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Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study.
Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the clinical outcome of RBC transfusions on skull base and non-skull base meningioma patients including the identification of risk factors for RBC transfusion. Between October 2009 and October 2016, 423 patients underwent primary meningioma resection. Of these, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; p = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher (p < 0.0001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anaesthesiologists (ASA) physical status score (p = 0.0247), tumor size (p = 0.0006), surgical time (p = 0.0018) and intraoperative blood loss (p < 0.0001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years). We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve the clinical outcome of meningioma patients.
Eukaryotic ribosome assembly starts in the nucleolus, where the ribosomal DNA (rDNA) is transcribed into the 35S pre-ribosomal RNA (pre-rRNA). More than two-hundred ribosome biogenesis factors (RBFs) and more than two-hundred small nucleolar RNAs (snoRNA) catalyze the processing, folding and modification of the rRNA in Arabidopsis thaliana. The initial pre-ribosomal 90S complex is formed already during transcription by association of ribosomal proteins (RPs) and RBFs. In addition, small nucleolar ribonucleoprotein particles (snoRNPs) composed of snoRNAs and RBFs catalyze the two major rRNA modification types, 2′-O-ribose-methylation and pseudouridylation. Besides these two modifications, rRNAs can also undergo base methylations and acetylation. However, the latter two modifications have not yet been systematically explored in plants. The snoRNAs of these snoRNPs serve as targeting factors to direct modifications to specific rRNA regions by antisense elements. Today, hundreds of different sites of modifications in the rRNA have been described for eukaryotic ribosomes in general. While our understanding of the general process of ribosome biogenesis has advanced rapidly, the diversities appearing during plant ribosome biogenesis is beginning to emerge. Today, more than two-hundred RBFs were identified by bioinformatics or biochemical approaches, including several plant specific factors. Similarly, more than two hundred snoRNA were predicted based on RNA sequencing experiments. Here, we discuss the predicted and verified rRNA modification sites and the corresponding identified snoRNAs on the example of the model plant Arabidopsis thaliana. Our summary uncovers the plant modification sites in comparison to the human and yeast modification sites.
The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular, we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here, we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.
Treatment outcomes of a CBT-based group intervention for adolescents with internet use disorders
(2021)
Background and aims: Instances of Internet use disorders (IUD) including Internet gaming disorder (IGD) and non-gaming pathological Internet use (ng-PIU) have the extent that they are now a growing mental health issue. Individuals suffering from IUD show a large range of symptoms, high comorbidities and impairments in different areas of life. To date there is a lack of efficient and evidence-based treatment programs for such adolescents. The present registered single-arm trial (ClinicalTrials.gov: NCT03582839) aimed to investigate the long-term effects of a brief manualized cognitive behavioral therapy (CBT) program for adolescents with IUD. Methods: N = 54 patients (16.7% female), aged 9–19 years (M = 13.48, SD = 1.72) received the CBT group program PROTECT+. IUD symptom severity (primary outcome variable) as well as comorbid symptoms, risk-related variables and potentially protective skills (secondary outcome variables) were assessed at pretest, posttest, as well as 4 and 12 months after admission. Results: Patients showed a significant reduction in IUD symptom severity at the 12-month follow-up. Effect sizes were medium to large depending on the measure. Beyond the statistical significance, the clinical significance was confirmed using the reliable change index. Secondary outcome variables showed a significant reduction in self-reported depression, social anxiety, performance anxiety and school anxiety as well as in parental-reported general psychopathology. Discussion and conclusions: The present study shows long-term effects of a manual-based CBT treatment for adolescents suffering from IUD. The results indicate that even a 4-session brief intervention can achieve a medium to large effect over 12 months. Future work is needed to confirm the efficacy within a randomized controlled trial (RCT).
Background: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery. Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. Methods: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. Results: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%. In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009). Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. Conclusion: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.
Background: Physical activity and sleep quality are both major factors for improving one's health. Knowledge on the interactions of sleep quality and the amount of physical activity may be helpful for implementing multimodal health interventions in older adults. Methods: This preliminary cross-sectional study is based on 64 participants [82.1 ± 6.4 years (MD ± SD); 22 male: 42 female]. The amount of physical activity was assessed by means of an accelerometer (MyWellness Key). Self-reported sleep parameters were obtained using the Pittsburgh Sleep Quality Index. The Barthel Index was used for physical disability rating. Bivariate correlations (Spearman's Rho) were used to explore relationships between the amount of physical activity and sleep quality. To analyse differences between categorial subgroups univariate ANOVAs were applied; in cases of significance, these were followed by Tukey-HSD post-hoc analyses. Results: No linear association between physical activity and sleep quality was found (r = 0.119; p > 0.05). In subgroup analyses (n = 41, Barthel Index ≥90 pts, free of pre-existing conditions), physical activity levels differed significantly between groups of different sleep duration (≥7 h; ≥6 to <7 h; ≥5 to <6 h; <5h; p = 0.037). Conclusion: There is no general association between higher activity levels and better sleep quality in the investigated cohort. However, a sleep duration of ≥5 to <6 h, corresponding to 7.6 h bed rest time, was associated with a higher level of physical activity.
In the Central German Uplands, Fagus sylvatica and Picea abies have been particularly affected by climate change. With the establishment of beech forests about 3000 years ago and pure spruce stands 500 years ago, they might be regarded as ‘neophytes’ in the Hessian forests. Palaeoecological investigations at wetland sites in the low mountain ranges and intramontane basins point to an asynchronous vegetation evolution in a comparatively small but heterogenous region. On the other hand, palynological data prove that sustainably managed woodlands with high proportions of Tilia have been persisting for several millennia, before the spread of beech took place as a result of a cooler and wetter climate and changes in land management. In view of increasingly warmer and drier conditions, Tilia cordata appears especially qualified to be an important silvicultural constituent of the future, not only due to its tolerance towards drought, but also its resistance to browsing, and the ability to reproduce vegetatively. Forest managers should be encouraged to actively promote the return to more stress-tolerant lime-dominated woodlands, similar to those that existed in the Subboreal chronozone.
Internet Gaming Disorder (IGD) has been included in the DSM-5 as a diagnosis for further study, and Gaming Disorder as a new diagnosis in the ICD-11. Nonetheless, little is known about the clinical prevalence of IGD in children and adolescents. Additionally, it is unclear if patients with IGD are already identified in routine psychotherapy, using the ICD-10 diagnosis F 63.8 (recommended classification of IGD in ICD-10). This study investigated N = 358 children and adolescents (self and parental rating) of an outpatient psychotherapy centre in Germany using the Video Game Dependency Scale. According to self-report 4.0% of the 11- to 17-year-old patients met criteria for a tentative IGD diagnosis and 14.0% according to the parental report. Of the 5- to 10-year-old patients, 4.1% were diagnosed with tentative IGD according to parental report. Patients meeting IGD criteria were most frequently diagnosed with hyperkinetic disorders, followed by anxiety disorders, F 63.8, conduct disorders, mood disorders and obsessive-compulsive disorders (descending order) as primary clinical diagnoses. Consequently, this study indicates that a significant amount of the clinical population presents IGD. Meaning, appropriate diagnostics should be included in routine psychological diagnostics in order to avoid “hidden” cases of IGD in the future.
The development of super-resolution microscopy (SRM) has widened our understanding of biomolecular structure and function in biological materials. Imaging multiple targets within a single area would elucidate their spatial localization relative to the cell matrix and neighboring biomolecules, revealing multi-protein macromolecular structures and their functional co-dependencies. SRM methods are, however, limited to the number of suitable fluorophores that can be imaged during a single acquisition as well as the loss of antigens during antibody washing and restaining for organic dye multiplexing. We report the visualization of multiple protein targets within the pre- and postsynapse in 350–400 nm thick neuronal tissue sections using DNA-assisted single-molecule localization microscopy (SMLM). In a single labeling step, antibodies conjugated with short DNA oligonucleotides visualized multiple targets by sequential exchange of fluorophore-labeled complementary oligonucleotides present in the imaging buffer. This approach avoids potential effects on structural integrity when using multiple rounds of immunolabeling and eliminates chromatic aberration, because all targets are imaged using a single excitation laser wavelength. This method proved robust for multi-target imaging in semi-thin tissue sections with a lateral resolution better than 25 nm, paving the way toward structural cell biology with single-molecule SRM.
Bioactive lipid mediators play a major role in regulating inflammatory processes. Herein, early pro-inflammatory phases are characterized and regulated by prostanoids and leukotrienes, whereas specialized pro-resolving mediators (SPM), including lipoxins, resolvins, protectins, and maresins, dominate during the resolution phase. While pro-inflammatory properties of prostanoids have been studied extensively, their impact on later phases of the inflammatory process has been attributed mainly to their ability to initiate the lipid-mediator class switch towards SPM. Yet, there is accumulating evidence that prostanoids directly contribute to the resolution of inflammation and return to homeostasis. In this mini review, we summarize the current knowledge of the resolution-regulatory properties of prostanoids and discuss potential implications for anti-inflammatory, prostanoid-targeted therapeutic interventions.
The NADPH oxidase Nox4 is a hydrogen peroxide (H2O2)-producing enzyme, with the highest expression in the kidney. As the kidney is involved in volume and blood pressure control through sodium handling, we set out to determine the impact of a low sodium diet on these parameters in WT and Nox4-/- mice. Nox4 expression in the murine kidney was restricted to the proximal tubule. Nevertheless, low-sodium-induced weight loss and sodium sparing function was similar in WT and Nox4-/- mice, disputing an important function of renal Nox4 in sodium handling. In contrast, a low sodium diet resulted in a reduction in systolic blood pressure in Nox4-/- as compared to WT mice. This was associated with a selectively lower pressure to heart-rate ratio, as well as heart to body weight ratio. In general, a low sodium diet leads to activation of sympathetic tone and the renin angiotensin system, which subsequently increases peripheral resistance. Our observations suggest that the control by this system is attenuated in Nox4-/- mice, resulting in lower blood pressure in response to low sodium.
Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.
11,12-Dihydrodibenzo[c,g]-1,2-diazocines have been established as a viable alternative to azobenzene for photoswitching, in particular, as they show an inverted switching behavior: the ground state is the Z isomer. In this paper, we present an improved method to obtain dibenzodiazocine and its derivatives from the respective 2-nitrotoluenes in two reaction steps, each proceeding in minutes. This fast access to a variety of derivatives permitted the study of substitution effects on the synthesis and on the photochemical properties. With biochemical applications in mind, methanol was chosen as a protic solvent system for the photochemical investigations. In contrast to the azobenzene system, none of the tested substitution patterns resulted in more efficient switching or in significantly prolonged half-lives, showing that the system is dominated by the ring strain.
The authors identify U.S. monetary and fiscal dominance regimes using machine learning techniques. The algorithms are trained and verified by employing simulated data from Markov-switching DSGE models, before they classify regimes from 1968-2017 using actual U.S. data. All machine learning methods outperform a standard logistic regression concerning the simulated data. Among those the Boosted Ensemble Trees classifier yields the best results. The authors find clear evidence of fiscal dominance before Volcker. Monetary dominance is detected between 1984-1988, before a fiscally led regime turns up around the stock market crash lasting until 1994. Until the beginning of the new century, monetary dominance is established, while the more recent evidence following the financial crisis is mixed with a tendency towards fiscal dominance.
This note argues that the European Central Bank should adjust its strategy in order to consider broader measures of inflation in its policy deliberations and communications. In particular, it points out that a broad measure of domestic goods and services price inflation such as the GDP deflator has increased along with the euro area recovery and the expansion of monetary policy since 2013, while HICP inflation has become more variable and, on average, has declined. Similarly, the cost of owner-occupied housing, which is excluded from the HICP, has risen during this period. Furthermore, it shows that optimal monetary policy at the effective lower bound on nominal interest rates aims to return inflation more slowly to the inflation target from below than in normal times because of uncertainty about the effects and potential side effects of quantitative easing.
Rising temperatures, falling ratings: the effect of climate change on sovereign creditworthiness
(2021)
How will a changing climate impact the creditworthiness of governments over the very long term? Financial markets need credible, digestible information on how climate change translates into material risks. To bridge the gap between climate science and real-world financial indicators, the authors simulate the effect of climate change on sovereign credit ratings for 108 countries, creating the world’s first climate-adjusted sovereign credit rating. The study offers a first methodological approach to extend the long-term rating to an ultra-long-term reality, aiming at long-term investors, but also regulators and rating agencies.
Central banks normally accept debt of their own governments as collateral in liquidity operations without reservations. This gives rise to a valuable liquidity premium that reduces the cost of government finance. The ECB is an interesting exception in this respect. It relies on external assessments of the creditworthiness of its member states, such as credit ratings, to determine eligibility and the haircut it imposes on such debt. The authors show how such features in a central bank’s collateral framework can give rise to cliff effects and multiple equilibria in bond yields and increase the vulnerability of governments to external shocks. This can potentially induce sovereign debt crises and defaults that would not otherwise arise.
Can boundedly rational agents survive competition with fully rational agents? The authors develop a highly nonlinear heterogeneous agents model with rational forward looking versus boundedly rational backward looking agents and evolving market shares depending on their relative performance. Their novel numerical solution method detects equilibrium paths characterized by complex bubble and crash dynamics. Boundedly rational trend-extrapolators amplify small deviations from fundamentals, while rational agents anticipate market crashes after large bubbles and drive prices back close to fundamental value. Overall rational and non-rational beliefs co-evolve over time, with time-varying impact, and their interaction produces complex endogenous bubble and crashes, without any exogenous shocks.
High-frequency changes in interest rates around FOMC announcements are a standard method of measuring monetary policy shocks. However, some recent studies have documented puzzling effects of these shocks on private-sector forecasts of GDP, unemployment, or inflation that are opposite in sign to what standard macroeconomic models would predict. This evidence has been viewed as supportive of a „Fed information effect“ channel of monetary policy, whereby an FOMC tightening (easing) communicates that the economy is stronger (weaker) than the public had expected.
The authors show that these empirical results are also consistent with a „Fed response to news“ channel, in which incoming, publicly available economic news causes both the Fed to change monetary policy and the private sector to revise its forecasts. They provide substantial new evidence that distinguishes between these two channels and strongly favors the latter; for example, regressions that include the previously omitted public macroeconomic news, high-frequency stock market responses to Fed announcements, and a new survey that they conduct of individual Blue Chip forecasters all indicate that the Fed and private sector are simply responding to the same public news, and that there is little if any role for a „Fed information effect“.
Die vorliegende Arbeit Zeitaufgelöste NMR-spektroskopische Untersuchung konformationeller Dynamiken in DNA G-Quadruplexen befasst sich mit der detaillierten biophysikalischen Untersuchung wichtiger strukturdynamischer Eigenschaften von nicht-kanonischen Nukleinsäure Sekundärstrukturelementen.
Im Genom aller eukaryotischer Lebewesen, insbesondere dem menschlichen Genom finden sich DNA-Sequenzabschnitte, die überdurchschnittlich Guanosin (G)-reich sind. Diese poly-G Abschnitte sind nicht zufällig im Genom verteilt, sondern häufen sich vermehrt in Genabschnitten, die besonders wichtig für die Regulation der Genexpression sind. G-reiche DNA-Sequenzen können unter geeigneten Umständen alternative Sekundärstrukturen ausbilden, die von der doppelsträngigen, kanonischen Watson-Crick Konformation abweichen. In Anwesenheit monovalenter Kationen können sich G-Nukleotide in einer Tetrade über Hoogsteen Interaktionen anlagern. Diese Tetraden können sich stapeln und dadurch sogenannte G-Quadruplexe (G4) ausbilden. Das menschliche cMYC Gen wird typischerweise als proto-Onkogen bezeichnet. Es kodiert für einen unspezifischen Transkriptionsfaktor, der bei einer Vielzahl von systematischen und soliden Tumorerkrankungen stark überexprimiert wird. Die zelluläre Konzentration des Genprodukts kann zu 90% über ein G4 cis-Element in der Promotorregion reguliert werden. Der cMYC G4 hat die Möglichkeit verschiedene Konformationen einzunehmen. Im Falle des cMYC G4 kann man zusätzliche, nicht-konventionelle Formen der konformationellen Isomerie finden. Zum einen gibt es die Möglichkeit, dass bei einem G4, der aus drei Tetraden und vier intramolekularen Strangabschnitten (dreistöckiger G4) besteht, einzelne Strangabschnitte mehr als drei konsekutive G-Nukleotide besitzen. Dadurch können sich Faltungs-Isomere bilden, die sich durch Verschieben des Strangs relativ zum verbleibenden dreistöckigen Tetradengerüst ergeben. Man spricht von G-Register Isomeren. Eine zweite Möglichkeit der Strukturisomerie ergibt sich, wenn in einer Nukleotidsequenz mehr als vier G-reiche Strangabschnitte aufeinander folgen. Jeweils vier dieser Strangabschnitte können in unterschiedlicher Weise kombiniert werden, um ein G4 Isomer auszubilden. In jedem dieser so zustande gekommenen G4 verbleibt ein (oder mehrere) G-reicher Strangabschnitt, der im konkreten Isomer nicht zur Faltung verwendet wird. Diese zusätzlichen G-Stränge werden daher auch Ersatzräder (engl. spare-tires) genannt; man erhält spare-tire Isomere.
Obwohl diese Formen des Polymorphismus, deren biologischer Kontext und die biophysikalischen Konsequenzen in Arbeiten von C. Burrows (2015) und A. Mittermaier (2016) erstmals umfassend beschrieben wurden, gab es bis zum Ausgangspunkt dieser Arbeit keine Kenntnisse über deren strukturelle Dynamik, den Faltungswegen und den zugrundeliegenden molekularen Mechanismen. Zeitaufgelöste Kernspinresonanz (engl. nuclear magnetic resonance, NMR) Spektroskopie ist eine bestens geeignete Methode, um die Dynamik von Biomakromolekülen mit atomarer Auflösung zu studieren. Um solche Experimente durchführen zu können, braucht es geeignete Herangehensweisen für die Präparation eines Nicht-Gleichgewichtszustands. In dieser Arbeit wird eine neu erarbeitete Strategie vorgestellt, die es erlaubt, Einblick in die Faltungs- und Umfaltungskinetiken eines dynamischen Konformations-Ensembles nicht-konventioneller Strukturisomere der cMYC G4 DNA-Sequenz zu erhalten.
Hierzu wurden photolabile Schutzgruppen (engl. Photocages) positionsspezifisch an bestimmten G-Nukleobasen (O6-(R)-NPE) angebracht. Die Schutzgruppen blockieren die Basenpaar-Interaktionen des Nukleotids, wodurch dieses sich nicht mehr an einer Tetradenbildung beteiligen kann. Die Photocages wurden jeweils an den Nukleotiden eingeführt, die nur in jeweils einem der G-Register Isomere an der Tetradenbildung beteiligt sind. Durch diese gezielte Destabilisierung konnten die Isomere getrennt und im gefalteten Zustand isoliert werden. Die so erhaltenen Konformationen wurden umfassend spektroskopisch charakterisiert. Der Ansatz, das konformationelle Gleichgewicht durch Photocages transient zu stören, wurde daraufhin weiterentwickelt. Mehrere Photocages wurden an Nukleobasen in zentraler Position einzelner G-Strangabschnitte angebracht. Dadurch konnte eine ausreichende Destabilisierung erreicht werden, die die Faltung jedweder G4 Strukturen unterbindet. Somit wurde ein ungefalteter Zustand erzeugt, der unter ansonsten frei wählbaren, physiologischen Bedingungen besteht. Durch in situ Photolyse der Schutzgruppen konnte so die Licht-induzierte G4 Faltung unter konstanten Puffer- und Temperaturbedingungen untersucht werden. Dieser Ansatz wurde auf die Untersuchung der Faltungswege, die zu verschiedenen spare-tire Isomeren führen, fokussiert.
Zusammenfassend kann festgestellt werden, dass es insgesamt erstmalig gelungen ist, die Kinetiken der wesentlichen Faltungs- und Umfaltungswege entlang der konformationellen Energielandschaft des cMYC G4 Elements zu untersuchen. Das komplexe, dynamische Zusammenspiel aller relevanten, nicht-konventionellen isomeren G4 Strukturen konnte entworren und umfassend experimentell beschrieben werden. Der dafür weiterentwickelte Ansatz über konformationelle Selektion mit Hilfe photolabiler Schutzgruppen hat dabei experimentelle Einblicke erlaubt, die bislang nicht zugänglich waren. Die Strukturen und Faltungszustämde, die mit den chemisch modifizierten Oligonukleotiden erhalten und isoliert wurden, sind umfassend spektroskopisch untersucht worden. Die Anwendung verschiedener spektroskopischer Ansätze und deren Kombination mit weiteren biophysikalischen Methoden hat eine Methoden-unabhängige Validierung der erhaltenen kinetischen und thermodynamischen Daten ermöglicht.
On the accuracy of linear DSGE solution methods and the consequences for log-normal asset pricing
(2021)
This paper demonstrates a failure of standard, generalized Schur (or QZ) decomposition based solutions methods for linear dynamic stochastic general equilibrium (DSGE) models when there is insufficient eigenvalue separation about the unit circle. The significance of this is demonstrated in a simple production-based asset pricing model with external habit formation. While the exact solution afforded by the simplicity of the model matches post-war US consumption growth and the equity premium, QZ-based numerical solutions miss the later by many annualized percentage points.
This in-depth analysis provides evidence on differences in the practice of supervising large banks in the UK and in the euro area. It identifies the diverging institutional architecture (partially supranationalised vs. national oversight) as a pivotal determinant for a higher effectiveness of supervisory decision making in the UK. The ECB is likely to take a more stringent stance in prudential supervision than UK authorities. The setting of risk weights and the design of macroprudential stress test scenarios document this hypothesis. This document was provided by the Economic Governance Support Unit at the request of the ECON Committee.
This document was requested by the European Parliament's Committee on Economic and Monetary Affairs. It was originally published on the European Parliament’s webpage: www.europarl.europa.eu/RegData/etudes/IDAN/2021/689443/IPOL_IDA(2021)689443_EN.pdf
The crisis management and deposit insurance (CMDI) framework in the euro area requires a reset. Although its policy objectives remain valid, the means of achieving them do not. As the euro area comes the end of the long transition period taken to implement the BRRD/SRMR, it should take the opportunity to reset expectations about resolution.
Above all, resolution should be for the many, not just the few. There should be a single presumptive path for dealing with failed banks: the use of bail-in to facilitate orderly liquidation under a solvent-wind down strategy. This will protect deposits and set the stage – together with the backstop that the European Stability Mechanism provides to the Single Resolution Fund (SRF) -- for the transformation of the SRF into the Single Deposit Guarantee Scheme (SDGS). To avoid forbearance, responsibility for emergency liquidity assistance (ELA) should rest, not with national central banks, but with the ECB as a single lender of last resort. Finally, national deposit guarantee schemes should function as institutional protection schemes and become investors of last resort in their member banks. Together, these measures would complete Banking Union, promote market discipline, avoid imposing additional burdens on taxpayers, help untie the doom loop between weak banks and weak governments, strengthen the euro and enhance financial stability.
This paper discusses policy implications of a potential surge in NPLs due to COVID-19. The study provides an empirical assessment of potential scenarios and draws lessons from previous crises for effective NPL treatment. The paper highlights the importance of early and realistic assessment of loan losses to avoid adverse incentives for banks. Secondary loan markets would help in this process and further facilitate bank resolution as laid down in the BRRD, which should be uphold even in extreme scenarios.
This in-depth analysis proposes ways to retract from supervisory COVID-19 support measures without perils for financial stability. It simulates the likely impact of the corona crisis on euro area banks’ capital and predicts a significant capital shortfall. We recommend to end accounting practices that conceal loan losses and sustain capital relief measures. Our in-depth analysis also proposes how to address the impending capital shortfall in resolution/liquidation and a supranational recapitalisation.
In this paper we put forward a legal argument in favour of granting more independence to BaFin, the German securities market supervisor. Following the Wirecard scandal, our reform proposal aims at strengthening the impartiality and credibility of the German supervisor and, as a consequence, at restoring capital market integrity. In order to achieve the necessary degree of democratic legitimacy for giving BaFin more independence and disassociating it from the Ministry of Finance, the paper sets out the necessary steps for a legal reform that creates accountability of BaFin vis-à-vis the Parliament, subjecting it to strict disclosure and reporting obligations.
Incentives, self-selection, and coordination of motivated agents for the production of social goods
(2021)
We study, theoretically and empirically, the effects of incentives on the self-selection and coordination of motivated agents to produce a social good. Agents join teams where they allocate effort to either generate individual monetary rewards (selfish effort) or contribute to the production of a social good with positive effort complementarities (social effort). Agents differ in their motivation to exert social effort. Our model predicts that lowering incentives for selfish effort in one team increases social good production by selectively attracting and coordinating motivated agents. We test this prediction in a lab experiment allowing us to cleanly separate the selection effect from other effects of low incentives. Results show that social good production more than doubles in the low- incentive team, but only if self-selection is possible. Our analysis highlights the important role of incentives in the matching of motivated agents engaged in social good production.
Managed portfolios that exploit positive first-order autocorrelation in monthly excess returns of equity factor portfolios produce large alphas and gains in Sharpe ratios. We document this finding for factor portfolios formed on the broad market, size, value, momentum, investment, prof- itability, and volatility. The value-added induced by factor management via short-term momentum is a robust empirical phenomenon that survives transaction costs and carries over to multi-factor portfolios. The novel strategy established in this work compares favorably to well-known timing strategies that employ e.g. factor volatility or factor valuation. For the majority of factors, our strategies appear successful especially in recessions and times of crisis.
We empirically examine the Capital Purchase Program (CPP) used by the US gov- ernment to bail out distressed banks with equity infusions during the Great Recession. We find strong evidence that a feature of the CPP – the government’s ability to ap- point independent directors on the board of an assisted bank that missed six dividend payments to the Treasury – helped attenuate bailout-related moral hazard. Banks were averse to these appointments – the empirical distribution of missed payments exhibits a sharp discontinuity at five. Director appointments by the Treasury led to improved bank performance, lower CEO pay, and higher stock market valuations.
Many proteins have been found to operate in a complex with various biomolecules such as proteins, nucleic acids, carbohydrates, or lipids. Protein complexes can be transient, stable or dynamic and their association is controlled under variable cellular conditions. Complexome profiling is a recently developed mass spectrometry-based method that combines mild separation techniques, native gel electrophoresis, and density gradient centrifugation with quantitative mass spectrometry to generate inventories of protein assemblies within a cell or subcellular fraction. This review summarizes applications of complexome profiling with respect to assembly ranging from single subunits to large macromolecular complexes, as well as their stability, and remodeling in health and disease.
Triathletes often experience incoordination at the start of a transition run (TR); this is possibly reflected by altered joint kinematics. In this study, the first 20 steps of a run after a warm-up run (WR) and TR (following a 90 min cycling session) of 16 elite, male, long-distance triathletes (31.3 ± 5.4 years old) were compared. Measurements were executed on the competition course of the Ironman Frankfurt in Germany. Pacing and slipstream were provided by a cyclist in front of the runner. Kinematic data of the trunk and leg joints, step length, and step rate were obtained using the MVN Link inertial motion capture system by Xsens. Statistical parametric mapping was used to compare the active leg (AL) and passive leg (PL) phases of the WR and TR. In the TR, more spinal extension (~0.5–1°; p = 0.001) and rotation (~0.2–0.5°; p = 0.001–0.004), increases in hip flexion (~3°; ~65% AL−~55% PL; p = 0.001–0.004), internal hip rotation (~2.5°; AL + ~0–30% PL; p = 0.001–0.024), more knee adduction (~1°; ~80–95% AL; p = 0.001), and complex altered knee flexion patterns (~2–4°; AL + PL; p = 0.001–0.01) occurred. Complex kinematic differences between a WR and a TR were detected. This contributes to a better understanding of the incoordination in transition running.
This paper explores the interplay of feature-based explainable AI (XAI) tech- niques, information processing, and human beliefs. Using a novel experimental protocol, we study the impact of providing users with explanations about how an AI system weighs inputted information to produce individual predictions (LIME) on users’ weighting of information and beliefs about the task-relevance of information. On the one hand, we find that feature-based explanations cause users to alter their mental weighting of available information according to observed explanations. On the other hand, explanations lead to asymmetric belief adjustments that we inter- pret as a manifestation of the confirmation bias. Trust in the prediction accuracy plays an important moderating role for XAI-enabled belief adjustments. Our results show that feature-based XAI does not only superficially influence decisions but re- ally change internal cognitive processes, bearing the potential to manipulate human beliefs and reinforce stereotypes. Hence, the current regulatory efforts that aim at enhancing algorithmic transparency may benefit from going hand in hand with measures ensuring the exclusion of sensitive personal information in XAI systems. Overall, our findings put assertions that XAI is the silver bullet solving all of AI systems’ (black box) problems into perspective.
We focus on the role of social media as a high-frequency, unfiltered mass information transmission channel and how its use for government communication affects the aggregate stock markets. To measure this effect, we concentrate on one of the most prominent Twitter users, the 45th President of the United States, Donald J. Trump. We analyze around 1,400 of his tweets related to the US economy and classify them by topic and textual sentiment using machine learning algorithms. We investigate whether the tweets contain relevant information for financial markets, i.e. whether they affect market returns, volatility, and trading volumes. Using high-frequency data, we find that Trump’s tweets are most often a reaction to pre-existing market trends and therefore do not provide material new information that would influence prices or trading. We show that past market information can help predict Trump’s decision to tweet about the economy.
Finding a bottle of milk in the bathroom would probably be quite surprising to most of us. Such a surprised reaction is driven by our strong expectations, learned through experience, that a bottle of milk belongs in the kitchen. Our environment is not randomly organized but governed by regularities that allow us to predict what objects can be found in which types of scene. These scene semantics are thought to play an important role in the recognition of objects. But when during development are the semantic predictions so far implemented that such scene-object inconsistencies would lead to semantic processing difficulties? Here we investigated how toddlers perceive their environments, and what expectations govern their attention and perception. To this aim, we used a purely visual paradigm in an ERP experiment and presented 24-month-olds with familiar scenes in which either a semantically consistent or an inconsistent object would appear. The scene-inconsistency effect has been previously studied in adults by means of the N400, a neural marker responding to semantic inconsistencies across many types of stimuli. Our results show that semantic object-scene inconsistencies indeed elicited an enhanced N400 over the left anterior brain region between 750 and 1150 ms post stimulus onset. This modulation of the N400 marker provides first indications that by the age of two toddlers have already established their scene semantics allowing them to detect a purely visual, semantic object-scene inconsistency. Our data suggest the presence of specific semantic knowledge regarding what objects occur in a certain scene category.
It is well known that lifestyle changes can alter several physiological functions in the human body. For exercise and diet, these effects are used sensibly in basic therapies, as in cardiovascular diseases. However, the physiological changes induced by exercise and a modified diet also have the capacity to influence the efficacy and toxicity of several drugs, mainly by affecting different pharmacokinetic mechanisms. This pharmacological plasticity is not clinically relevant in all cases but might play an important role in altering the effects of very common drugs, particularly drugs with a narrow therapeutic window. Therefore, with this review, we provide insights into possible food–drug and exercise–drug interactions to sharpen awareness of the potential occurrence of such effects.
We define a sentiment indicator that exploits two contrasting views of return predictability, and study its properties. The indicator, which is based on option prices, valuation ratios and interest rates, was unusually high during the late 1990s, reflecting dividend growth expectations that in our view were unreasonably optimistic. We interpret it as helping to reveal irrational beliefs about fundamentals. We show that our measure is a leading indicator of detrended volume, and of various other measures associated with financial fragility. We also make two methodological contributions. First, we derive a new valuation-ratio decomposition that is related to the Campbell and Shiller (1988) loglinearization, but which resembles the traditional Gordon growth model more closely and has certain other advantages for our purposes. Second, we introduce a volatility index that provides a lower bound on the market's expected log return.
The pricing of an ambiguous asset, whose cash flow stream is uncertain, may be affected by three factors: the belief regarding the realization likelihood of cash flows, the subjective attitude towards risk, and the attitude towards ambiguity. While previous literature looks at the total price discount under ambiguity, this paper investigates with laboratory experiments how much effect each factor can induce. We apply both non-parametric and parametric methods to cleanly separate the belief effects, the risk premiums, and the ambiguity premiums from each other. Both methods lead to similar results: Overall, subjects have substantial ambiguity aversion, and ambiguity premiums account for the largest price deviation component when the degree of ambiguity is high. As information accumulates, ambiguity premiums decrease. We also find that beliefs do influence prices under ambiguity. This is not because beliefs are biased towards either good or bad scenarios per se, but because subjects display sticky belief updating as new information becomes available. The clear separation performed in this paper between belief and attitude also enables a more accurate estimation of the parameter of ambiguity aversion compared to previous studies, since the effect of beliefs is partialled out. Overall, we find empirically that both factors, belief and attitude towards ambiguity, are important factors in pricing under ambiguity.
During the course of sepsis in critically ill patients, kidney dysfunction and damage are among the first events of a complex scenario toward multi-organ failure and patient death. Acute kidney injury triggers the release of lipocalin-2 (Lcn-2), which is involved in both renal injury and recovery. Taking into account that Lcn-2 binds and transports iron with high affinity, we aimed at clarifying if Lcn-2 fulfills different biological functions according to its iron-loading status and its cellular source during sepsis-induced kidney failure. We assessed Lcn-2 levels both in serum and in the supernatant of short-term cultured renal macrophages (MΦ) as well as renal tubular epithelial cells (TEC) isolated from either Sham-operated or cecal ligation and puncture (CLP)-treated septic mice. Total kidney iron content was analyzed by Perls’ staining, while Lcn-2-bound iron in the supernatants of short-term cultured cells was determined by atomic absorption spectroscopy. Lcn-2 protein in serum was rapidly up-regulated at 6 h after sepsis induction and subsequently increased up to 48 h. Lcn-2-levels in the supernatant of TEC peaked at 24 h and were low at 48 h with no change in its iron-loading. In contrast, in renal MΦ Lcn-2 was low at 24 h, but increased at 48 h, where it mainly appeared in its iron-bound form. Whereas TEC-secreted, iron-free Lcn-2 was associated with renal injury, increased MΦ-released iron-bound Lcn-2 was linked to renal recovery. Therefore, we hypothesized that both the cellular source of Lcn-2 as well as its iron-load crucially adds to its biological function during sepsis-induced renal injury.
The salience of ESG ratings for stock pricing: evidence from (potentially) confused investors
(2021)
We exploit the a modification to Sustainanlytics’ environmental, social, and governance (ESG) rating methodology, which is subsequently adopted by Morningstar, to study whether ESG ratings are salient for stock pricing. We show that the inversion of the rating scale but not new information leads some investors to make incorrect assessments about the meaning of the change in ESG ratings. They buy (sell) stocks they misconceive as ESG upgraded (downgraded) even when the opposite is true. This trading behavior exerts transitory price pressure on affected stocks. Our paper highlights the importance of ESG ratings for investors and consequently for asset prices.
Nisitrus Saussure, 1878 is a diurnal and monophyletic group of eneopterine crickets found in parts of Southeast Asia. Species often have vivid colourations which make them charismatic photograph subjects among macro photographers. However, their taxonomy has not been revised since their original descriptions, whereas there are also species awaiting to be discovered and described. A synoptic revision is therefore needed prior to studying the phylogenetic relationships of the genus, and before undertaking more precise studies on biogeography and evolution of traits. By holistically incorporating information about general morphology, male and female genitalia, and bioacoustics, we revise the taxonomy of these crickets and recognise 10 valid species of Nisitrus. Five new species are described: N. crucius Robillard & Tan sp. nov. from Borneo; N. danum Robillard & Tan sp. nov. from Borneo; N. hughtani Robillard & Tan sp. nov. from Sumatra; N. malaya Robillard & Tan sp. nov. from Malay Peninsula; and N. rindu Robillard & Tan sp. nov. from Borneo. We redescribe N. brunnerianus and N. insignis; describe the calls of N. malaya sp. nov., N. musicus and N. vittatus. We consider N. sumatrensis as a junior synonym of N. insignis; and N. marginata as a junior synonym of N. vittatus. Nisitrus hyalinus requires further revision. We also consider N. maculosus as a dubious name.
A new species of abyssal Neanthes Kinberg, 1865, N. goodayi sp. nov., is described from the Clarion-Clipperton Zone in the central Pacific Ocean, a region targeted for seabed mineral exploration for polymetallic nodules. It is a relatively large animal found living inside polymetallic nodules and in xenophyophores (giant Foraminifera) growing on nodules, highlighting the importance of the mineral resource itself as a distinct microhabitat. Neanthes goodayi sp. nov. can be distinguished from its congeners primarily by its distinctive, enlarged anterior pair of eyes in addition to characters of the head, pharynx and parapodia. Widespread, abundant, and easily recognisable, N. goodayi sp. nov. is also considered to be a suitable candidate as a potential indicator taxon for future monitoring of the impacts of seabed mining.
The ICON single-column mode
(2021)
The single-column mode (SCM) of the ICON (ICOsahedral Nonhydrostatic) modeling framework is presented. The primary purpose of the ICON SCM is to use it as a tool for research, model evaluation and development. Thanks to the simplified geometry of the ICON SCM, various aspects of the ICON model, in particular the model physics, can be studied in a well-controlled environment. Additionally, the ICON SCM has a reduced computational cost and a low data storage demand. The ICON SCM can be utilized for idealized cases—several well-established cases are already included—or for semi-realistic cases based on analyses or model forecasts. As the case setup is defined by a single NetCDF file, new cases can be prepared easily by the modification of this file. We demonstrate the usage of the ICON SCM for different idealized cases such as shallow convection, stratocumulus clouds, and radiative transfer. Additionally, the ICON SCM is tested for a semi-realistic case together with an equivalent three-dimensional setup and the large eddy simulation mode of ICON. Such consistent comparisons across the hierarchy of ICON configurations are very helpful for model development. The ICON SCM will be implemented into the operational ICON model and will serve as an additional tool for advancing the development of the ICON model.
Background Polypharmacy interventions are resource-intensive and should be targeted to those at risk of negative health outcomes. Our aim was to develop and internally validate prognostic models to predict health-related quality of life (HRQoL) and the combined outcome of falls, hospitalisation, institutionalisation and nursing care needs, in older patients with multimorbidity and polypharmacy in general practices.
Methods Design: two independent data sets, one comprising health insurance claims data (n=592 456), the other data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomised controlled trial (n=502). Population: ≥60 years, ≥5 drugs, ≥3 chronic diseases, excluding dementia. Outcomes: combined outcome of falls, hospitalisation, institutionalisation and nursing care needs (after 6, 9 and 24 months) (claims data); and HRQoL (after 6 and 9 months) (trial data). Predictor variables in both data sets: age, sex, morbidity-related variables (disease count), medication-related variables (European Union-Potentially Inappropriate Medication list (EU-PIM list)) and health service utilisation. Predictor variables exclusively in trial data: additional socio-demographics, morbidity-related variables (Cumulative Illness Rating Scale, depression), Medication Appropriateness Index (MAI), lifestyle, functional status and HRQoL (EuroQol EQ-5D-3L). Analysis: mixed regression models, combined with stepwise variable selection, 10-fold cross validation and sensitivity analyses.
Results Most important predictors of EQ-5D-3L at 6 months in best model (Nagelkerke’s R² 0.507) were depressive symptoms (−2.73 (95% CI: −3.56 to −1.91)), MAI (−0.39 (95% CI: −0.7 to −0.08)), baseline EQ-5D-3L (0.55 (95% CI: 0.47 to 0.64)). Models based on claims data and those predicting long-term outcomes based on both data sets produced low R² values. In claims data-based model with highest explanatory power (R²=0.16), previous falls/fall-related injuries, previous hospitalisations, age, number of involved physicians and disease count were most important predictor variables.
Conclusions Best trial data-based model predicted HRQoL after 6 months well and included parameters of well-being not found in claims. Performance of claims data-based models and models predicting long-term outcomes was relatively weak. For generalisability, future studies should refit models by considering parameters representing well-being and functional status.
Lockdown measures during the COVID-19 pandemic have led to reductions in physical activity (PA) worldwide. Leading public health organizations have recommended the use of online exercise classes (OEC) to compensate the loss of regular exercise classes. As of now, no data are available on the uptake of OEC and on users’ attitudes. The aim of the current online survey was to assess the use of and attitudes towards OEC in Germany. Respondents indicated awareness and use of OEC, and levels of agreement with statements on OEC. Frequency of awareness and use of OEC according to PA status were calculated with contingency tables and the Χ2 test. Differences between users and non-users were tested with the Student’s t-test and the Mann–Whitney U test. Data on attitudes are presented as percentages, and Spearman correlations were calculated between attitudes and activity status, frequency of use, educational attainment, age and body mass index. A total of 979 datasets were analyzed. Of the respondents, 681 were aware of and 180, 118 and 84 used them <1 per week, 1–2 per week and ≥3 per week, respectively. Significantly more active respondents were aware of and used OEC compared to less active respondents. All in all, regular OEC use was quite limited. OEC was differentially attractive to people according to PA status, frequency of use, BMI and age. Tailoring OEC to current non-users and adding motivational support might enhance the regular use of OEC.
Background: Estimating prognosis of periodontally affected teeth at the beginning of supportive periodontal care (SPC) is an important component for further treatment planning. This study aimed to evaluate tooth loss (TL) during 10 years of SPC in periodontally compromised patients and to identify tooth-related factors affecting TL.
Methods: Patients were re-examined 120 ± 12 months after accomplishment of active periodontal therapy. TL was defined as primary outcome variable and tooth-related factors (abutment status, furcation involvement [FI], tooth mobility, mean periodontal probing depth [PD], and clinical attachment level [CAL] at beginning of SPC, and initial bone loss [BL]) were estimated based on an adjusted regression analyses model.
Results: Ninety-seven patients (51 females and 46 males; mean age, 65.3 ± 11 years) lost 119 of 2,323 teeth (overall TL [OTL]: 0.12 teeth/patient/y) during 10 years of SPC. Forty of these teeth (33.6%) were lost for periodontal reasons (TLP; 0.04 teeth/patient/y). Significantly more teeth were lost due to other reasons (P <0.0001). TLP (OTL) only occurred in 5.9% (14.7%) of all teeth, when BL was at least 80%. Use as abutment tooth, FI degree III, tooth mobility degrees I and II, mean PD, and CAL positively correlated with OTL (P <0.05). For TLP, FI and tooth mobility degree III as well as mean CAL were identified as tooth-related prognostic factors (P <0.05).
Conclusions: During 10 years of SPC, most of the teeth (93.4%) of periodontally compromised patients were retained, showing the positive effect of a well-established treatment concept. Well-known tooth-related prognostic factors were confirmed.
Small ORF (sORF)-encoded small proteins have been overlooked for a long time due to challenges in prediction and distinguishing between coding- and noncoding-predicted sORFs and in their biochemical detection and characterization. We report on the first biochemical and functional characterization of a small protein (sP26) in the archaeal model organism Methanosarcina mazei, comprising 23 amino acids. The corresponding encoding leaderless mRNA (spRNA26) is highly conserved on nucleotide level as well as on the coded amino acids within numerous Methanosarcina strains strongly arguing for a cellular function of the small protein. spRNA26 level is significantly enhanced under nitrogen limitation, but also under oxygen and salt stress conditions. Using heterologously expressed and purified sP26 in independent biochemical approaches [pull-down by affinity chromatography followed by MS analysis, reverse pull-down, microscale thermophoresis, size-exclusion chromatography, and nuclear magnetic resonance spectroscopy (NMR) analysis], we observed that sP26 interacts and forms complexes with M. mazei glutamine synthetase (GlnA1) with high affinity (app. KD = 0.76 µm ± 0.29 µm). Moreover, seven amino acids were identified by NMR analysis to directly interact with GlnA1. Upon interaction with sP26, GlnA1 activity is significantly stimulated, independently and in addition to the known activation by the metabolite 2-oxoglutarate (2-OG). Besides, strong interaction of sP26 with the PII-like protein GlnK1 was demonstrated (app. KD = 2.9 µm ± 0.9 µm). On the basis of these findings, we propose that in addition to 2-OG, sP26 enhances GlnA1 activity under nitrogen limitation most likely by stabilizing the dodecameric structure of GlnA1.
The prevalence of peri-implant diseases around subcrestally placed implants: a cross-sectional study
(2021)
Objectives: To evaluate the prevalence of peri-implant health, peri-implant mucositis or periimplantitis for subcrestally placed implants (1–3 mm) on the short-, medium- and long term.
Material and Methods: Two hundred patients were enrolled in this cross-sectional study that were treated and screened during regular maintenance visits at one university center. A total of 657 implants were evaluated. Peri-implant health and diseases were assessed according to predefined case definitions. Binary logistic regression was used to assess the correlation with local and systemic factors.
Results: After a median function time of 9.36 ± 6.44 years (range: 1–26 years), the prevalence of peri-implant mucositis and peri-implantitis was 66.5% and 15.0%, at the patient level, corresponding to 62.6% and 7.5%, at the implant level, respectively. Peri-implantitis was significantly associated with patients’ history of periodontitis (odds ratio, OR 5.33).
Conclusion: Peri-implant diseases were a common finding around subcrestally placed implants.
Biological and environmental factors as sources of variation in nocturnal behavior of giraffe
(2021)
Upon a drastic decline of the giraffe population in the wild, conservation efforts and therefore the role of zoos have become more important than ever. With their unique opportunities, zoos provide excellent conditions to study animal behavior, expanding the knowledge about the giraffe's behavior repertoire and their ability to adapt. This study therefore examined the nocturnal behavior of 63 giraffe living in 13 different EAZA zoos across Germany and the Netherlands. Giraffe were observed and videos recorded via infrared sensitive cameras during the winter seasons 2015–2018. The observation period spanned nightly from 17:00 to 7:00. Thus, 198 nights, with a total of 2772 h were recorded and analyzed. Linear mixed models were then used to assess potential biological and environmental factors influencing behavior during the dark phase. Results show that individual variables such as age, subspecies and motherhood determined nocturnal activity and sleep behavior most. Among the variables studied, husbandry conditions and environmental factors complying with EAZA standards had no influence on the giraffe's nocturnal behavior. By combining nocturnal activity analyses and an assessment of potential influencing factors, our findings present a holistic approach to a better understanding of captive giraffe behavior and allow for management implications.