Identification of Succinate Dehydrogenase Gene Variant Carriers by Blood Biomarkers.

Background: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes () are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance.

Wire Arc Additive Manufacturing of NiTi 4D Structures: Influence of Interlayer Delay.

Shape memory alloy structures for actuator and vibration damper applications may be manufactured using wire arc additive manufacturing (WAAM), which is one of the additive manufacturing technologies. Multilayer deposition causes heat accumulation during WAAM, which rises the preheat temperature of the previously created layer. This leads to process instabilities, which result in deviations from the desired dimensions and mechanical properties changes.

Tumour catabolism independent of malnutrition and inflammation in upper GI cancer patients revealed by longitudinal metabolomics.

Background: The detrimental impact of malnutrition and cachexia in cancer patients subjected to surgical resection is well established. However, how systemic and local metabolic alterations in cancer patients impact the serum metabolite signature, thereby leading to cancer-specific differences, is poorly defined. In order to implement metabolomics as a potential tool in clinical diagnostics and disease follow-up, targeted metabolite profiling based on quantitative measurements is essential.

Oxidation of hyperpolarized [1- C]pyruvate in isolated rat kidneys.

Kidneys play a central role in numerous disorders but current imaging methods have limited utility to probe renal metabolism. Hyperpolarized (HP) C magnetic resonance imaging is uniquely suited to provide metabolite-specific information about key biochemical pathways and it offers the further advantage that renal imaging is practical in humans. This study evaluated the feasibility of hyperpolarization examinations in a widely used model for analysis of renal physiology, the isolated kidney, which enables isolation of renal metabolism from the effects of other organs and validation of HP results by independent measurements.

Circulating Dickkopf1 Parallels Metabolic Adaptations and Predicts Disease Trajectories in Patients With COVID-19.

Context And Aims: Coronavirus disease 19 (COVID-19) trajectories show high interindividual variability, ranging from asymptomatic manifestations to fatal outcomes, the latter of which may be fueled by immunometabolic maladaptation of the host. Reliable identification of patients who are at risk of severe disease remains challenging. We hypothesized that serum concentrations of Dickkopf1 (DKK1) indicate disease outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals.

Searching for biological feedstock material: 3D printing of wood particles from house borer and drywood termite frass.

Frass (fine powdery refuse or fragile perforated wood produced by the activity of boring insects) of larvae of the European house borer (EHB) and of drywood termites was tested as a natural and novel feedstock for 3D-printing of wood-based materials. Small particles produced by the drywood termite Incisitermes marginipennis and the EHB Hylotrupes bajulus during feeding in construction timber, were used. Frass is a powdery material of particularly consistent quality that is essentially biologically processed wood mixed with debris of wood and faeces.

A Frequency-Selective pH-Responsive paraCEST Agent.

Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well-suited for imaging tissue pH because the basis of CEST, chemical exchange, is inherently sensitive to pH. Several previous pH-sensitive paraCEST agents were based on an exchanging Ln -bound water molecule as the CEST antenna but this design often added additional line-broadening to the bulk water signal due to T exchange. We report herein a pH-sensitive paraCEST agent that lacks an inner-sphere water molecule but contains one Ln-bound -OH group for CEST activation.

Short communication: Levels of land use and land cover in Phoenix, Arizona are associated with elevated plasma triglycerides in the Gambel's Quail, Callipepla gambelii.

Gambel's Quail, Callipepla gambelii, are gregarious birds commonly found in the southwestern deserts of the United States and Northwestern Mexico. With expanding urbanization, these birds are often found in exurban and suburban areas where they have access to food sources that may differ from those used by birds living in rural habitats and, as a result, also differ morphologically and physiologically. To investigate this hypothesis, we compared the morphology and nutritional physiology of quail sampled at sites varying with respect to land use and cover.

Effects of deuteration on transamination and oxidation of hyperpolarized C-Pyruvate in the isolated heart.

This study was designed to determine the effects of deuteration in pyruvate on exchange reactions in alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and flux through pyruvate dehydrogenase (PDH). Although deuteration of a C enriched substrate is commonly used to increase the lifetime of a probe for hyperpolarization experiments, the potential impact of kinetic isotope effects on such substitutions has not been studied in detail. Metabolism of deuterated pyruvate was investigated in isolated rat hearts.

Esterase-Catalyzed Production of Hyperpolarized C-Enriched Carbon Dioxide in Tissues for Measuring pH.

C Magnetic resonance imaging of hyperpolarized (HP) C-enriched bicarbonate (HCO) and carbon dioxide (CO) is a novel and sensitive technique for tissue pH mapping in vivo. Administration of the HP physiological buffer pair is attractive, but poor polarization and the short T of C-enriched inorganic bicarbonate salts are major drawbacks for this approach. Here, we report a new class of mixed anhydrides for esterase-catalyzed production of highly polarized CO and HCO in tissue.

Lanthanide DO3A-tropone complexes: efficient dual MR/NIR imaging probes in aqueous medium.

In this work, we describe a novel DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) based ligand with a chromophoric tropone coordinating sidearm (). Ln complexes of have one inner sphere water molecule. The r relaxivity of Gd is similar to that of the commercial Gd-based MRI agents.

Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo.

Clear cell renal cell carcinoma (ccRCC) is the most common form of human kidney cancer. Histological and molecular analyses suggest that ccRCCs have significantly altered metabolism. Recent human studies of lung cancer and intracranial malignancies demonstrated an unexpected preservation of carbohydrate oxidation in the tricarboxylic acid (TCA) cycle.

Microstructure and Deformation Response of TRIP-Steel Syntactic Foams to Quasi-Static and Dynamic Compressive Loads.

The implementation of hollow S60HS glass microspheres and Fillite 106 cenospheres in a martensitically transformable AISI 304L stainless steel matrix was realized by means of metal injection molding of feedstock with varying fractions of the filler material. The so-called TRIP-steel syntactic foams were studied with respect to their behavior under quasi-static compression and dynamic impact loading. The interplay between matrix material behavior and foam structure was discussed in relation to the findings of micro-structural investigations, electron back scatter diffraction EBSD phase analyses and magnetic measurements.

Electrochemical investigation of the Eu redox couple in complexes with variable numbers of glycinamide and acetate pendant arms.

The Eu redox couple provides a convenient design platform for responsive O sensors for magnetic resonance imaging (MRI). Specifically the Eu ion provides contrast enhancement under hypoxic conditions in tissues, whereas, under normoxia, the Eu ion can produce contrast from chemical exchange saturation transfer in MRI. The oxidative stability of the Eu redox couple for a series of tetraaza macrocyclic complexes was investigated in this work using cyclic voltammetry.

Rational Design of [ C,D ]Tert-butylbenzene as a Scaffold Structure for Designing Long-lived Hyperpolarized C Probes.

Dynamic nuclear polarization (DNP) is a technique to polarize the nuclear spin population. As a result of the hyperpolarization, the NMR sensitivity of the nuclei in molecules can be dramatically enhanced. Recent application of the hyperpolarization technique has led to advances in biochemical and molecular studies.

The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose.

This study was designed to determine whether perdeuterated glucose experiences a kinetic isotope effect (KIE) as glucose passes through glycolysis and is further oxidized in the tricarboxylic acid (TCA) cycle. Metabolism of deuterated glucose was investigated in two groups of perfused rat hearts. The control group was supplied with a 1:1 mixture of [U-C]glucose and [1,6-C]glucose, while the experimental group received [U-C,U-H]glucose and [1,6-C]glucose.

Imaging Extracellular Lactate In Vitro and In Vivo Using CEST MRI and a Paramagnetic Shift Reagent.

Overproduction of lactate is a hallmark of cancer, yet a method to quantitatively measure lactate production by cancer cells is not straight-forward. Chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) can potentially be used to image lactate but the small difference in chemical shift of the lactate -OH proton and water proton resonances make it challenging. Like other spectroscopic methods, CEST MRI cannot discriminate intracellular lactate from extracellular lactate.

Highly Concentrated Alginate-Gellan Gum Composites for 3D Plotting of Complex Tissue Engineering Scaffolds.

In tissue engineering, additive manufacturing (AM) technologies have brought considerable progress as they allow the fabrication of three-dimensional (3D) structures with defined architecture. 3D plotting is a versatile, extrusion-based AM technology suitable for processing a wide range of biomaterials including hydrogels. In this study, composites of highly concentrated alginate and gellan gum were prepared in order to combine the excellent printing properties of alginate with the favorable gelling characteristics of gellan gum.

Oxidative Conversion of a Europium(II)-Based T1 Agent into a Europium(III)-Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging.

The Eu(II) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most Eu(II) chelates reported to date. The reduced Eu(II) form acts as an efficient water proton T1 relaxation reagent, while the Eu(III) form acts as a water-based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate.

A new paramagnetically shifted imaging probe for MRI.

Purpose: To develop and characterize a new paramagnetic contrast agent for molecular imaging by MRI.

Methods: A contrast agent was developed for direct MRI detection through the paramagnetically shifted proton magnetic resonances of two chemically equivalent tert-butyl reporter groups within a dysprosium(III) complex. The complex was characterized in phantoms and imaged in physiologically intact mice at 7 Tesla (T) using three-dimensional (3D) gradient echo and spectroscopic imaging (MRSI) sequences to measure spatial distribution and signal frequency.

Challenging lanthanide relaxation theory: erbium and thulium complexes that show NMR relaxation rates faster than dysprosium and terbium analogues.

Measurements of the proton NMR paramagnetic relaxation rates for several series of isostructural lanthanide(III) complexes have been performed in aqueous solution over the field range 1.0 to 16.5 Tesla.

Critical analysis of the limitations of Bleaney's theory of magnetic anisotropy in paramagnetic lanthanide coordination complexes.

The origins of the breakdown of Bleaney's theory of magnetic anisotropy are described, based on an analysis of eleven different complexes of the second half of the 4f elements that form isostructural series. An examination of the chemical shift and relaxation rate behaviour of resonances located at least four bonds away from the paramagnetic centre was undertaken, and correlated to theoretical predictions. The key limitations relate to comparability of ligand field splitting with spin-orbit coupling, variation in the position of the principal magnetic axis between Ln complexes and the importance of multipolar terms in describing lanthanide ligand field interactions.

Synthesis, stereocontrol and structural studies of highly luminescent chiral tris-amidepyridyl-triazacyclononane lanthanide complexes.

The configuration of the remote amide chiral moiety determines the helicity of the metal complex in Ln(III) complexes of nonadentate N6O3 ligands based on triazacyclononane. Solution NMR studies revealed the presence of a dominant isomer whose proportion varies from 9 : 1 to 4 : 1 from Ce to Yb and X-ray crystallographic studies at 120 K of the Yb and two enantiomeric Eu complexes confirmed the configuration as S-Δ-λ in the major isomer. Global minimisation methods allowed magnetic susceptibility and electronic relaxation times of the lanthanide ions to be estimated by analysis of variable field longitudinal relaxation rate (R1) data sets.

Direct and selective tagging of cysteine residues in peptides and proteins with 4-nitropyridyl lanthanide complexes.

A cysteine-selective tagging method in water is reported, based on rapid displacement of a pyridyl nitro-substituent in simple pyridines and lanthanide complexes. The conjugation reaction creates a short link between the tag and peptide, holding the peptide closer to the Ln(3+) ion and with reduced flexibility compared to existing methods.

Experimental measurement and theoretical assessment of fast lanthanide electronic relaxation in solution with four series of isostructural complexes.

The rates of longitudinal relaxation for ligand nuclei in four isostructural series of lanthanide(III) complexes have been measured by solution state NMR at 295 K at five magnetic fields in the range 4.7-16.5 T.