High field level crossing studies on spin dimers in the low dimensional quantum spin system Na2_2T2_2(C2_2O4_4)3_3(H2_2O)2_2 with T=Ni,Co,Fe,Mn

In this paper we demonstrate the application of high magnetic fields to study the magnetic properties of low dimensional spin systems. We present a case study on the series of 2-leg spin-ladder compounds Na$_2$T$_2$(C$_2$O$_4$)$_3$(H$_2$O)$_2$ with T = Ni, Co, Fe and Mn. In all compounds the transition metal is in the $T^{2+}$ high spin configuation. The localized spin varies from S=1 to 3/2, 2 and 5/2 within this series. The magnetic properties were examined experimentally by magnetic susceptibility, pulsed high field magnetization and specific heat measurements. The data are analysed using a spin hamiltonian description. Although the transition metal ions form structurally a 2-leg ladder, an isolated dimer model consistently describes the observations very well. This behaviour can be understood in terms of the different coordination and superexchange angles of the oxalate ligands along the rungs and legs of the 2-leg spin ladder. All compounds exhibit magnetic field driven ground state changes which at very low temperatures lead to a multistep behaviour in the magnetization curves. In the Co and Fe compounds a strong axial anisotropy induced by the orbital magnetism leads to a nearly degenerate ground state and a strongly reduced critical field. We find a monotonous decrease of the intradimer magnetic exchange if the spin quantum number is increased

Targeting Methylglyoxal in Diabetic Kidney Disease Using the Mitochondria-Targeted Compound MitoGamide.

Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during food processing. Methylglyoxal is thought to impair the mitochondrial function and may contribute to the pathogenesis of DKD. Here, we sought to target methylglyoxal within the mitochondria using MitoGamide, a mitochondria-targeted dicarbonyl scavenger, in an experimental model of diabetes. Male 6-week-old heterozygous Akita mice (C57BL/6-Ins2-Akita/J) or wildtype littermates were randomized to receive MitoGamide (10 mg/kg/day) or a vehicle by oral gavage for 16 weeks. MitoGamide did not alter the blood glucose control or body composition. Akita mice exhibited hallmarks of DKD including albuminuria, hyperfiltration, glomerulosclerosis, and renal fibrosis, however, after 16 weeks of treatment, MitoGamide did not substantially improve the renal phenotype. Complex-I-linked mitochondrial respiration was increased in the kidney of Akita mice which was unaffected by MitoGamide. Exploratory studies using transcriptomics identified that MitoGamide induced changes to olfactory signaling, immune system, respiratory electron transport, and post-translational protein modification pathways. These findings indicate that targeting methylglyoxal within the mitochondria using MitoGamide is not a valid therapeutic approach for DKD and that other mitochondrial targets or processes upstream should be the focus of therapy

Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, ‘Dormancy Associated Translation Inhibitor (DATIN)’

Mycobacterium tuberculosis is a major human pathogen that has evolved survival mechanisms to persist in an immune-competent host under a dormant condition. The regulation of M. tuberculosis metabolism during latent infection is not clearly known. The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis. We describe functional characterization of an important gene of DosR regulon, Rv0079, which appears to be involved in the regulation of translation through the interaction of its product with bacterial ribosomal subunits. The protein encoded by Rv0079, possibly, has an inhibitory role with respect to protein synthesis, as revealed by our experiments. We performed computational modelling and docking simulation studies involving the protein encoded by Rv0079 followed by in vitro translation and growth curve analysis experiments, involving recombinant E. coli and Bacille Calmette Guérin (BCG) strains that overexpressed Rv0079. Our observations concerning the interaction of the protein with the ribosomes are supportive of its role in regulation/inhibition of translation. We propose that the protein encoded by locus Rv0079 is a ‘dormancy associated translation inhibitor’ or DATIN

Complement C5a induces renal injury in diabetic kidney disease by disrupting mitochondrial metabolic agility

The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes; conventional renoprotective agents did not therapeutically target this elevation. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several diverse rodent models of diabetes. Genetic deletion of C5aR1 in mice conferred protection against diabetes-induced renal injury. Transcriptomic profiling of kidney revealed diabetes-induced downregulation of pathways involved in mitochondrial fatty acid metabolism. Interrogation of the lipidomics signature revealed abnormal cardiolipin remodeling in diabetic kidneys, a cardinal sign of disrupted mitochondrial architecture and bioenergetics. In vivo delivery of an orally active inhibitor of C5aR1 (PMX53) reversed the phenotypic changes and normalized the renal mitochondrial fatty acid profile, cardiolipin remodeling, and citric acid cycle intermediates. In vitro exposure of human renal proximal tubular epithelial cells to C5a led to altered mitochondrial respiratory function and reactive oxygen species generation. These experiments provide evidence for a pivotal role of the C5a/C5aR1 axis in propagating renal injury in the development of DKD by disrupting mitochondrial agility, thereby establishing a new immunometabolic signaling pathway in DKD

Quantitative sequence-function relationships in proteins based on gene ontology

<p>Abstract</p> <p>Background</p> <p>The relationship between divergence of amino-acid sequence and divergence of function among homologous proteins is complex. The assumption that homologs share function – the basis of transfer of annotations in databases – must therefore be regarded with caution. Here, we present a quantitative study of sequence and function divergence, based on the Gene Ontology classification of function. We determined the relationship between sequence divergence and function divergence in 6828 protein families from the PFAM database. Within families there is a broad range of sequence similarity from very closely related proteins – for instance, orthologs in different mammals – to very distantly-related proteins at the limit of reliable recognition of homology.</p> <p>Results</p> <p>We correlated the divergence in sequences determined from pairwise alignments, and the divergence in function determined by path lengths in the Gene Ontology graph, taking into account the fact that many proteins have multiple functions. Our results show that, among homologous proteins, the proportion of divergent functions decreases dramatically above a threshold of sequence similarity at about 50% residue identity. For proteins with more than 50% residue identity, transfer of annotation between homologs will lead to an erroneous attribution with a totally dissimilar function in fewer than 6% of cases. This means that for very similar proteins (about 50 % identical residues) the chance of completely incorrect annotation is low; however, because of the phenomenon of recruitment, it is still non-zero.</p> <p>Conclusion</p> <p>Our results describe general features of the evolution of protein function, and serve as a guide to the reliability of annotation transfer, based on the closeness of the relationship between a new protein and its nearest annotated relative.</p

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice

Environmental Modeling and Exposure Assessment of Sediment-Associated Pyrethroids in an Agricultural Watershed

Synthetic pyrethroid insecticides have generated public concerns due to their increasing use and potential effects on aquatic ecosystems. A modeling system was developed in this study for simulating the transport processes and associated sediment toxicity of pyrethroids at coupled field/watershed scales. The model was tested in the Orestimba Creek watershed, an agriculturally intensive area in California' Central Valley. Model predictions were satisfactory when compared with measured suspended solid concentration (R2 = 0.536), pyrethroid toxic unit (0.576), and cumulative mortality of Hyalella azteca (0.570). The results indicated that sediment toxicity in the study area was strongly related to the concentration of pyrethroids in bed sediment. Bifenthrin was identified as the dominant contributor to the sediment toxicity in recent years, accounting for 50–85% of predicted toxicity units. In addition, more than 90% of the variation on the annual maximum toxic unit of pyrethroids was attributed to precipitation and prior application of bifenthrin in the late irrigation season. As one of the first studies simulating the dynamics and spatial variability of pyrethroids in fields and instreams, the modeling results provided useful information on new policies to be considered with respect to pyrethroid regulation. This study suggested two potential measures to efficiently reduce sediment toxicity by pyrethroids in the study area: [1] limiting bifenthrin use immediately before rainfall season; and [2] implementing conservation practices to retain soil on cropland

The NMR restraints grid at BMRB for 5,266 protein and nucleic acid PDB entries

Several pilot experiments have indicated that improvements in older NMR structures can be expected by applying modern software and new protocols (Nabuurs et al. in Proteins 55:483–186, 2004; Nederveen et al. in Proteins 59:662–672, 2005; Saccenti and Rosato in J Biomol NMR 40:251–261, 2008). A recent large scale X-ray study also has shown that modern software can significantly improve the quality of X-ray structures that were deposited more than a few years ago (Joosten et al. in J. Appl Crystallogr 42:376–384, 2009; Sanderson in Nature 459:1038–1039, 2009). Recalculation of three-dimensional coordinates requires that the original experimental data are available and complete, and are semantically and syntactically correct, or are at least correct enough to be reconstructed. For multiple reasons, including a lack of standards, the heterogeneity of the experimental data and the many NMR experiment types, it has not been practical to parse a large proportion of the originally deposited NMR experimental data files related to protein NMR structures. This has made impractical the automatic recalculation, and thus improvement, of the three dimensional coordinates of these structures. We here describe a large-scale international collaborative effort to make all deposited experimental NMR data semantically and syntactically homogeneous, and thus useful for further research. A total of 4,014 out of 5,266 entries were ‘cleaned’ in this process. For 1,387 entries, human intervention was needed. Continuous efforts in automating the parsing of both old, and newly deposited files is steadily decreasing this fraction. The cleaned data files are available from the NMR restraints grid at http://restraintsgrid.bmrb.wisc.edu

Spatio-temporal distribution of pyrethroids in soil in Mediterranean paddy fields

[EN] The demand of rice by the increase in population in many countries has intensified the application of pesticides and the use of poor quality water to irrigate fields. The terrestrial environment is one compartment affected by these situations, where soil is working as a reservoir, retaining organic pollutants. Therefore, it is necessary to develop methods to determine insecticides in soil and monitor susceptible areas to be contaminated, applying adequate techniques to remediate them. Materials and methods This study investigates the occurrence of ten pyrethroid insecticides (PYs) and its spatio-temporal variance in soil at two different depths collected in two periods (before plow and during rice production), in a paddy field area located in the Mediterranean coast. Pyrethroids were quantified using gas chromatography mass spectrometry (GC MS) after ultrasound-assisted extraction with ethyl acetate. The results obtained were assessed statistically using non-parametric methods, and significant statistical differences (p&#8201;<&#8201;0.05) in pyrethroids content with soil depth and proximity to wastewater treatment plants were evaluated. Moreover, a geographic information system (GIS) was used to monitor the occurrence of PYs in paddy fields and detect risk areas. Results and discussion Pyrethroids were detected at concentrations &#8804;57.0 ng g&#8722;1 before plow and &#8804;62.3 ng g&#8722;1 during rice production, being resmethrin and cyfluthrin the compounds found at higher concentrations in soil. Pyrethroids were detected mainly at the top soil, and a GIS program was used to depict the obtained results, showing that effluents from wastewater treatment plants (WWTPs) were the main sources of soil contamination. No toxic effects were expected to soil organisms, but it is of concern that PYs may affect aquatic organisms, which represents the worst case scenario. Conclusions A methodology to determine pyrethroids in soil was developed to monitor a paddy field area. The use of water from WWTPs to irrigate rice fields is one of the main pollution sources of pyrethroids. It is a matter of concern that PYs may present toxic effects on aquatic organisms, as they can be desorbed from soil. Phytoremediation may play an important role in this area, reducing the possible risk associated to PYs levels in soil.Authors wish to thank INIA for the predoctoral fellowship (R. Aznar) and Spanish Ministry of Economy and Competitiveness RTA2014-00012-C03-01 for financial support and Jonathan Villanueva Martin for his contribution to this work.Aznar, R.; Moreno-Ramón, H.; Albero, B.; Sánchez Brunete, C.; Tadeo, JL. (2016). Spatio-temporal distribution of pyrethroids in soil in Mediterranean paddy fields. Journal of Soils and Sediments. 17(5):1503-1513. https://doi.org/10.1007/s11368-016-1417-2S15031513175Albaseer SS, Rao RN, Swamy YV, Mukkanti K (2010) An overview of sample preparation and extraction of synthetic pyrethroids from water, sediment and soil. J Chromatogr A 1217(35):5537–5554Alonso MB, Feo ML, Corcellas C, Vidal LG, Bertozzi CP, Marigo J, Secchi ER, Bassoi M, Azevedo AF, Dorneles PR, Torres JPM, Lailson-Brito J, Malm O, Eljarrat E, Barcelo D (2012) Pyrethroids: a new threat to marine mammals? Environ Int 47:99–106Amweg EL, Weston DP, Ureda NM (2005) Use and toxicity of pyrethroid pesticides in the Central Valley, California, USA. Environ Toxicol Chem 24(4):966–972Arias-Estevez M, Lopez-Periago E, Martinez-Carballo E, Simal-Gandara J, Mejuto JC, Garcia-Rio L (2008) The mobility and degradation of pesticides in soils and the pollution of groundwater resources. Agric Eco Environ 123(4):247–260Aznar R, Albero B, Sanchez-Brunete C, Miguel E, Tadeo JL (2014) Multiresidue analysis of insecticides and other selected environmental contaminants in poultry manure by gas chromatography/mass spectrometry. J AOAC Int 97(4):978–986Campo J, Masia A, Blasco C, Pico Y (2013) Occurrence and removal efficiency of pesticides in sewage treatment plants of four Mediterranean River Basins. J Hazard Mater 263:146–157European Commission (2002) Review report for the active substance Cyfluthrin, 6843/VI/97-finalEuropean Commission (2004) Review report for the active substance α-Cypermethrin, SANCO/4335/2000-finalEuropean Commission (2005) Review report for the active substance Esfenvalerate, 6846/VI/97-finalFeo ML, Ginebreda A, Eljarrat E, Barcelo D (2010) Presence of pyrethroid pesticides in water and sediments of Ebro River Delta. J Hydrol 393(3-4):156–162Fojut TL, Palumbo AJ, Tjeerdema RS (2012) Aquatic life water quality criteria derived via the UC Davis method: II. Pyrethroid insecticides. Rev Environ Contam Toxicol 216:51–103Gan J, Lee SJ, Liu WP, Haver DL, KAbashima JN (2005) Distribution and persistence of pyrethroids in runoff sediments. J Environ Qual 34:836–841Hill IR (1985) Aquatic organisms and pyrethroids. Pestic Sci 27:429–465Huang LM, Thompson A, Zhang GL, Chen LM, Han GZ, Gong ZT (2015) The use of chronosequences in studies of paddy soil evolution: a review. Geoderma 237:199–210Katagi T (2004) Photodegradation of pesticides on plant and soil surfaces. Rev Environ Contam Toxicol 182:1–189Laskowski DA (2002) Physical and chemical properties of pyrethroids. Rev Environ Contam Toxicol 174:49–170Mahabali S, Spagnoghe P (2014) Mitigation of two insecticides by wetlands plants: feasibility study for the treatment of agricultural runoff in Suriname (South America). Water Air Soil Pollut 225:1771Maund SJ, Hamer MJ, Lane MCG, Farrelly E, Rapley JH, Goggin UM, Gentle WE (2002) Partitioning, bioavailability, and toxicity of the pyrethroid insecticide cypermethrin in sediments. Environ Toxicol Chem 21(1):9–15Maund SJ, Campbell PJ, Giddings JM, Hamer MJ, Henry K, Pilling ED, Warinton JS, Wheeler JR (2012) Ecotoxicology of synthetic pyrethroids. Top Curr Chem 314:137–165Money E, Carter GP, Serre ML (2009) Using river distances in the space/time estimation of dissolved oxygen along two impaired river networks in New Jersey. Water Res 43(7):1948–1958Moore MT, Cooper CM, Smith S, Jr Cullum RF, Knight SS, Locke MA, Bennett ER (2009) Mitigation of two pyrethroid insecticides in Mississippi Delta constructed wetland. Environ Pollut 157:250–256Moreno-Ramón H, Marqués-Mateu A, Ibáñez-Asensio S, Gisbert JM (2015) Wetland soils under rice management and seawater intrusion: characterization and classification. Spa J Soil Sci 5(2):111–129Nawaz MF, Bourrie G, Trolard F, Mouret JC, Henry P (2013) Effects of agronomic practices on the physico-chemical properties of soil waters in rice culture. Turk J Agric For 37(2):195–202Oros DR, Werner I (2005) Pyrethroid insecticides: an analysis of use patterns, distributions, potential toxicity and fate in the Sacramento-San Joaquin Delta and Central Valley. White Paper for the Interagency Ecological Program. SFEI Contribution 415. San Francisco Estuary Institute, Oakland, CAPascual-Aguilar J, Andreu V, Gimeno-Garcia E, Pico Y (2015) Current anthropogenic pressures on agro-ecological protected coastal wetlands. Sci Total Environ 03:190–199Soil Survey Staff (2014a) Soil survey field and laboratory methods manual. Soil survey investigations report no. 51, version 2.0. In: Burt R, Soil Survey Staff (eds). U.S. Department of Agriculture, Natural Resources Conservation Service, Washington, p 407Soil Survey Staff (ed) (2014b) Keys to soil taxonomy, 12th edn. USDA-Natural Resources Conservation Service, Washington, p 372Song Y, Kai J, Song X, Zhang W, Li L (2015) Long-term toxic effects of deltamethrin and fenvalerate in soil. J Hazard Mater 289:158–164Weston DP, Holmes RW, You J, Lydy MJ (2005) Aquatic toxicity due to residential use of pyrethroid insecticides. Environ Sci Technol 39(24):9778–9784Weston DP, Ramil HL, Lydy MJ (2013) Pyrethroid insecticides in municipal wastewater. Environ Toxicol Chem 32(11):2460–2468Zhou JL, Rowland S, Mantoura RFC (1995) Partition of synthetic pyrethroid insecticides between dissolved and particulate phases. Water Res 29:1023–110