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1.
Proc Natl Acad Sci U S A ; 120(11): e2218680120, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36877836

ABSTRACT

Social media are at the forefront of modern political campaigning. They allow politicians to communicate directly with constituents and constituents to endorse politicians' messages and share them with their networks. Analyzing every tweet of all US senators holding office from 2013 to 2021 (861,104 tweets from 140 senators), we identify a psycholinguistic factor, greed communication, that robustly predicts increased approval (favorites) and reach (retweets). These effects persist when tested against diverse established psycholinguistic predictors of political content dissemination on social media and various other psycholinguistic variables. We further find that greed communication in the tweets of Democratic senators is associated with greater approval and retweeting compared to greed communication in the tweets of Republican senators, especially when those tweets also mention political outgroups.


Subject(s)
Administrative Personnel , Social Media , Humans , Communication , Psycholinguistics
2.
Appl Environ Microbiol ; 90(1): e0135023, 2024 01 24.
Article in English | MEDLINE | ID: mdl-38084999

ABSTRACT

Manganese (Mn) is an essential element for bacteria, but the overload of manganese is toxic. In a previous study, we showed that the cation diffusion facilitator protein MetA and the resistance-nodulation-division efflux pump MetB are responsible for Mn efflux in the bacterial pathogen Riemerella anatipestifer CH-1. However, whether this bacterium encodes additional manganese efflux proteins is unclear. In this study, we show that R. anatipestifer CH-1 encodes a tellurium resistance C (TerC) family protein with low similarity to other characterized TerC family proteins. Compared to the wild type (WT), the terC mutant of R. anatipestifer CH-1 (∆terC) is sensitive to Mn(II) intoxication. The ability of TerC to export manganese is higher than that of MetB but lower than that of MetA. Consistently, terC deletion (∆terC) led to intracellular accumulation of Mn2+ under excess manganese conditions. Further study showed that ∆terC was more sensitive than the WT to the oxidant hypoclorite but not to hydrogen peroxide. Mutagenesis studies showed that the mutant at amino acid sites of Glu116 (E116), Asp122 (D122), Glu245 (E245) Asp248 (D248), and Asp254 (D254) may be involved in the ability of TerC to export manganese. The transcription of terC was upregulated under excess manganese and downregulated under iron-limited conditions. However, this was not dependent on the manganese metabolism regulator MetR. In contrast to a strain lacking the manganese efflux pump MetA or MetB, the terC mutant is attenuated in virulence in a duckling model of infection due to increased sensitivity to duck serum. Finally, comparative analysis showed that homologs of TerC are distributed across the bacterial kingdom, suggesting that TerC exerts a conserved manganese efflux function.IMPORTANCERiemerella anatipestifer is a notorious bacterial pathogen of ducks and other birds. In R. anatipestifer, the genes involved in manganese efflux have not been completely identified, although MetA and MetB have been identified as two manganese exporters. Additionally, the function of TerC family proteins in manganese efflux is controversial. Here, we demonstrated that a TerC family protein helps prevent Mn(II) intoxication in R. anatipestifer and that the ability of TerC to export manganese is intermediate compared to that of MetA and MetB. Sequence analysis and mutagenesis studies showed that the conserved key amino sites of TerC are Glu116, Asp122, Glu245, Asp248, and Asp254. The transcription of terC was regulated by manganese excess and iron limitation. Finally, we show that TerC plays a role in the virulence of R. anatipestifer due to the increased sensitivity to duck serum, rather than the increased sensitivity to manganese. Taken together, these results expand our understanding of manganese efflux and the pathogenic mechanisms of R. anatipestifer.


Subject(s)
Flavobacteriaceae Infections , Poultry Diseases , Riemerella , Animals , Virulence/genetics , Bacterial Proteins/genetics , Manganese/metabolism , Tellurium/metabolism , Riemerella/genetics , Ducks/microbiology , Iron/metabolism , Poultry Diseases/microbiology , Flavobacteriaceae Infections/microbiology
3.
Chemistry ; 30(46): e202401955, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-38860572

ABSTRACT

In response to the pressing global challenge of antibiotic resistance, time efficient design and synthesis of novel antibiotics are of immense need. Polycyclic polyprenylated acylphloroglucinols (PPAP) were previously reported to effectively combat a range of gram-positive bacteria. Although the exact mode of action is still not clear, we conceptualized a late-stage divergent synthesis approach to expand our natural product-based PPAP library by 30 additional entities to perform SAR studies against methicillin-resistant Staphylococcus aureus (MRSA). Although at this point only data from cellular assays are available and understanding of molecular drug-target interactions are lacking, the experimental data were used to generate 3D-QSAR models via an artificial intelligence training and to identify a common pharmacophore model. The experimentally validated QSAR model enabled the estimation of anti-MRSA activities of a virtual compound library consisting of more than 100,000 in-silico generated B PPAPs, out of which the 20 most promising candidates were synthesized. These novel PPAPs revealed significantly improved cellular activities against MRSA with growth inhibition down to concentrations less than 1 µm.


Subject(s)
Anti-Bacterial Agents , Biological Products , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Phloroglucinol , Quantitative Structure-Activity Relationship , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Biological Products/chemistry , Biological Products/pharmacology , Biological Products/chemical synthesis , Phloroglucinol/chemistry , Phloroglucinol/pharmacology , Phloroglucinol/chemical synthesis , Drug Design , Polycyclic Compounds/chemistry , Polycyclic Compounds/pharmacology , Polycyclic Compounds/chemical synthesis
4.
Neuropediatrics ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39084244

ABSTRACT

PURPOSE: Hamartomas of tuber cinereum present as ectopic tissue in the hypothalamic region. Clinically, the usual hypothalamic hamartomas manifest themself by gelastic seizures and pubertas praecox. We observed an increased coincidence of the presence of X-linked recessive deafness DFNX2 (DFN3) and a hamartoma of the tuber cinereum. Initially five patients presented with hearing loss in childhood, two additional were already adults, not showing any characteristic symptoms for a hamartoma but signs of delayed puberty. METHODS: Seven patients who underwent computed tomography imaging due to a sensorineural hearing loss and had a hamartoma of the tuber cinereum in addition to X-linked deafness DFNX2 (DFN3) were included in a retrospective study. Patients underwent initial neurologic, endocrinologic, and genetic evaluation. Long-term follow-up was performed after 10 to 12 years. RESULTS: The average age at the initial exam was 12.9 years (range 4-29). All patients genetically proven nonsyndromic, X-linked deafness associated with the POU3F4 gene. Three out of six patients presented signs of delayed puberty. None of all seven showed any evidence of pubertas praecox or gelastic seizures at mean age of 17 years (range 17-29 years) at any time. CONCLUSION: Hamartomas of tuber cinereum are often coincident with DFNX2. Clinically, half of the cases are-in contrary to the usual pubertas praecox-associated with growth hormone deficiency and delayed puberty, in the sense of pubertas tarda, when coincident. Clinicians' and radiologists' knowledge and awareness of this rare combination are crucial to identify children early enough for hormone-sensitive treatment.

5.
J Thromb Thrombolysis ; 57(6): 936-946, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38853210

ABSTRACT

Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients' blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke.


Subject(s)
Biomarkers , Extracellular Traps , Ischemic Stroke , Humans , Extracellular Traps/metabolism , Biomarkers/blood , Male , Female , Aged , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Middle Aged , Prospective Studies , Peroxidase/blood , Aged, 80 and over , Cell-Free Nucleic Acids/blood , Thrombectomy , Thrombosis/blood , Thrombosis/diagnosis , Neutrophils/metabolism
6.
J Pers ; 92(1): 88-110, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36776098

ABSTRACT

OBJECTIVE: Personality traits cluster across countries, regions, cities, and neighborhoods. What drives the formation of these clusters? Ecological theory suggests that physical locations shape humans' patterns of behaviors and psychological characteristics. Based on this theory, we examined whether and how differential land-cover relates to individual personality. METHOD: We followed a preregistered three-pronged analysis approach to investigate the associations between personality (N = 2,690,878) and land-cover across the United States. We used eleven land-cover categories to classify landscapes and tested their association with personality against broad physical and socioeconomic factors. RESULTS: Urban areas were positively associated with openness to experience and negatively associated with conscientiousness. Coastal areas were positively associated with openness to experience and neuroticism but negatively associated with agreeableness and conscientiousness. Cultivated areas were negatively associated with openness. Landscapes at the periphery of human activity, such as shrubs, bare lands, or permanent snows, were not reliably associated with personality traits. CONCLUSIONS: Bivariate correlations, multilevel, and random forest models uncovered robust associations between landscapes and personality traits. These findings align with ecological theory suggesting that an individual's environment contributes to their behaviors, thoughts, and feelings.


Subject(s)
Personality Disorders , Personality , Humans , United States , Personality Inventory , Neuroticism , Emotions
7.
Int J Mol Sci ; 25(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39273203

ABSTRACT

Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. An mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2/bicarbonate deficiency. Electron microscopy revealed that ΔmpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant's lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower α-glycosylated and higher ß-glycosylated WTA, explaining the mutant's increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, like in vancomycin-intermediate S. aureus mutants (VISA). Genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents.


Subject(s)
Bicarbonates , Cell Wall , Staphylococcus aureus , Staphylococcus aureus/metabolism , Staphylococcus aureus/genetics , Bicarbonates/metabolism , Cell Wall/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Stress, Physiological , Gene Expression Regulation, Bacterial , Carbon Dioxide/metabolism
8.
Int J Mol Sci ; 25(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125595

ABSTRACT

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. The chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here, we studied the antimicrobial activity of two synthetic PPAP-derivatives, the water-insoluble PPAP23 and the water-soluble sodium salt PPAP53. In vitro, both compounds exhibited good activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar effect was also seen with serum albumin. In silico docking studies with PPAP53 revealed that it binds to the F1 pocket of human serum albumin with a binding energy of -7.5 kcal/mol. In an infection model of septic arthritis, PPAP23 decreased the formation of abscesses and S. aureus load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced S. aureus counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing Clostridium, Enterococcus or Ruminococcus species. Based on these results, we foresee possible applications in the decolonization of pathogens.


Subject(s)
Ketones , Methicillin-Resistant Staphylococcus aureus , Spiro Compounds , Animals , Humans , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Enterococcus faecium/drug effects , Ketones/chemistry , Ketones/pharmacology , Larva/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Moths/drug effects , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Staphylococcal Infections/drug therapy
9.
Behav Res Methods ; 56(3): 1863-1899, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37382812

ABSTRACT

Interest in the psychology of misinformation has exploded in recent years. Despite ample research, to date there is no validated framework to measure misinformation susceptibility. Therefore, we introduce Verification done, a nuanced interpretation schema and assessment tool that simultaneously considers Veracity discernment, and its distinct, measurable abilities (real/fake news detection), and biases (distrust/naïvité-negative/positive judgment bias). We then conduct three studies with seven independent samples (Ntotal = 8504) to show how to develop, validate, and apply the Misinformation Susceptibility Test (MIST). In Study 1 (N = 409) we use a neural network language model to generate items, and use three psychometric methods-factor analysis, item response theory, and exploratory graph analysis-to create the MIST-20 (20 items; completion time < 2 minutes), the MIST-16 (16 items; < 2 minutes), and the MIST-8 (8 items; < 1 minute). In Study 2 (N = 7674) we confirm the internal and predictive validity of the MIST in five national quota samples (US, UK), across 2 years, from three different sampling platforms-Respondi, CloudResearch, and Prolific. We also explore the MIST's nomological net and generate age-, region-, and country-specific norm tables. In Study 3 (N = 421) we demonstrate how the MIST-in conjunction with Verification done-can provide novel insights on existing psychological interventions, thereby advancing theory development. Finally, we outline the versatile implementations of the MIST as a screening tool, covariate, and intervention evaluation framework. As all methods are transparently reported and detailed, this work will allow other researchers to create similar scales or adapt them for any population of interest.


Subject(s)
Communication , Judgment , Humans , Psychometrics/methods , Language , Factor Analysis, Statistical
10.
Appl Environ Microbiol ; 89(12): e0130823, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38038982

ABSTRACT

IMPORTANCE: Riemerella anatipestifer (RA) is a notorious duck pathogen, characterized by a multitude of serotypes that exhibit no cross-reaction with one another. Moreover, RA is resistant to various antibacterial agents. Consequently, understanding the mechanisms behind resistance and identifying potential targets for drug development have become pressing needs. In this study, we show that the two TolC proteins play a role in the resistance to different drugs and metals and in the virulence. The results suggest that TolCA has a wider range of efflux substrates than TolCB. Except for gentamicin, neither TolCA nor TolCB was involved in the efflux of the other tested antibiotics. Strikingly, TolCA but not TolCB enhanced the frequency of resistance-conferring mutations. Moreover, TolCA was involved in RA virulence. Given its conservation in RA, TolCA has potential as a drug target for the development of therapeutics against RA infections.


Subject(s)
Flavobacteriaceae Infections , Poultry Diseases , Riemerella , Animals , Virulence/genetics , Riemerella/metabolism , Ducks/microbiology , Virulence Factors/genetics , Metals/metabolism , Flavobacteriaceae Infections/microbiology , Poultry Diseases/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
11.
Immunity ; 41(5): 762-75, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-25456159

ABSTRACT

Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.


Subject(s)
Myeloid Cells/immunology , Skin/immunology , Staphylococcal Skin Infections/immunology , Toll-Like Receptor 2/immunology , Adaptive Immunity/immunology , Animals , Antigens/immunology , CD11b Antigen/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/microbiology , Humans , Interleukin-6/biosynthesis , Lipopeptides/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Myeloid Differentiation Factor 88/biosynthesis , Skin/microbiology , Staphylococcus aureus/immunology , Toll-Like Receptor 1/immunology , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/immunology , Toll-Like Receptor 6/immunology
12.
Pers Individ Dif ; 208: 112189, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37008556

ABSTRACT

As COVID-19 continues to incur enormous personal and societal costs, widespread vaccination against the virus remains the most effective strategy to end the pandemic. However, vaccine hesitancy is rampant and has been steadily rising for decades. Seeking to remedy this, personality psychologists have begun to explore psychological drivers of vaccine hesitancy, including the Big Five. Openness to Experience presents itself as a vexing case as previous attempts to study its association with vaccine hesitancy have yielded mixed findings. In this preregistered study, we hypothesise that the impact of Openness to Experience on Vaccine Hesitancy depends on its interplay with other factors, namely conspiracy beliefs. To test this, we apply logistic regressions, simple slopes analyses, and propensity score matching to a nationally representative sample of 2500 Italian citizens, collected in May 2021. Contrary to our original hypothesis (i.e., Openness will have a positive association with Vaccine Hesitancy at high - and a negative at low - levels of Conspiracy Beliefs) we find that high Openness diminishes the impact of Belief in Conspiracy Theories on Vaccine Hesitancy. Consistent with previous research, we propose that Openness serves as a buffer against extreme positions by allowing individuals to be exposed to a greater diversity of information.

13.
Int J Mol Sci ; 24(6)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36982293

ABSTRACT

Despite continuing progress in medical and surgical procedures, staphylococci remain the major Gram-positive bacterial pathogens that cause a wide spectrum of diseases, especially in patients requiring the utilization of indwelling catheters and prosthetic devices implanted temporarily or for prolonged periods of time. Within the genus, if Staphylococcus aureus and S. epidermidis are prevalent species responsible for infections, several coagulase-negative species which are normal components of our microflora also constitute opportunistic pathogens that are able to infect patients. In such a clinical context, staphylococci producing biofilms show an increased resistance to antimicrobials and host immune defenses. Although the biochemical composition of the biofilm matrix has been extensively studied, the regulation of biofilm formation and the factors contributing to its stability and release are currently still being discovered. This review presents and discusses the composition and some regulation elements of biofilm development and describes its clinical importance. Finally, we summarize the numerous and various recent studies that address attempts to destroy an already-formed biofilm within the clinical context as a potential therapeutic strategy to avoid the removal of infected implant material, a critical event for patient convenience and health care costs.


Subject(s)
Staphylococcal Infections , Staphylococcus , Humans , Biofilms , Staphylococcus aureus/physiology , Staphylococcal Infections/microbiology , Staphylococcus epidermidis , Anti-Bacterial Agents/therapeutic use , Biology
14.
Stroke ; 53(4): 1235-1244, 2022 04.
Article in English | MEDLINE | ID: mdl-34991335

ABSTRACT

BACKGROUND: Cell-free DNA (cfDNA) and endogenous deoxyribonuclease activity are opposing mediators and might influence the inflammatory response following acute ischemic stroke. In this cohort study, we investigated the relation between these markers, circulating inflammatory mediators and clinical course including occurrence of stroke-associated infections (SAI) in patients with acute stroke. METHODS: Ninety-two patients with stroke due to large vessel occlusion undergoing mechanical thrombectomy were prospectively recruited at Hannover Medical School from March 2018 to August 2019. Deoxyribonuclease activity, cfDNA, damage-associated molecular patterns, and circulating cytokines were measured in venous blood collected immediately before mechanical thrombectomy and 7 days later. Reperfusion status was categorized (sufficient/insufficient). Clinical outcome was evaluated using the modified Rankin Scale after 90 days, where a score of 3 to 6 was considered unfavorable. To validate findings regarding SAI, another stroke cohort (n=92) was considered with blood taken within 24 hours after stroke onset. RESULTS: Patients with unfavorable clinical outcome had higher cfDNA concentrations. After adjustment for confounders (Essen Stroke Risk Score, National Institutes of Health Stroke Scale, and sex), 7-day cfDNA was independently associated with clinical outcome and especially mortality (adjusted odds ratio: 3.485 [95% CI, 1.001-12.134] and adjusted odds ratio: 9.585 [95% CI, 2.006-45.790]). No association was found between reperfusion status and cfDNA or deoxyribonuclease activity. While cfDNA concentrations correlated positively, deoxyribonuclease activity inversely correlated with distinct biomarkers. Baseline deoxyribonuclease activity was lower in patients who developed SAI compared with patients without SAI. This association was confirmed after adjustment for confounding factors (adjusted odds ratio: 0.447 [95% CI, 0.237-0.844]). In cohort 2, differences of deoxyribonuclease activity between patients with and without SAI tended to be higher with higher stroke severity. CONCLUSIONS: The interplay of endogenous deoxyribonuclease activity and cfDNA in acute stroke entails interesting novel diagnostic and potential therapeutic approaches. We confirm an independent association of cfDNA with a detrimental clinical course after stroke due to large vessel occlusion. This study provides first evidence for lower endogenous deoxyribonuclease activity as risk factor for SAI after severe stroke.


Subject(s)
Brain Ischemia , Cell-Free Nucleic Acids , Ischemic Stroke , Stroke , Brain Ischemia/therapy , Cohort Studies , Deoxyribonucleases , Humans , Retrospective Studies , Stroke/therapy , Thrombectomy/adverse effects , Treatment Outcome
15.
Neuroradiology ; 64(6): 1135-1144, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34773479

ABSTRACT

PURPOSE: To investigate the role of the diffusion weighted imaging (DWI) in the acute dissection of internal carotid artery (ICA) and vertebral artery (VA) and assessing the length of intramural hematoma (IMH), caused by dissection. METHODS: We analyzed 28 patients presenting with a dissection of the ICA and/or VA with respect to the presence of high signal intensity areas on DWI suggestive of dissection and 20 control subjects without arterial dissection, some with and some without atherosclerotic lesions. ICA or VA dissection was defined by clinical and imaging, computed tomography angiography (CTA), MR angiography (MRA), and digital subtraction angiography (DSA) findings. The length of DWI hyperintensity was compared to length of the occlusion or stenosis on the angiographic examination. RESULTS: In 28 patients, 30 dissected arteries were analyzed. Time intervals from the onset of the first clinical symptoms to the radiological evaluation ranged from 1.5 h to 42 days. In 28 (93%) of the dissections, a high signal intensity of the affected artery was present on DWI. The measurement of the dissection length on DWI compared to DSA showed a mean deviation of 2.7 mm and a standard deviation of 3.7 mm. CONCLUSION: DWI is a highly sensitive and valuable pulse sequence for the detection of dissected cervical arteries even in the first hours after symptom onset. In contrast to CTA and MRA, DWI can be a potential tool for a reliable measurement of the dissection length.


Subject(s)
Carotid Artery, Internal, Dissection , Vertebral Artery Dissection , Angiography, Digital Subtraction , Carotid Arteries/pathology , Carotid Artery, Internal, Dissection/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Angiography/methods , Vertebral Artery/diagnostic imaging , Vertebral Artery Dissection/diagnostic imaging
16.
J Pers ; 2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35866366

ABSTRACT

OBJECTIVE: This research investigates how economic inequality shapes basic human values across three cross-national, cross-regional, and longitudinal studies (Ntotal  = 219,697). METHODS: Study 1 examined the relationship between objective economic inequality and values across 77 societies from all five continents (n = 170,525). Study 2 examined the relationship between objective economic inequality and values across 51 regions in the United States (n = 48,559). Study 3 used a two-year longitudinal design to examine the relationship between perceived economic inequality and values (n = 613). RESULTS: Results from multilevel modeling and longitudinal analysis suggested that people who lived in areas with higher economic inequality and who perceived higher economic inequality were more likely to endorse achievement and power values. Moreover, people who perceived higher economic inequality were less likely to endorse benevolence values. These effects were robust in within-country tests (Studies 2 and 3) but not in the cross-country tests (Study 1) when accounting for sociodemographic characteristics. CONCLUSIONS: Our findings suggest that economic inequality may act as an antecedent of self-enhancement values, particularly within countries. In a world of rising economic inequality, this may over time lead to an overemphasis on achievement and power which have been shown to erode social cohesion.

17.
Proc Natl Acad Sci U S A ; 116(38): 19145-19154, 2019 09 17.
Article in English | MEDLINE | ID: mdl-31488708

ABSTRACT

Quorum sensing (QS) is the central mechanism by which social interactions within the bacterial community control bacterial behavior. QS-negative cells benefit by exploiting public goods produced by the QS-proficient population. Mechanisms to keep the balance between producers and nonproducers within the population are expected but have not been elucidated for peptide-based QS systems in gram-positive pathogens. The Agr system of Staphylococcus aureus comprises the secretion and sensing of an autoinducing peptide to activate its own expression via the response regulator AgrA as well as the expression of a regulatory RNAIII and psmα/psmß coding for phenol-soluble modulins (PSMs). Agr mutants can be monitored on blood agar due to their nonhemolytic phenotype. In vitro evolution and competition experiments show that they readily accumulate in a process that is accelerated by ciprofloxacin, while the wild type (WT) is retained in the population at low numbers. However, agr mutants possess a fitness advantage only under aerobic conditions. Under hypoxia, Agr activity is increased but without the expected fitness cost. The Agr-imposed oxygen-dependent fitness cost is not due to a metabolic burden but due to the reactive oxygen species (ROS)-inducing capacity of the PSMs and RNAIII-regulated factors. Thus, selection of mutants is dictated by the QS system itself. Under aerobic conditions, emergence of agr-negative mutants may provide the population with a fitness advantage while hypoxia favors QS maintenance and even affords increased toxin production. The oxygen-driven tuning of the Agr system might be of importance to provide the pathogen with capabilities crucial for disease progression.


Subject(s)
Bacterial Proteins/metabolism , Mutation , Oxidative Stress , Quorum Sensing , Staphylococcal Infections/microbiology , Staphylococcus aureus/genetics , Trans-Activators/metabolism , Bacterial Proteins/genetics , Bacterial Toxins/pharmacology , Evolution, Molecular , Gene Expression Regulation, Bacterial , Staphylococcal Infections/genetics , Staphylococcal Infections/metabolism , Staphylococcus aureus/drug effects , Staphylococcus aureus/pathogenicity , Trans-Activators/genetics , Virulence
18.
Behav Brain Sci ; 45: e163, 2022 09 13.
Article in English | MEDLINE | ID: mdl-36098438

ABSTRACT

Uchiyama et al. present a dual inheritance framework for conceptualizing how behavioural genetics and cultural evolution interact and affect heritability. We posit that to achieve a holistic and nuanced representation of the cultural environment and evolution against which genetic effects should be evaluated, it is imperative to consider the multiple geographic cultural layers impacting individuals and genetic heritability.


Subject(s)
Biological Evolution , Cultural Evolution , Humans
19.
J Econ Behav Organ ; 193: 473-496, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34955573

ABSTRACT

We conducted a large-scale survey covering 58 countries and over 100,000 respondents between late March and early April 2020 to study beliefs and attitudes towards citizens' and governments' responses at the onset of the COVID-19 pandemic. Most respondents reported holding normative beliefs in support of COVID-19 containment measures, as well as high rates of adherence to these measures. They also believed that their government and their country's citizens were not doing enough and underestimated the degree to which others in their country supported strong behavioral and policy responses to the pandemic. Normative beliefs were strongly associated with adherence, as well as beliefs about others' and the government's response. Lockdowns were associated with greater optimism about others' and the government's response, and improvements in measures of perceived mental well-being; these effects tended to be larger for those with stronger normative beliefs. Our findings highlight how social norms can arise quickly and effectively to support cooperation at a global scale.

20.
PLoS Pathog ; 15(6): e1007877, 2019 06.
Article in English | MEDLINE | ID: mdl-31226163

ABSTRACT

Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.


Subject(s)
Arthritis/immunology , Bacterial Proteins/immunology , Lipoproteins/immunology , Neutrophils/immunology , Staphylococcus aureus/immunology , Animals , Arthritis/genetics , Arthritis/microbiology , Arthritis/pathology , Bacterial Proteins/genetics , Female , Lipoproteins/genetics , Mice , Neutrophils/pathology , Receptors, Interleukin-8B/genetics , Receptors, Interleukin-8B/immunology , Staphylococcal Infections/genetics , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Staphylococcus aureus/genetics , Staphylococcus aureus/pathogenicity , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
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