The Molecular Footprint of Peptides on the Surface of Ultrasmall Gold Nanoparticles (2 nm) Is Governed by Steric Demand.

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone. The particles were characterized by UV spectroscopy, differential centrifugal sedimentation (DCS), high-resolution transmission electron microscopy (HRTEM), and small-angle X-ray scattering (SAXS). This confirmed the uniform metal core (2 nm diameter). The hydrodynamic diameter was probed by 1H-DOSY NMR spectroscopy and showed an increase in thickness of the hydrated peptide layer with increasing peptide size (up to 1.4 nm for heptapeptides; 0.20 nm per amino acid in the peptide). 1H NMR spectroscopy of water-dispersed nanoparticles showed the integrity of the peptides and the effect of the metal core on the peptide. Notably, the NMR signals were very broad near the metal surface and became increasingly narrow in a distance. In particular, the methyl groups of alanine can be used as probe for the resolution of the NMR spectra. The number of peptide ligands on each nanoparticle was determined using quantitative 1H NMR spectroscopy. It decreased with increasing peptide length from about 100 for a dipeptide to about 12 for a heptapeptide, resulting in an increase of the molecular footprint from about 0.1 to 1.1 nm2.

Peptide Self-Assembly into Amyloid Fibrils: Unbiased All-Atom Simulations.

Protein self-assembly plays an important role in biological systems, accounting for the formation of mesoscopic structures that can be highly symmetric as in the capsid of viruses or disordered as in molecular condensates or exhibit a one-dimensional fibrillar morphology as in amyloid fibrils. Deposits of the latter in tissues of individuals with degenerative diseases like Alzheimer's and Parkinson's has motivated extensive efforts to understand the sequence of molecular events accounting for their formation. These studies aim to identify on-pathway intermediates that may be the targets for therapeutic intervention. This detailed knowledge of fibril formation remains obscure, in part due to challenges with experimental analyses of these processes. However, important progress is being achieved for short amyloid peptides due to advances in our ability to perform completely unbiased all-atom simulations of the self-assembly process. This perspective discusses recent developments, their implications, and the hurdles that still need to be overcome to further advance the field.

Ordered mesoporous silicas for potential applications in solid vaccine formulations.

In an effort to develop efficient vaccine formulations, the use of ordered mesoporous silica (SBA-15) as an antigen carrier has been investigated. SBA-15 has required properties such as high surface area and pore volume, including narrow pore size distribution to protect antigens inside its matrix. This study aimed to examine the impact of solvent removal methods, specifically freeze-drying and evaporation on the intrinsic properties of an immunogenic complex. The immunogenic complexes, synthesized and incorporated with BSA, were characterized by various physicochemical techniques. Small Angle X-ray Scattering measurements revealed the characteristic reflections associated to pure SBA-15, indicating the preservation of the silica mesostructured following BSA incorporation and the formation of BSA aggregates within the macropore region. Nitrogen Adsorption Isotherm measurements demonstrated a decrease in surface area and pore volume for all samples, indicating that the BSA was incorporated into the SBA-15 matrix. Fluorescence spectroscopy evidenced that the tryptophan residues in BSA inside SBA-15 or in solution displayed similar spectra, showing the preservation of the aromatic residues' environment. The Circular Dichroism spectra of BSA in both conditions suggest the preservation of its native secondary structure after the encapsulation process. The immunogenic analysis with the detection of anti-BSA IgG did not give any significant difference between the non-dried, freeze-dried or evaporated groups. However, all groups containing BSA and SBA-15 showed results almost three times higher than the groups with pure BSA (control group). These facts indicate that none of the BSA incorporation methods interfered with the immunogenicity of the complex. In particular, the freeze-dried process is regularly used in the pharmaceutical industry, therefore its adequacy to produce immunogenic complexes was proved Furthermore, the results showed that SBA-15 increased the immunogenic activity of BSA.

Nucleation and Growth of Amyloid Fibrils.

The formation of amyloid fibrils is a complex phenomenon that remains poorly understood at the atomic scale. Herein, we perform extended unbiased all-atom simulations in explicit solvent of a short amphipathic peptide to shed light on the three mechanisms accounting for fibril formation, namely, nucleation via primary and secondary mechanisms, and fibril growth. We find that primary nucleation takes place via the formation of an intermediate state made of two laminated ß-sheets oriented perpendicular to each other. The amyloid fibril spine subsequently emerges from the rotation of these ß-sheets to account for peptides that are parallel to each other and perpendicular to the main axis of the fibril. Growth of this spine, in turn, takes place via a dock-and-lock mechanism. We find that peptides dock onto the fibril tip either from bulk solution or after diffusing on the fibril surface. The latter docking pathway contributes significantly to populate the fibril tip with peptides. We also find that side chain interactions drive the motion of peptides in the lock phase during growth, enabling them to adopt the structure imposed by the fibril tip with atomic fidelity. Conversely, the docked peptide becomes trapped in a local free energy minimum when docked-conformations are sampled randomly. Our simulations also highlight the role played by nonpolar fibril surface patches in catalyzing and orienting the formation of small cross-ß structures. More broadly, our simulations provide important new insights into the pathways and interactions accounting for primary and secondary nucleation as well as the growth of amyloid fibrils.

Ultrastructure and Surface Composition of Glutathione-Terminated Ultrasmall Silver, Gold, Platinum, and Alloyed Silver-Platinum Nanoparticles (2 nm).

Alloyed ultrasmall silver-platinum nanoparticles (molar ratio Ag:Pt = 50:50) were prepared and compared to pure silver, platinum, and gold nanoparticles, all with a metallic core diameter of 2 nm. They were surface-stabilized by a layer of glutathione (GSH). A comprehensive characterization by high-resolution transmission electron microscopy (HRTEM), electron diffraction (ED), X-ray diffraction (XRD), small-angle X-ray scattering (SAXS), differential centrifugal sedimentation (DCS), and UV spectroscopy showed their size both in the dry and in the water-dispersed state (hydrodynamic diameter). Solution NMR spectroscopy (1H, 13C, COSY, HSQC, HMBC, and DOSY) showed the nature of the glutathione shell including the number of GSH ligands on each nanoparticle (about 200 with a molecular footprint of 0.063 nm2 each). It furthermore showed that there are at least two different positions for the GSH ligand on the gold nanoparticle surface. Platinum strongly reduced the resolution of the NMR spectra compared to silver and gold, also in the alloyed nanoparticles. X-ray photoelectron spectroscopy (XPS) showed that silver, platinum, and silver-platinum particles were at least partially oxidized to Ag(+I) and Pt(+II), whereas the gold nanoparticles showed no sign of oxidation. Platinum and gold nanoparticles were well crystalline but twinned (fcc lattice) despite the small particle size. Silver was crystalline in electron diffraction but not in X-ray diffraction. Alloyed silver-platinum nanoparticles were almost fully amorphous by both methods, indicating a considerable internal disorder.

Self-assembly of perovskite nanoplates in colloidal suspensions.

In recent years, perovskite nanocrystal superlattices have been reported with collective optical phenomena, offering a promising platform for both fundamental science studies and device engineering. In this same avenue, superlattices of perovskite nanoplates can be easily prepared on different substrates, and they too present an ensemble optical response. However, the self-assembly and optical properties of these aggregates in solvents have not been reported to date. Here, we report on the conditions for this self-assembly to occur and show a simple strategy to induce the formation of these nanoplate stacks in suspension in different organic solvents. We combined wide- and small-angle X-ray scattering and scanning transmission electron microscopy to evaluate CsPbBr3 and CsPbI3 perovskite nanoplates with different thickness distributions. We observed the formation of these stacks by changing the concentration of nanoplates and the viscosity of the colloidal suspensions, without the need for antisolvent addition. We found that, in hexane, the concentration for the formation of the stacks is rather high and approximately 80 mg mL-1. In contrast, in decane, dodecane, and hexadecane, we observe a much easier self-assembly of the nanoplates, presenting a clear correlation between the degree of aggregation and viscosity. We, then, discuss the impact of the self-assembly of perovskite nanoplates on Förster resonant energy transfer. Our predictions suggest an energy transfer efficiency higher than 50% for all the donor-acceptor systems evaluated. In particular, we demonstrate how the aggregation of these particles in hexadecane induces FRET for CsPbBr3 nanowires. For the n = 2 nanowires (donor) to the n = 3 nanowires (acceptor), the FRET rate was found to be 4.1 ns-1, with an efficiency of 56%, in agreement with our own predictions.

The role of hydrophobic interactions in the molten globule state of globular protein modulated by surfactants.

In order to highlight the role of hydrophobic interactions in the molten globule (MG) state of globular protein modulated by surfactants, the interactions of bovine α-lactalbumin (α-LA) with alkyl trimethylammonium bromides (CnTAB, n = 10, 12, 14, and 16) have been studied by experimental and theoretical techniques. Isothermal titration calorimetry (ITC) showed that the enthalpy changes (ΔH) and area of the enthalpogram increased with increasing the chain length of CnTAB. The result of fluorescence, circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectrum suggested that C10TAB and C12TAB unfolded α-LA partially, C14TAB reconstructed protein with a native-like secondary structure content, and C16TAB induced an MG state α-LA. The SAXS results confirmed that the tertiary structure of α-LA was disrupted by C16TAB forming an MG state complex with a micelle-like structure even at the surfactants concentrations below CMC. As indicated by MD results, the ß-domain and unstructured region(s) were involved in the MG state α-LA modulated by CnTAB. This work not only provides molecular insights into the role of hydrophobic interactions in the MG state of a globular protein but also helps understand the mechanism of preparing α-LA based biomacromolecule modulated by hydrophobic interactions.

Peptide-Membrane Binding: Effects of the Amino Acid Sequence.

An understanding of how the amino acid sequence affects the interaction of peptides with lipid membranes remains mostly unknown. This type of knowledge is required to rationalize membrane-induced toxicity of amyloid peptides and to design peptides that can interact with lipid bilayers. Here, we perform a systematic study of how variations in the sequence of the amphipathic Ac-(FKFE)2-NH2 peptide affect its interaction with zwitterionic lipid bilayers using extensive all-atom molecular dynamics simulations in explicit solvent. Our results show that peptides with a net positive charge bind more frequently to the lipid bilayer than neutral or negatively charged sequences. Moreover, neutral amphipathic peptides made with the same numbers of phenylalanine (F), lysine (K), and glutamic (E) amino acids at different positions in the sequence differ significantly in their frequency of binding to the membrane. We find that peptides bind with a higher frequency to the membrane if their positive lysine side chains are more exposed to the solvent, which occurs if they are located at the extremity (as opposed to the middle) of the sequence. Non-polar residues play an important role in accounting for the adsorption of peptides onto the membrane. In particular, peptides made with less hydrophobic non-polar residues (e.g., valine and alanine) are significantly less adsorbed to the membrane compared to peptides made with phenylalanine. We also find that sequences where phenylalanine residues are located at the extremities of the peptide have a higher tendency to be adsorbed.

Atomic Insights into Amyloid-Induced Membrane Damage.

Amphipathic peptides can cause biological membranes to leak either by dissolving their lipid content via a detergent-like mechanism or by forming pores on the membrane surface. These modes of membrane damage have been related to the toxicity of amyloid peptides and to the activity of antimicrobial peptides. Here, we perform the first all-atom simulations in which membrane-bound amphipathic peptides self-assemble into ß-sheets that subsequently either form stable pores inside the bilayer or drag lipids out of the membrane surface. An analysis of these simulations shows that the acyl tail of lipids interact strongly with non-polar side chains of peptides deposited on the membrane. These strong interactions enable lipids to be dragged out of the bilayer by oligomeric structures accounting for detergent-like damage. They also disturb the orientation of lipid tails in the vicinity of peptides. These distortions are minimized around pore structures. We also show that membrane-bound ß-sheets become twisted with one of their extremities partially penetrating the lipid bilayer. This allows peptides on opposite leaflets to interact and form a long transmembrane ß-sheet, which initiates poration. In simulations, where peptides are deposited on a single leaflet, the twist in ß-sheets allows them to penetrate the membrane and form pores. In addition, our simulations show that fibril-like structures produce little damage to lipid membranes, as non-polar side chains in these structures are unavailable to interact with the acyl tail of lipids.

Changes in lipoproteins associated with lipid-lowering and antiplatelet strategies in patients with acute myocardial infarction.

BACKGROUND: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. METHODS: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. RESULTS: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. CONCLUSIONS: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.

Improved Design for Hardware Implementation of Graph-Based Large Margin Classifiers for Embedded Edge Computing.

The number of connected embedded edge computing Internet of Things (IoT) devices has been increasing over the years, contributing to the significant growth of available data in different scenarios. Thereby, machine learning algorithms arise to enable task automation and process optimization based on those data. However, due to some learning methods' computational complexity implementing geometric classifiers, it is a challenge to map these on embedded systems or devices with limited resources in size, processing, memory, and power, to accomplish the desired requirements. This hampers the applicability of these methods to complex industrial embedded edge applications. This work evaluates strategies to reduce classifiers' implementation costs based on the CHIP-clas model, independent of hyperparameter tuning and optimization algorithms. The proposal aims to evaluate the tradeoff between numerical precision and model performance and analyze the hardware implementations of a distance-based classifier. Two 16 -b floating-point formats were compared to the 32 -b floating-point precision implementation. Also, a new hardware architecture was developed and then compared to the state-of-the-art reference. The results indicate that the model is robust to low precision computation, providing statistically equivalent results compared to the baseline model, also pointing out statistically equivalent performance and a global speed-up factor of approx 4.39 in processing time.

Impact of silver nanoparticles size on SERS for detection and identification of filamentous fungi.

Using the proper size of nanoparticles as an active substrate, Surface-enhanced Raman scattering (SERS) can provide a reliable technique for detecting and identifying fungi, including Alternaria alternata, Aspergillus flavus, Fusarium verticilliodes, and Aspergillus parasiticus that have been associated to biodeterioration and biodegradation of cultural heritage materials. In this research spherical silver nanoparticles (AgNPs) of average size of 10, 30 and 60 nm were synthesized using the wet chemical method with good yield and their size and shape distributions were examined using small-angle X-ray scattering (SAXS). The protocol for fungi sample preparation proved to be critical for producing high-quality and reproducible SERS spectra. We found that the effect of AgNPs on SERS signal enhancement is size dependent under the same experimental conditions; the SERS intensity of fungal strains using 60 nm achieved up to 2.3x105 enhancement, about twice as intense as those produced with 30 nm, and 10 nm produced a minor broad weak peak barely discernible around 1400 cm-1, similar to the NR spectra profile in the 550-1700 cm-1 spectral region, and the SERS signals using 60 nm showed high reproducibility, with less than 20% variance. Furthermore, we used principal component analysis (PCA) to statistically classify the SERS spectrum into four separate clusters with 99 percent variability so that the four fungal strains could be clearly detected and identified. The SERS technique, in combination with the PCA developed in this study, provides a simple, rapid, accurate, and cost-effective analytical tool for detecting and identifying filamentous fungal strains.

The changing face of SDS denaturation: Complexes of Thermomyces lanuginosus lipase with SDS at pH 4.0, 6.0 and 8.0.

HYPOTHESIS: Lipases are widely used in the detergent industry and must withstand harsh conditions involving both anionic and zwitterionic surfactants at alkaline pH. Thermomyces lanuginosus lipase (TlL) is often used and stays active at high concentrations of the anionic surfactant sodium dodecyl sulfate (SDS) at pH 8.0, but is sensitive to SDS at pH 6.0 and below. We propose that enhanced stability at pH 8.0 results from a structurally distinct complex formation with SDS. EXPERIMENTS: We use small-angle X-ray scattering (SAXS) to elucidate structures of TlL:SDS at pH 4.0, 6.0, and 8.0 and further investigate the complexes at pH 8.0 using hydrogen/deuterium exchange mass spectrometry (HDX-MS). FINDINGS: At pH 4.0, large dense aggregates are formed at low [SDS], which become gradually less dense at higher [SDS], resulting in a core-shell structure. At pH 6.0, SDS induces a TlL dimer and forms a hemi-micelle along the side of the dimer. At higher [SDS], TlL adopts a core-shell structure. At pH 8.0, TlL forms a dimer with a SDS hemi-micelle but avoids a core-shell structure and maintains activity. Three helices are identified as SDS anchor points. This study provides important structural insight into the stability of TlL towards SDS under alkaline conditions.

Functionalized mesoporous silicas SBA-15 for heterogeneous photocatalysis towards CECs removal from secondary urban wastewater.

The photocatalytic activity of TiO2 nanoparticles (NPs) supported on mesoporous silica SBA-15 (TiO2/SBA-15) was evaluated for the photodegradation of sulfadiazine (SDZ), as target contaminant of emerging concern (CEC), using either pure water solutions (PW) or a real secondary urban wastewater (UWW) spiked with SDZ. For this purpose, TiO2/SBA-15 samples with 10, 20 and 30% TiO2 (w/w) were prepared by the sol-gel post synthetic method on pre-formed SBA-15, using titanium (IV) isopropoxide as a precursor. The TiO2/SBA-15 materials were characterized by HRTEM, SAXS and XRD, nitrogen adsorption isotherms and UV-vis diffuse reflectance spectroscopy. TiO2 NPs were shown to be attached onto the external surface, decorating the SBA-15 particles. The TiO2/SBA-15 catalysts were active in SDZ photodegradation using the annular FluHelik photoreactor, when irradiated with UVA light. The 30% TiO2/SBA-15 sample presented the best performance in optimization tests performed using PW, and it was further used for the tests with UWW. The photocatalytic activity of 30% TiO2/SBA-15 was higher (56% SDZ degradation) than that of standard TiO2-P25 (32% SDZ degradation) in the removal of SDZ spiked in the UWW ([SDZ] = 2 mg L-1). The photodegradation of SDZ with 30% TiO2/SBA-15 eached 90% for UWW spiked with a lower SDZ concentration ([SDZ] = 40 µg L-1). Aside of SDZ, a suit of 65 other CECs were also identified in the UWW sample using LC-MS spectrometry. A fast-screening test showed the heterogeneous photocatalytic system was able to remove most of the detected CECs from UWW, by either adsorption and/or photocatalysis.

Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy.

Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells.

Molecular insights on CALX-CBD12 interdomain dynamics from MD simulations, RDCs, and SAXS.

Na+/Ca2+ exchangers (NCXs) are secondary active transporters that couple the translocation of Na+ with the transport of Ca2+ in the opposite direction. The exchanger is an essential Ca2+ extrusion mechanism in excitable cells. It consists of a transmembrane domain and a large intracellular loop that contains two Ca2+-binding domains, CBD1 and CBD2. The two CBDs are adjacent to each other and form a two-domain Ca2+ sensor called CBD12. Binding of intracellular Ca2+ to CBD12 activates the NCX but inhibits the NCX of Drosophila, CALX. NMR spectroscopy and SAXS studies showed that CALX and NCX CBD12 constructs display significant interdomain flexibility in the apo state but assume rigid interdomain arrangements in the Ca2+-bound state. However, detailed structure information on CBD12 in the apo state is missing. Structural characterization of proteins formed by two or more domains connected by flexible linkers is notoriously challenging and requires the combination of orthogonal information from multiple sources. As an attempt to characterize the conformational ensemble of CALX-CBD12 in the apo state, we applied molecular dynamics (MD) simulations, NMR (1H-15N residual dipolar couplings), and small-angle x-ray scattering (SAXS) data in a combined strategy to select an ensemble of conformations in agreement with the experimental data. This joint approach demonstrated that CALX-CBD12 preferentially samples closed conformations, whereas the wide-open interdomain arrangement characteristic of the Ca2+-bound state is less frequently sampled. These results are consistent with the view that Ca2+ binding shifts the CBD12 conformational ensemble toward extended conformers, which could be a key step in the NCXs' allosteric regulation mechanism. This strategy, combining MD with NMR and SAXS, provides a powerful approach to select ensembles of conformations that could be applied to other flexible multidomain systems.

Sleep and self-control: A systematic review and meta-analysis.

Controlling impulses and overcoming temptations (i.e., self-control) are key aspects of living a productive life. There is a growing yet disperse literature indicating that sleep is an important predictor of self-control. The goal of this meta-analysis is to empirically integrate the findings from multiple literatures, and investigate whether sleep quality, and sleep duration predict self-control. To provide a thorough understanding of the proposed relationships, this meta-analysis also investigated potential differences between the level of analysis (between-individual vs. within-individual), research design (experiment vs. correlation; and cross-sectional vs. time-lagged), and types of measure (subjective vs. objective for sleep and self-control). A systematic review was conducted through ABI/Inform (including PsycInfo), ERIC, ProQuest Dissertation & Theses, PubMed, and Psychology Database using keywords related to self-control and sleep. Sixty-one independent studies met the inclusion criteria. The results, in general, suggest that sleep quality (between-individual 0.26, CI 0.21; 0.31; and within-individual 0.35, CI 0.24; 0.45), and sleep duration (between-individual 0.14, CI 0.07; 0.21; and within-individual 0.20, CI 0.09; 0.31) are all related to self-control. Given the impact of self-control on how individuals live productive lives, a future research agenda should include a deeper investigation in the causal process (potentially via prefrontal cortex activity) linking sleep and self-control, and an examination of the moderators (individual and contextual variables) that could impact the relationship between sleep and self-control.

Head pre-cooling improves 5-km time-trial performance in male amateur runners in the heat.

This study aimed to evaluate the effect of head pre-cooling on the 5-km time-trial performance of amateur runners in the heat. In a counterbalanced design, 15 male amateur runners (22.6 ± 3.5 y; VO2 max in heat 42.3 ± 4.4 mLO2 /kg/min) completed two 5-km time trials performed in the heat (35°C, 50% relative humidity). In one trial (HCOOL), participants underwent 20 min of head cooling in a temperate environment (23°C, 70% relative humidity) prior to exercise. In another trial (CON), exercise was preceded by 20 min of rest under the same temperature conditions. Exercise time was shorter in HCOOL (25 min and 36 s ± 3 min) compared to CON (27 ± 3 min; p = 0.02). Rectal temperature was reduced during the pre-exercise intervention in HCOOL (p < 0.001), but not in CON (p = 0.55). Relative changes in rectal temperature and mean head temperature were lower throughout HCOOL when compared with CON condition (p = 0.005 and p = 0.022, respectively). Mean skin temperature, heart rate, and rating of perceived exertion did not differ between HCOOL and CON conditions throughout exercise (p = 0.20, p = 0.52 and 0.31, respectively). Thermal comfort was lower in HCOOL condition in pre-exercise (p = 0.014) with no differences observed throughout exercise (p = 0.61). 5-km running performance in a hot environment was improved after a 20-min head cooling intervention, suggesting that this method may be practical as pre-cooling strategy and easily administered to both professional and amateur runners alike.

Binding Mechanisms of Amyloid-like Peptides to Lipid Bilayers and Effects of Divalent Cations.

In several neurodegenerative diseases, cell toxicity can emerge from damage produced by amyloid aggregates to lipid membranes. The details accounting for this damage are poorly understood including how individual amyloid peptides interact with phospholipid membranes before aggregation. Here, we use all-atom molecular dynamics simulations to investigate the molecular mechanisms accounting for amyloid-membrane interactions and the role played by calcium ions in this interaction. Model peptides known to self-assemble into amyloid fibrils and bilayer made from zwitterionic and anionic lipids are used in this study. We find that both electrostatic and hydrophobic interactions contribute to peptide-bilayer binding. In particular, the attraction of peptides to lipid bilayers is dominated by electrostatic interactions between positive residues and negative phosphate moieties of lipid head groups. This attraction is stronger for anionic bilayers than for zwitterionic ones. Hydrophobicity drives the burial of nonpolar residues into the interior of the bilayer producing strong binding in our simulations. Moreover, we observe that the attraction of peptides to the bilayer is significantly reduced in the presence of calcium ions. This is due to the binding of calcium ions to negative phosphate moieties of lipid head groups, which leaves phospholipid bilayers with a net positive charge. Strong binding of the peptide to the membrane occurs less frequently in the presence of calcium ions and involves the formation of a "Ca2+ bridge".

Methane Clathrate Formation is Catalyzed and Kinetically Inhibited by the Same Molecule: Two Facets of Methanol.

Here, we perform molecular dynamics simulations to provide atomic-level insights into the dual roles of methanol in enhancing and delaying the rate of methane clathrate hydrate nucleation. Consistent with experiments, we find that methanol slows clathrate hydrate nucleation above 250 K but promotes clathrate formation at temperatures below 250 K. We show that this behavior can be rationalized by the unusual temperature dependence of the methane-methanol interaction in an aqueous solution, which emerges due to the hydrophobic effect. In addition to its antifreeze properties at temperatures above 250 K, methanol competes with water to interact with methane prior to the formation of clathrate nuclei. Below 250 K, methanol encourages water to occupy the space between methane molecules favoring clathrate formation and it may additionally promote water mobility.