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Inhibition of MMP2 activity mitigates N-omega-nitro-l-arginine-methyl ester (l-NAME)-induced right heart failure
(2024) Schreckenberg, Rolf; Schulz, Rainer; Itani, Nadja; Ferdinandy, Peter; Bencsik, Peter; Szabados, Tamara; Rohrbach, Susanne; Niemann, Bernd; Schlüter, Klaus-Dieter
In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received l-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. l-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.
Robust marker detection and identification using deep learning in underwater images for close range photogrammetry
(2024) Wittmann, Jost; Chatterjee, Sangam; Sure, Thomas
The progressing industrialization of oceans mandates reliable, accurate and automatable subsea survey methods. Close-range photogrammetry is a promising discipline, which is frequently applied by archaeologists, fish-farmers, and the offshore energy industry. This paper presents a robust approach for the reliable detection and identification of photogrammetric markers in subsea images. The proposed method is robust to severe image degradation, which is frequently observed in underwater images due to turbidity, light absorption, and optical aberrations. This is the first step towards a highly automated work-flow for single-camera underwater photogrammetry. The newly developed approach comprises several machine learning models, which are trained by 10,122 real-world subsea images, showing a total of 338,301 photogrammetric markers. The performance is evaluated using an object detection metrics, and through a comparison with the commercially available software Metashape by Agisoft. Metashape delivers satisfactory results when the image quality is good. In images with strong noise, haze or little light, only the novel approach retrieves sufficient information for a high degree of automation of the subsequent bundle adjustment. While the need for offshore personnel and the time-to-results decreases, the robustness of the survey increases.
The effect of the COVID-19 pandemic on immigration and immigrant wellbeing in the United States
(2024) Krannich, Sascha; Massey, Douglas S.
This article highlights the effect of the COVID-19 pandemic on immigration and immigrant wellbeing in the United States by focusing on all categories of migrants, documented and undocumented. We argue that in the wake of the pandemic, immigrants disproportionately experienced higher rates of unemployment, greater losses of income, more exposure occupational risks, and higher rates of food and housing insecurity, all of which exacerbated preexisting differentials in access to health and health care to generate higher rates of COVID infection, morbidity, and mortality among adults and stunted educational outcomes for their children. The prospects for a full post-pandemic recovery of immigrants' wellbeing are dampened by the severe nature of COVID's negative effects on immigrants; the unusually hostile context of reception immigrants face after the pandemic; the large number of immigrants lacking legal status or holding tenuous documentation; and the formidable deportation regime that prevails in the United States that puts a great strain on immigrant communities. Undocumented migration has surged to restart undocumented population growth, further clouding the future for immigrants in the country. It is unclear whether reforms proposed by the Biden Administration be enacted and successful in improving their prospects. In general, this article aims to contribute to the broader discussion about migration and health policies.
Signalment and laboratory findings in cats with diabetes mellitus in Germany: a retrospective review of laboratory submissions of 129,505 cats
(2024) Guse, Bente; Langenstein, Judith; Bauer, Natali; Hazuchova, Katarina
Objectives: The aims of this study were to compare signalment and laboratory parameters between diabetic (D) and non-diabetic (ND) cats and poorly-controlled diabetic (PD) and well-controlled diabetic (WD) cats in Germany. Methods: Laboratory data from Antech Lab Germany between 2015 and 2018 were retrospectively analysed. Age, sex, red blood cell count (RBC), creatinine (CREA), alkaline phosphatase (AP), alanine aminotransferase (ALT), bilirubin (BILI), cholesterol (CHOL), triglycerides (TRI), glucose (GLU) and total thyroxine (TT4) were compared between D (fructosamine ⩾340 µmol/l) and ND cats, and PD (fructosamine >500 µmol/l) and WD (fructosamine 340–500 µmol/l) cats. The proportion of cats with anaemia (RBC ⩽4.21 ×1012/l), CREA >250 µmol/l, ALT >455 U/l, AP >315 U/l, BILI ⩾35 µmol/l and TT4 > reference interval (RI) was compared between PD and WD cats. Data are presented as median and interquartile range (IQR) and analysed using non-parametric tests. Significance was P<0.05, and effect size was assessed by Cramér V or r. Results: In total, 129,505 cats were included (D: n = 9334 [prevalence 7.2%], WD: n = 5670/9334 [60.7%]). The median age of D and ND cats was 12 years (IQR D 9–14; ND 9–15); there was no difference in sex. A significant difference was found between groups (D vs ND; PD vs WD) for all parameters studied. Considering the effect sizes and medians outside the RI, the only relevant difference was higher CHOL, TRI, AP and GLU in PD compared with WD (CHOL: PD 7.46 [5.85–9.32] vs WD 5.44 [4.32–6.97] mmol/l, P<0.001, r = 0.39; TRI: PD 1.44 [0.84–3.66] vs WD 0.78 [0.5–1.35] mmol/l, P <0.001, r = 0.35; AP: PD 66 [47–92] vs WD 35 [23–59] U/l, P <0.001, r = 0.39; GLU: PD 23.7 [20.15–27.3] vs WD 6.89 [5–11.31] mmol/l, P <0.001, r = 0.69). Conclusions and relevance: Laboratory changes in diabetic cats were mild and mainly associated with lipid derangements.
The well-tempered color circle: A chromatic Gestalt
(2024) Koenderink, Jan J.; van Doorn, Andrea J.; Braun, Doris I.
The “Color Circle” is an important chromatic Gestalt in the visual arts. There is not really a formal equivalent in conventional colorimetry. The fact that the hues can be linearly ordered and that such an order is necessarily periodic was intuited by artists in the early 19th century, but only formally explained by Ostwald and later Schrödinger a century later. As with musical keys, various metrical orders are in common use. Is there such a thing as a “well tempered” order? We consider this an issue for experimental phenomenology. We discuss an attempt based on observations by 30 (nonartist) observers.
Sensorimotor confidence for tracking eye movements
(2024) Goettker, Alexander; Locke, Shannon M.; Gegenfurtner, Karl R.; Mamassian, Pascal
For successful interactions with the world, we often have to evaluate our own performance. Although eye movements are one of the most frequent actions we perform, we are typically unaware of them. Here, we investigated whether there is any evidence for metacognitive sensitivity for the accuracy of eye movements. Participants tracked a dot cloud as it followed an unpredictable sinusoidal trajectory and then reported if they thought their performance was better or worse than their average tracking performance. Our results show above-chance identification of better tracking behavior across all trials and also for repeated attempts of the same target trajectories. Sensitivity in discriminating performance between better and worse trials was stable across sessions, but judgements within a trial relied more on performance in the final seconds. This behavior matched previous reports when judging the quality of hand movements, although overall metacognitive sensitivity for eye movements was significantly lower.
The PornLoS Treatment Program: Study protocol of a new psychotherapeutic approach for treating pornography use disorder
(2024) Stark, Rudolf; Markert, Charlotte; Golder, Sarah; Psarros, Rhea; Discher, Julian P.; Khatib, Said; Metzger, Julia; Palmer, Sebastian; Rechmann, Johanna; Storz, Florian; Walter, Bertram; Allard, Sarah; Antons, Stephanie; Bledzka, Marta; Brand, Matthias; Dörrenbächer, Sandra; Englisch, Julia; Friehs, Thilo; Da Cunha Gonçalves, Katja; Haberkamp, Anke; Hall, Mila; Kananian, Schahryar; Kemmerer, Pascal; Klingelhöfer, Doerthe; Lutz, Wolfgang; Melzig, Christiane A.; Michael, Tanja; Neumann, Anja; Neusser, Silke; Niemann, Anja; Odenthal, Michael; Rubel, Julian; Schlierenkamp, Sarah; Speckemeier, Christian; Ünlü, Luisa; Vogt, Rabea; Wölfling, Klaus; Zachariassen, Wiebke; zur Hausen, Gerrit; Heinz, Christine
Background: The introduction of Compulsive Sexual Behavior Disorder (CSBD) into the 11th International Classification of Diseases has raised expectations for better treatment options for CSBD. Furthermore, the treatment demand has increased, particularly for pornography use disorder (PUD), a subtype of CSBD. Presumably due to the easy access to Internet pornography an increasing prevalence of PUD is observed. Consequently, providing tailored and effective treatment is essential. Methods: This article provides an overview of the manualized short-term PornLoS Treatment Program (Pornografienutzungsstörung effektiv behandeln– Leben ohne Suchtdruck; translation: Treating pornography use disorder effectively - life without craving). The program combines 24 individual and 6 group psychotherapy sessions with an interdisciplinary approach by offering a novel treatment framework. This includes, e.g., a mobile app, establishment of self-help groups, and access to other social services such as couple counseling. The cognitive-behavioral treatment program contains interventions addressing psychoeducation, cue exposure, impulse control, cognitive restructuring, emotional regulation, and relapse management. We here also describe the study protocol of an ongoing four-arm randomized controlled trial. The aim is to test two variants of the PornLoS Treatment Program differing with respect to their treatment goal (abstinence or reduced pornography use) against cognitive-behavioral treatment as usual and against a waitlist control group. The primary outcome is the absence of a PUD diagnosis at the end of therapy. The total target sample size will comprise n = 316 patients with PUD across eight study sites. Results: The results will be presented at international conferences and published in a scientific peer-reviewed journal.
Comparison of vascular risk profile and clinical outcomes among patients with central (branch) retinal artery occlusion versus amaurosis fugax
(2024) Diel, Norma J.; Gerner, Stefan T.; Doeppner, Thorsten R.; Juenemann, Martin; Maxhuni, Toska; Frühwald, Tobias; Worm, Andre; Alhaj Omar, Omar; Lytvynchuk, Lyubomyr; Struffert, Tobias; Bauer, Pascal; Huttner, Hagen B.
Background: Retinal artery occlusions lead to sudden, painless vision loss, affecting millions globally. Despite their significance, treatment strategies remain unestablished, contrasting with acute ischemic stroke (AIS), where IVT has proven efficacy. Similar to AIS, retinal artery occlusions demand urgent evaluation and treatment, reflecting the principle "time is retina". Even for patients with transient monocular vision loss, also known as amaurosis fugax (AF), pertinent guidelines meanwhile recommend immediate emergency assessment in a specialized facility. However, data on the clinical benefit and comparability with persistent occlusions are missing. This study aimed to compare the results of a comprehensive stroke-workup among patients with persistent retinal artery occlusions (RAO), including both central retinal (CRAO) and branch retinal artery occlusion (BRAO) and those with AF. Methods: Conducted at the University Hospital Giessen, Germany, this exploratory cross-sectional study enrolled patients with transient or permanent unilateral vision loss of non-arteritic origin. The primary outcome were differences between the two groups RAO and AF with regard to cardiovascular risk profiles and comorbidities, vascular and pharmacological interventions and clinical neurological and ophthalmological outcomes. Secondary outcome was a sub-group analysis of patients receiving IVT. Results: Out of 166 patients assessed, 76 with RAO and 40 with AF met the inclusion criteria. Both groups exhibited comparable age, gender distribution, and cardiovascular risk profiles. Notably, RAO patients did not show significantly more severe vascular comorbidities than AF patients. However, AF patients received vascular interventions more frequently. Pharmacological intervention rates were similar across groups. RAO patients had slightly worse neurological outcomes, and IVT did not yield favorable ophthalmological outcomes within any observed patients. Conclusion: The study found similar vascular burden and risk factors in patients with RAO and AF, with implications for clinical workflows. IVT for RAO may only be effective in very early treatment windows. This emphasizes the need for public awareness and collaborative protocols between ophthalmologists and neurologists to improve outcomes.
Comparison of preoperative NT-proBNP and simple cardiac risk scores for predicting postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk
(2024) Schmidt, Götz; Frieling, Nora; Schneck, Emmanuel; Habicher, Marit; Koch, Christian; Aßmus, Birgit; Sander, Michael
Background: Chronic heart failure (HF) is frequent in elderly patients undergoing non-cardiac surgery. Preoperative risk stratification is vital and can be achieved using simple clinical risk scores or preoperative N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurement. This study aimed to compare the predictivity of the revised cardiac risk index (RCRI), the American University of Beirut cardiovascular risk index (AUB-HAS2), and a score proposed by Andersson et al. for postoperative 30-day morbidity to preoperative NT-proBNP. Methods: Preoperative NT-proBNP was measured in 199 consecutive patients aged ≥ 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk. The areas under the receiver operating characteristic curve (AUCROC) for the composite morbidity endpoint (CME) comprising the incidence of any rehospitalisation, acute decompensated HF, acute kidney injury, and any infection at postoperative day 30 were assessed. Multivariable logistic regression analysis derived new scores from the simple risk scores and the NT-proBNP cut-off of 450 pg/mL. Results: AUB-HAS2, but not RCRI or Andersson score, significantly predicted the CME (AUB-HAS2: AUCROC 0.646, p < 0.001; RCRI: AUCROC 0.560, p = 0.126; Andersson: AUCROC 0.487, p = 0.760). The AUCROC was comparable between preoperative NT-proBNP (0.679, p < 0.001) and AUB-HAS2 (p = 0.334). Multivariable analyses revealed a preoperative NT-proBNP ≥ 450 pg/mL to be the strongest predictor of CME among the individual score components (p < 0.001). Adding preoperative NT-proBNP improved the predictive value of AUB-HAS2 and RCRI (modified AUB-HAS2: AUCROC 0.703, p < 0.001; modified RCRI: AUCROC 0.679, p < 0.001; both p < 0.001 vs original scores). The predictive value of the modified RCRI and AUB-HAS2 was comparable to preoperative NT-proBNP alone (p = 0.988 vs modified RCRI, p = 0.367 vs modified AUB-HAS2). Conclusions: The predictive value of postoperative morbidity varies significantly between the available simple perioperative risk scores and can be enhanced by preoperative NT-proBNP. New scores, including preoperative NT-proBNP, should be evaluated in large multicentre cohorts.
Epicardial fat volume is associated with primary coronary slow-flow phenomenon in patients with severe aortic stenosis undergoing transcatheter valve implantation
(2024) Weferling, Maren; Rolf, Andreas; Treiber, Julia; Fischer-Rasokat, Ulrich; Liebetrau, Christoph; Hamm, Christian W.; Dey, Damini; Kim, Won-Keun
Background: Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF. Methods: Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms. Results: Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107–180] vs. 113 ml [IQR 89–147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002–1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004–1.026]; p = 0.009). Conclusion: Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.
Mitogenomes do not substantially improve phylogenetic resolution in a young non-model adaptive radiation of freshwater gastropods
(2024) Stelbrink, Björn; von Rintelen, Thomas; Marwoto, Ristiyanti M.; Salzburger, Walter
Background: Species flocks in ancient lakes, and particularly those arising from adaptive radiation, make up the bulk of overall taxonomic and morphological diversity in these insular ecosystems. For these mostly young species assemblages, classical mitochondrial barcoding markers have so far been key to disentangle interspecific relationships. However, with the rise and further development of next-generation sequencing (NGS) methods and mapping tools, genome-wide data have become an increasingly important source of information even for non-model groups. Results: Here, we provide, for the first time, a comprehensive mitogenome dataset of freshwater gastropods endemic to Sulawesi and thus of an ancient lake invertebrate species flock in general. We applied low-coverage whole-genome sequencing for a total of 78 individuals including 27 out of the 28 Tylomelania morphospecies from the Malili lake system as well as selected representatives from Lake Poso and adjacent catchments. Our aim was to assess whether mitogenomes considerably contribute to the phylogenetic resolution within this young species flock. Interestingly, we identified a high number of variable and parsimony-informative sites across the other ‘non-traditional’ mitochondrial loci. However, although the overall support was very high, the topology obtained was largely congruent with previously published single-locus phylogenies. Several clades remained unresolved and a large number of species was recovered polyphyletic, indicative of both rapid diversification and mitochondrial introgression. Conclusions: This once again illustrates that, despite the higher number of characters available, mitogenomes behave like a single locus and thus can only make a limited contribution to resolving species boundaries, particularly when introgression events are involved.
Toxoplasma gondii modulates the host cell cycle, chromosome segregation, and cytokinesis irrespective of cell type or species origin
(2024) Rojas-Baron, Lisbeth; Senk, Kira; Hermosilla, Carlos; Taubert, Anja; Velásquez, Zahady D.
Background: Toxoplasma gondii is an apicomplexan intracellular obligate parasite and the etiological agent of toxoplasmosis in humans, domestic animals and wildlife, causing miscarriages and negatively impacting offspring. During its intracellular development, it relies on nutrients from the host cell, controlling several pathways and the cytoskeleton. T. gondii has been proven to control the host cell cycle, mitosis and cytokinesis, depending on the time of infection and the origin of the host cell. However, no data from parallel infection studies have been collected. Given that T. gondii can infect virtually any nucleated cell, including those of humans and animals, understanding the mechanism by which it infects or develops inside the host cell is essential for disease prevention. Therefore, we aimed here to reveal whether this modulation is dependent on a specific cell type or host cell species. Methods: We used only primary cells from humans and bovines at a maximum of four passages to ensure that all cells were counted with appropriate cell cycle checkpoint control. The cell cycle progression was analysed using fluorescence-activated cell sorting (FACS)-based DNA quantification, and its regulation was followed by the quantification of cyclin B1 (mitosis checkpoint protein). The results demonstrated that all studied host cells except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Additionally, we used an immunofluorescence assay to track mitosis and cytokinesis in uninfected and T. gondii-infected cells. Results: The results demonstrated that all studied host cell except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Our findings showed that the analysed cells developed chromosome segregation problems and failed to complete cytokinesis. Also, the number of centrosomes per mitotic pole was increased after infection in all cell types. Therefore, our data suggest that T. gondii modulates the host cell cycle, chromosome segregation and cytokinesis during infection or development regardless of the host cell origin or type.
Culture of care: the question of animal agency in laboratory animal science
(2024) Ameli, Katharina; Krämer, Stephanie
Background: A majority of the current debates in experimental animal science research focus to a large extent on the significance and implementation of the 3Rs principle according to Russell and Burch. In this context, not least due to the EU Directive 2010/63/EU, the concept of a culture of care has become more prevalent. Although animals are essential actors in the field of laboratory science, the discussion around animal agency, as well as the resulting consequences for laboratory animal science, is currently unconsidered. Methods: The purpose of this qualitative survey was to identify the perception and understanding of professional workers in laboratory animal science regarding the culture of care in general and aspects of animal agency in particular. Using a non-standardized qualitative survey method (topic-oriented, guideline-based expert interviews), persons involved in animal experimentation in different groups (management, science, regulation, and care) were interviewed. Results: Overall, the results of the qualitative survey showed that animal agency plays a subordinate role in the question of a culture of care in animal research. Although not all groups explicitly applied the construct of animal agency or comparable terminology for this, there were links to the theoretical construct. Overall, the interviews showed a recognized network between humans and animals and that animals can interact dialogically in research. This is justified, for example, by the transfer of emotions from carers or scientists to animals. Nevertheless, a differentiated reflection of an animal’s agency remains disregarded. Conclusion: The present qualitative survey approached the understanding of a culture of care among experts in the field of animal research. Animal agency does occur in the theoretical reception of the culture of care model. However, it is not conclusively established in everyday practice. Rather, the results lead to the assumption that strategies are being implemented to largely fade out animal agency.
Dopamine, norepinephrine, and vasopressin accelerate particle transport velocity in murine tracheal epithelium via substance-specific receptor pathways: dependency on intra- and extracellular Ca2+ sources
(2024) Schmidt, Götz; Greif, Isabelle; Müller, Sabrina; Markmann, Melanie; Edinger, Fabian; Sander, Michael; Koch, Christian; Henrich, Michael
Background: The unique ability of the respiratory tract to protect the integrity of the airways by removing potentially harmful substances is defined as mucociliary clearance. This complex physiological mechanism protects the lower airways by ridding them of pollutants and pathogens. This study aimed to evaluate the potential influence of clinically relevant vasopressors on mucociliary clearance. Material and methods: The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance under the influence of dopamine, norepinephrine, and vasopressin. Inhibitory substances were applied to elucidate relevant signal transduction cascades and the value and origin of calcium ions. Reverse-transcription polymerase chain reactions (RT-PCR) were performed to identify the expression of vasopressin receptor subtypes. Results: Dopamine, norepinephrine, and vasopressin significantly increased the PTV in a dose-dependent manner with half maximal effective concentrations of 0.58 µM, 1.21 µM, and 0.10 µM, respectively. Each substance increased the PTV via separate receptor pathways. While dopamine acted on D1-like receptors to increase the PTV, norepinephrine acted on β-adrenergic receptors, and vasopressin acted on V1a receptors. RT-PCR revealed the expression of V1a in the murine whole trachea and tracheal epithelium. PTV increased when protein kinase A was inhibited and norepinephrine or vasopressin were applied, but not when dopamine was applied. Phospholipase C inhibition decreased the PTV when vasopressin was applied. In general, maximum PTV was significantly reduced when extracellular calcium entry was inhibited. When intracellular calcium stores were depleted, no increase in PTV was observed after administering all three substances. Inositol trisphosphate receptor activation was found to be pivotal in the increase in murine PTV after applying dopamine and vasopressin. Discussion: Dopamine, norepinephrine, and vasopressin accelerate the murine PTV via substance-specific receptor pathways. Further investigations should assess the value and interaction of these substances on mucociliary clearance in clinical practice.
Glycosylation signature of plasma IgA of critically ill COVID-19 patients
(2024) Potaczek, Daniel P.; van Tol, Bianca D. M.; Falck, David; Krolczik, Christina; Zlatina, Kristina; Bertrams, Wilhelm; Wilhelm, Jochen; Schmeck, Bernd; Seeliger, Benjamin; David, Sascha; Skevaki, Chrysanthi; Mack, Elisabeth; Seeger, Werner; Schaefer, Liliana; Galuska, Sebastian P.; Wuhrer, Manfred; Wygrecka, Malgorzata
Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases.
Top-down modulation of dichotic listening affects interhemispheric connectivity: an electroencephalography study
(2024) Elyamany, Osama; Iffland, Jona; Lockhofen, Denise; Steinmann, Saskia; Leicht, Gregor; Mulert, Christoph
Introduction: Dichotic listening (DL) has been extensively used as a task to investigate auditory processing and hemispheric lateralisation in humans. According to the “callosal relay model,” the typical finding of a right ear advantage (REA) occurs because the information coming from the right ear has direct access to the left dominant hemisphere while the information coming from the left ear has to cross via the corpus callosum. The underlying neuroanatomical correlates and neurophysiological mechanisms have been described using diffusion tensor imaging (DTI) and lagged phase synchronization (LPS) of the interhemispheric auditory pathway. During the non-forced condition of DL, functional connectivity (LPS) of interhemispheric gamma-band coupling has been described as a relevant mechanism related to auditory perception in DL. In this study, we aimed to extend the previous results by exploring the effects of top-down modulation of DL (forced-attention condition) on interhemispheric gamma-band LPS. Methods: Right-handed healthy participants (n = 31; 17 females) performed three blocks of DL with different attention instructions (no-attention, left-ear attention, right-ear attention) during simultaneous EEG recording with 64 channels. Source analysis was done with exact low-resolution brain electromagnetic tomography (eLORETA) and functional connectivity between bilateral auditory areas was assessed as LPS in the gamma-band frequency range. Results: Twenty-four participants (77%) exhibited a right-ear advantage in the no-attention block. The left- and right-attention conditions significantly decreased and increased right-ear reports, respectively. Similar to the previous studies, functional connectivity analysis (gamma-band LPS) showed significantly increased connectivity between left and right Brodmann areas (BAs) 41 and 42 during left ear reports in contrast with right ear reports. Our new findings notably indicated that the right-attention condition exhibited significantly higher connectivity between BAs 42 compared with the no-attention condition. This enhancement of connectivity was more pronounced during the perception of right ear reports. Discussion: Our results are in line with previous reports describing gamma-band synchronization as a relevant neurophysiological mechanism involved in the interhemispheric connectivity according to the callosal relay model. Moreover, we newly added some evidence of attentional effects on this interhemispheric connectivity, consistent with the attention-executive model. Our results suggest that reciprocal inhibition could be involved in hemispheric lateralization processes.
Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report
(2024) Trzebiatowski, Lukas; Kowalewski, Mariusz Pawel; Schmid, Sarah; Skaar, Kirstin; Müller, Jana; Wehrend, Axel
Background: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. Case presentation: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. Conclusions: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.
Neural correlates of dynamic lightness induction
(2024) Malik, Amna; Boyaci, Huseyin
The lightness of a surface depends not only on the amount of light reflected off, it but also on the context in which it is embedded. Despite a long history of research, neural correlates of context-dependent lightness perception remain a topic of ongoing debate. Here, we seek to expand on the existing literature by measuring functional magnetic resonance imaging (fMRI) responses to lightness variations induced by the context. During the fMRI experiment, we presented 10 participants with a dynamic stimulus in which either the luminance of a disk or its surround is modulated at four different frequencies ranging from 1 to 8 Hz. Behaviorally, when the surround luminance is modulated at low frequencies, participants perceive an illusory change in the lightness of the disk (lightness induction). In contrast, they perceive little or no induction at higher frequencies. Using this frequency dependence and controlling for long-range responses to border contrast and luminance changes, we found that activity in the primary visual cortex (V1) correlates with lightness induction, providing further evidence for the involvement of V1 in the processing of context-dependent lightness.
Protein aggregation is a consequence of the dormancy-inducing membrane toxin TisB in Escherichia coli
(2024) Leinberger, Florian H.; Cassidy, Liam; Edelmann, Daniel; Schmid, Nicole E.; Oberpaul, Markus; Blumenkamp, Patrick; Schmidt, Sebastian; Natriashvili, Ana; Ulbrich, Maximilian H.; Tholey, Andreas; Koch, Hans-Georg; Berghoff, Bork A.
Bacterial dormancy is a valuable strategy to survive stressful conditions. Toxins from chromosomal toxin-antitoxin systems have the potential to halt cell growth, induce dormancy, and eventually promote a stress-tolerant persister state. Due to their potential toxicity when overexpressed, sophisticated expression systems are needed when studying toxin genes. Here, we present a moderate expression system for toxin genes based on an artificial 5′ untranslated region. We applied the system to induce expression of the toxin gene tisB from the chromosomal type I toxin-antitoxin system tisB/istR-1 in Escherichia coli. TisB is a small hydrophobic protein that targets the inner membrane, resulting in depolarization and ATP depletion. We analyzed TisB-producing cells by RNA-sequencing and revealed several genes with a role in recovery from TisB-induced dormancy, including the chaperone genes ibpAB and spy. The importance of chaperone genes suggested that TisB-producing cells are prone to protein aggregation, which was validated by an in vivo fluorescent reporter system. We moved on to show that TisB is an essential factor for protein aggregation upon DNA damage mediated by the fluoroquinolone antibiotic ciprofloxacin in E. coli wild-type cells. The occurrence of protein aggregates correlates with an extended dormancy duration, which underscores their importance for the life cycle of TisB-dependent persister cells.
Epicardial adipose tissue and muscle distribution affect outcomes in very old patients after transcatheter aortic valve replacement
(2024) Rohrbach, Susanne; Uluocak, Oezge; Junge, Marieke; Knapp, Fabienne; Schulz, Rainer; Böning, Andreas; Nef, Holger M; Krombach, Gabriele A; Niemann, Bernd
Aims: To analyse the relevance of body composition and blood markers for long-term outcomes in very old patients after transcatheter aortic valve replacement (TAVR). Methods and results: A total of 403 very old patients were characterized with regard to subcutaneous, visceral, and epicardial fat, psoas muscle area, plasma growth differentiation factor 15 (GDF-15), and leptin. Cohorts grouped by body mass index (BMI) were analysed for long-term outcomes. Patients underwent transapical and transfemoral TAVR (similar 30-day/1-year survival). Body mass index >35 kg/m2 showed increased 2- and 3-year mortality compared with BMI 25–34.9 kg/m2 but not compared with BMI <25 kg/m2. Fat areas correlated positively to BMI (epicardial: R2 = 0.05, P < 0.01; visceral: R2 = 0.20, P < 0.001; subcutaneous: R2 = 0.13, P < 0.001). Increased epicardial or visceral but not subcutaneous fat area resulted in higher long-term mortality. Patients with high BMI (1781.3 mm2 ± 75.8, P < 0.05) and lean patients (1729.4 ± 52.8, P < 0.01) showed lower psoas muscle area compared with those with mildly elevated BMI (2055.2 ± 91.7). Reduced psoas muscle area and increased visceral fat and epicardial fat areas were independent predictors of long-term mortality. The levels of serum GDF-15 were the highest in BMI >40 kg/m2 (2793.5 pg/mL ± 123.2) vs. BMI <25 kg/m2 (2017.6 pg/mL ±130.8), BMI 25–30 kg/m2 (1881.8 pg/mL ±127.4), or BMI 30–35 kg/m2 (2054.2 pg/mL ±124.1, all P < 0.05). Increased GDF-15 level predicted mortality (2587 pg/mL, area under the receiver operating characteristic curve 0.94). Serum leptin level increased with BMI without predictive value for long-term mortality. Conclusion: Morbidly visceral and epicardial fat accumulation, reduction in muscle area, and GDF-15 increase are strong predictors of adverse outcomes in very old patients post-TAVR.

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