Search

The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection. [ABSTRACT FROM AUTHOR]

We investigate the asymptotic safety scenario for a scalar-gravity system. This system contains two avatars of the dynamical Newton coupling, a gravitational self-coupling and a scalar-graviton coupling. We uncover an effective universality for the dynamical Newton coupling on the quantum level: its momentum-dependent avatars are in remarkable quantitative agreement in the scaling regime of the UV fixed point. For the background Newton coupling, this effective universality is not present, but qualitative agreement remains.

In the environment, organic micropollutants such as pharmaceuticals can be degraded via various biotic and abiotic transformation routes. In surface waters, for example, photodegradation may constitute a relevant natural attenuation process for drug residues that have been discharged from sewage treatment facilities. In the present work, the photochemical fate of the prodrug enalapril (376 Da, [C.sub.20][H.sub.28][N.sub.2][O.sub.5]) and its active metabolite enalaprilat (348 Da, [C.sub.18][H.sub.24][N.sub.2] [O.sub.5]), a hypotensive cardioprotector previously reported to occur in contaminated rivers, was investigated in aqueous media under the influence of irradiation generated by a sunlight simulator. The experiments yielded three detectable photodegradates for enalapril (346 Da, 2 x 207 Da) whereas the photolysis of enalaprilat went hand in hand with the intermittent buildup of one photodegradate (304 Da). Fragmentation patterns of the parent compounds were established on a hybrid quadrupole-linear ion trap-mass spectrometer exploiting its M[S.sup.3] capabilities. Accurate mass measurements recorded on a hybrid quadrupole-time-of-flight instrument in MS/MS mode allowed us to propose elemental compositions for the molecular ions of the degradates (346 Da, [C.sub.19][H.sub.26][N.sub.2][O.sub.4]; 207 Da, [C.sub.12][H.sub.17]N[O.sub.2]; 304 Da, [C.sub.17][H.sub.24] [N.sub.2][O.sub.3]) as well as of their fragment ions. Based on these complementary data sets from the two distinct mass spectrometric instruments, plausible structures were postulated for the four photodegradates. The compounds formed by enalapril corresponded to the loss of formaldehyde out of the proline residue (346 Da), cleavage of the central amide bond (207 Da) followed by migration of the ethylester side chain (207 Da) while decarboxylation of the free carboxylic acid was described for enalaprilat (304 Da). The study emphasized the potential of sunlight for breaking down an environmentally relevant drug and its metabolite.

Identification of degradation products of environmental contaminants is a challenging task because not only are they present in very low concentrations but they are also mixed with complex matrixes that interfere with detection. This work illustrates a simple approach using ion trap mass spectrometry combined with H/D-exchange experiments to elucidate the structures of iopromide metabolites formed during biodegradafion in activated sludge. Iopromide is an X-ray contrast agent that has been detected frequently in effluents of wastewater treatment plants and in surface waters due to its persistence and high usage. Three metabolites produced by oxidation of the primary alcohols (forming carboxylates) on the side chains of iopromide were identified in a batch reactor with mixed liquor from a conventional activated sludge. Derivatization of the carboxylic acid to form a methyl ester and interpretation of the M[S.sup.2] data of this derivative aided in the confirmation of the identifies of these metabolites. Furthermore, one metabolite formed by dehydroxylation at the two side chains was identified in a batch reactor with mixed liquor from a nitrifying activated sludge. The M[S.sup.2] fragmentation pattern of iopromide and its metabolites revealed that the iodinated ring remains intact and that minor transformations in the structure occur during biodegradafion of iopromide in biological wastewater treatment plants.

In this work, the identification of two microbial degradation products of the antimicrobial trimethoprim (290 Da) is described. The structural elucidation of the metabolites, which were produced by nitrifying activated sludge bacteria in a small-scale laboratory batch reactor, was accomplished by electrospray ionization--ion trap mass spectrometry conducting consecutive fragmentation steps (M[S.sup.n]) combined with H/D-exchange experiments. Although one metabolite corresponded to [alpha]-hydroxytrimethoprim (306 Da), oxidation of the aromatic ring within the diaminopyrimidine substructure was determined for the second degradate (324 Da). Accurate mass measurements of the two metabolites were provided by a hybrid quadrupole time-of-flight-mass spectrometer operated in MS/MS mode. With absolute mass errors of

In the present work, a photoproduct of chlortetracycline (CTC) was identified for the first time in hog lagoon samples from confined animal feeding operations. Screening of several samples by LC/ESI-MS indicated the presence of a potential photooxygenation product of CTC with a nominal mass that was 32 Da higher than the parent drug. Generation of this assumed photoproduct (designated M510) was achieved in a 24-h irradiation experiment of an oxygenated alkaline medium containing 50 mg [L.sup.-1] CTC. Accurate mass measurements with an ESI-TOF-MS of the protonated isomerization product of CTC (iCTC) and the postulated photooxygenation product, bearing two oxygen atoms more than iCTC, were m/z 479.1229 and 511.1109, respectively. These corresponded to errors of -2.8 ppm for iCTC and +1.0 ppm for M510 relative to the theoretical masses. The generation of second- and third-stage mass spectra in an ESI-ion trap-MS showed similar characteristic fragmentation patterns for iCTC and the photoproduct M510, leading to the conclusion that the M510 structure consisted of an iCTC-like skeleton bearing two additional hydroxy groups. The site and configuration of one hydroxylation was confidently assigned, while the position of the other hydroxy group was tentatively assigned. Comparison of the (+)-[ESI-MS.sup.3] spectrum and the retention time of M510 in the sample from the irradiation experiment with those from the hog lagoon samples yielded excellent agreement, suggesting that the compounds were identical. Quantitative analysis of seven hog lagoon samples showed iCTC concentrations of 1910-15 800 [micro]g [L.sup.-1], while the levels of M510 were found to be between 46 and 303 [micro]g [L.sup.-1].

A new method for the quantification of benzoxazinone derivatives in extracts of wheat foliage and root samples using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) is described. Using this method, the characterization, separation, and quantitative detection of a mixture of six naturally occurring 1,4-benzoxazin-3(4H)-one derivatives, including the hydroxamic acids (DIMBOA, DIBOA), lactams (HBOA, and HMBOA), benzoxazilinones (BOA, MBOA), and two synthetic methoxylated variations of DIBOA and HBOA, was achieved. The application of a novel, highly modified reversed-phase LC column, the dodecyl ([C.sub.12]) TMS end-capped Synergi MAX-RP, enhanced the on-line chromatographic separation through improvements to component resolution, analyte stability and peak shape and also to the column lifetime. The complete ESI-MS-MS precursor-product ion fragmentation pathways for the benzoxazinone derivatives are described for the first time and used to deduce a generic fragmentation pattern for the compound class. Characteristic transitions for the benzoxazinones were thus used in the developed analytical method enabling reliable quantification with simultaneous screening for other potentially present derivatives, while eliminating interferences from other coeluting contaminants from the complex plant extract matrix. Quantitative analysis was done in the multiple reaction monitoring mode, using two specific combinations of a precursor-product ion transitions for each compound. The ESI-MS-MS detection method offered improvements to the sensitivity and selectivity, as compared with previously applied LC methods, with detection limits down to 0.002-0.023 ng/ [micro] L. The developed method was demonstrated by analyzing foliages and roots of six different wheat cultivars using pressurized liquid extraction-solid-phase extraction cleanup-LC-ESI-MS-MS. The analytes were detected in the range of 0.7-207 [micro] g/g of dry weight.

Background The role of inflammatory processes in the etiology of schizophrenia is increasingly being investigated. A link between psychosis and inflammation measured with different biomarkers has been reported in the literature and needs to be further explored. To investigate the presence of inflammatory biomarkers in first-episode psychosis (FEP) we analyzed the largest available FEP cohort to date regarding routine CSF and blood diagnostics. Methods We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with a ICD-10 diagnosis of F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture. Results A total of n = 314 FEP patients were included in our sample. 42.7% patients (134/314) showed cerebrospinal fluid (CSF) alterations. Oligoclonal bands in the CSF were present in 21.8% of patients (67/307) with 12.4% (27/217) of patients presenting OCBs type 2 or 3. 15.8% (49/310) of our cohort revealed signs of blood-brain-barrier (BBB) dysfunction with increased albumin ratios. Mean serum CRP levels were 2.4 mg/l (SD = 9.5). CRP elevation was present in 116/280 cases (41.4%). Conclusions This large retrospective analysis on FEP cohort greatly enriches the clinical data available on this population and contributes to the discussion around inflammation in psychosis. Of note, even though several inflammatory alterations were found both in CSF and in blood tests, we found no evidence for a significant relationship between peripheral inflammation and inflammatory CSF. Furthermore, no significant relationship between CSF alterations and peripheral inflammation measured with CRP could be established. [ABSTRACT FROM AUTHOR]

A deeper understanding of COVID‐19 on human molecular pathophysiology is urgently needed as a foundation for the discovery of new biomarkers and therapeutic targets. Here we applied mass spectrometry (MS)‐based proteomics to measure serum proteomes of COVID‐19 patients and symptomatic, but PCR‐negative controls, in a time‐resolved manner. In 262 controls and 458 longitudinal samples of 31 patients, hospitalized for COVID‐19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co‐regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP, and LGALS3BP decreased early in the time course. Regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a system‐wide functional association between proteins, biological processes, and clinical chemistry parameters. Importantly, five SARS‐CoV‐2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS‐based proteomics. The high‐resolution profile of all immunoglobulin regions showed individual‐specific differences and commonalities of potential pathophysiological relevance. SYNOPSIS: A total of 720 proteomes from 458 longitudinal serum samples of hospitalized COVID‐19 cases and 262 symptomatic controls were measured. In‐depth analysis revealed regulation of innate immune and coagulation systems and individual‐specific trajectories of immunoglobulin regions. 26% of the 502 quantified proteins are significantly changed in COVID‐19 patients.The innate immune and the coagulation systems are strongly regulated.MS‐based profiles of immunoglobulin regions allow the detection of seroconversion in a highly detailed fashion on the patient level.ITIH4 may be a prospective marker of COVID‐19 mortality. [ABSTRACT FROM AUTHOR]

Objectives: During the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts. Methods: 443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland). Results: Median seroconversion occurred earlier in ARDS patients (8–9 days) than in non-ARDS patients (11–17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9%) compared to all other assays (≥98.8%) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8%) than that of Elecsys Anti-SARS-CoV-2 (100%). Conclusions: Serial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients. [ABSTRACT FROM AUTHOR]

Abstract Background Testing for cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) by isoelectric focusing is used to detect intrathecally produced total IgG. By contrast, antibody indices (AI) are assessed to test for intrathecally produced antigen-specific IgG. A number of previous cases reports have suggested that AI testing might be more sensitive than OCB testing in detecting intrathecal IgG synthesis. Findings Here we report on 21 patients with positive AI for either herpes simplex virus, varicella zoster virus, cytomegalovirus, measles virus, rubella virus, or Borrelia burgdorferi in the absence of total-IgG OCB and, accordingly, in the presence of a normal total-IgG CSF/serum ratio. Conclusion Our findings indicate that AI testing should not generally be omitted in OCB-negative patients and provide a rationale for systematic and prospective studies on the comparative sensitivity and specificity of AI and total-IgG OCB testing in infectious and other diseases of the CNS.

The degradation of centrally substituted congeners of commercial linear alkylbenzenesulfonate (LAS) by DS-[1.sup.T] strain of Parvibaculum lavamentivorans was examined. LAS yielded both sulfophenyl carboxylates and sulfophenyl dicarboxylates and some minor products and other array of compounds.