The role of post-translational modifications for learning and memory formation

Learning and memory depend on molecular mechanisms involving the protein machinery. Recent evidence proposes that post-translational modifications (PTMs) play a major role in these cognitive processes. PTMs including phosphorylation of serine, threonine, and tyrosine are already well-documented to play a role for synaptic plasticity of the brain, neurotransmitter release, vesicle trafficking and synaptosomal or synaptosomal-associated proteins are substrates of a series of specific protein kinases and their counterparts, protein phosphatases. But protein phosphorylation is only one out of many possible PTMs and first work shows a role of palmitoylation as well as glycosylation for proteins involved in memory formation. Recent technology may now allow reliable detection and even quantification of PTMs of proteins involved in the cognitive system. This will contribute to the understanding of mechanisms for learning and memory formation at the chemical level and has to complement determination of protein levels and indeed determination of protein expression per se generates limited information. The many other PTMs expected including protein nitrosylation and alkylation will even represent targets for pharmacological interventions but in turn increase the complexity of the system. Nevertheless, determination of the presence and the function of PTMs is mandatory and promising cognitive research at the protein chemical level.     

The role of peptides and proteins in melanoidin formation

High‐molecular‐weight (HMW) coloured compounds called melanoidins are widely distributed, particularly in foods. It has been proposed that they originate through the Maillard reaction, a non‐enzymatic browning reaction, due to the interaction between protein or peptide amino groups and carbohydrates. The melanoidin structure is not definitively known, and they have been generally defined as HMW nitrogen‐containing brown polymers. In order to gain information on the nature of melanoidins, a simple in vitro model was chosen to investigate the products of the reactions between sugars and peptide/proteins. This approach would elucidate whether melanoidin formation is due to the binding of different sugar units to a peptide/protein or vice versa. With this aim, the reactivity of two different peptides, EPK177 and physalaemin, and a low‐molecular‐weight (LMW) protein, lysozyme, was tested towards different saccharides (glucose, maltotriose (MT), maltopentaose and dextran 1000) in aqueous solutions at different temperatures. The incubation mixtures were analysed at different reaction times by MALDI/MS. Furthermore, in order to verify the possible role of sugar pyrolysis products in melanoidin formation, the products arising from the thermal treatment at 200 °C of MT were incubated with lysozyme, and the reaction products were analysed by the same MS approach. The obtained results allowed the establishment of some general views: melanoidins cannot simply originate by reactions of sugar moieties with proteins. In fact, the reaction easily occurs, but it does not lead to any coloured product, as melanoidins have been described to be; melanoidins cannot originate from the thermal degradation products of glycated proteins. In fact, the thermal treatment of glycated lysozyme leads to a severe degradation of the protein with the formation of LMW species, far from the view of melanoidins as HMW compounds; experimental evidence has been gained on the melanoidin formation through reaction of intact protein with the pyrolysis products of MT. This hypothesis has been supported either from MALDI measurements or from spectroscopic data that show an absorption band in the range 300–600 nm, typical of melanoidins. Copyright © 2009 John Wiley & Sons, Ltd.     

The role of salivary peptides in dental caries

Dental caries is a complex disease, characterized by demineralization of tooth structure. With a protective role, several salivary phosphopeptides appear to be involved in remineralization processes, delaying the loss of tooth structure. In this work we have correlated peptide saliva composition with dental caries susceptibility through the analysis of saliva and hydroxyapatite-adsorbed salivary peptides samples. Saliva samples were obtained from two groups, a caries-free and a cariessusceptible group, and were analysed using HPLC-MS and a sequential extraction with 6 m of guanidine followed by tri fluoroacetate. Data analysis has allowed us to verify a strong correlation between large amounts phosphopeptides (PRP1/3, histatin 1 and statherin), and the absence of dental caries, which reinforces the importance of these peptides in the maintenance of tooth integrity. In addition, in the caries-susceptible group a high number of peptide fragments was observed, suggesting a high proteolytic activity.     

雌激素改善学习记忆的机制

雌激素是维持妇女生理与心理所必需的内源性活性物质。很多研究已证明其具有促进学习记忆的作用。其作用机制与胆碱能、谷氨酸能、单胺类能等神经系统密切相关。应用此激素替代疗法有助于预防绝经后妇女患年痴呆症。     

Agave fructans and oligofructose decrease oxidative stress in brain regions involved in learning and memory of overweight mice

Obesity is currently a public health problem worldwide. Recently, non-reducing carbohydrates, that include β(2→1) and β(2→6) linkages in their structure, have been of particular interest in the field of obesity because they are involved in lipid metabolism. Some of these are agave fructans (AF) and oligofructose (OF). In this study, we evaluated both AF and OF on oxidative stress (OS) markers in the brain of overweight mice (OM). AF and OF decreased TBARS levels and carbonyls at different levels in hippocampus (HP), frontal cortex (FC) and cerebellum (CB) of OM. The results indicated that fructans may have anti-oxidative potential and can be used as an alternative treatment for the prevention of the consequences of this pathology.     

The role of ion-pairing in peak deformations in overloaded reversed-phase chromatography of peptides

The paper reports a study on the role of ion-pairing behind peak deformations, e.g. peak splitting and even peak disappearance, during the elution of a peptide at highly overloaded conditions in reversed-phase chromatography. Deformation of component peaks is not uncommon in chromatography. There are reports which discuss their occurrence, but mostly at analytical scale, while their occurrence is quite common also in the preparative scale, as in the case discussed in this work. This paper first describes the conditions leading to peak splitting and peak disappearance of an industrial peptide, then explains the plausible reasons behind such behaviour, and finally with experimental analysis demonstrates the role of ion-pairing in causing such behaviour.     

The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization

The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO-(Ala)(1-6)-NH(2)](2) and (For-Ala(1-2)-NH(2))(1-6) peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms "holding tight" the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.     

Constituent analysis of stress memory in semicrystalline polyurethane

Similar to shape memory, the stress in a stimulus responsive polymer can also be programmed, stored, and retrieved reversibly upon an external stimulus, and known as stress memory. Herein, the stress analysis in a semicrystalline polyurethane is investigated to unveil the total stress–strain components of the memory polymer. The evolution of stress under different temperature and strain levels is determined experimentally. A constitutive model based on phase transition was further used to predict and characterize the individual stress components during the thermomechanical process. In contrast to earlier models, a new approach of using relaxed modulus (RM) has been proposed to predict the stress components in tensile programming condition. The predicted results are having significant agreement with the experimental data. The quantitative stress analysis can help in engineering the products more precisely, where the controllable stimulus responsive stress is needed in multidisciplinary arenas such as pressure garments, massage devices, and artificial muscles etc. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 941–947     

The effects of olibanum administered to methimazole-treated dams during lactation on learning and memory of offspring rats

The effect of olibanum administered during lactation to methimazole-treated dams on the learning of offspring was evaluated. The animals were treated for 60 days from the first day of lactation period: group 1--tap water, group 2-0.03% methimazole and groups 3 and 4-0.03% methimazole with 0.25% or 0.125% olibanum, respectively. The serum thyroxin level in the offspring of group 2 was significantly lower than that of group 1. However, there was no difference compared to groups 3 and 4. In a Morris water maze, the distance and time latency to reach the platform in offspring of group 2 was significantly higher than groups 1, 3 and 4. In probe trial, the time spent in target quadrant (Q?) by offspring of group 2 was lower than groups 1,?3 and 4. It is suggested that impaired learning and memory in the offspring of hypothyroid rats may be prevented by olibanum.     

The energy landscape of unsolvated peptides: the role of context in the stability of alanine/glycine helices

Ion mobility measurements have been used to examine the conformations present for unsolvated Ac-(AG)(7)A+H(+) and (AG)(7)A+H(+) peptides (Ac = acetyl, A = alanine, and G = glycine) over a broad temperature range (100-410 K). The results are compared to those recently reported for Ac-A(4)G(7)A(4)+H(+) and A(4)G(7)A(4)+H(+), which have the same compositions but different sequences. Ac-(AG)(7)A+H(+) shows less conformational diversity than Ac-A(4)G(7)A(4)+H(+); it is much less helical than Ac-A(4)G(7)A(4)+H(+) at the upper end of the temperature range studied, and at low temperatures, one of the two Ac-A(4)G(7)A(4)+H(+) features assigned to helical conformations is missing for Ac-(AG)(7)A+H(+). Molecular dynamics simulations suggest that the different conformational preferences are not due to differences in the stabilities of the helical states, but differences in the nonhelical states: it appears that Ac-(AG)(7)A+H(+) is more flexible and able to adopt lower energy globular conformations (compact random looking three-dimensional structures) than Ac-A(4)G(7)A(4)+H(+). The helix to globule transition that occurs for Ac-(AG)(7)A+H(+) at around 250-350 K is not a direct (two-state) process, but a creeping transition that takes place through at least one and probably several intermediates.     

The physics and physiology of lung surfactants

Langmuir monolayers have provided experimentally accessible models for studies of lung surfactants at the air-alveolus interface since the medical necessity of lung surfactant was demonstrated by the pioneering work of Avery and Clements in the early 1960s. The fundamental goal of these in vitro studies is a molecular level understanding of the relationships between lung surfactant composition, monolayer morphology, and monolayer physical parameters such as minimum surface tension, spreading, viscosity, etc.     

Structure prediction of cyclic peptides by molecular dynamics + machine learning

Recent computational methods have made strides in discovering well-structured cyclic peptides that preferentially populate a single conformation. However, many successful cyclic-peptide therapeutics adopt multiple conformations in solution. In fact, the chameleonic properties of some cyclic peptides are likely responsible for their high cell membrane permeability. Thus, we require the ability to predict complete structural ensembles for cyclic peptides, including the majority of cyclic peptides that have broad structural ensembles, to significantly improve our ability to rationally design cyclic-peptide therapeutics. Here, we introduce the idea of using molecular dynamics simulation results to train machine learning models to enable efficient structure prediction for cyclic peptides. Using molecular dynamics simulation results for several hundred cyclic pentapeptides as the training datasets, we developed machine-learning models that can provide molecular dynamics simulation-quality predictions of structural ensembles for all the hundreds of thousands of sequences in the entire sequence space. The prediction for each individual cyclic peptide can be made using less than 1 second of computation time. Even for the most challenging classes of poorly structured cyclic peptides with broad conformational ensembles, our predictions were similar to those one would normally obtain only after running multiple days of explicit-solvent molecular dynamics simulations. The resulting method, termed StrEAMM (Structural Ensembles Achieved by Molecular Dynamics and Machine Learning), is the first technique capable of efficiently predicting complete structural ensembles of cyclic peptides without relying on additional molecular dynamics simulations, constituting a seven-order-of-magnitude improvement in speed while retaining the same accuracy as explicit-solvent simulations.

The StrEAMM method enables predicting the structural ensembles of cyclic peptides that adopt multiple conformations in solution.     

The role of nucleophile--electrophile interactions in the unimolecular and bimolecular gas-phase ion chemistry of peptides and related systems

This account describes the experimental tools (multi-stage mass spectrometric experiments, isotopic and structural labelling, kinetics and theoretical modelling) and physical organic concepts (influence of charge, the intermediacy of ion-molecule complexes, etc.) that can be used to unravel the mechanisms of gas-phase unimolecular and bimolecular ionic reactions of peptides. The role that nucleophile-electrophile interactions play in charge-directed reactions is highlighted for both unimolecular fragmentations (examples are illustrated for protonated sulfur-containing amino acids and peptides) and bimolecular ion-molecule reactions which cleave peptide bonds.     

Some advances in plant stress physiology and their implications in the systems biology era

The study for biointerfaces at different scales in the past years has pricked up the march of biological sciences, in which biomembrane concept and its characteristics, receptor proteins, ion channel proteins, LEA proteins, calcium and newly recognized second messengers, ROS, MAPKs and their related sensors and new genes in osmoregulation, signal transduction, and other aspects have been understood fully, widening area of understanding the extensive interactions from biosystem and biointerfaces. The related discipline, plant stress physiology, especially, crop stress physiology has gained much attention world widely, the important reason of which is from the reducing quality of global ecoenvironment and decreasing food supply. This short review will place a stress on the recent progresses in plant stress physiology, combined with the new results from our State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau.     

The role of memory effects in scholastics approach to collinear diatom—diatom collisions

The role of memory effects in the stochastic approach to vibrational—vibrational transitions in collinear diatom—diatom collisions is studied. It is shown that with the help of a new recurrence relation for Clebsch—Gordan coefficients we were able to solve exactly a non-markovian master equation for a model hamiltonian. The derived solution for probabilities of V—V transitions is compared with markovian as well as exact semiclassical results over a wide range of velocities of the colliding molecules. We have found a substantial improvement of markovian results, both qualitative and quantitative, when the non-markovian effects have been included in the stochastic theory. This is in contrast with a recent study by King and Schatz who got for a restricted V—T model more accurate probabilities from the markovian approach than from the non-markovian one. The reasons for this are also discussed.     

Investigation into stress recovery behavior of shape memory polyurethane fiber

In this work, the stress recovery behavior of shape memory polyurethane (SMPU) fiber was investigated. The as‐spun SMPU fibers were subjected to various programing‐recovery conditions. It was observed that recovering at 100 °C generated higher recovery stress than recovering at 150 °C. It was also found that, while hot‐drawn programed fiber has higher recovery stress than cold‐drawn programed fiber if recovered at 100 °C, cold‐drawn programed fiber has higher stabilized recovery stress than hot‐drawn programed counterpart when recovered at 150 °C. A morphological model was proposed based on the results from differential scanning calorimetry, Fourier transform infrared spectrometry, and X‐ray diffraction to understand the physics behind the different stress recovery behaviors. It is found that SMPU experiences different phase transitions and phase separations under different programing and stress recovery conditions. It is concluded that the two sequential phase separations taking place at 100 and 150 °C are primarily responsible for the differences in the stress recovery behavior. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1429–1440     

The role of the βAsp residue in copper(II) binding by modified peptides

The synthesis and binding abilities of peptides containing β-amino acids towards Cu(II) ions are presented. The peptides studied were: Ala-βAsp-Ser-Gly and Arg-Lys-βAsp-Val-Tyr. Potentiometric titrations were carried out to establish the stoichiometry of the resulting metal-ligand complexes. The copper(II) coordination mode of the complexes was investigated by performing detailed spectroscopic analyses (UV–Vis, CD) in strict correlation with potentiometric measurements. The results obtained on the β-peptides studied allowed the characterization of the influence of this structural modification on the coordination abilities of the peptides. Moreover, the role of the α-Asp position in the peptide chain was also described.     

4(R/S)-Guanidinylprolyl collagen peptides: on-resin synthesis, complexation with plasmid DNA, and the role of peptides in enhancement of transfection

Chimeric collagen peptides containing cationic 4(R/S)-guanidinylproline are synthesized by in situ amidinylation of 4(R/S)-aminoproline residues. These peptides uniquely enhance the transfection efficiency of GFP-encoded plasmid DNA (pRmHa3-GFP) into cells through efficient DNA condensation resulting from nonspecific electrostatic interactions of cationic guanidino groups and localize in subcytoplasmic organelles.