Is it better to combine predictions?

We have compared the accuracy of the individual protein secondarystructure prediction methods: PHD, DSC, NNSSP and Predator againstthe accuracy obtained by combing the predictions of the methods.A range of ways of combing predictions were tested: voting,biased voting, linear discrimination, neural networks and decisiontrees. The combined methods that involve `learning' (the non-votingmethods) were trained using a set of 496 non-homologous domains;this dataset was biased as some of the secondary structure predictionmethods had used them for training. We used two independenttest sets to compare predictions: the first consisted of 17non-homologous domains from CASP3 (Third Community Wide Experimenton the Critical Assessment of Techniques for Protein StructurePrediction); the second set consisted of 405 domains that wereselected in the same way as the training set, and were non-homologousto each other and the training set. On both test datasets themost accurate individual method was NNSSP, then PHD, DSC andthe least accurate was Predator; however, it was not possibleto conclusively show a significant difference between the individualmethods. Comparing the accuracy of the single methods with thatobtained by combing predictions it was found that it was betterto use a combination of predictions. On both test datasets itwas possible to obtain a ~3% improvement in accuracy by combingpredictions. In most cases the combined methods were statisticallysignificantly better (at P = 0.05 on the CASP3 test set, andP = 0.01 on the EBI test set). On the CASP3 test dataset therewas no significant difference in accuracy between any of thecombined method of prediction: on the EBI test dataset, lineardiscrimination and neural networks significantly outperformedvoting techniques. We conclude that it is better to combinepredictions.     

Intracellular imaging of nanoparticles: Is it an elemental mistake to believe what you see?

In order to understand how nanoparticles (NPs <100 nm) interact with cellular systems, potentially causing adverse effects, it is important to be able to detect and localize them within cells. Due to the small size of NPs, transmission electron microscopy (TEM) is an appropriate technique to use for visualizing NPs inside cells, since light microscopy fails to resolve them at a single particle level. However, the presence of other cellular and non-cellular nano-sized structures in TEM cell samples, which may resemble NPs in size, morphology and electron density, can obstruct the precise intracellular identification of NPs. Therefore, elemental analysis is recommended to confirm the presence of NPs inside the cell. The present study highlights the necessity to perform elemental analysis, specifically energy filtering TEM, to confirm intracellular NP localization using the example of quantum dots (QDs). Recently, QDs have gained increased attention due to their fluorescent characteristics, and possible applications for biomedical imaging have been suggested. Nevertheless, potential adverse effects cannot be excluded and some studies point to a correlation between intracellular particle localization and toxic effects. J774.A1 murine macrophage-like cells were exposed to NH₂ polyethylene (PEG) QDs and elemental co-localization analysis of two elements present in the QDs (sulfur and cadmium) was performed on putative intracellular QDs with electron spectroscopic imaging (ESI). Both elements were shown on a single particle level and QDs were confirmed to be located inside intracellular vesicles. Nevertheless, ESI analysis showed that not all nano-sized structures, initially identified as QDs, were confirmed. This observation emphasizes the necessity to perform elemental analysis when investigating intracellular NP localization using TEM.     

Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand—Relevance to Subarachnoid Hemorrhage

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and may be responsible for important complications of SAH. Signaling by Toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NFκB) in microglia plays a critical role in neuronal damage after SAH. Three molecules derived from erythrocyte breakdown have been postulated to be endogenous TLR4 ligands: methemoglobin (metHgb), heme and hemin. However, poor water solubility of heme and hemin, and lipopolysaccharide (LPS) contamination have confounded our understanding of these molecules as endogenous TLR4 ligands. We used a 5-step process to obtain highly purified LPS-free metHgb, as confirmed by Fourier Transform Ion Cyclotron Resonance mass spectrometry and by the Limulus amebocyte lysate assay. Using this preparation, we show that metHgb is a TLR4 ligand at physiologically relevant concentrations. metHgb caused time- and dose-dependent secretion of the proinflammatory cytokine, tumor necrosis factor α (TNFα), from microglial and macrophage cell lines, with secretion inhibited by siRNA directed against TLR4, by the TLR4-specific inhibitors, Rs-LPS and TAK-242, and by anti-CD14 antibodies. Injection of purified LPS-free metHgb into the rat subarachnoid space induced microglial activation and TNFα upregulation. Together, our findings support the hypothesis that, following SAH, metHgb in the subarachnoid space can promote widespread TLR4-mediated neuroinflammation.     

Is It Time to Standardize Ethics Guiding the Peer Review Process?

While most scientific journals have well defined ethics requirements for authors, very few journals explicitly specify the ethics standards that govern the actions of editors, editorial board members, and reviewers. We believe it is time to create a standardized policy for all medical and scientific journals that guides the ethical conduct of all stakeholders in the peer review process.     

Is Fine‐Grained Simulation Able to Propose New Polyelectrolyte Membranes?

An extensive understanding in the molecular motions that occur in Nafion^® should lead to important development of improved proton exchange membrane for use in fuel cells (PEMFC). As water molecules are added in the system, changes within the Nafion^® chain definitely take place. To visualize such a process, molecular dynamics is especially useful. Can information gained at this level of details be useful to propose new molecules, with ultimately better physical properties, such as higher proton conductivity? For this purpose, we first computed non‐bond parameters stemming from the study of the trifluorosufonic acid. They are inserted in the pcff force field. We then applied the procedure developed in our lab to extract the glass transition temperature of Nafion^® with different water uptakes. The plasticization effect is first confirmed, fostering a molecular analysis. The particular behavior of the sulfur‐sulfur distance is revealed, guiding the design of new monomers.     

Antiviral Effects of Animal Toxins: Is There a Way to Drugs?

Viruses infect all types of organisms, causing viral diseases, which are very common in humans. Since viruses use the metabolic pathways of their host cells to replicate, they are difficult to eradicate without affecting the cells. The most effective measures against viral infections are vaccinations and antiviral drugs, which selectively inhibit the viral replication cycle. Both methods have disadvantages, which requires the development of new approaches to the treatment of viral diseases. In the study of animal venoms, it was found that, in addition to toxicity, venoms exhibit other types of biological activity, including an antiviral one, the first mention of which dates back to middle of the last century, but detailed studies of their antiviral activity have been conducted over the past 15 years. The COVID-19 pandemic has reinforced these studies and several compounds with antiviral activity have been identified in venoms. Some of them are very active and can be considered as the basis for antiviral drugs. This review discusses recent antiviral studies, the found compounds with high antiviral activity, and the possible mechanisms of their action. The prospects for using the animal venom components to create antiviral drugs, and the expected problems and possible solutions are also considered.     

Time to Say Goodbye to the 16 EPA PAHs? Toward an Up-to-Date Use of PACs for Environmental Purposes

The 16 EPA PAHs have played an exceptionally large role above all in environmental and analytical sciences in the last 40 years, but now there are good reasons to question their utility in many circumstances even though their use is so established and comfortable. Here we review the reasons why the list has been so successful and why sometimes it is seen as less relevant. Three groups of polycyclic aromatic compounds (PAC) are missing: larger and highly relevant PAHs, alkylated PACs, and compounds containing heteroatoms. Attempts to improve the situation for certain matrixes are known and here: (1) an updated list of PAHs (including the 16 EPA PAHs) for the evaluation of the toxicity in the environment (40 EnvPAHs); (2) a list of 23 NSO-heterocyclic compounds and 6 heterocyclic metabolites; and (3) lists of 10 oxy-PAHs and 10 nitro-PAHs are proposed for practical use in the future. A discussion in the scientific community about these lists is invited. Although the state of knowledge has improved dramatically since the introduction of the 16 EPA PAHs in the 1970s, this summary also shows that more research is needed about the toxicity, occurrence in the environment and chemical analysis, particularly of alkylated PAHs, higher molecular weight PAHs and substituted PACs such as amino-PAHs, cyano-PAHs, etc.. We also suggest that a long overdue discussion of an update of regulatory environmental PAH analysis is initiated.     

Enhancing surface heat transfer by carbon nanofins: towards an alternative to nanofluids?

Background  

Nanofluids are suspensions of nanoparticles and fibers which have recently attracted much attention because of their superior thermal properties. Nevertheless, it was proven that, due to modest dispersion of nanoparticles, such high expectations often remain unmet. In this article, by introducing the notion of nanofin, a possible solution is envisioned, where nanostructures with high aspect-ratio are sparsely attached to a solid surface (to avoid a significant disturbance on the fluid dynamic structures), and act as efficient thermal bridges within the boundary layer. As a result, particles are only needed in a small region of the fluid, while dispersion can be controlled in advance through design and manufacturing processes.     

It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Recently, using natural products as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians. In this review, the authors present the most recent randomized controlled trials (RCTs) and lines of evidence from animal models about the efficacy of nutraceutics in alleviating NAFLD. Among the most studied substances in the literature, the following molecules were chosen because of their presence in the literature of both clinical and preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain.     

Complexity of CO2 adsorption on nanoporous sulfur-doped carbons – Is surface chemistry an important factor?

Nanoporous S-doped carbon and its composites with graphite oxide were tested as adsorbents of CO₂ (1 MPa at 0 °C) after degassing either at 120 °C or 350 °C. The adsorption capacities were over 4 mmol/g at ambient pressure and 8 mmol/g at 0.9 MPa in spite of a low volume of micropores. The nitrogen adsorption experiments showed an increase in porosity upon an increase in the degassing temperature. The extent of this effect depends on the stability of surface groups. Interestingly, the CO₂ adsorption, especially at low pressure, was not affected. The good performance is due to the presence of ultramicropores similar in sizes to CO₂ molecule and to sulfur in various functionalities. Sulfur incorporated to aromatic rings enhances CO₂ adsorption via acid–base interactions in micropores. Moreover, sulfonic acids, sulfoxides and sulfones attract CO₂ via polar interactions. Hydrogen bonding of CO₂ with acidic groups on the surface can also play an important role in the CO₂ retention. These carbons have high potential for application as CO₂ removal media owing to their high degree of pore space utilization. The results obtained also show that high degassing temperatures might result in the decomposition of surface groups and thus in changes in surface interactions.     

Is Correction of Iron Deficiency a New Addition to the Treatment of the Heart Failure?

Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF patients). Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure.     

Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation

There is still no answer to the mechanism of penetration of AMP peptides through the membrane bilayer. Several mechanisms for such a process have been proposed. It is necessary to understand whether it is possible, using the molecular dynamics method, to determine the ability of peptides of different compositions and lengths to pass through a membrane bilayer. To explain the passage of a peptide through a membrane bilayer, a method for preparing a membrane phospholipid bilayer was proposed, and 656 steered molecular dynamics calculations were carried out for pulling 7 amyloidogenic peptides with antimicrobial potential, and monopeptides (homo-repeats consisting of 10 residues of the same amino acid: Poly (Ala), Poly (Leu), Poly (Met), Poly (Arg), and Poly (Glu)) with various sequences through the membrane. Among the 15 studied peptides, the peptides exhibiting the least force resistance when passing through the bilayer were found, and the maximum reaction occurred at the boundary of the membrane bilayer entry. We found that the best correlation between the maximum membrane reaction force and the calculated parameters corresponds to the instability index (the correlation coefficient is above 0.9). One of the interesting results of this study is that the 10 residue amyloidogenic peptides and their extended peptides, with nine added residue cell-penetrating peptides and four residue linkers, both with established antimicrobial activity, have the same bilayer resistance force. All calculated data are summarized and posted on the server.     

Is “Delayed Onset Muscle Soreness” a False Friend? The Potential Implication of the Fascial Connective Tissue in Post-Exercise Discomfort

Strenuous and unaccustomed exercise frequently lead to what has been coined “delayed onset muscle soreness” (DOMS). As implied by this term, it has been proposed that the associated pain and stiffness stem from micro-lesions, inflammation, or metabolite accumulation within the skeletal muscle. However, recent research points towards a strong involvement of the connective tissue. First, according to anatomical studies, the deep fascia displays an intimate structural relationship with the underlying skeletal muscle and may therefore be damaged during excessive loading. Second, histological and experimental studies suggest a rich supply of algogenic nociceptors whose stimulation evokes stronger pain responses than muscle irritation. Taken together, the findings support the hypothesis that DOMS originates in the muscle-associated connective tissue rather than in the muscle itself. Sports and fitness professionals designing exercise programs should hence consider fascia-oriented methods and techniques (e.g., foam rolling, collagen supplementation) when aiming to treat or prevent DOMS.     

Partial oxidation of methane to syngas over Co/MgO catalysts. Is it low temperature?

Co/MgO catalysts with high Co-loading (>28 wt%) are able to initiate the reaction of methane with oxygen at temperatures around 500 °C. High conversions of methane ( 70%) and very high selectivities for hydrogen and carbon monoxide ( 90%) are obtained at very high reactant gas space velocities (10⁵–10⁶ h^–1). The temperature of the catalyst at the conditions of partial oxidation of methane to form syngas was found to be extremely high (1200–1300 °C); it is about 600–850 °C higher than that previously reported by others. At these temperatures, high temperature homogeneous reactions may prevail. It is suggested that combustion of methane to carbon dioxide occurs on the catalyst with major heat release and that methane and water, respectively methane and carbon dioxide are reformed thermally in an endothermic reaction leading to syngas.