catena-Poly[[diaqua­cadmium(II)]-μ-(methyl morpholino dichloro­methylene­diphospho­nato)-κ3 O,O′:O′′-[tetra­aqua­cadmium(II)]-μ-(methyl morpholino dichloro­methyl­enediphospho­nato)-κ3 O:O′,O′′]

The asymmetric unit of the title compound, [Cd(C6H11Cl2NO6P2)(H2O)3]n, contains two octahedrally coordinated Cd atoms located in special positions, one on a twofold rotation axis and the other on a centre of symmetry. The metal atoms are connected by methyl morpholino dichloro­methyl­enediphospho­nate ligands into chains in the c-axis direction. These chains are further connected by O—H⋯O hydrogen bonds into a layer-like construction along (100)

Synthesis of novel (1-alkanoyloxy-4- alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives

Abstract A novel strategy for the synthesis of (1-alkanoyloxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (1a-d) via (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), starting from alendronate has been developed with reasonable 51-77% overall yields. Intermediate products, (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), were prepared in water with reasonable to high yields (52-94%)

Slow pyrolysis liquid in reducing NH3 emissions from cattle slurry-Impacts on plant growth and soil organisms

A substantial percentage of manure nitrogen (N) can be lost as gaseous ammonia (NH3) during storage and field spreading. Lowering slurry pH is a simple and accepted method for preserving its N. Efficiency of slow pyrolysis liquid (PL) produced from birch (Betula sp.) as an acidifying agent, and its ability to reduce NH3 emissions following surface application of cattle slurry, was studied in a field experiment. Untreated slurry (US) and slurries acidified with PL and sulfuric acid (SA) were applied to the second harvest of a grass ley. Immediate NH3 emissions, grass biomass, N-yield and possible toxic impacts on soil nematodes and enchytraeids were examined. Furthermore, the effects on soil respiration, nitrogen dynamics and seed germination were studied in subsequent laboratory experiments. In the field, over one third of the water-extractable ammonium-N (NH4-N) applied was lost through NH3 volatilization from US. SA and PL acidified slurries reduced NH3-N emission rate equally from 3.4 to (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Poly[[μ-aqua-aqua­[μ4-ethyl (dichloro­methyl­ene)diphospho­nato]sesqui­calcium(II)] acetone hemisolvate 4.5-hydrate]

The title compound, {[Ca1.5(C3H5Cl2O6P2)(H2O)2]·0.5CH3COCH3·4.5H2O}n, has a two-dimensional polymeric structure. The asymmetric unit contains two crystallographically independent Ca2+ cations connected by a chelating and bridging ethyl (dichloro­methyl­ene)diphos­pho­n­ate(3−) ligand and an aqua ligand. One of the Ca atoms, lying on a centre of symmetry, has a slightly distorted octa­hedral geometry, while the other Ca atom is seven-coordinated in a distorted monocapped trigonal-prismatic geometry. The polymeric layers are further connected by extensive O—H⋯O hydrogen bonding into a three-dimensional supra­molecular network. The acetone solvent mol­ecule and one uncoordin­ated water mol­ecule are located on twofold rotation axes

Extractives of Stemwood and Sawmill Residues of Scots Pine (Pinus sylvestris L.) for Biorefining in Four Climatic Regions in Finland—Phenolic and Resin Acid Compounds

This study aimed to identify and quantify phenolic and resin acid extractive compounds in Scots pine stemwood and sawmill residues in four climatic regions of Finland to evaluate their most optimal sources for bio-based chemical biorefining and bioenergy products. The sample consisted of 140 trees from 28 stands, and sawdust lots from 11 log stands. NMR for the overall extractive analysis and HPLC for the quantitative estimation of phenolic and resin acid compounds were employed. Correlation analysis, multivariate factor analysis, principle component analysis and multiple linear regression modelling were applied for statistical analysis. HPLC identified 12 extractive compounds and NMR five more resin acids. Pinosylvin (PS), pinosylvin monomethyl ether (PSMME), and partly neolignans/lignans occurred in the largest concentrations. Wood type caused the most variation, heartwood having larger concentrations than sapwood (sawdust between them). Regional differences in the concentrations were smaller, but factor analysis distinguished the northern and the southern regions into their own groups. The results indicated higher concentrations of PS, PSMME, and vanillic acid in southern regions and those of, e.g., PSMME glycoside, lignan 2, and neolignan 1 in northern regions. The rather low concentrations of extractives in stemwood and sawdust imply value-added products, efficient sorting and/or large raw material volumes

Extractives of Stemwood and Sawmill Residues of Scots Pine (Pinus sylvestris L.) for Biorefining in Four Climatic Regions in Finland—Phenolic and Resin Acid Compounds

This study aimed to identify and quantify phenolic and resin acid extractive compounds in Scots pine stemwood and sawmill residues in four climatic regions of Finland to evaluate their most optimal sources for bio-based chemical biorefining and bioenergy products. The sample consisted of 140 trees from 28 stands, and sawdust lots from 11 log stands. NMR for the overall extractive analysis and HPLC for the quantitative estimation of phenolic and resin acid compounds were employed. Correlation analysis, multivariate factor analysis, principle component analysis and multiple linear regression modelling were applied for statistical analysis. HPLC identified 12 extractive compounds and NMR five more resin acids. Pinosylvin (PS), pinosylvin monomethyl ether (PSMME), and partly neolignans/lignans occurred in the largest concentrations. Wood type caused the most variation, heartwood having larger concentrations than sapwood (sawdust between them). Regional differences in the concentrations were smaller, but factor analysis distinguished the northern and the southern regions into their own groups. The results indicated higher concentrations of PS, PSMME, and vanillic acid in southern regions and those of, e.g., PSMME glycoside, lignan 2, and neolignan 1 in northern regions. The rather low concentrations of extractives in stemwood and sawdust imply value-added products, efficient sorting and/or large raw material volumes

Systematic study of the physicochemical properties of a homologous series of aminobisphosphonates

ABSTRACT: Aminobisphosphonates, e.g., alendronate and neridronate, are a well known class of molecules used as drugs for various bone diseases. Although these molecules have been available for decades, a detailed understanding of their most important physicochemical properties under comparable conditions is lacking. In this study, ten aminobisphosphonates, H2N(CH2)nC(OH)[P(O)(OH)2]2, in which n = 2-5, 7-11 and 15 have been synthesized. Their aqueous solubility as a function of temperature and pH, pKa-values, thermal stability, IR absorptions, and NMR spectral data for both liquid (1H, 13C, 31P-NMR) and solid state (13C, 15N and 31P-CPMAS NMR) were determined.Peer reviewe

Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions

Funding: This work was supported by grants from the Russian Science Foundation (grant # 17-74-20049—synthesis of C-methylated Spd analogues, ITC studies of dimerization of OAZ1, and frameshifting experiments), the Russian Science Foundation (grant # 19-74-10086—isolation of OAZ1, electrophoresis studies of dimerization of OAZ1), and the Academy of Finland (grants # 292574 and # 315487). Acknowledgments: The authors thank A. Karppinen, A. Korhonen, T. Reponen, M. Salminkoski, and S.D. Negrya for their skillful technical assistance.Peer reviewedPublisher PD

Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics

Background:Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available. Methods:We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative line shape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n = 995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n = 578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n = 4548). Results:Intra-assay metabolite variations were mostly <5%, indicating high robustness and accuracy of urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found to be clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance. Conclusion:Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders