262 research outputs found
Easy and convenient millimoleâscale synthesis of new, potential biomarkers for gammaâhydroxybutyric acid (GHB) intake: Feasible for analytical laboratories
New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved drug, gamma-hydroxybutyric acid (GHB), is often illegally used for drug-facilitated crimes by spiking GHB into alcoholic beverages. Analytical detection windows of only 6 h in blood and 12 h in urine are often too short to provide reliable proof of GHB ingestion. Therefore, new biomarkers are needed to prove exogenous GHB administration. Previously, amino acid GHB conjugates were discovered in an untargeted metabolomics screening and fatty acid esters with GHB were recently discussed as promising biomarkers to enlarge the analytical detection time windows. However, the development of analytical methods is still slowed down since reference compounds for targeted screenings are still missing. In this paper, we describe simple procedures for the rapid synthesis and purification of amino acid GHB conjugates as well as fatty acid esters, which can be adopted in analytical and clinical/forensic laboratories. Structural characterization data, together with IR, H-nuclear magnetic resonance (NMR), C-NMR, high-resolution mass spectra (MS), and MS/MS spectra in positive and negative ionization mode are reported for all obtained GHB conjugates and GHB conjugate precursors
The diversity of cyanobacterial metabolism: genome analysis of multiple phototrophic microorganisms
<p>Abstract</p> <p>Background</p> <p>Cyanobacteria are among the most abundant organisms on Earth and represent one of the oldest and most widespread clades known in modern phylogenetics. As the only known prokaryotes capable of oxygenic photosynthesis, cyanobacteria are considered to be a promising resource for renewable fuels and natural products. Our efforts to harness the sun's energy using cyanobacteria would greatly benefit from an increased understanding of the genomic diversity across multiple cyanobacterial strains. In this respect, the advent of novel sequencing techniques and the availability of several cyanobacterial genomes offers new opportunities for understanding microbial diversity and metabolic organization and evolution in diverse environments.</p> <p>Results</p> <p>Here, we report a whole genome comparison of multiple phototrophic cyanobacteria. We describe genetic diversity found within cyanobacterial genomes, specifically with respect to metabolic functionality. Our results are based on pair-wise comparison of protein sequences and concomitant construction of clusters of likely ortholog genes. We differentiate between core, shared and unique genes and show that the majority of genes are associated with a single genome. In contrast, genes with metabolic function are strongly overrepresented within the core genome that is common to all considered strains. The analysis of metabolic diversity within core carbon metabolism reveals parts of the metabolic networks that are highly conserved, as well as highly fragmented pathways.</p> <p>Conclusions</p> <p>Our results have direct implications for resource allocation and further sequencing projects. It can be extrapolated that the number of newly identified genes still significantly increases with increasing number of new sequenced genomes. Furthermore, genome analysis of multiple phototrophic strains allows us to obtain a detailed picture of metabolic diversity that can serve as a starting point for biotechnological applications and automated metabolic reconstructions.</p
Aufregung, schöne Bilder und enttĂ€uschte Erwartungen Wie die Medien ĂŒber den Deutschlandbesuch von Papst Benedikt XVI. berichtet haben
Es kommt selten vor, dass Ansprachen im Bundestag anmoderiert werden â ein kurzes Aufrufen des Redners muss normalerweise genĂŒgen. Wenn aber, wie am 22. September geschehen, im deutschen Parlament der Papst ans Rednerpult tritt, dann lĂ€sst sich der BundestagsprĂ€sident Vorbemerkungen nicht nehmen: âSelten hat eine Rede in diesem Haus, noch bevor sie gehalten wurde, so viel Aufmerksamkeit und Interesse gefundenâ, sagte Norbert Lammert unmittelbar nach der BegrĂŒĂung Benedikts XVI., und das klang fast wie bei den BegrĂŒĂungsworten jener zahlreicher Talkshows, die in den Tagen vor der Ankunft des Papstes ĂŒber den Bildschirm geflimmert waren und unter anderem den bevorstehenden Auftritt im Bundestag und das Fernbleiben einiger Parlamentarier erörterten. (...
Magnetoelectrically driven catalytic degradation of organics
Here, we report the catalytic degradation of organic compounds by exploiting
the magnetoelectric (ME) nature of cobalt ferrite-bismuth ferrite (CFO-BFO)
core-shell nanoparticles. The combination of magnetostrictive CFO with the
multiferroic BFO gives rise to a magnetoelectric engine that purifies water
under wireless magnetic fields via advanced oxidation processes, without
involvement of any sacrificial molecules or co-catalysts. Magnetostrictive
CoFe2O4 nanoparticles are fabricated using hydrothermal synthesis, followed by
sol-gel synthesis to create the multiferroic BiFeO3 shell. We perform
theoretical modeling to study the magnetic field induced polarization on the
surface of magnetoelectric nanoparticles. The results obtained from these
simulations are consistent with the experimental findings of the piezo-force
microscopy analysis, where we observe changes in the piezoresponse of the
nanoparticles under magnetic fields. Next, we investigate the magnetoelectric
effect induced catalytic degradation of organic pollutants under AC magnetic
fields and obtained 97% removal efficiency for synthetic dyes and over 85%
removal efficiency for routinely used pharmaceuticals. Additionally, we perform
trapping experiments to elucidate the mechanism behind the magnetic field
induced catalytic degradation of organic pollutants by using scavengers for
each of the reactive species. Our results indicate that hydroxyl and superoxide
radicals are the main reactive species in the magnetoelectrically induced
catalytic degradation of organic compounds
Urinary concentrations of GHB and its novel amino acid and carnitine conjugates following controlled GHB administration to humans
Gamma-hydroxybutyrate (GHB) remains a challenging clinical/forensic toxicology drug. Its rapid elimination to endogenous levels mainly causes this. Especially in drug-facilitated sexual assaults, sample collection often occurs later than the detection window for GHB. We aimed to investigate new GHB conjugates with amino acids (AA), fatty acids, and its organic acid metabolites for their suitability as ingestion/application markers in urine following controlled GHB administration to humans. We used LCâMS/MS for validated quantification of human urine samples collected within two randomized, double-blinded, placebo-controlled crossover studies (GHB 50 mg/kg, 79 participants) at approximately 4.5, 8, 11, and 28 h after intake. We found significant differences (placebo vs. GHB) for all but two analytes at 4.5 h. Eleven hours post GHB administration, GHB, GHB-AAs, 3,4-dihydroxybutyric acid, and glycolic acid still showed significantly higher concentrations; at 28 h only GHB-glycine. Three different discrimination strategies were evaluated: (a) GHB-glycine cut-off concentration (1 ”g/mL), (b) metabolite ratios of GHB-glycine/GHB (2.5), and (c) elevation threshold between two urine samples (>â5). Sensitivities were 0.1, 0.3, or 0.5, respectively. Only GHB-glycine showed prolonged detection over GHB, mainly when compared to a second time- and subject-matched urine sample (strategy c)
The functional connectome of 3,4âmethyldioxymethamphetamineârelated declarative memory impairments
The chronic intake of 3,4âmethylenedioxymethamphetamine (MDMA, âecstasyâ) bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a dataâdriven multiâvoxel pattern analysis (MVPA) approach on participants' restingâstate functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to wellâmatched controls with moderateâtoâstrong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seedâbased connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seedâbased connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMAârelated memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing
Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP).; We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome.; Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin.; In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation
Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex
Background: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used recreational substance inducing acute release of serotonin. Previous studies in chronic MDMA users demonstrated selective adaptations in the serotonin system, which were assumed to be associated with cognitive deficits. However, serotonin functions are strongly entangled with glutamate as well as Îł-aminobutyric acid (GABA) neurotransmission, and studies in MDMA-exposed rats show long-term adaptations in glutamatergic and GABAergic signaling.
Methods: We used proton magnetic resonance spectroscopy (MRS) to measure the glutamate-glutamine complex (GLX) and GABA concentrations in the left striatum and medial anterior cingulate cortex (ACC) of 44 chronic but recently abstinent MDMA users and 42 MDMA-naĂŻve healthy controls. While the Mescher-Garwood point-resolved-spectroscopy sequence (MEGA-PRESS) is best suited to quantify GABA, recent studies reported poor agreement between conventional shortâecho-time PRESS and MEGA-PRESS for GLX measures. Here, we applied both sequences to assess their agreement and potential confounders underlying the diverging results.
Results: Chronic MDMA users showed elevated GLX levels in the striatum but not the ACC. Regarding GABA, we found no group difference in either region, although a negative association with MDMA use frequency was observed in the striatum. Overall, GLX measures from MEGA-PRESS, with its longer echo time, appeared to be less confounded by macromolecule signal than the shortâecho-time PRESS and thus provided more robust results.
Conclusion: Our findings suggest that MDMA use affects not only serotonin but also striatal GLX and GABA concentrations. These insights may offer new mechanistic explanations for cognitive deficits (e.g., impaired impulse control) observed in MDMA users
Following the TraCS of exoplanets with Pan-Planets: Wendelstein-1b and Wendelstein-2b
Hot Jupiters seem to get rarer with decreasing stellar mass. The goal of the
Pan-Planets transit survey was the detection of such planets and a statistical
characterization of their frequency. Here, we announce the discovery and
validation of two planets found in that survey, Wendelstein-1b and
Wendelstein-2b, which are two short-period hot Jupiters that orbit late K host
stars. We validated them both by the traditional method of radial velocity
measurements with the HIgh Resolution Echelle Spectrometer (HIRES) and the
Habitable-zone Planet Finder (HPF) instruments and then by their Transit Color
Signature (TraCS). We observed the targets in the wavelength range of Angstr\"om and performed a simultaneous multiband transit fit and
additionally determined their thermal emission via secondary eclipse
observations. Wendelstein-1b is a hot Jupiter with a radius of
and mass of ,
orbiting a K7V dwarf star at a period of d, and has an estimated surface
temperature of about K. Wendelstein-2b is a hot Jupiter with
a radius of and a mass of
, orbiting a K6V dwarf star at a period of
d, and has an estimated surface temperature of about
K. With this, we demonstrate that multiband photometry is
an effective way of validating transiting exoplanets, in particular for fainter
targets since radial velocity (RV) follow-up becomes more and more costly for
those targets.Comment: 14 pages, 12 figures. Accepted for publication in A&
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