Exploring the Applications of Carbon-Detected NMR in Living and Dead Organisms Using a C-Optimized Comprehensive Multiphase NMR Probe.

Comprehensive multiphase-nuclear magnetic resonance (CMP-NMR) is a non-invasive approach designed to observe all phases (solutions, gels, and solids) in intact samples using a single NMR probe. Studies of dead and living organisms are important to understand processes ranging from biological growth to environmental stress. Historically, such studies have utilized H-based phase editing for the detection of soluble/swollen components and H-detected 2D NMR for metabolite assignments/screening.

Sequence-specific H, C and N backbone NMR assignments for the N-terminal IgV-like domain (D1) and full extracellular region (D1D2) of PD-L1.

The co-inhibitory immune checkpoint interaction between programmed cell death-protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) serves to regulate T-cell activation, promoting self-tolerance. Over-expression of PD-L1 is a mechanism through which tumour cells can evade detection by the immune system. Several therapeutic antibodies targeting PD-L1 or PD-1 have been approved for the treatment of a variety of cancers, however, the discovery and development of small-molecule inhibitors of PD-L1 remains a challenge.

Study of Carbamoyl Fluoride: Synthesis, Properties and Applications.

Carbamoyl fluoride is a fluorinated group that, to this date, remains underexplored, probably due to the lack of data concerning its properties. In this paper, a study of carbamoyl fluoride is presented. Stability studies, in particular under physiological conditions, and lipophilicity measurement were performed.

Polyphenols in Ruminant Nutrition and Their Effects on Reproduction.

The feeding of domestic animals with diets in which polyphenols are present is increasingly attracting the attention of nutritionists and scientists. This review summarizes the knowledge regarding polyphenols' possible positive and negative effects and their bioavailability. The bioavailability of substances is a prerequisite for any postabsorption effect in vivo.

Structural characterization of polysaccharides from Geranium sanguineum L. and their immunomodulatory effects in response to inflammatory agents.

Ethnopharmacological Relevance: Geranium sanguineum L. is used for treatment of inflammations, anemia, malignant diseases of the blood-forming organs, diarrhea, respiratory infections, etc. Only flavonoids in root extracts have been elucidated as immunostimulating and anti-inflammatory compounds, and polysaccharides in the herb have not been examined.

Mercury methylation and methylmercury demethylation in boreal lake sediment with legacy sulphate pollution.

Sulphate and dissolved organic matter (DOM) in freshwater systems may regulate the formation of methylmercury (MeHg), a potent neurotoxin that biomagnifies in aquatic ecosystems. While many boreal lakes continue to recover from decades of elevated atmospheric sulphate deposition, little research has examined whether historically high sulphate concentrations can result in persistently elevated MeHg production and accumulation in aquatic systems. This study used sediment from a historically sulphate-impacted lake and an adjacent reference lake in northwestern Ontario, Canada to investigate the legacy effects of sulphate pollution, as well as the effects of newly added sulphate, natural organic matter (NOM) of varying sulphur content and a sulphate reducing bacteria (SRB) inhibitor on enhancing or inhibiting the Hg methylation and demethylation activity ( and ) in the sediment.

Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets.

The structure assignment and conformational analysis of thiosemicarbazone and thiocarbohydrazone were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the configuration.

Azetidomonamide and Diazetidomonapyridone Metabolites Control Biofilm Formation and Pigment Synthesis in .

Synthesis of azetidine-derived natural products by the opportunistic pathogen is controlled by quorum sensing, a process involving the production and sensing of diffusible signal molecules that is decisive for virulence regulation. In this study, we engineered for the titratable expression of the biosynthetic gene cluster, which allowed the purification and identification of two new products, azetidomonamide C and diazetidomonapyridone. Diazetidomonapyridone was shown to have a highly unusual structure with two azetidine rings and an open-chain diimide moiety.

Portable Hyperpolarized Xe-129 Apparatus with Long-Time Stable Polarization Mediated by Adaptable Rb Vapor Density.

The extraordinary sensitivity of Xe, hyperpolarized by spin-exchange optical pumping, is essential for magnetic resonance imaging and spectroscopy in life and materials sciences. However, fluctuations of the polarization over time still limit the reproducibility and quantification with which the interconnectivity of pore spaces can be analyzed. Here, we present a polarizer that not only produces a continuous stream of hyperpolarized Xe but also maintains stable polarization levels on the order of hours, independent of gas flow rates.

Structural Analysis of the Black-Legged Tick Saliva Protein Salp15.

Salp15 is one of the proteins in the saliva of the tick . Together with other biomolecules injected into the mammalian host at the biting site, it helps the tick to sustain its blood meal for days. Salp15 interferes with the cellular immune response of the mammalian host by inhibiting the activation of CD4 T-lymphocytes.

HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation.

HOIL-1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL-1's E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation.

Longitudinal Serum Metabolomics in Extremely Premature Infants: Relationships With Gestational Age, Nutrition, and Morbidities.

An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant's metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) <28 weeks [mean GA (SD) 25.

Medications Activating Tubular Fatty Acid Oxidation Enhance the Protective Effects of Roux-en-Y Gastric Bypass Surgery in a Rat Model of Early Diabetic Kidney Disease.

Background: Roux-en-Y gastric bypass surgery (RYGB) improves biochemical and histological parameters of diabetic kidney disease (DKD). Targeted adjunct medical therapy may enhance renoprotection following RYGB.

Methods: The effects of RYGB and RYGB plus fenofibrate, metformin, ramipril, and rosuvastatin (RYGB-FMRR) on metabolic control and histological and ultrastructural indices of glomerular and proximal tubular injury were compared in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of DKD.

Understanding self-assembly at molecular level enables controlled design of DNA G-wires of different properties.

A possible engineering of materials with diverse bio- and nano-applications relies on robust self-assembly of oligonucleotides. Bottom-up approach utilizing guanine-rich DNA oligonucleotides can lead to formation of G-wires, nanostructures consisting of continuous stacks of G-quartets. However, G-wire structure and self-assembly process remain poorly understood, although they are crucial for optimizing properties needed for specific applications.

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease.

In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2-year follow-up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary H-NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6-month follow-up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host-microbial co-metabolites (N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA)) and amino acids (arginine and glutamine).

DREAMTIME NMR Spectroscopy: Targeted Multi-Compound Selection with Improved Detection Limits.

NMR/MRI are critical tools for studying molecular structure and interactions but suffer from relatively low sensitivity and spectral overlap. Here, a Nuclear Magnetic Resonance (NMR) approach, termed DREAMTIME, is introduced that provides "a molecular window" inside complex systems, capable of showing only what the user desires, with complete molecular specificity. The user chooses a list of molecules of interest, and the approach detects only those targets while all other molecules are invisible.

Chemoselective and Regioselective Synthesis of Spiroisoindolinone Indenes via an Intercepted Meyer-Schuster Rearrangement/Intramolecular Friedel-Crafts Alkylation Relay.

A Brønsted acid-catalyzed reaction between isoindolinone-derived propargylic alcohols and external aromatic nucleophiles for the construction of spiroisoindolinone indenes is described. The reaction proceeds rapidly with a broad range of substrates to generate spiroindenes chemoselectively and regioselectively in moderate to high yields. Key to the success of this transformation is an intercepted Meyer-Schuster rearrangement/intramolecular Friedel-Crafts alkylation relay that offers a modular approach in the synthesis of target compounds.

pH dependence of C•A, G•A and A•A mismatches in the stem of precursor microRNA-31.

MicroRNAs (miRNAs) are important regulators of post-transcriptional gene expression. Mature miRNAs are generated from longer transcripts (primary, pri- and precursor, pre-miRNAs) through a series of highly coordinated enzymatic processing steps. The sequence and structure of these pri- and pre-miRNAs play important roles in controlling their processing.

Structural basis of Nrd1-Nab3 heterodimerization.

Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1-Nab3 chimera reveals the basis of heterodimerization, filling a missing gap in knowledge of this system. The free form of the Nrd1 interaction domain of Nab3 (NRID) forms a multi-state three-helix bundle that is clamped in a single conformation upon complex formation with the Nab3 interaction domain of Nrd1 (NAID).

The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints.

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation.

Placental metabolite profiles in late gestation for healthy mice.

Introduction: During pregnancy, appropriate placental metabolism is essential for fetuses to reach their growth potential. However, metabolic mechanisms during pregnancy remain poorly understood. Determination of the levels of placental metabolites in healthy pregnancy and how they change throughout gestation is critical for understanding placental function.

Supposedly identical microplastic particles substantially differ in their material properties influencing particle-cell interactions and cellular responses.

Microplastics and its putative adverse effects on environmental and human health increasingly gain scientific and public attention. Systematic studies on the effects of microplastics are currently hampered by using rather poorly characterised particles, leading to contradictory results for the same particle type. Here, surface properties and chemical composition of two commercially available nominally identical polystyrene microparticles, frequently used in effect studies, were characterised.

Development of Quebracho () Tannin-Based Thermoset Resins.

One of the major challenges currently in the field of material science is finding natural alternatives to the high-performing plastics developed in the last century. Consumers trust synthetic products for their excellent properties, but they are becoming aware of their impact on the planet. One of the most attractive precursors for natural polymers is tannin extracts and in particular condensed tannins.