Charge Clusters Research Articles

Cluster intercalation of aluminum tetrachloride in AlN cathode: Exploration and analysis of aluminum ion batteries.

When chloroaluminate (AlCl4-) serves as the electrolyte, aluminum nitride (AlN) has shown promise as a cathode material in aluminum ion batteries. However, there is currently a lack of research on the mechanisms of charge transfer and cluster intercalation between AlCl4 and AlN cathode materials. Herein, first-principles calculations are employed to investigate the intercalation mechanism of AlCl4 within the AlN cathode. By calculating the formation energies of stage-1-5 AlN-AlCl4 intercalation compounds with the insertion of individual AlCl4 cluster, we found that the structure of the stage-4 intercalation compounds exhibits the highest stability, suggesting that when the clusters begin to intercalate, it is important to start with the formation of the stage-4 intercalation compounds. In the subsequent phases of the charging process (stages 1 and 2), the stabilized structure with four inserted clusters demonstrates two characteristics: the coexistence of standing and lying clusters and the insertion of two standing clusters in an upside-down doubly stacked configuration, which further improve the spatial utilization while maintaining the structural stability. In addition, we infer that a phenomenon of coexisting intercalation compounds with mixed stages will occur in the course of the charging and discharging processes. More importantly, the diffusion barrier of AlCl4 in AlN-AlCl4 intercalation compounds decreases with the reduction of stage number, ensuring the rate performance of batteries. Therefore, we expect that our work will contribute to comprehend the intercalation mechanism of AlCl4 into the AlN cathode materials of aluminum ion batteries, providing guidance for related experimental work.

Smart pixel sensors: towards on-sensor filtering of pixel clusters with deep learning

Abstract Highly granular pixel detectors allow for increasingly precise measurements of charged particle tracks. Next-generation detectors require that pixel sizes will be further reduced, leading to unprecedented data rates exceeding those foreseen at the High- Luminosity Large Hadron Collider. Signal processing that handles data incoming at a rate of O (40 MHz) and intelligently reduces the data within the pixelated region of the detector at rate will enhance physics performance at high luminosity and enable physics analyses that are not currently possible. Using the shape of charge clusters deposited in an array of small pixels, the physical properties of the traversing particle can be extracted with locally customized neural networks. In this first demonstration, we present a neural network that can be embedded into the on-sensor readout and filter out hits from low momentum tracks, reducing the detector’s data volume by 57.1%–75.7%. The network is designed and simulated as a custom readout integrated circuit with 28 nm CMOS technology and is expected to operate at less than 300 μ W with an area of less than 0.2 mm2. The temporal development of charge clusters is investigated to demonstrate possible future performance gains, and there is also a discussion of future algorithmic and technological improvements that could enhance efficiency, data reduction, and power per area.

Clustering of negative topological charges precedes plastic failure in 3D glasses.

The deformation mechanism in amorphous solids subjected to external shear remains poorly understood because of the absence of well-defined topological defects mediating the plastic deformation. The notion of soft spots has emerged as a useful tool to characterize the onset of irreversible rearrangements and plastic flow, but these entities are not clearly defined in terms of geometry and topology. In this study, we unveil the phenomenology of recently discovered, precisely defined topological defects governing the microscopic mechanical and yielding behavior of a model 3D glass under shear deformation. We identify the existence of vortex-like and antivortex-like topological defects within the 3D nonaffine displacement field. The number density of these defects exhibits a significant anticorrelation with the plastic events, with defect proliferation-annihilation cycles matching the alternation of elastic-like segments and catastrophic plastic drops, respectively. Furthermore, we observe collective annihilation of these point-like defects via plastic events, with large local topological charge fluctuations in the vicinity of regions that feature strong nonaffine displacements. We reveal that plastic yielding is driven by several large sized clusters of net negative topological charge, the massive annihilation of which triggers the onset of plastic flow. These findings suggest a geometric and topological characterization of soft spots and pave the way for the mechanistic understanding of topological defects as mediators of plastic deformation in glassy materials.

Screening clusters of charged residues in plants’ mitochondrial proteins and biological significance

Protein function is dependent on charge interactions and charge biased regions, which are involved in a wide range of cellular and biochemical processes. We report the development of a new algorithm implemented in Python and its use to identify charge clusters CC (NegativeCC: NCC, PositiveCC: PCC and MixedCC: MCC) and compare their presence in mitochondrial proteins of plant groups. To characterize the resulting CC, statistical, structural and functional analyses were conducted. The screening of 105 399 protein sequences showed that 2.6 %, 0.48 % and 0.03 % of the proteins contain NCC, PCC and MCC, respectively. Mitochondrial proteins encoded by the nuclear genome of green algae have the biggest proportion of both PCC (1.6 %) and MCC (0.4 %) and mitochondrial proteins coded by the nuclear genome of other plants group have the highest portion of NCC (7.5 %). The mapping of the identified CC showed that they are mainly located in the terminal regions of the protein. Annotation showed that proteins with CC are classified as binding proteins, are included in the transmembrane transport processes, and are mainly located in the membrane. The CC scanning revealed the presence of 2373 and 784 sites and 192 and 149 motif profiles within NCC and PCC, respectively. The investigation of CC within pentatricopeptide repeat-containing proteins revealed that they are involved in correct and specific RNA editing. CC were proven to play a key role in providing insightful structural and functional information of complex protein assemblies which could be useful in biotechnological applications.

Cluster Formation of Self-Assembled Triarylbismuthanes and Charge Transport Characterizations of Gold-Triarylbismuthane-Gold Junctions.

Organometallic molecules are promising for molecular electronic devices due to their potential to improve electrical conductance through access to complex orbital covalency that is not available to light-element organic molecules. However, studies of the formation of organometallic monolayers and their charge transport properties are scarce. Here, we report the cluster formation and charge transport properties of gold-triarylbismuthane-gold molecular junctions. We found that triarylbismuthane molecules with -CN anchoring groups form clusters during the creation of self-assembled submonolayers. This clustering is attributed to strong interactions between the bismuth (Bi) center and the nitrogen atom in the -CN group of adjacent molecules. Examination of the influence of -NH2 and -CN anchoring groups on junction conductance revealed that, despite a stronger binding energy between the -NH2 group and gold, the conductance per molecular unit (i.e., molecule for the -NH2 group and cluster for the -CN group) is higher with the -CN anchoring group. Further analysis showed that an increase in the number of -CN groups from one to three within the junctions leads to a decrease in conductance while increasing the size of the cluster. This demonstrates the significant effects of different anchoring groups and the impact of varying the number of -CN groups on both the charge transport and cluster formation. This study highlights the importance of selecting the appropriate anchoring group in the design of molecular junctions. Additionally, controlling the size and formation of clusters can be a strategic approach to engineering charge transport in molecular junctions.

Label-Free Tracking of Hepatitis B Virus Core Protein Capsid Assembly in Real-Time Using Protein Charge Transfer Spectra.

Hepatitis B virions are double-shelled particles, with a diameter of 40-42 nm, consisting of a nucleocapsid called the HBV core protein (HBV Cp). It is an ordered assembly of 90-120 homodimers arranged in an icosahedral symmetry. Both the full-length HBV Cp and the first-149 residue domain, HBV Cp149, can spontaneously assemble in vitro into capsids with 120 Cp dimers (T = 4) or 90 Cp dimers (T = 3), triggered by high ionic strength of 0.25-0.5 M NaCl. The assembly disassembly of HBV Cp149 capsids are generally studied by light scattering, size-exclusion chromatography, atomic force microscopy, transmission electron microscopy, and other high-end expensive techniques. Here, we report a simple, yet robust, label-free technique exploiting protein charge transfer spectra (ProCharTS) to monitor the capsid assembly in real-time. ProCharTS absorption in the near UV-visible region (250-800 nm) arises when photoinduced electron transfer occurs from HOMO of COO- in glutamate (donor) to LUMO of NH3+ in lysine or polypeptide backbone (acceptor) of the protein. Alternatively, it can also occur from polypeptide backbone (donor) to acceptor in arginine, histidine, or lysine cation. ProCharTS is observed profusely among proximal charge clusters in folded proteins. Here, we show that, ProCharTS absorption among growing HBV capsids is amplified when HBV Cp homodimers assemble, generating new contacts among charged residues in the dimer-dimer interface. We notice a time-dependent sigmoidal increase in ProCharTS absorbance and luminescence during capsid formation in comparison to pure dimers. Additionally, a combined approach of anisotropy-based fluorescence assay is reported, where an increased fluorescence anisotropy was observed in capsids as compared to native and unfolded dimers. We conclude that ProCharTS can serve as a sensitive label-free tool for rapid tracking of capsid assembly in real-time and characterize the assembled capsids from dimers.

Charge block-driven liquid-liquid phase separation - mechanism and biological roles.

Liquid-liquid phase separation (LLPS) has increasingly been found to play pivotal roles in a number of intracellular events and reactions, and has introduced a new paradigm in cell biology to explain protein-protein and enzyme-ligand interactions beyond conventional molecular and biochemical theories. LLPS is driven by the cumulative effects of weak and promiscuous interactions, including electrostatic, hydrophobic and cation-π interactions, among polypeptides containing intrinsically disordered regions (IDRs) and describes the macroscopic behaviours of IDR-containing proteins in an intracellular milieu. Recent studies have revealed that interactions between 'charge blocks' - clusters of like charges along the polypeptide chain - strongly induce LLPS and play fundamental roles in its spatiotemporal regulation. Introducing a new parameter, termed 'charge blockiness', into physicochemical models of disordered polypeptides has yielded a better understanding of how the intrinsic amino acid sequence of a polypeptide determines the spatiotemporal occurrence of LLPS within a cell. Charge blockiness might also explain why some post-translational modifications segregate within IDRs and how they regulate LLPS. In this Review, we summarise recent progress towards understanding the mechanism and biological roles of charge block-driven LLPS and discuss how this new characteristic parameter of polypeptides offers new possibilities in the fields of structural biology and cell biology.

Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator

Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa. We identified residues required for FRQ’s interaction with its partner protein FRH, the mutation of which demonstrated FRH is necessary for persistent clock oscillations but not repression of transcriptional activity. Additionally, the microarray demonstrated an enrichment of FRH binding to FRQ peptides with a net positive charge. We found that positively charged residues occurred in significant “blocks” within the amino acid sequence of FRQ and that ablation of one of these blocks affected both core clock timing and physiological clock output. Finally, we found positive charge clusters were a commonly shared molecular feature in repressive circadian clock proteins. Overall, our study suggests a mechanistic purpose for positive charge blocks and yielded insights into repressive arm protein roles in clock function.

Ion correlations in quaternary ionic liquids electrolytes

Lithium-ion batteries are currently the most popular and widely used energy storage devices, almost omnipresent within modern society in portable devices, electrical vehicles, energy storage stations, and so on. The demand for more efficient, more durable, and more sustainable batteries is rapidly growing. The electrolyte is a key element to improve the performance of lithium-ion batteries. In this work, we focus on quaternary ionic liquid electrolyte (ILE), which uses a four-component ionic liquid as the solvent. Quaternary ILE has found wide applications in energy storage systems, but the ion transport in the electrolyte has not been fully characterized to provide the best strategy for performance optimisation. In this work, we systematically analyse the ion transport in the quaternary ILE and uncover how the correlations between various ions affect the conductivity of the electrolyte. We have found that lithium ions are transported in charge clusters, leading to a negative effective transference number of lithium ions. Furthermore, we identify the stable cluster conformations in ILE by cluster analysis and quantum chemical computing. This work highlights the necessity of considering ion correlations in multi-component electrolyte systems.

Charge cluster occurrence in land plants’ mitochondrial proteomes with functional and structural insights

The Charge Clusters (CCs) are involved in key functions and are distributed according to the organism, the protein’s type, and the charge of amino acids. In the present study, we have explored the occurrence, position, and annotation as a first large-scale study of the CCs in land plants mitochondrial proteomes. A new python script was used for data curation. The Finding Clusters Charge in Protein Sequences Program was performed after adjusting the reading window size. A 44316 protein sequences belonging to 52 species of land plants were analysed. The occurrence of Negative Charge Clusters (NCCs) (1.2%) is two times more frequent than the Positive Charge Clusters (PCCs) (0.64%). Moreover, 39 and 30 NCCs were conserved in 88 and 41 proteins in intra and in inter proteomes respectively, while 14 and 21 PCCs were conserved in 53 and 85 protein sequences in intra and inter proteomes consecutively. Sequences carrying mixed CCs are rare (0.12%). Despite this low abundance, CCs play a crucial role in protein function. The CCs tend to be located mainly in the terminal regions of proteins which guarantees specific protein targeting and import into the mitochondria. In addition, the functional annotation of CCs according to Gene Ontology shows that CCs are involved in binding functions of either proteins or macromolecules which are deployed in different metabolic and cellular processes such as RNA editing and transcription. This study may provide valuable information while considering the CCs in understanding the environmental adaptation of plants. Communicated by Ramaswamy H. Sarma

CO2 activation by copper oxide clusters: size, composition, and charge state dependence.

The interaction of CO2 with copper oxide clusters of different size, composition, and charge is investigated via infrared multiple-photon dissociation (IR-MPD) spectroscopy and density functional theory (DFT) calculations. Laser ablation of a copper target in the presence of an O2/He mixture leads to the preferred formation of oxygen-rich copper oxide cluster cations, CuxOy+ (y > x; x ≤ 8), while the anionic cluster distribution is dominated by stoichiometric (x = y) and oxygen-deficient (y < x; x ≤ 8) species. Subsequent reaction of the clusters with CO2 in a flow tube reactor results in the preferred formation of near-stoichiometric CuxOy(CO2)+/- complexes. IR-MPD spectroscopy of the formed complexes reveals the non-activated binding of CO2 to all cations while CO2 is activated by all anions. The great resemblance of spectra for all sizes investigated demonstrates that CO2 activation is largely independent of cluster size and Cu/O ratio but mainly determined by the cluster charge state. Comparison of the IR-MPD spectra with DFT calculations of the model systems Cu2O4(CO2)- and Cu3O4(CO2)- shows that CO2 activation exclusively results in the formation of a CO3 unit. Subsequent CO2 dissociation to CO appears to be unfavorable due to the instability of CO on the copper oxide clusters indicating that potential hydrogenation reactions will most likely proceed via formate or bicarbonate intermediates.

Activation of the Complement Lectin Pathway by Iron Oxide Nanoparticles and Induction of Pro-inflammatory Immune Response by Macrophages

Aims:: Nanoparticles are important agents for targeted drug delivery to tissues or organs, or even solid tumour in certain instances. However, their surface charge distribution makes them amenable to recognition by the host immune mechanisms, especially the innate immune system, which interferes with their intended targeting, circulation life, and eventual fate in the body. We aimed to study the immunological response of iron oxide nanoparticles (Fe-NPs) and the role of the complement system in inducing an inflammatory cascade. Background:: The complement system is an important component of the innate immune system that can recognise molecular patterns on the pathogens (non-self), altered self (apoptotic and necrotic cells, and aggregated proteins such as beta-amyloid peptides), and cancer cells. It is no surprise that clusters of charge on nanoparticles are recognised by complement subcomponents, thus activating the three complement pathways: classical, alternative, and lectin. Objective:: This study aimed to examine the ability of Fe-NPs to activate the complement system and interact with macrophages in vitro. Methods:: Complement activation following exposure of macrophage-like cell line (THP-1) to Fe-NPs or positive control was analysed by standard protocol. Real-time PCR was used for mRNA-level gene expression analysis, whereas multiplex cytokine array was used for proteinlevel expression analysis of cytokines and chemokines. Results:: Fe-NPs activated all three pathways to a certain extent; however, the activation of the lectin pathway was the most pronounced, suggesting that Fe-NPs bind mannan-binding lectin (MBL), a pattern recognition soluble receptor (humoral factor). MBL-mediated complement activation on the surface of Fe-NPs enhanced their uptake by THP-1 cells, in addition to dampening inflammatory cytokines, chemokines, growth factors, and soluble immune ligands. Conclusion:: Selective complement deposition (via the lectin pathway in this study) can make pro-inflammatory nanoparticles biocompatible and render them anti-inflammatory properties.

A SOC Correction Method Based on Unsynchronized Full Charge and Discharge Control Strategy in Multi-Branch Battery System

LiFePO4 batteries exhibit voltage plateau and voltage hysteresis characteristics during charging and discharging processes; however, the estimation of state-of-charge relies on voltage detection. Thus, the estimation accuracy of SOC is low in a traditional method. In this paper, a full charge and discharge SOC correction method is proposed; i.e., the SOC is corrected to 100% when the battery is fully charged and to 0% when fully discharged, and the actual usable capacity is corrected using the fully discharged capacity after being fully charged. Thereby, the cumulative error of the ampere-hour integration method is dynamically corrected. In engineering applications, however, the battery systems do not always undergo full charge and discharge cycling due to the operating conditions. By making full use of the distributed control characteristics of the multi-branch topology battery system, the present work proposes an optimized system control strategy to realize the unsynchronized full charge and discharge cluster by cluster, which extends the application of the full charge and discharge SOC correction method. The experimental results verify the accuracy of the proposed SOC correction method and the feasibility of the control strategy. A more reliable and efficient battery management scheme is provided for LFP battery system, which has high practical value in engineering.

A pH-dependent cluster of charges in a conserved cryptic pocket on flaviviral envelopes.

Flaviviruses are enveloped viruses which include human pathogens that are predominantly transmitted by mosquitoes and ticks. Some, such as dengue virus, exhibit the phenomenon of antibody-dependent enhancement (ADE) of disease, making vaccine-based routes of fighting infections problematic. The pH-dependent conformational change of the envelope (E) protein required for fusion between the viral and endosomal membranes is an attractive point of inhibition by antivirals as it has the potential to diminish the effects of ADE. We examined six flaviviruses by employing large-scale molecular dynamics (MD) simulations of raft systems that represent a substantial portion of the flaviviral envelope. We utilised a benzene-mapping approach that led to a discovery of shared hotspots and conserved cryptic sites. A cryptic pocket previously shown to bind a detergent molecule exhibited strain-specific characteristics. An alternative conserved cryptic site at the E protein domain interfaces showed a consistent dynamic behaviour across flaviviruses and contained a conserved cluster of ionisable residues. Constant-pH simulations revealed cluster and domain-interface disruption under low pH conditions. Based on this, we propose a cluster-dependent mechanism that addresses inconsistencies in the histidine-switch hypothesis and highlights the role of cluster protonation in orchestrating the domain dissociation pivotal for the formation of the fusogenic trimer.

A basic charge cluster near the C-terminus of the cytoplasmic tail contributes to the molecular stability of human herpesvirus 8 E3 ubiquitin ligases.

Human herpesvirus 8 (HHV8; also known as Kaposi's sarcoma-associated herpesvirus [KSHV]) utilizes the viral E3 ubiquitin ligase family members K3 and K5 for immune evasion. Both K3 and K5 mediate the ubiquitination of host MHC class I (MHC-I) molecules, which play a key role in antigen presentation to cytotoxic T lymphocytes (CTLs). Because ubiquitinated MHC-I is immediately down-regulated from the cell surface, HHV8-infected cells can escape surveillance by CTLs. K3 and K5 have similar domain structures and topologies. They contain an N-terminal RINGv ubiquitin ligase domain, two transmembrane helices, and an intrinsically disordered cytoplasmic tail at the C-terminus. The cytoplasmic tail contains a membrane-proximal "conserved region" involved in ligase activity. On the other hand, the role of the membrane-distal region of the cytoplasmic tail, termed the "C-tail" in this study, remains unclear. Here, we demonstrate that the C-tail contributes to the protein expression of both K3 and K5. The C-tail-truncated K3 and K5 mutants were rapidly reduced in cells. The recombinant C-tail proteins bind to acidic lipids via a basic charge cluster located near the C-terminus of the C-tails. Similar to the C-tail-truncated mutants, the basic charge cluster-substituting mutants showed decreased protein expression of K3 and K5. These findings suggest that the basic charge cluster near the C-terminus of the cytoplasmic tail contributes to the molecular stability of K3 and K5.

Highly Efficient CO Oxidation on Atomically Thin Pt Plates Supported on Irreducible Si 7 × 7

Electronic interaction between metal nanoparticles and irreducible supports is an important aspect of heterogeneous catalysis due to its capability of controlling the associated catalytic performance. We elucidate the relationship between metal–support electronic interactions and catalytic activity on size-selected singe layered platinum plates Ptn (n = 10, 20, 30, and 45) supported on a Si (111)-7 × 7 reconstructed surface (Si-RS). Our first-principles density functional theory study shows that CO oxidation catalysis over Pt supported on the nonreducible Si-RS is affected by variations in charge transfer, cluster size, and electronic interactions between clusters and support. CO adsorbs on Ptn adsorption sites in two distinct ranges of adsorption energies, which explains the experimentally observed two different desorption temperatures of CO. Pt30/Si-RS is more active than other Ptn/Si-RS under the same conditions, showing markedly enhanced catalytic activity in terms of high turnover frequency of CO2 production. This superior activity originates from the optimum CO and O2 adsorption on Pt30 arising from the position of the d-band center being midway between their π orbitals. Experimental observations convey that the TOFs of CO2 production on Pt30(45)/Si-RS are very high, and these are tolerant to CO poisoning between 450 and 550 K. DFT computations of TOF on Pt30(45)/Si-RS for CO2 validate the experimentally observed trends at 350, 450, and 550 K and exhibit that the CO oxidation activity exceeds that of the conventional catalysts between 450 and 550 K. Our results depict the importance of size control and electronic structure tailoring while designing Pt-based catalysts and will motivate the effective utilization of rare elements on irreducible substrates.

Counter charge cluster formation in molecular doping of molybdenum disulfide

Studies of molybdenum disulfide (MoS2) gas sensor prototypes report orders of magnitude higher sensitivity toward nitrogen dioxide (NO2) over ammonia (NH3). Based on the cluster formation model and density functional theory calculations of charge transfer, NO2 was found to form a tightly bound cluster of counter charges upon carrier donation. In contrast, NH3 forms only a semi-localized cluster of counter charges over a wide area of MoS2, creating a larger collision cross section of coulomb interaction between the charge carrier and the counter charges. We discuss the potential effect of counter charge cluster localization on the efficiency of molecular doping.

Protein charge transfer spectra in a monomeric protein with no lysine.

UV-Visible absorption and luminescence originating from non-aromatic groups in proteins is being intensely investigated today. Earlier work has shown that non-aromatic charge clusters in a folded monomeric protein can collectively act like a chromophore. Incident light in the near UV-Visible wavelength causes photoinduced electron transfer from the Highest Occupied Molecular Orbital (HOMO) of the electron-rich donor (like a carboxylate anion) to the Lowest Unoccupied Molecular Orbital (LUMO) of the electron-deficient acceptor (like a protonated amine or the polypeptide backbone) in the protein giving rise to absorption spectra in the 250-800 nm range referred to as Protein Charge Transfer Spectra (ProCharTS). The transferred electron can relax back from the LUMO to fill up the hole in the HOMO by a charge recombination process, emitting weak ProCharTS luminescence. Previous studies in monomeric proteins displaying ProCharTS absorption/luminescence always involved lysine-containing proteins. The lysine (Lys) sidechain plays a dominant role in ProCharTS; however, experimental evidence for ProCharTS among proteins/peptides devoid of Lys is lacking. Recently, the absorption features of charged amino acids have been examined using time-dependent density functional theory calculations. In this study, we show that amino acids: arginine (Arg), histidine (His) and aspartate (Asp); homo-polypeptides: poly-arginine and poly-aspartate; and a protein: Symfoil PV2 that is rich in Asp, His and Arg, but lacks Lys, profusely display ProCharTS. The folded Symfoil PV2 protein displayed maximum ProCharTS absorptivity in the near UV-Vis region, in comparison to the homo-polypeptides and amino acids. Furthermore, features like overlapping ProCharTS absorption spectra, decreasing ProCharTS luminescence intensity with longer excitation wavelength, large Stokes shift, multiple excitation bands and multiple luminescence lifetime components appeared to be conserved across peptides, proteins and amino acids studied. Our results underscore the utility of ProCharTS as an intrinsic spectral probe to monitor the structure of any protein that is rich in charged amino acids.

Prion Propagation is Dependent on Key Amino Acids in Charge Cluster 2 within the Prion Protein

To dissect the N-terminal residues within the cellular prion protein (PrPC) that are critical for efficient prion propagation, we generated a library of point, double, or triple alanine replacements within residues 23–111 of PrP, stably expressed them in cells silenced for endogenous mouse PrPC and challenged the reconstituted cells with four common but biologically diverse mouse prion strains. Amino acids (aa) 105–111 of Charge Cluster 2 (CC2), which is disordered in PrPC, were found to be required for propagation of all four prion strains; other residues had no effect or exhibited strain-specific effects. Replacements in CC2, including aa105-111, dominantly inhibited prion propagation in the presence of endogenous wild type PrPC whilst other changes were not inhibitory. Single alanine replacements within aa105-111 identified leucine 108 and valine 111 or the cluster of lysine 105, threonine 106 and asparagine 107 as critical for prion propagation. These residues mediate specific ordering of unstructured CC2 into β-sheets in the infectious prion fibrils from Rocky Mountain Laboratory (RML) and ME7 mouse prion strains.

Comparative performance of theoretical tools in order to quantify the effect of the electric potential on the vibrational wavenumbers and intensities of the SERS of 2‐methylpyrazine adsorbed on a nanostructured silver electrode

AbstractThe effect of the electrode potential in surface‐enhanced Raman scattering (SERS) intensities and wavenumbers of 2‐methylpyrazine (2MP) was analyzed on the basis of a resonant charge transfer (CT) mechanism by using a simple theoretical model in which the metallic surface and its charge density were simulated by atomic silver clusters of different size (n) and charge (q), [Agn]q. Two linear silver atoms (n = 2) with zero charge (q = 0) and three linear silver atoms (n = 3) with positive and negative charges (q = ±1) linked to the two nonequivalent aromatic nitrogen atoms in 2MP were taken into account. The wavenumber shifts of the most intense bands and the SERS‐CT spectra of these two types of metal‐adsorbate supermolecule, [Agn‐N1]q and [Agn‐N4]q, were calculated by using a time‐dependent density functional theory (TD‐DFT) method and the independent mode displaced harmonic oscillator (IMDHO) approximation. A comparison of the effect of different levels of calculation, ab initio/DFT, on the predictions from the two theoretical models (isolated adsorbate/supermolecule) is also performed. Only DFT theoretical results of the metal‐adsorbate supermolecule allow to explain the main role of the pair of bands assigned to totally symmetric ring‐stretching 8a,b modes. The 8a vibration is the strongest band at any electrode potential, whereas the 8b mode reaches a maximum enhancement at −0.50 V and then decreases at −0.75 V. This model of a charged metal‐adsorbate interface allows for detecting the presence of a CT mechanism in a SERS record.