Publications by authors named "Frank Schmidt"

219 Publications

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells.

Stem Cells Int 2021 15;2021:8274936. Epub 2021 Oct 15.

Basic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha, Qatar.

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2 phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells.
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http://dx.doi.org/10.1155/2021/8274936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538399PMC
October 2021

Criterion Validity of the Implicit Positive and Negative Affect Test: Prediction of Facial Affect Perception.

Front Psychol 2021 1;12:635368. Epub 2021 Oct 1.

Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig Medical Centre, Leipzig, Germany.

This study focused on the criterion-related validity of the Implicit Positive and Negative Affect Test (IPANAT). The IPANAT is thought to be a measure of automatic activation of cognitive representations of affects. In this study, it was investigated whether implicit affect scores differentially predict ratings of facial emotions over and above explicit affectivity. Ninety-six young female participants completed the IPANAT, the Positive and Negative Affect Schedule (PANAS) as an explicit measure of state and trait affectivity, and a task for the perception of facial emotions. Implicit negative affect predicted the perception of negative but not positive facial emotions, whereas implicit positive affect predicted the perception of positive but not negative facial emotions. The observed double-dissociation in the correlational pattern strongly supports the validity of the IPANAT as a measure of implicit affectivity and is indicative of the orthogonality and thus functional distinctness of the two affect dimensions of the IPANAT. Moreover, such affect-congruent correlations were absent for explicit affect scales, which additionally supports the incremental validity of the IPANAT.
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http://dx.doi.org/10.3389/fpsyg.2021.635368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517336PMC
October 2021

Clinical Use and Outcome of Extracorporeal Membrane Oxygenation in Patients with Pulmonary Embolism.

Resuscitation 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiology, University Medical Center Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center, Mainz, Germany; Medical Clinic VII, University Hospital Heidelberg, Heidelberg, Germany.

Aim: of the study: Extracorporeal membrane oxygenation (ECMO) is considered a life-saving treatment option for patients in cardiogenic shock or cardiac arrest undergoing cardiopulmonary resuscitation (CPR) due to acute pulmonary embolism (PE). We sought to analyze use and outcome of ECMO with or without adjunctive treatment strategies in patients with acute PE.

Methods: We retrospectively analyzed data on patient characteristics, treatments, and in-hospital outcomes for all PE patients (ICD-code I26) undergoing ECMO in Germany between 2005 and 2018.

Results: At total of 1,172,354 patients were hospitalized with PE; of those, 2,197 (0.2%) were treated with ECMO support. Cardiac arrest requiring cardiopulmonary resuscitation was present in 77,196 (6.5%) patients. While more than one fourth of those patients were treated with systemic thrombolysis alone (n=20,839 patients; 27.0%), a minority of patients received thrombolysis and VA-ECMO (n=165; 0.2%), embolectomy and VA-ECMO (n=385; 0.5%) or VA-ECMOalone (n=588; 0.8%). A multivariable logistic regression analysis indicated the lowest risk for in-hospital death in patients who received embolectomy in combination with VA-ECMO (OR, 0.50 [95%CI, 0.41-0.61], P<0.001), thrombolysis and VA-ECMO (0.60 [0.43-0.85], P=0.003) or VA-ECMO alone (0.68 [0.57-0.82], P<0.001) compared to thrombolysis alone (1.04 [0.99-1.01], P=0.116).

Conclusion: Our findings suggest that the use of VA-ECMO alone or as part of a multi-pronged reperfusion approach including embolectomy or thrombolysis might offer survival advantages compared to thrombolysis alone in patients with PE deteriorating to cardiac arrest.
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http://dx.doi.org/10.1016/j.resuscitation.2021.10.007DOI Listing
October 2021

TNF-α blockade may lead to improvement of vascular function in psoriasis patients.

Exp Dermatol 2021 Aug 25. Epub 2021 Aug 25.

Department of Dermatology, University of Cologne, University Hospital Cologne and Faculty of Medicine Cologne, Cologne, Germany.

Psoriasis is one of the most common chronic inflammatory skin diseases and at the same time a risk factor for cardiovascular disease. Interleukin-17A (IL-17A)-mediated inflammation in psoriasis may lead to vascular dysfunction. This study aimed at investigating whether anti-inflammatory treatment by tumor necrosis factor (TNF)-α blockade alters vascular function in psoriasis patients. A total of 11 patients with psoriasis who underwent treatment with either adalimumab (n = 8) or etanercept (n = 3), 10 healthy control individuals and 14 patients with coronary artery disease (CAD) were included in this study. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI) score. Endothelial reactivity and resting endothelium-dependent vascular tone were assessed by ultrasound measurement of flow-mediated dilation (FMD) and low-flow-mediated constriction (l-FMC), respectively. FMD was slightly impaired in psoriasis patients compared to healthy controls. Anti-TNF-α treatment did not significantly change FMD levels. Psoriasis patients showed a trend towards increased baseline vascular activity compared to healthy controls. Anti-TNF-α treatment significantly improved l-FMC in psoriasis patients. Noteworthy, both FMD and l-FMC in psoriasis patients were comparable to those in patients with CAD; however, an important influence of age differences between the groups or co-existent classical cardiovascular risk factors on FMD and l-FMC cannot be ruled out by our small study. The results suggest that anti-inflammatory treatment with TNF-α blockade improves vascular function in patients with psoriasis, mainly by altering baseline vascular tone. Further studies will be necessary to establish the potentially protective impact of anti-inflammatory therapy on vascular function in patients with chronic inflammatory diseases.
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http://dx.doi.org/10.1111/exd.14452DOI Listing
August 2021

Inflammation and the Association of Vitamin D and Depressive Symptomatology.

Nutrients 2021 Jun 8;13(6). Epub 2021 Jun 8.

Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, 04103 Leipzig, Germany.

Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample ( = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes' PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: -0.0042) and a model including covariates (ab: -0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.
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http://dx.doi.org/10.3390/nu13061972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229745PMC
June 2021

Attentional processes during emotional face perception in social anxiety disorder: A systematic review and meta-analysis of eye-tracking findings.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Dec 15;111:110353. Epub 2021 May 15.

Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig Medical Center, Leipzig, Germany. Electronic address:

Background In recent years, a growing body of eye-tracking research has investigated gaze behavior in individuals with social anxiety during the visual perception of emotional stimuli. The aim of this article was to review and synthesize studies examining attention orientation in patients with clinical social anxiety by means of eye-tracking methodology. Methods Through a systematic search, 30 articles were identified, including 11 studies in which single emotional faces were used as stimuli and seven eligible studies in which threatening faces were paired with neutral stimuli. Meta-analyses were conducted to compare prolonged eye-contact behavior and early attentional biases to threats in individuals with social anxiety disorder (SAD) and healthy controls. Results Moderate group differences were revealed for single face viewing studies, with SAD patients showing significantly reduced eye contact with negative (Hedges' g = -0.67) and positive emotional faces (g = -0.49) compared to that of healthy participants. Type of task and duration of stimulus presentation were (marginally) significant moderators of between-study variance in effect size. Small but significant group differences were found for early attentional biases toward angry faces versus neutral stimuli (g = 0.21) but not toward happy faces versus neutral stimuli (g = 0.05). Preliminary evidence for a hyperscanning strategy in SAD patients relative to healthy controls emerged (g = 0.42). Limitations The number of included studies with face pairings was low, and two studies were excluded due to unavailable data. Conclusions Our results suggest that eye contact avoidance with emotional faces is a prominent feature in SAD patients. Patients might benefit from guidance to learn to make adequate eye contact during therapeutic interventions, such as exposure therapy. SAD patients demonstrated slightly heightened attention allocation toward angry faces relative to that of healthy participants during early processing stages. Threat biases can be potential targets for attention modification training as an adjuvant to other treatments. Future research on early attentional processes may benefit from improved arrangements of paired stimuli to increase the psychometric properties of initial attention indices.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110353DOI Listing
December 2021

SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways.

Sci Rep 2021 04 14;11(1):8177. Epub 2021 Apr 14.

Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar.

The NAD-dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote SIRT1 function such as SIRT1 overexpression or NAD boosters alleviate metabolic complications. We previously reported that SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, and dysregulated adipocyte metabolism. Here, we characterized SIRT1-depleted adipocytes by quantitative mass spectrometry-based proteomics, gene-expression and biochemical analyses, and mitochondrial studies. We found that SIRT1 promoted mitochondrial biogenesis and respiration in adipocytes and expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, and thyroid responsive protein was SIRT1-dependent. Independent validation of the proteomics dataset uncovered SIRT1-dependence of SREBF1c and PPARα signaling in adipocytes. SIRT1 promoted nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) expression during 3T3-L1 differentiation and constitutively repressed NMNAT1 and 3 levels. Supplementing preadipocytes with the NAD booster nicotinamide mononucleotide (NMN) during differentiation increased expression levels of leptin, SIRT1, and PGC-1α and its transcriptional targets, and reduced levels of pro-fibrotic collagens (Col6A1 and Col6A3) in a SIRT1-dependent manner. Investigating the metabolic impact of the functional interaction of SIRT1 with SREBF1c and PPARα and insights into how NAD metabolism modulates adipocyte function could potentially lead to new avenues in developing therapeutics for obesity complications.
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http://dx.doi.org/10.1038/s41598-021-87759-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046990PMC
April 2021

A Comprehensive View on the Human Antibody Repertoire Against Antigens in the General Population.

Front Immunol 2021 10;12:651619. Epub 2021 Mar 10.

Department Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

Our goal was to provide a comprehensive overview of the antibody response to antigens in the general population as a basis for defining disease-specific profiles and diagnostic signatures. We tested the specific IgG and IgA responses to 79 staphylococcal antigens in 996 individuals from the population-based Study of Health in Pomerania. Using a dilution-based multiplex suspension array, we extended the dynamic range of specific antibody detection to seven orders of magnitude, allowing the precise quantification of high and low abundant antibody specificities in the same sample. The observed IgG and IgA antibody responses were highly heterogeneous with differences between individuals as well as between bacterial antigens that spanned several orders of magnitude. Some antigens elicited significantly more IgG than IgA and vice versa. We confirmed a strong influence of colonization on the antibody response and quantified the influence of sex, smoking, age, body mass index, and serum glucose on anti-staphylococcal IgG and IgA. However, all host parameters tested explain only a small part of the extensive variability in individual response to the different antigens of .
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http://dx.doi.org/10.3389/fimmu.2021.651619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987813PMC
September 2021

Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity.

mSystems 2021 Mar 2;6(2). Epub 2021 Mar 2.

Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany.

Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as "sputa") from ventilated patients was only partially explained by antibiotic therapy. Here we report that sputa from these patients presented distinct proteome signatures depending on the presence or absence of antimicrobial activity. Moreover, we show that the same distinction applied to antibodies against , which is a major causative agent of pneumonia. Specifically, the investigated sputa that inhibited growth of , while containing subinhibitory levels of the antibiotic cefotaxime, presented elevated levels of proteins implicated in innate immune defenses, including complement and apolipoprotein-associated proteins. In contrast, -inhibiting sputa with relatively high cefotaxime concentrations or noninhibiting sputa contained higher levels of proteins involved in inflammatory responses, such as neutrophil elastase-associated proteins. In an immunoproteomics analysis, 18 out of 55 antigens tested showed significantly increased levels of IgGs in inhibiting sputa. Hence, proteomics and immunoproteomics revealed elevated levels of antimicrobial host proteins or antigen-specific IgGs in pneumococcal growth-inhibiting sputa, thus explaining their anti-pneumococcal activity. Respiratory pathogens like can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. This suggests the presence of potentially protective antimicrobial agents in their lung environment. Our present study shows for the first time that bronchoalveolar aspirates, "sputa," of ventilated patients in a Dutch intensive care unit were characterized by three distinct groups of proteome abundance signatures that can explain their anti-pneumococcal activity. Importantly, this anti-pneumococcal sputum activity was related either to elevated levels of antimicrobial host proteins or to antibiotics and -specific antibodies. Further, the sputum composition of some patients changed over time. Therefore, we conclude that our study may provide a novel tool to measure changes that are indicative of infection-related conditions in the lungs of mechanically ventilated patients.
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http://dx.doi.org/10.1128/mSystems.00702-20DOI Listing
March 2021

Specific domain V reduction of beta-2-glycoprotein I induces protein flexibility and alters pathogenic antibody binding.

Sci Rep 2021 Feb 25;11(1):4542. Epub 2021 Feb 25.

Institute of Biochemistry, University of Greifswald, Greifswald, Germany.

Beta-2-glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder antiphospholipid syndrome (APS). β2GPI exists mainly in closed or open conformations and comprises of 11 disulfides distributed across five domains. The terminal Cys288/Cys326 disulfide bond at domain V has been associated with different cysteine redox states. The role of this disulfide bond in conformational dynamics of this protein has not been investigated so far. Here, we report on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine; TCEP) of β2GPI. Specific reduction was demonstrated by Western blot and mass spectrometry analyses confirming majority targeting to the fifth domain of β2GPI. Atomic force microscopy images suggested that reduced β2GPI shows a slightly higher proportion of open conformation and is more flexible compared to the untreated protein as confirmed by modelling studies. We have determined a strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI as demonstrated by ELISA. Our study is relevant for understanding the effect of β2GPI reduction on the protein structure and its implications for antibody binding in APS patients.
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http://dx.doi.org/10.1038/s41598-021-84021-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907366PMC
February 2021

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

Eur Heart J Acute Cardiovasc Care 2021 May;10(3):258-264

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstrasse 1, 55131 Mainz, Germany.

Aims: Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.

Methods And Results: Data from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving systemic thrombolysis (OPS code 8-020.8), and those without thrombolytic or other reperfusion treatment. The analysis was not prespecified; therefore, our findings can only be considered to be hypothesis generating. We analysed data from 978 094 hospitalized patients with PE. Of these, 41 903 (4.3%) patients received thrombolytic treatment [systemic thrombolysis in 4.2%, CDT in 0.1% (1175 patients)]. Among patients with shock, CDT was associated with lower in-hospital mortality compared to systemic thrombolysis [odds ratios (OR) 0.30 (95% 0.14-0.67); P = 0.003]. Intracranial bleeding occurred in 14 (1.2%) patients who received CDT. Among haemodynamically stable patients with right ventricular dysfunction (intermediate-risk PE), CDT also was associated with a lower risk of in-hospital mortality compared to systemic thrombolysis {OR 0.55 [95% confidence interval (CI) 0.40-0.75]; P < 0.001} or no thrombolytic treatment [0.45 (95% CI 0.33-0.62); P < 0.001].

Conclusion: In the German nationwide inpatient cohort, based on administrative data, CDT was associated with lower in-hospital mortality rates compared to systemic thrombolysis, but the overall rate of intracranial bleeding in patients who received CDT was not negligible. Prospective controlled data are urgently needed to determine the true value of this treatment option in acute PE.
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http://dx.doi.org/10.1093/ehjacc/zuaa026DOI Listing
May 2021

Fatigue and brain arousal in patients with major depressive disorder.

Eur Arch Psychiatry Clin Neurosci 2021 Apr 4;271(3):527-536. Epub 2020 Dec 4.

Depression Research Center, German Depression Foundation, Leipzig, Germany.

Fatigue is considered a key symptom of major depressive disorder (MDD), yet the term lacks specificity. It can denote a state of increased sleepiness and lack of drive (i.e., downregulated arousal) as well as a state of high inner tension and inhibition of drive with long sleep onset latencies (i.e., upregulated arousal), the latter typically found in depression. It has been proposed to differentiate fatigue along the dimension of brain arousal. We investigated whether such stratification within a group of MDD patients would reveal a subgroup with distinct clinical features. Using an automatic classification of EEG vigilance stages, an arousal stability score was calculated for 15-min resting EEGs of 102 MDD patients with fatigue. 23.5% of the patients showed signs of hypoarousal with EEG patterns indicating drowsiness or sleep; this hypoaroused subgroup was compared with remaining patients (non-hypoaroused subgroup) concerning self-rated measures of depressive symptoms, sleepiness, and sleep. The hypoaroused subgroup scored higher on the Beck Depression Inventory items "loss of energy" (Z = - 2.13, p = 0.033; ɳ = 0.044, 90% CI 0.003-0.128) and "concentration difficulty" (Z = - 2.40, p = 0.017; ɳ = 0.056, 90% CI 0.009-0.139), and reported higher trait and state sleepiness (p < 0.05) as compared to the non-hypoaroused group. The non-hypoaroused subgroup, in contrast, reported more frequently the presence of suicidal ideation (Chi = 3.81, p = 0.051; ɳ = 0.037, 90% CI 0.0008-0.126). In this study, we found some evidence that stratifying fatigued MDD patients by arousal may lead to subgroups that are pathophysiologically and clinically more homogeneous. Brain arousal may be a worth while target in clinical research for better understanding the mechanisms underlying suicidal tendencies and to improve treatment response.
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http://dx.doi.org/10.1007/s00406-020-01216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981331PMC
April 2021

Exploring metal availability in the natural niche of to discover potential vaccine antigens.

Virulence 2020 12;11(1):1310-1328

Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.

Nasopharyngeal colonization by is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of . Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.
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http://dx.doi.org/10.1080/21505594.2020.1825908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550026PMC
December 2020

Comparative Proteomic Profiling of 3T3-L1 Adipocyte Differentiation Using SILAC Quantification.

J Proteome Res 2020 12 8;19(12):4884-4900. Epub 2020 Oct 8.

Proteomics Core, Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, PO 24144 Doha, Qatar.

Adipocyte differentiation is a general physiological process that is also critical for metabolic syndrome. In spite of extensive study in the past two decades, adipogenesis is a still complex cellular process that is accompanied by complicated molecular mechanisms. Here, we performed SILAC-based quantitative global proteomic profiling of 3T3-L1 adipocyte differentiation. We report protein changes to the proteome profiles, with 354 proteins exhibiting significant increase and 56 proteins showing decrease in our statistical analysis. Our results show that adipocyte differentiation is involved not only in metabolic processes by increasing TCA cycle, fatty acid synthesis, lipolysis, acetyl-CoA production, antioxidants, and electron transport, but also in nicotinamide metabolism, cristae formation, mitochondrial protein import, and Ca transport into mitochondria and ER. A search for Chromosome-Centric Human Proteome Project (C-HPP) using neXtprot highlighted one protein with a protein existence uncertain (PE5) and 17 proteins as functionally uncharacterized protein existence 1 (uPE1). This study provides quantitative information on proteome changes in adipogenic differentiation, which is helpful in improving our understanding of the processes of adipogenesis.
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http://dx.doi.org/10.1021/acs.jproteome.0c00475DOI Listing
December 2020

The impact of aircraft noise on vascular and cardiac function in relation to noise event number: a randomized trial.

Cardiovasc Res 2021 04;117(5):1382-1390

Department of Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.

Aims: Nighttime aircraft noise exposure has been associated with increased risk of hypertension and myocardial infarction, mechanistically linked to sleep disturbance, stress, and endothelial dysfunction. It is unclear, whether the most widely used metric to determine noise exposure, equivalent continuous sound level (Leq), is an adequate indicator of the cardiovascular impact induced by different noise patterns.

Methods And Results: In a randomized crossover study, we exposed 70 individuals with established cardiovascular disease or increased cardiovascular risk to two aircraft noise scenarios and one control scenario. Polygraphic recordings, echocardiography, and flow-mediated dilation (FMD) were determined for three study nights. The noise patterns consisted of 60 (Noise60) and 120 (Noise120) noise events, respectively, but with comparable Leq, corresponding to a mean value of 45 dB. Mean value of noise during control nights was 37 dB. During the control night, FMD was 10.02 ± 3.75%, compared to 7.27 ± 3.21% for Noise60 nights and 7.21 ± 3.58% for Noise120 nights (P < 0.001). Sleep quality was impaired after noise exposure in both noise scenario nights (P < 0.001). Serial echocardiographic assessment demonstrated an increase in the E/E' ratio, a measure of diastolic function, within the three exposure nights, with a ratio of 6.83 ± 2.26 for the control night, 7.21 ± 2.33 for Noise60 and 7.83 ± 3.07 for Noise120 (P = 0.043).

Conclusions: Nighttime exposure to aircraft noise with similar Leq, but different number of noise events, results in a comparable worsening of vascular function. Adverse effects of nighttime aircraft noise exposure on cardiac function (diastolic dysfunction) seemed stronger the higher number of noise events.
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http://dx.doi.org/10.1093/cvr/cvaa204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064430PMC
April 2021

Is There an Association or Not?-Investigating the Association of Depressiveness, Physical Activity, Body Composition and Sleep With Mediators of Inflammation.

Front Psychiatry 2020 25;11:563. Epub 2020 Jun 25.

Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Germany.

Background: Cytokines are mediators of inflammation that contribute to a low-grade inflammation in different disorders like major depression and obesity. It still remains unclear which psychological and medical factors interact with cytokine regulation. In the current investigation, the association between levels of pro-and anti-inflammatory cytokines and anthropometrics, mood state (depressiveness), physical activity and sleep were investigated in a sample of community-dwelled adults.

Methods: Forty-nine subjects met the inclusion criteria for analyses and were assessed at two time-points (baseline (T1) and follow-up (T2), average T1-T2-interval = 215 days). Serum cytokine measures included the pro-inflammatory cytokines interleukin (IL)-2, IL-12, IFN-γ and TNF-α, the anti-inflammatory cytokines IL-4, IL-5, IL-10 and IL-13 and the granulocyte-macrophage colony-stimulating factor (GM-CSF); anthropometrics were assessed physical examination, depressiveness was assessed Beck Depression Inventory (BDI)2, parameters of physical activity (steps, METs) and sleep (night/total sleep duration) were measured a 1-week actigraphy.

Results: Correlation analyses showed low-to moderate significant relationships between the majority of cytokines and the BDI2 at T1, positive correlation with weight and BMI at T1 and T2, and negative correlations with the number of steps and METs at T2 and T2. Regression analyses for T1 revealed that the BDI2 score was the best positive predictor for the concentrations of all nine cytokines, followed by the number of steps and the nightsleep duration as negative predictors. At T2, the amount of steps was found to be negatively associated with IL-4, IL5, IL-10, GM-CSF, IFN-γ, and TNF-α, whereas the BMI could significantly predict IL-12 and IL-13. The BDI2-score was not significantly associated with any of the cytokines. No associations could be found between dynamics in cytokines from T1 and T2 and changes in any of the variables.

Discussion: The present results indicate an influence of physical activity, subjective well-being and body composition on inflammatory mediators. Since there was no standardized intervention targeting the independent variables between T1 and T2, no assumptions on causality can be drawn from the association results.
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http://dx.doi.org/10.3389/fpsyt.2020.00563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330708PMC
June 2020

Reported and Recorded Sleepiness in Obesity and Depression.

Front Psychiatry 2020 2;11:200. Epub 2020 Apr 2.

Institute for Statistics, Ludwig-Maximilians-Universität München, München, Germany.

Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.

Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.

Methods: Healthy controls (HC, N = 66), normal-weighted depressed (DEP, N = 16), non-depressed obese (OB, N = 68), and obese depressed patients (OBDEP, N = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.

Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.

Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
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http://dx.doi.org/10.3389/fpsyt.2020.00200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144401PMC
April 2020

Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology.

Proc Natl Acad Sci U S A 2020 03 6;117(12):6752-6761. Epub 2020 Mar 6.

Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, United Kingdom;

A type of chromosome-free cell called SimCells (simple cells) has been generated from , , and The removal of the native chromosomes of these bacteria was achieved by double-stranded breaks made by heterologous I-CeuI endonuclease and the degradation activity of endogenous nucleases. We have shown that the cellular machinery remained functional in these chromosome-free SimCells and was able to process various genetic circuits. This includes the glycolysis pathway (composed of 10 genes) and inducible genetic circuits. It was found that the glycolysis pathway significantly extended longevity of SimCells due to its ability to regenerate ATP and NADH/NADPH. The SimCells were able to continuously express synthetic genetic circuits for 10 d after chromosome removal. As a proof of principle, we demonstrated that SimCells can be used as a safe agent (as they cannot replicate) for bacterial therapy. SimCells were used to synthesize catechol (a potent anticancer drug) from salicylic acid to inhibit lung, brain, and soft-tissue cancer cells. SimCells represent a simplified synthetic biology chassis that can be programmed to manufacture and deliver products safely without interference from the host genome.
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http://dx.doi.org/10.1073/pnas.1918859117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104398PMC
March 2020

Air filters for indoor environments: Interlaboratory evaluation of the new international filter testing standard ISO 16890.

Indoor Air 2020 05 9;30(3):473-480. Epub 2020 Mar 9.

Nanoparticle Process Technology (NPPT), University of Duisburg-Essen, Duisburg, Germany.

Electret filters are widely used in HVAC systems to decrease particulate matter in indoor environments. The previous standard in Europe for testing air filters for general ventilation was EN 779. In July 2018, it was replaced by the new international standard ISO 16890. One major change is the discharging process: It is now performed by treating the filters with saturated isopropyl alcohol (IPA) vapor. The process is intended to simulate a worst-case scenario of the filtration efficiency due to the reduction of the electret effect. These minimal efficiencies are a principal part of the filter classification. Therefore, two round robin tests with different filter classes (F9 and F7 according to EN 779) and up to eleven participants were carried out to evaluate the new test method by comparing the filtration efficiencies and pressure drops before and after the IPA treatment. Pressure drop measurements showed no mechanical altering of the material due to the discharging process. The calculated filter classes had a maximum deviation of 5%. Even with different equipment, the results indicate that the new ISO 16890 seems to be a viable test standard and a decent replacement for previous national standards.
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http://dx.doi.org/10.1111/ina.12660DOI Listing
May 2020

Long-term cardiovascular risk of e-cigarettes.

Eur Heart J 2020 04;41(15):1526

Department of Cardiology, University Medical Center Mainz, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehaa079DOI Listing
April 2020

Early-Stage Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors.

mSystems 2020 Jan 21;5(1). Epub 2020 Jan 21.

ZIK-FunGene, Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

Systemic and quantitative investigations of human plasma proteins (proteomics) and -specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in bloodstream infection (SABSI). Usually, data-dependent acquisition (DDA) is used for proteome analysis of serum or plasma, but data-independent acquisition (DIA) is more comprehensive and reproducible. In this prospective cohort study, we aimed to identify biomarkers associated with the early stages of SABSI using a serum DIA proteomic and immunoproteomic approach. Sera from 49 SABSI patients and 43 noninfected controls were analyzed. In total, 608 human serum proteins were identified with DIA. A total of 386 proteins could be quantified, of which 9 proteins, mainly belonging to acute-phase proteins, were significantly increased, while 7 high-density lipoproteins were lower in SABSI. In SABSI, total anti- serum IgG was reduced compared with controls as shown by immunoproteomic quantification of IgG binding to 143 antigens. IgG binding to 48 of these anti- proteins was significantly lower in SABSI, while anti-Ecb IgG was the only one increased in SABSI. Serum IgG binding to autoinducing peptide MsrB, FadB, EsxA, Pbp2, FadB, SspB, or SodA was very low in SABSI. This marker panel discriminated early SABSI from controls with 95% sensitivity and 100% specificity according to random forest prediction. This holds promise for patient stratification according to their risk of infection, underlines the protective function of the adaptive immune system, and encourages further efforts in the development of a vaccine against sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic infection patients had low preexisting anti- antibody levels. This strengthens the notion that a robust immune memory for protects against infections with the pathogen.
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http://dx.doi.org/10.1128/mSystems.00632-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977072PMC
January 2020

Adverse Cardiovascular Effects of Traffic Noise with a Focus on Nighttime Noise and the New WHO Noise Guidelines.

Annu Rev Public Health 2020 04 10;41:309-328. Epub 2020 Jan 10.

Diet, Genes and Environment Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Exposure to traffic noise is associated with stress and sleep disturbances. The World Health Organization (WHO) recently concluded that road traffic noise increases the risk for ischemic heart disease and potentially other cardiometabolic diseases, including stroke, obesity, and diabetes. The WHO report focused on whole-day noise exposure, but new epidemiological and translational field noise studies indicate that nighttime noise, in particular,is an important risk factor for cardiovascular disease (CVD) through increased levels of stress hormones and vascular oxidative stress, leading to endothelial dysfunction and subsequent development of various CVDs. Novel experimental studies found noise to be associated with oxidative stress-induced vascular and brain damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial and neuronal nitric oxide synthase, and vascular/brain infiltration with inflammatory cells. Noise-induced pathophysiology was more pronounced in response to nighttime as compared with daytime noise. This review focuses on the consequences of nighttime noise.
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http://dx.doi.org/10.1146/annurev-publhealth-081519-062400DOI Listing
April 2020

Comprehensive Analysis of the Alternaria Mycobolome Using Mass Spectrometry Based Metabolomics.

Mol Nutr Food Res 2020 02 9;64(3):e1900558. Epub 2020 Jan 9.

Chair of Analytical Food Chemistry, Technical University of Munich, Maximus-von-Imhof Forum 2, 85354, Freising, Germany.

Scope: Alternaria fungi are widely distributed plant pathogens infecting grains and vegetables and causing major harvest losses in the field and during postharvest storage. Besides, consumers are endangered by the formation of toxic secondary metabolites. Some of these secondary metabolites are chemically characterized as mycotoxins, but the majority of the Alternaria mycobolome still remains unknown.

Methods And Results: Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) and LC-MS/MS are combined for the non-targeted and targeted analysis of the metabolome of three A. alternata isolates and one A. solani isolate. Due to the ultra-high resolution of FTICR-MS, unique molecular formulae are assigned to measured m/z signals. The molecular formulae are matched to entries of the databases Antibase and Kyoto Encyclopedia of Genes and Genomes. The non-targeted analysis of the fungal extracts reveals variations in the secondary metabolite profile of A. alternata and A. solani. Differences in the biosynthesis of dibenzo-α-pyrones, perylene quinones, tentoxin, and tenuazonic acid of the A. alternata and A. solani isolates are determined applying targeted LC-MS/MS.

Conclusion: FTICR-MS analyses reveal clear differences in the metabolic profile of the A. solani and the A. alternata isolates.
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http://dx.doi.org/10.1002/mnfr.201900558DOI Listing
February 2020

Editorial: Recent Advances on the Multimodal Search for Markers of Treatment Response in Affective Disorders: From Bench to Bedside?

Front Psychiatry 2019 30;10:790. Epub 2019 Oct 30.

Clinical Affective Neuroimaging Laboratory, Otto von Guericke University of Magdeburg, Magdeburg, Germany.

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http://dx.doi.org/10.3389/fpsyt.2019.00790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831642PMC
October 2019

Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2).

Eur Heart J 2020 07;41(26):2472-2483

Center for Cardiology, University Medical Center, Mainz, Germany.

Aims: Electronic (e)-cigarettes have been marketed as a 'healthy' alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms.

Methods And Results: Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow-mediated dilation. In mice, e-cigarette vapour without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation, and lipid peroxidation than vapour containing nicotine. These effects of e-cigarette vapour were largely absent in mice lacking phagocytic NADPH oxidase (NOX-2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e-cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX-2-dependent effects of e-cigarette vapour using in vitro blood vessel incubation.

Conclusions: E-cigarette vapour exposure increases vascular, cerebral, and pulmonary oxidative stress via a NOX-2-dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e-cigarettes have the potential to induce marked adverse cardiovascular, pulmonary, and cerebrovascular consequences. Since e-cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit their health risks.
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http://dx.doi.org/10.1093/eurheartj/ehz772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340357PMC
July 2020

Technical report: xMAPr - High-dynamic-range (HDR) quantification of antigen-specific antibody binding.

J Proteomics 2020 02 1;212:103577. Epub 2019 Nov 1.

Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Straße 8, D-17475 Greifswald, Germany. Electronic address:

Here, we demonstrate a high-dynamic-range quantification of antibody binding to single antigens in a multiplexed suspension bead array format. Using a dilution-based approach and the newly developed data analysis tool the quantitative dynamic range is increased by three orders of magnitude in the selected samples. The strong increase in dynamic range results in a more robust data basis for downstream analyses.
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http://dx.doi.org/10.1016/j.jprot.2019.103577DOI Listing
February 2020

Hfq modulates global protein pattern and stress response in Bordetella pertussis.

J Proteomics 2020 01 24;211:103559. Epub 2019 Oct 24.

CINDEFI, UNLP CONICET La Plata, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina. Electronic address:

B. pertussis is the etiological agent of whooping cough, a highly contagious respiratory disease which remains uncontrolled worldwide. Understanding how this pathogen responds to the environmental changes and adapts to different niches found inside the host might contribute to gain insight into bacterial pathogenesis. Comparative analyses of previous transcriptomic and proteomic data suggested that post-transcriptional regulatory mechanisms modulate B. pertussis virulence in response to iron availability. Iron scarcity represents one of the major stresses faced by bacterial pathogens inside the host. In this study, we used gel-free nanoLC-MS/MS-based proteomics to investigate whether Hfq, a highly conserved post-transcriptional regulatory protein, is involved in B. pertussis adaptation to low iron environment. To this end, we compared the protein profiles of wild type B. pertussis and its isogenic hfq deletion mutant strain under iron-replete and iron-depleted conditions. Almost of 33% of the proteins identified under iron starvation was found to be Hfq-dependent. Among them, proteins involved in oxidative stress tolerance and virulence factors that play a key role in the early steps of host colonization and bacterial persistence inside the host cells. Altogether these results suggest that Hfq shapes the infective phenotype of B. pertussis. SIGNIFICANCE: In the last years, it became evident that post-transcriptional regulation of gene expression in ba cteria plays a central role in host-pathogen interactions. Hfq is a bacterial protein that regulates gene expression at post-transcriptional level found pivotal in the establishment of successful infections. In this study, we investigated the role of Hfq in Bordetella pertussis response to iron starvation, one of the main stresses imposed by the host. The data demonstrate that Hfq regulates the abundance of a significant number of B. pertussis proteins in response to iron starvation. Among them, virulence factors and proteins involved in oxidative stress tolerance, key players in host colonization and intracellular bacterial survival. Altogether, our results suggest a relevant role of Hfq in B. pertussis adaptation to the different niches found inside the host eventually granting bacterial pathogenesis.
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http://dx.doi.org/10.1016/j.jprot.2019.103559DOI Listing
January 2020

Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.

Basic Res Cardiol 2019 10 29;114(6):46. Epub 2019 Oct 29.

Cardiology I, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Nocturnal train noise exposure has been associated with hypertension and myocardial infarction. It remains unclear whether acute nighttime train exposure may induce subclinical atherosclerosis, such as endothelial dysfunction and other functional and/or biochemical changes. Thus, we aimed to expose healthy subjects to nocturnal train noise and to assess endothelial function, changes in plasma protein levels and clinical parameters. In a randomized crossover study, we exposed 70 healthy volunteers to either background or two different simulated train noise scenarios in their homes during three nights. After each night, participants visited the study center for measurement of vascular function and assessment of other biomedical and biochemical parameters. The three nighttime noise scenarios were exposure to either background noise (control), 30 or 60 train noise events (Noise30 or Noise60), with average sound pressure levels of 33, 52 and 54 dB(A), respectively. Flow-mediated dilation (FMD) of the brachial artery was 11.23 ± 4.68% for control, compared to 8.71 ± 3.83% for Noise30 and 8.47 ± 3.73% for Noise60 (p < 0.001 vs. control). Sleep quality was impaired after both Noise30 and Noise60 nights (p < 0.001 vs. control). Targeted proteomic analysis showed substantial changes of plasma proteins after the Noise60 night, mainly centered on redox, pro-thrombotic and proinflammatory pathways. Exposure to simulated nocturnal train noise impaired endothelial function. The proteomic changes point toward a proinflammatory and pro-thrombotic phenotype in response to nocturnal train noise and provide a molecular basis to explain the increased cardiovascular risk observed in epidemiological noise studies.
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http://dx.doi.org/10.1007/s00395-019-0753-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817813PMC
October 2019

Ligands and receptors of the TNF superfamily are decreased in major depression and during early antidepressant therapy.

J Psychiatr Res 2019 12 24;119:116-121. Epub 2019 Sep 24.

Department of Psychological Medicine, King's College London, London, UK.

Background: The up-regulation of pro-inflammatory agents, amongst them tumor necrosis factor (TNF), may represent low-grade inflammation in major depression. To further elucidate inflammatory mechanisms related to TNF in depression, the aim of the current study was to investigate the involvement of ligands and receptors of the TNF/TNF-receptor-superfamily yet un- or little explored in major depression.

Methods: Serum levels of ligands (TNF, TNF-related weak inducer of apoptosis [TWEAK], B-cell activating factor [BAFF], tumor necrosis factor superfamily member 14 [TNFSF14; LIGHT], A proliferation-inducing ligand [APRIL]) and receptor molecules (TNF receptor superfamily member 8 [TNFRSF8; sCD30], soluble TNF receptor type 1 [sTNFR1] and type 2 [sTNFR2]) of the TNF/TNF-receptor-superfamily were measured in 50 unmedicated patients suffering from major depression and 48 healthy controls and were reassessed in 37 of the depressed patients two weeks after the initiation of antidepressive treatment.

Results: In comparison to the healthy controls, the interrelated serum levels of TWEAK, BAFF, TNFSF8, sTNFR1 and sTNFR2 were reduced both in the unmedicated and medicated depressed patients. Serum levels of BAFF and TNF significantly increased during the initiation of antidepressive treatment. In the combined sample of unmedicated depressed and healthy controls, but not the separate groups, scores of the BDI-II inversely correlated with levels of TWEAK, BAFF, sTNFR1, sTNFR2 and TNFSF8.

Conclusion: The current findings give evidence for a role of the TNF/TNF-receptor-superfamily in the pathophysiology of major depression that may involve reduced tissue regeneration and neurogenesis rather than an acceleration of pro-inflammatory pathways.
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http://dx.doi.org/10.1016/j.jpsychires.2019.09.010DOI Listing
December 2019

Defensive Function of Transposable Elements in Bacteria.

ACS Synth Biol 2019 09 19;8(9):2141-2151. Epub 2019 Aug 19.

Department of Engineering Science , University of Oxford , Parks Road , OX1 3PJ Oxford , United Kingdom.

It has been widely debated whether transposable elements have a positive or a negative effect on their host cells. This study demonstrated that transposable elements, specifically insertion sequences (ISs), can adopt a defensive role in . In three different strains (S17, DH5α, and Nissle 1917), IS1 and IS10 rapidly disrupted the gene (encoding I-CeuI endonuclease) on the plasmid pLO11-ICeuI as early as the first generation, despite the gene-circuit being under control of an arabinose promoter. Proteomics analysis showed that the protein abundance profile of DH5α with pLO11-ICeuI in the fifth generation was nearly opposite to that of control strain ( with pLO11, no I-CeuI). The DNA damage caused by the leaky expression of was enough to trigger a SOS response and alter lipid synthesis, ribosomal activity, RNA/DNA metabolism, central dogma and cell cycle processes in DH5α. After the ISs disrupted the expression of , cells fully recovered by the 31st generation had a protein abundance profile similar to that of the control strain. This study showed that ISs readily mutated a harmful gene which subsequently restored host fitness. These observations have implications for the stability of designed gene circuits in synthetic biology.
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http://dx.doi.org/10.1021/acssynbio.9b00218DOI Listing
September 2019
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