Methodology of materials discovery in complex metal hydrides using experimental and computational tools

We present a review of the experimental and theoretical methods used in the discovery of new metal–hydrogen materials systems for hydrogen storage applications. Rather than a comprehensive review of all new materials and methods used in the metal hydride community, we focus on a specific subset of successful methods utilizing theoretical crystal structure prediction methods, computational approaches for screening large numbers of compound classes, and medium-throughput experimental methods for the preparation of such materials. Monte Carlo techniques paired with a simplified empirical Hamiltonian provide crystal structure candidates that are refined using density functional theory. First-principle methods using high-quality structural candidates are further screened for an estimate of reaction energetics, decomposition enthalpies, and determination of reaction pathways. Experimental synthesis utilizes a compacted-pellet sintering technique under high-pressure hydrogen at elevated temperatures. Crystal structure determination follows from a combination of Rietveld refinements of diffraction patterns and first-principles computation of total energies and dynamical stability of competing structures. The methods presented within are general and applicable to a wide class of materials for energy storage.     

The effect of probiotics (Lactobacillus rhamnosus HN001, Lactobacillus paracasei LPC-37, and Lactobacillus acidophilus NCFM) on the availability of minerals from Dutch-type cheese

The use of probiotic cultures in the production of Dutch-type cheeses did not lead to significant changes in their chemical composition but it lowered their acidity. The availability of calcium and magnesium analyzed by in vitro enzymatic hydrolysis was 19 and 35%, respectively; the availability of phosphorus was significantly higher, at >90%. The use of probiotic cultures significantly increased the availability of calcium (~2.5%), phosphorus (~6%), and magnesium (~18%). The in vitro method supports accurate determination of the effect of the Lactobacillus spp. cultures on the availability of mineral compounds ingested with Dutch-type cheese.     

Toughening of syndiotactic polypropylene with chalk

We hypothesized that polymer crystal anisotropy is advantageous for toughening of polymer composites involving easy slip network of oriented crystalline layers around filler particles. To this end, composites of syndiotactic polypropylene (sPP) with high concentration of submicrometer calcium carbonate particles were prepared and examined because usual sPP crystals exhibit high packing anisotropy. The specific orientation of sPP lamellae around chalk grains was found, which is supposed to facilitate the plastic deformation of polymer matrices. The compression molded bars of the composite exhibited markedly higher Izod impact strength than those of neat sPP. Toughening was even enhanced in the injection molded composite, for which 4.5‐fold increase in the impact strength was achieved. Injection‐induced orientation of the disordered form I sPP crystals was enhanced in the composite. The injection molded tensile specimens exhibited also a good drawability. Debonding at chalk–sPP interface occurred both during the impact and tensile tests facilitating the plastic deformation of sPP matrix. Chalk did not have any significant influence on the thermal properties of the composites but it affected the rheological behavior, increasing the loss and storage moduli, and the viscosity. Highly filled sPP composite exhibited solid‐like behavior in a molten state with the storage modulus exceeding the loss modulus in the entire frequency range. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43651.     

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.     

The Effect of Long-Lasting Swimming on Rats Skeletal Muscles Energy Metabolism after Nine Days of Dexamethasone Treatment

This study investigates the effect of Dexamethasone (Dex) treatment on blood and skeletal muscle metabolites level and skeletal muscle activity of enzymes related to energy metabolism after long-duration swimming. To evaluate whether Dex treatment, swimming, and combining these factors act on analyzed data, rats were randomly divided into four groups: saline treatment non-exercise and exercise and Dex treatment non-exercised and exercised. Animals in both exercised groups underwent long-lasting swimming. The concentration of lipids metabolites, glucose, and lactate were measured in skeletal muscles and blood according to standard colorimetric and fluorimetric methods. Also, activities of enzymes related to aerobic and anaerobic metabolism were measured in skeletal muscles. The results indicated that Dex treatment induced body mass loss and increased lipid metabolites in the rats’ blood but did not alter these changes in skeletal muscles. Interestingly, prolonged swimming applied after 9 days of Dex treatment significantly intensified changes induced by Dex; however, there was no difference in skeletal muscle enzymatic activities. This study shows for the first time the cumulative effect of exercise and Dex on selected elements of lipid metabolism, which seems to be essential for the patient’s health due to the common use of glucocorticoids like Dex.     

Bifunctional Opioid/Melanocortin Peptidomimetics for Use in Neuropathic Pain: Variation in the Type and Length of the Linker Connecting the Two Pharmacophores

Based on the mechanism of neuropathic pain induction, a new type of bifunctional hybrid peptidomimetics was obtained for potential use in this type of pain. Hybrids consist of two types of pharmacophores that are connected by different types of linkers. The first pharmacophore is an opioid agonist, and the second pharmacophore is an antagonist of the pronociceptive system, i.e., an antagonist of the melanocortin-4 receptor. The results of tests in acute and neuropathic pain models of the obtained compounds have shown that the type of linker used to connect pharmacophores had an effect on antinociceptive activity. Peptidomimetics containing longer flexible linkers were very effective at low doses in the neuropathic pain model. To elucidate the effect of linker lengths, two hybrids showing very high activity and two hybrids with lower activity were further tested for affinity for opioid (mu, delta) and melanocortin-4 receptors. Their complexes with the target receptors were also studied by molecular modelling. Our results do not show a simple relationship between linker length and affinity for particular receptor types but suggest that activity in neuropathic pain is related to a proper balance of receptor affinity rather than maximum binding to any or all of the target receptors.     

Respiratory Abnormalities in Parkinson’s Disease: What Do We Know from Studies in Humans and Animal Models?

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease characterized by movement disorders due to the progressive loss of dopaminergic neurons in the ventrolateral region of the substantia nigra pars compacta (SNpc). Apart from the cardinal motor symptoms such as rigidity and bradykinesia, non-motor symptoms including those associated with respiratory dysfunction are of increasing interest. Not only can they impair the patients’ quality of life but they also can cause aspiration pneumonia, which is the leading cause of death among PD patients. This narrative review attempts to summarize the existing literature on respiratory impairments reported in human studies, as well as what is newly known from studies in animal models of the disease. Discussed are not only respiratory muscle dysfunction, apnea, and dyspnea, but also altered central respiratory control, responses to hypercapnia and hypoxia, and how they are affected by the pharmacological treatment of PD.     

Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue

In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg⁻¹/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.