structure of Glycerol chains. Insights on the long-range charge transfer mechanism and Glycerol relaxation events are also discussed.These studies are carried out by Inductively-Coupled Plasma Atomic Emission Spectroscopy, IR and Raman spectroscopies, DSC, TGA, and Broadband Electrical Spectroscopy.

Facial and neural mechanisms during interactive disclosure of biographical information

Pairs of participants mutually communicated (or not) biographical information to each other. By combining simultaneous eye-tracking, face-tracking and functional near-infrared spectroscopy, we examined how this mutual sharing of information modulates social signalling and brain activity. When biographical information was disclosed, participants directed more eye gaze to the face of the partner and presented more facial displays. We also found that spontaneous production and observation of facial displays was associated with activity in the left SMG and right dlPFC/IFG, respectively. Moreover, mutual information-sharing increased activity in bilateral TPJ and left dlPFC, as well as cross-brain synchrony between right TPJ and left dlPFC. This suggests that a complex long-range mechanism is recruited during information-sharing. These multimodal findings support the second-person neuroscience hypothesis, which postulates that communicative interactions activate additional neurocognitive mechanisms to those engaged in non-interactive situations. They further advance our understanding of which neurocognitive mechanisms underlie communicative interactions.

Structure of inhibitor-bound mammalian complex I

Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I.

Influence of M23C6 carbides on the heterogeneous strain development in annealed 420 stainless steel

Understanding the local strain enhancement and lattice distortion resulting from different microstructure features in metal alloys is crucial in many engineering processes. The development of heterogeneous strain not only plays an important role in the work hardening of the material but also in other processes such as recrystallization and damage inheritance and fracture. Isolating the contribution of precipitates to the development of heterogeneous strain can be challenging due to the presence of grain boundaries or other microstructure features that might cause ambiguous interpretation. In this work a statistical analysis of local strains measured by electron back scatter diffraction and crystal plasticity based simulations are combined to determine the effect of M23C6 carbides on the deformation of an annealed AISI 420 steel. Results suggest that carbides provide a more effective hardening at low plastic strain by a predominant long-range interaction mechanism than that of a pure ferritic microstructure. Carbides not only influence local strain directly by elastic incompatibilities with the ferritic matrix, but also the spatial interactions between ferrite grains. Carbides placed at the grain boundaries enhanced the development of strain near ferrite grain boundaries. However the positive effect of carbides and grain boundaries to develop high local strains is mitigated at regions with high density of carbides and ferrite grain boundaries.

Cryoconite Hole Location in East-Antarctic Untersee Oasis Shapes Physical and Biological Diversity.

Antarctic cryoconite holes (CHs) are mostly perennially ice-lidded and sediment-filled depressions that constitute important features on glaciers and ice sheets. Once being hydrologically connected, these microbially dominated mini-ecosystems provide nutrients and biota for downstream environments. For example, the East Antarctic Anuchin Glacier gradually melts into the adjacent perennially ice-covered Lake Untersee, and CH biota from this glacier contribute up to one third of the community composition in benthic microbial mats within the lake. However, biogeochemical features of these CHs and associated spatial patterns across the glacier are still unknown. Here we hypothesized about the CH minerogenic composition between the different sources such as the medial moraine and other zones. Further, we intended to investigate if the depth of the CH mirrors the CH community composition, organic matter (OM) content and would support productivity. In this study we show that both microbial communities and biogeochemical parameters in CHs were significantly different between the zones medial moraine and the glacier terminus. Variations in microbial community composition are the result of factors such as depth, diameter, organic matter, total carbon, particle size, and mineral diversity. More than 90% of all ribosomal sequence variants (RSV) reads were classified as Proteobacteria, Cyanobacteria, Bacteroidetes, Actinobacteria, and Acidobacteria. Archaea were detected in 85% of all samples and exclusively belonged to the classes Halobacteria, Methanomicrobia, and Thermoplasmata. The most abundant genus was Halorubrum (Halobacteria) and was identified in nine RSVs. The core microbiome for bacteria comprised 30 RSVs that were affiliated with Cyanobacteria, Bacteroidetes, Actinobacteria, and Proteobacteria. The archaeal fraction of the core microbiome consisted of three RSVs belonging to unknown genera of Methanomicrobiales and Thermoplasmatales and the genus Rice_Cluster_I (Methanocellales). Further, mean bacterial carbon production in cryoconite was exceptionally low and similar rates have not been reported elsewhere. However, bacterial carbon production insignificantly trended toward higher rates in shallow CHs and did not seem to be supported by accumulation of OM and nutrients, respectively, in deeper holes. OM fractions were significantly different between shallower CHs along the medial moraine and deeper CHs at the glacier terminus. Overall, our findings suggest that wind-blown material originating south and southeast of the Anuchin Glacier and deposits from a nunatak are assumed to be local inoculation sources. High sequence similarities between samples from the Untersee Oasis and other Antarctic sites further indicate long-range atmospheric transport mechanisms that complement local inoculation sources.

(Invited) New Ionic Liquids (ILs) for Secondary Batteries: Interplay between Structure, Electrical Response and Conductivity Mechanism

The main bottleneck towards the development of high-performing “beyond Lithium ion” batteries in the portable electronic, electric automotive, and stationary applications [1] is the lack of electrolytes that are safe, electrochemically stable, and compatible with the electrode materials [2-3].Recently published papers demonstrated that halo-aluminate ionic liquids (ILs) can provide an appealing alternative to conventional ethereal solvent-based electrolytes due to their low volatility, negligible flammability, and excellent electrochemical performance [4-7].Following this, an overview on recent advancements on electrolytes for secondary batteries is presented, with a particular reference to imidazolium- and pyrrolidinium-based ILs. Insights on the interplay between thermal properties, structure and conductivity of BF4 -, Cl-/AlCl3, Cl-/TiCl4, and I-/AlI3-based systems are given, thus providing an in-depth understanding of the relation existing between ion speciation, long-range charge transfer mechanism, conductivity mechanisms and electrochemical performance of this very promising class of materials.

A New Glass Forming Electrolyte Based on Lithium Glycerolate

The study of the interplay between structure and conductivity in lithium-conducting electrolytes is a pivotal point for the development of future secondary batteries [1]. The use of Glycerol as a low molecular weight component in electrolytes is particularly interesting due to its glass-forming behavior and low glass transition temperature (-78.5°C). In addition, a high flexibility of the alkyl backbone chain and the well-known capability of oxygen functionalities to coordinate lithium cations make Glycerol very appealing as ion-conducting media as well as building block to obtain hybrid polymer electrolytes [2].On this basis a family of eleven electrolytes based on Lithium Glycerolate with general formula C3H8-xO3Lix, where 0 ≤ x ≤ 1, is prepared and investigated [3]. In these electrolytes the Glycerolate (C3H8-xO3 x-) component acts as a large and flexible macro-anion which is able to provide a high single-ion conductivity to the material (8.36∙10-5 S∙cm-1 at 20°C and 1.55∙10-2 S∙cm-1 at 150°C for x = 0.25).Finally, the Glycerol∙∙∙Li+ interactions in these electrolytes are studied on T and x, with a particular reference to the detection of: a) macro-anion coordination sites; and b) the secondary structure of Glycerol chains. Insights on the long-range charge transfer mechanism and Glycerol relaxation events are also discussed.These studies are carried out by Inductively-Coupled Plasma Atomic Emission Spectroscopy, IR and Raman spectroscopies, DSC, TGA, and Broadband Electrical Spectroscopy.

Influence of M <sub>23</sub>C <sub>6</sub> Carbides on the Heterogeneous Strain Development in Annealed 420 Stainless Steel

Understanding the local strain enhancement resulting from different microstructure features in metal alloys is crucial in many engineering processes as it plays an important role in the work hardening and in other processes such as recrystallization and damage. Isolating the contribution of precipitates to the development of heterogeneous strain can be challenging due to the presence of grain boundaries or other microstructure features that might cause ambiguous interpretation. In this work a statistical analysis of local strains measured by electron back scatter diffraction and crystal plasticity based simulations are combined to determine the effect of M23 C6 carbides on the deformation of an annealed AISI 420 steel. Results suggest that carbides provide a more effective hardening at low plastic strain by a predominant long-range interaction mechanism than that of a pure ferritic microstructure. Carbides influence local strain by elastic incompatibilities with the ferritic matrix and also the spatial interactions between ferrite grains. The development of strain observed near ferrite grain boundaries is enhanced by the presence of carbides. However, this effect is mitigated at regions with high density of carbides and ferrite grain boundaries. Generation of artificial microstructures with controlled distribution of precipitates emerges as a powerful tool for the understanding of heterogeneous strains development.

Scorpion toxin inhibits the voltage-gated proton channel using a Zn2+ -like long-range conformational coupling mechanism.

Blocking the voltage-gated proton channel HV 1 is a promising strategy for the treatment of diseases like ischaemia stroke and cancer. However, few HV 1 channel antagonists have been reported. Here, we have identified a novel HV 1 channel antagonist from scorpion venom and have elucidated its action mechanism. HV 1 and NaV channels were heterologously expressed in mammalian cell lines and their currents recorded using whole-cell patch clamp. Site-directed mutagenesis was used to generate mutants. Toxins were recombinantly produced in Escherichia coli. AGAP/W38F-HV 1 interaction was modelled by molecular dynamics simulations. The scorpion toxin AGAP (anti-tumour analgesic peptide) potently inhibited HV 1 currents. One AGAP mutant has reduced NaV channel activity but intact HV 1 activity (AGAP/W38F). AGAP/W38F inhibited HV 1 channel activation by trapping its S4 voltage sensor in a deactivated state and inhibited HV 1 currents with less pH dependence than Zn2+ . Mutation analysis showed that the binding pockets of AGAP/W38F and Zn2+ in HV 1 channel partly overlapped (common sites are His140 and His193). The E153A mutation at the intracellular Coulombic network (ICN) in HV 1 channel markedly reduced AGAP/W38F inhibition, as observed for Zn2+ . Experimental data and MD simulations suggested that AGAP/W38F inhibited HV 1 channel using a Zn2+ -like long-range conformational coupling mechanism. Our results suggest that the Zn2+ binding pocket in HV 1 channel might be a hotspot for modulators and valuable for designing HV 1 channel ligands. Moreover, AGAP/W38F is a useful molecular probe to study HV 1 channel and a lead compound for drug development.

Understanding the Driving Mechanisms of Enhanced Luminescence Emission of Oligo(styryl)benzenes and Tri(styryl)-s-triazine.

This work is focused on unraveling the mechanisms responsible for the aggregation-induced enhanced emission and solid-state luminescence enhancement effects observed in star-shaped molecules based on 1,3,5-tris(styryl)benzene and tri(styryl)-s-triazine cores. To achieve this, the photophysical properties of this set of molecules were analyzed in three states: free molecules, molecular aggregates in solution, and the solid state. Different spectroscopy and microscopy experiments and DFT calculations were conducted to scrutinize the causative mechanisms of the luminescence enhancement phenomenon observed in some experimental conditions. Enhanced luminescence emission was interpreted in the context of short- and long-range excitonic coupling mechanisms and the restriction of intramolecular vibrations. Additionally, we found that the formation of π-stacking aggregates could block E/Z photoisomerization through torsional motions between phenylene rings in the excited state, and hence, enhancing the luminescence of the system.

Mediation of resonance energy transfer by two polarisable particles.

The molecular quantum electrodynamics theory is employed to calculate the matrix element and Fermi golden rule rate for resonant transfer of electronic excitation energy between a donor and an acceptor in the vicinity of two neutral electric dipole polarizable particles, which play the role of bridging species. The emitter and absorber couple linearly to the electric displacement field via their electric dipole moments, while each mediator interacts quadratically with this field through its dynamic polarizability. This form of interaction Hamiltonian enables fourth-order perturbation theory to be used to compute the probability amplitude together with summation over 24 time-ordered diagrams representing a single virtual photon exchange between each pair of coupled particles. Expressions for the migration rate mediated by two inert molecules are obtained for an arbitrary arrangement of the four species that are in fixed mutual orientation or are freely tumbling. These formulae are valid for all interparticle separation distances outside the orbital overlap region. From the general result, rate equations applicable to an equidistant collinear configuration of the four bodies are evaluated. Near- and far-zone limiting forms of the transfer rate for the relay pathway are also calculated and exhibit inverse sixth and inverse square dependences on relative separation distances between pairs of particles, confirming the short-range (radiationless) and long-range (radiative) energy transfer mechanisms associated with two-body theory. The distance behavior of interference terms between two-, three-, and four-body terms is also examined, and the relative importance of each contribution to the total transfer rate is discussed.

Quantum mechanics of proteins in explicit water: The role of plasmon-like solute-solvent interactions.

Quantum-mechanical van der Waals dispersion interactions play an essential role in intraprotein and protein-water interactions-the two main factors affecting the structure and dynamics of proteins in water. Typically, these interactions are only treated phenomenologically, via pairwise potential terms in classical force fields. Here, we use an explicit quantum-mechanical approach of density-functional tight-binding combined with the many-body dispersion formalism and demonstrate the relevance of many-body van der Waals forces both to protein energetics and to protein-water interactions. In contrast to commonly used pairwise approaches, many-body effects substantially decrease the relative stability of native states in the absence of water. Upon solvation, the protein-water dispersion interaction counteracts this effect and stabilizes native conformations and transition states. These observations arise from the highly delocalized and collective character of the interactions, suggesting a remarkable persistence of electron correlation through aqueous environments and providing the basis for long-range interaction mechanisms in biomolecular systems.

(Invited) Electric Dipole-Electric Dipole Non-Radiative Energy Transfer Mediated By Surface Plasmons on a Metal Surface

We present the surface plasmon-mediated energy transfer between two optically active ions in vacuum near a metallic surface using methods of molecular quantum electrodynamics. We have studied the electric dipole-electric dipole energy transfer process only, this being the most dominant mechanism in interionic interaction between two ions in a medium when their wavefunctions do not significantly overlap. The matrix elements for energy transfer, hence energy transfer rates, are calculated using two classes of Feynman diagrams. The intermediate states for one class of diagrams do not satisfy the energy conservation principle, hence they are purely virtual states. Of particular interest are the dependencies of the energy transfer process on (1) the positions of the ions with respect to one another projected on the interface and (2) the distance of each ion from the metal surface. The overall energy transfer process has been found to have both the short range and long-range components, the former being driven by virtual plasmons and the latter by the real plasmons in a non-lossy medium. The dependence of the energy transfer process on the relative separation of the ions projected on the interface is a function of the relative separation, ρ, and the surface plasmon wavevector, p. The transfer rate is proportional to a function F(pρ). In order to observe the behavior of this function, we chose a case of the photon of energy corresponding to a wavelength of 500 nm. For a silver interface, the dielectric constant corresponding to this wavelength is -9. For any given wavevector, p, the plot of F(pρ) in Fig. 1 shows that the maximum energy transfer rate occurs when ρ=0; that is, when ion A and ion B have the same x and y coordinates, only differing in their z coordinates. Thus, the maximum transfer rate occurs when one ion is “on top” of the other as observed from nearest point on the plane of the interface. As ρ increases, the energy transfer rate initially decreases rapidly. At longer distances, the transfer rate continues to decrease, but much more slowly. Oscillations in F(pρ) are present at large and small values of ρ. The “fast” and “slow” rates of decrease in F(pρ) indicate the presence of both short-range and long-range transfer mechanisms. To estimate the distance of the short-range mechanism, let us assume a surface plasmon of wavelength 500 nm, so p~2π/500 nm-1. Using the Fig. 1, we estimate that the “fast” component of the transfer rate extends to p~ 2.5, corresponding to ρ~ 200 nm, which is less than one wavelength. When pρ = 50, however, we find that ρ~ 4000 nm, which is several wavelengths long. Our interpretation is that the short-range mechanism results from energy transfer mediated by primarily by virtual surface plasmons, and the long-range mechanism corresponds formally to energy transfer mediated by primarily by real surface plasmons. Moving from small ρ to large ρ, the mediating surface plasmons change from virtual to real in a continuous fashion. We note here that we have considered a loss-less medium. In a lossy medium, the long-range interactions will be inhibited. Figure 1. A plot of F(pρ) (black line) normalized to unity at ρ=0. For comparison, also shown is the plot of [J0 (pρ)]2. (red line). Figure 1

Conformational proofreading of distant 40S ribosomal subunit maturation events by a long-range communication mechanism

Eukaryotic ribosomes are synthesized in a hierarchical process driven by a plethora of assembly factors, but how maturation events at physically distant sites on pre-ribosomes are coordinated is poorly understood. Using functional analyses and cryo-EM, we show that ribosomal protein Rps20 orchestrates communication between two multi-step maturation events across the pre-40S subunit. Our study reveals that during pre-40S maturation, formation of essential contacts between Rps20 and Rps3 permits assembly factor Ltv1 to recruit the Hrr25 kinase, thereby promoting Ltv1 phosphorylation. In parallel, a deeply buried Rps20 loop reaches to the opposite pre-40S side, where it stimulates Rio2 ATPase activity. Both cascades converge to the final maturation steps releasing Rio2 and phosphorylated Ltv1. We propose that conformational proofreading exerted via Rps20 constitutes a checkpoint permitting assembly factor release and progression of pre-40S maturation only after completion of all earlier maturation steps.

On the spatiotemporal extensiveness of sense-making: ultrafast cognition and the historicity of normativity

The enactive approach conceives of cognition as acts of sense-making. A requirement of sense-making is adaptivity, i.e., the agent’s capacity to actively monitor and regulate its own trajectories with respect to its viability constraints. However, there are examples of sense-making, known as ultrafast cognition, that occur faster than the time physiologically required for the organism to centrally monitor and regulate movements, for example, via long-range neural feedback mechanisms. These examples open a clarificatory challenge for the enactive approach with respect to how to operationalize monitoring and regulation, and with respect to the temporal scale of sense-making, which has traditionally been limited to the here-and-now in accordance with the axiom of structural determinism. We explore possible responses to this challenge and suggest that this axiom should be explicitly rejected, in particular, we suggest that adaptivity is a property of organism–environment interactions over a time span that includes both present and past conditions. Ultrafast performances are thus no longer a challenge for the enactive approach, because the constitutive basis of their normativity is spatiotemporally extensive. This is in agreement with recent developments in different varieties of enactivism, which all converge toward assigning a constitutive role to an agent’s history of interactions.

HLA-DM Stabilizes the Empty MHCII Binding Groove: A Model Using Customized Natural Move Monte Carlo.

MHC class II molecules bind peptides derived from extracellular proteins that have been ingested by antigen-presenting cells and display them to the immune system. Peptide loading occurs within the antigen-presenting cell and is facilitated by HLA-DM. HLA-DM stabilizes the open conformation of the MHCII binding groove when no peptide is bound. While a structure of the MHCII/HLA-DM complex exists, the mechanism of stabilization is still largely unknown. Here, we applied customized Natural Move Monte Carlo to investigate this interaction. We found a possible long-range mechanism that implicates the configuration of the membrane-proximal globular domains in stabilizing the open state of the empty MHCII binding groove.

Grooves Accelerate Dew Shedding.

Gravity-driven drainage of small volumes of condensates, such as natural dew, is a challenge because small drops usually remain pinned to inclined surfaces. We report that submillimetric grooves substantially reduce dew retention by modifying the repartition of liquid: Because of a long-range coalescence mechanism mediated by grooves imbibition, the growth and shedding of large drops are accelerated. Such findings can be applied to increase the passive harvesting of dew as well as to accelerate the drainage of other condensates.