Comparison of Measurements for Recording Postural Control in Standing and Seated Position in Healthy Individuals.

: A standard method of assessing postural control is to measure while standing. However, its implementation is usually limited. Recording postural control directly on the trunk in a seated position could provide an alternative diagnostic method for quantifying neuromuscular control.

A Statistical and AI Analysis of the Frequency Spectrum in the Measurement of the Center of Pressure Track in the Seated Position in Healthy Subjects and Subjects with Low Back Pain.

Measuring postural control in an upright standing position is the standard method. However, this diagnostic method has floor or ceiling effects and its implementation is only possible to a limited extent. Assessing postural control directly on the trunk in a sitting position and consideration of the results in the spectrum in conjunction with an AI-supported evaluation could represent an alternative diagnostic method quantifying neuromuscular control.

The Influence of Anthropometric Variables and Filtering Frequency on Center of Pressure Data.

Good postural control is considered to be a key component of an active lifestyle, and numerous studies have investigated the Center of Pressure (CoP) as a way of identifying motor deficits. However, the optimal frequency range for assessing CoP variables and the effect of filtering on the relationships between anthropometric variables and CoP are unclear. The aim of this work is to show the relationship between anthropometric variables and different ways of filtering the CoP data.

Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase.

The cooperative interplay between the functional devices of a preorganized active site is fundamental to enzyme catalysis. An in-depth understanding of this phenomenon is central to elucidating the remarkable efficiency of natural enzymes and provides an essential benchmark for enzyme design and engineering. Here, we study the functional interconnectedness of the catalytic nucleophile (His18) in an acid phosphatase by analyzing the consequences of its replacement with aspartate.

Biosynthesis of the Fungal Organophosphonate Fosfonochlorin Involves an Iron(II) and 2-(Oxo)glutarate Dependent Oxacyclase.

The fungal metabolite Fosfonochlorin features a chloroacetyl moiety that is unusual within known phosphonate natural product biochemistry. Putative biosynthetic genes encoding Fosfonochlorin in Fusarium and Talaromyces spp. were investigated through reactions of encoded enzymes with synthetic substrates and isotope labelling studies.

Overall Retention of Methyl Stereochemistry during B-Dependent Radical SAM Methyl Transfer in Fosfomycin Biosynthesis.

Methylcobalamin-dependent radical -adenosylmethionine (SAM) enzymes methylate non-nucleophilic atoms in a range of substrates. The mechanism of the methyl transfer from cobalt to the receiving atom is still mostly unresolved. Here we determine the stereochemical course of this process at the methyl group during the biosynthesis of the clinically used antibiotic fosfomycin.

C-H Bond Cleavage Is Rate-Limiting for Oxidative C-P Bond Cleavage by the Mixed Valence Diiron-Dependent Oxygenase PhnZ.

PhnZ utilizes a mixed valence diiron(II/III) cofactor and O to oxidatively cleave the carbon-phosphorus bond of ()-2-amino-1-hydroxyethylphosphonic acid to form glycine and orthophosphate. The active site residues Y24 and E27 are proposed to mediate induced-fit recognition of the substrate and access of O to one of the active site Fe ions. H62 is proposed to deprotonate the C1-hydroxyl of the substrate during catalysis.

An Oxidative Pathway for Microbial Utilization of Methylphosphonic Acid as a Phosphate Source.

Methylphosphonic acid is synthesized by marine bacteria and is a prominent component of dissolved organic phosphorus. Consequently, methylphosphonic acid also serves as a source of inorganic phosphate (Pi) for marine bacteria that are starved of this nutrient. Conversion of methylphosphonic acid into Pi is currently only known to occur through the carbon-phosphorus lyase pathway, yielding methane as a byproduct.

2-Nitroimidazole-Furanoside Derivatives for Hypoxia Imaging-Investigation of Nucleoside Transporter Interaction, F-Labeling and Preclinical PET Imaging.

The benefits of PET imaging of tumor hypoxia in patient management has been demonstrated in many examples and with various tracers over the last years. Although, the optimal hypoxia imaging agent has yet to be found, 2-nitroimidazole (azomycin) sugar derivatives-mimicking nucleosides-have proven their potential with [F]FAZA ([F]fluoro-azomycin--arabinoside) as a prominent representative in clinical use. Still, for all of these tracers, cellular uptake by passive diffusion is postulated with the disadvantage of slow kinetics and low tumor-to-background ratios.

C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration.

Fom3, a cobalamin-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase, catalyzes C-methylation at the C2 position of cytidylylated 2-hydroxyethylphosphonate (HEP-CMP) to afford cytidylylated 2-hydroxypropylphosphonate (HPP-CMP) in fosfomycin biosynthesis. In this study, the Fom3 reaction product HPP-CMP was reanalyzed by chiral ligand exchange chromatography to confirm its stereochemistry. The Fom3 methylation product was found to be ( S)-HPP-CMP only, indicating that the stereochemistry of the C-methylation catalyzed by Fom3 is ( S)-selective.

The α-hydroxyphosphonate-phosphate rearrangement of a noncyclic substrate - some new observations.

Racemic ethyl hydrogen (1-hydroxy-2-methylsulfanyl-1-phenylethyl)phosphonate was resolved with (R)-1-phenylethylamine. The (R)-configuration of the (-)-enantiomer was determined by chemical correlation. Esterification of the (-)-enantiomer with a substituted diazomethane derived from 3-hydroxy-1,3,5(10)-estratrien-17-one delivered two epimeric phosphonates separated by HPLC.

Preparation of Phosphonic Acid Analogues of Proline and Proline Analogues and Their Biological Evaluation as δ-Pyrroline-5-carboxylate Reductase Inhibitors.

Racemic 1-hydroxy-3-butenyl-, 3-chloro-1-hydroxypropyl-, and 3-bromo-1-hydroxypropylphosphonate and the corresponding ()-enantiomers obtained by lipase-catalyzed resolution of the respective racemic chloroacetates were subjected to functional group manipulations. These comprised ozonolysis, Mitsunobu reactions with hydrazoic acid and -hydroxyphthalimide, alkylation of hydrazine derivative, removal of phthaloyl group followed by intramolecular substitution, and global deprotection to deliver the racemates and ()-enantiomers (ee 92-99% by chiral high-performance liquid chromatography) of pyrrolidin-2-yl-, oxazolidin-3-yl-, oxazolidin-5-yl-, pyrazolidin-3-yl-, and 1,2-oxazinan-3-ylphosphonic acids. These phosphonic acids were evaluated as analogues of proline and proline analogues for the ability to inhibit γ-glutamyl kinase, δ-pyrroline-5-carboxylate synthetase, and δ-pyrroline-5-carboxylate reductase.

Stereochemical Course of Methyl Transfer by Cobalamin-Dependent Radical SAM Methyltransferase in Fosfomycin Biosynthesis.

The methyl groups of [ methyl-( S)]- and [ methyl-( R)]-[ methyl-D,T]-l-methionine fed to Streptomyces fradiae were incorporated into fosfomycin, which was chemically degraded to chiral AcONa. The enzymatic test gave the ( S)-configuration for the chiral AcONa derived from methionine with the ( S)-[D,T]methyl group ( F = 31.7) and ( R) for the one derived from methionine with the ( R)-[D,T]methyl group ( F = 83.

On the rearrangement of -aryl--Boc-phosphoramidates to -Boc-protected -aminoarylphosphonates.

Abstract: Various arylamines were converted in two steps to -Boc--arylphosphoramidates. LiTMP and LDA induced directed -metalation at temperatures from -78 to 0 °C. The ensuing [1,3]-migration of the phosphorus atom with its substituents from the nitrogen to the -carbanionic carbon atom gave -Boc-protected -aminoarylphosphonates.

A Methylidene Group in the Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases.

Aromatic amino acid ammonia-lyases and aromatic amino acid 2,3-aminomutases contain the post-translationally formed prosthetic 3,5-dihydro-4-methylidene-5-imidazol-5-one (MIO) group. MIO enzymes catalyze the stereoselective synthesis of α- or β-amino acid enantiomers, making these chemical processes environmentally friendly and affordable. Characterization of novel inhibitors enables structural understanding of enzyme mechanism and recognizes promising herbicide candidates as well.

Chemical Synthesis of (R)- and (S)-[O,O,O]Phosphoenol Pyruvate.

Enzymes and chirality are intimately associated. For their mechanisms to be studied, chiral substrates are needed as probes. Here, we report a concise synthesis of (R)- and (S)-[O,O,O]phosphoenol pyruvate starting from enantiomerically pure (R)-2-chloro-1-phenylethanol, which was transformed into O-labeled 3-methyl-1-phenylbutane-1,3-diol.

Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate decarboxylase from Bacteroides fragilis.

Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal abscesses and is involved in 90% of anaerobic peritoneal infections. Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component of the cell wall of B. fragilis.

Hepatitis E virus in wild rabbits and European brown hares in Germany.

Recently, a change of hepatitis E from being a typical travel-associated disease to an autochthonous zoonosis in Germany was observed. An increasing number of autochthonous infections with the hepatitis E Virus (HEV) have been recognized in developed countries. Venison from wild boar is already known to be a potential source of infection, if not prepared properly by the consumer.

Towards the biodegradation pathway of fosfomycin.

Three functionalised propylphosphonic acids were synthesised to study C-P bond cleavage in R. huakuii PMY1. (R)-1-Hydroxy-2-oxopropylphosphonic acid [(R)-5] was prepared by chiral resolution of (±)-dimethyl 1-hydroxy-2-methylallyllphosphonate [(±)-12], followed by ozonolysis and deprotection.

Efficient preparation of 2-nitroimidazole nucleosides as precursors for hypoxia PET tracers.

Abstract: 2-Deoxy-D-ribose was converted to /-mixtures of methyl 3--acetyl- and methyl 3--benzoyl-2-deoxy-5-(-toluenesulfonyl)-D-ribofuranosides. These were reacted with boron trichloride to generate ribofuranosyl chlorides, which afforded precursors for tracers to image tumor hypoxia on substitution with salts of 2-nitroimidazole. The anomeric ratio of the nucleosides was delicately influenced by the reaction conditions.

[F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [F]FAZA.

Introduction: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [F]Fluoro-azomycin-α-arabinoside ([F]FAZA) - already in clinical use - may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [F]FAZA our objective was to F-radiolabel an azomycin-2´-deoxyriboside with β-configuration ([F]FAZDR, [F]-β-8) to mimic nucleosides more closely and comparatively evaluate it versus [F]FAZA.

A competitive ELISA for species-independent detection of Crimean-Congo hemorrhagic fever virus specific antibodies.

Crimean-Congo hemorrhagic fever virus (CCHFV) circulates in many countries of Asia, Africa, and Europe. CCHFV can cause a severe hemorrhagic fever in humans with case-fatality rates of up to 80%. CCHF is considered to be one of the major emerging diseases spreading to and within Europe.

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

Positron emission tomography (PET) using fluorine-18 (F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10).

The Stereochemical Course of the α-Hydroxyphosphonate-Phosphate Rearrangement.

The phosphonate-phosphate rearrangement is an isomerisation of α-hydroxyphosphonates bearing electron-withdrawing substituents at the α-carbon atom. We studied the stereochemical course of this rearrangement with respect to phosphorus. A set of four diastereomeric α-hydroxyphosphonates was prepared by a Pudovik reaction from two diastereomeric cyclic phosphites.

Phosphonate–phosphinate rearrangement.

LiTMP metalated dimethyl N-Boc-phosphoramidates derived from 1-phenylethylamine and 1,2,3,4-tetrahydronaphthalen-1-ylamine highly selectively at the CH3O group to generate short-lived oxymethyllithiums. These isomerized to diastereomeric hydroxymethylphosphonamidates (phosphate–phosphonate rearrangement). However, s-BuLi converted the dimethyl N-Boc-phosphoramidate derived from 1-phenylethylamine to the N-Boc α-aminophosphonate preferentially.