Search

This paper investigates the atomic and nano-scale structures of a 50-year-old hydrated alite paste. Imaged by TEM, the outer product C-S-H fibers are composed of particles that are 1.5-2 nm thick and several tens of nanometers long. 29Si NMR shows 47.9% Q1 and 52.1% Q2, with a mean SiO4 tetrahedron chain length (MCL) of 4.18, indicating a limited degree of polymerization after 50 years' hydration. A Scanning Transmission X-ray Microscopy (STXM) study was conducted on this late-age paste and a 1.5 year old hydrated C3S solution. Near Edge X-ray Absorption Fine Structure (NEXAFS) at Ca L3,2-edge indicates that Ca2 + in C-S-H is in an irregular symmetric coordination, which agrees more with the atomic structure of tobermorite than that of jennite. At Si K-edge, multi-scattering phenomenon is sensitive to the degree of polymerization, which has the potential to unveil the structure of the SiO44 - tetrahedron chain.

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrPC) to the disease-associated isoform (PrPSc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases. [ABSTRACT FROM AUTHOR]

Copper is an essential nutrient for the normal development of the brain and nervous system, although the hallmark of several neurological diseases is a change in copper concentrations in the brain and central nervous system. Prion protein (PrP) is a copper-binding, cell-surface glycoprotein that exists in two alternatively folded conformations: a normal isoform (PrPC) and a disease-associated isoform (PrPSc). Prion diseases are a group of lethal neurodegenerative disorders that develop as a result of conformational conversion of PrPC into PrPSc. The pathogenic mechanism that triggers this conformational transformation with the subsequent development of prion diseases remains unclear. It has, however, been shown repeatedly that copper plays a significant functional role in the conformational conversion of prion proteins. In this review, we focus on current research that seeks to clarify the conformational changes associated with prion diseases and the role of copper in this mechanism, with emphasis on the latest applications of NMR and EPR spectroscopy to probe the interactions of copper with prion proteins. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies. [ABSTRACT FROM AUTHOR]

Abstract: Blood serum is commonly used for clinical diagnostics because its protein composition bears a wealth of information about the health of an organism. More recently the analysis of the small molecule composition, the metabolome, has received increased attention because the metabolite composition is influenced by many diseases, by the administration of drugs and toxins, and by the diet and life style of an individual. When nuclear magnetic resonance spectroscopy is used as an analytical tool it is often preferable to remove catalytically active proteins, in particular for longer measurements, because metabolite concentrations are otherwise in constant flux. Here we have compared different protocols for the separation of proteins and metabolites, including precipitation methods and ultrafiltration. Whereas most extraction methods involving protein precipitation deplete some metabolites, ultrafiltration is superior in retaining metabolite concentrations and offers excellent reproducibility. We also describe a new method to recover the hydrophobic fraction for ultrafiltration with good reproducibility. [Copyright &y& Elsevier]

A healthy condition is defined by complex human metabolic pathways that only function properly when fully satisfied by nutritional inputs. Poor nutritional intakes are associated with a number of metabolic diseases, such as diabetes, obesity, atherosclerosis, hypertension, and osteoporosis. In recent years, nutrition science has undergone an extraordinary transformation driven by the development of innovative software and analytical platforms. However, the complexity and variety of the chemical components present in different food types, and the diversity of interactions in the biochemical networks and biological systems, makes nutrition research a complicated field. Metabolomics science is an "-omic", joining proteomics, transcriptomics, and genomics in affording a global understanding of biological systems. In this review, we present the main metabolomics approaches, and highlight the applications and the potential for metabolomics approaches in advancing nutritional food research. [ABSTRACT FROM AUTHOR]

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a "gold standard" platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development. [ABSTRACT FROM AUTHOR]

Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of the three principal analytical techniques used in metabolomics (the other two being gas chromatography coupled to mass spectrometry (GC-MS) and liquid chromatography coupled with single-stage mass spectrometry (LC-MS)). The relative ease of sample preparation, the ability to quantify metabolite levels, the high level of experimental reproducibility, and the inherently nondestructive nature of NMR spectroscopy have made it the preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by the fact that most other analytical techniques, including both LC-MS and GC-MS, are inherently more sensitive than NMR, with lower limits of detection typically being 10 to 100 times better. This review is intended to introduce readers to the field of NMR-based metabolomics and to highlight both the advantages and disadvantages of NMR spectroscopy for metabolomic studies. It will also explore some of the unique strengths of NMR-based metabolomics, particularly with regard to isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, and the ability to noninvasively analyze native tissue specimens. Finally, this review will highlight a number of emerging NMR techniques and technologies that are being used to strengthen its utility and overcome its inherent limitations in metabolomic applications. [ABSTRACT FROM AUTHOR]

• Systematically compared ODS of model oil between mechanical stirring and sonication. • Activate energy (E a) for ODS of DBT under sonication is 8.92 kJ/mol. • The viscosity of AXL increased after oxidative desulfurization. • APPI FT-ICR characterized sulfur-containing compounds distribution. • A decrease in aromatic hydrocarbon content after ODS was evidenced by NMR. The oxidative desulfurization (ODS) of model oil (BT, DBT, and 4,6-DMDBT) was studied with Mo/Ti-TUD-1 catalyst under mechanical stirring and ultrasonic-assisted conditions. ODS of DBT followed the pseudo-first-order kinetic model under both conditions and achieved a maximum conversion of 99%. The use of ultrasound instead of mechanical stirring significantly shortens the reaction time from 80 to 15 min. The oxidative reactivity of sulfur compounds in the model oil followed the same order under the mechanical stirring and ultrasound: 4,6-DMDBT > DBT > BT. Then ultrasound-assisted oxidative desulfurization of Arabia extra light oil was performed at 60 °C. It removed 56.5% of sulfur from the Arabian extra light oil feedstock. APPI FT-ICR characterized the sulfur compounds distribution. The S 1 , S 2 , O 2 S 1 , and O 4 S 2 class species were identified in Arabian extra light oil feedstock, raffinate, and methanol extraction phase samples. The abundant O 2 S 1 class species which had 9–15 Double Bond Equivalent (DBE) values and 15–30 carbon numbers, O 4 S 2 class species with 11–20 DBE and 20 < carbon number < 40 were detected in the extraction phase. 1H NMR and 13C NMR results revealed that the molecular structure in Arabian extra light oil is aromatic-base with a high alkylation degree. Combined with the FT-ICR and NMR results, those sulfur-containing compounds with lower alkylation degrees were converted to sulfone over Mo/Ti-TUD-1 catalyst and extracted by methanol. [ABSTRACT FROM AUTHOR]

• Structural level characterization of different TPO distillate fractions is presented. • Sulfur species are mainly in the form of dibenzothiophene and benzonaphthothiophene. • Distillation allowed concentrating sulfur containing compounds in the heavy fraction. Tire pyrolysis oil (TPO) is a complex mixture of hydrocarbons spanning a wide boiling point range. Due to its complexity, direct implementation of TPO to combustion applications has been challenging. Distillation is a simple method for grouping similar compounds, based on their volatility, thereby facilitating further upgrading and use. In this work, TPO was distilled at atmospheric pressure into different fractions (light, low-middle, high-middle, and heavy), and the structural characteristics of each fraction were explored. Therefore, advanced analytical techniques such as GC–MS, APPI FT-ICR MS and 1H and 13C NMR were utilized. For the light fraction, the GC–MS revealed a significant presence of benzene, toluene, and xylene, as well as limonene. From the APPI FT-ICR MS results, the low-middle, high-middle, and heavy fractions were classified into a number of molecular classes. Among these, pure hydrocarbons (HC), hydrocarbons containing one sulfur atom (S 1), hydrocarbons containing two oxygen atoms (O 2), etc. Here, HC and S 1 were found to be the most abundant molecular classes in all fractions. Finally, a structural analysis of the functional groups present in each TPO fraction was conducted by 1H and 13C NMR. Average molecular parameters (AMPs), such as the number of aromatic, naphthenic, and olefinic carbons/hydrogens, were determined. In addition, derived AMPs, such as the aromaticity factor (fa), C/H paraffinic, C/H aromatic, etc., were calculated. Fractionation by distillation resulted in concentration of both the sulfur and aromatic compounds in the heaviest fraction. In this manner, effective application and upgrading strategies could be individually designed for each fraction. [ABSTRACT FROM AUTHOR]