Multipartite Nonlocal Quantum Correlations Resistant to Imperfections

We use techniques for lower bounds on communication to derive necessary conditions in terms of detector efficiency or amount of super-luminal communication for being able to reproduce with classical local hidden-variable theories the quantum correlations occurring in EPR-type experiments in the presence of noise. We apply our method to an example involving n parties sharing a GHZ-type state on which they carry out measurements and show that for local-hidden variable theories, the amount of super-luminal classical communication c and the detector efficiency eta are constrained by eta 2^(-c/n) = O(n^(-1/6)) even for constant general error probability epsilon = O(1)

Unrealistic pessimism and obsessive‐compulsive symptoms during the COVID‐19 pandemic: two longitudinal studies

OBJECTIVE: Unrealistic pessimism (UP) is an aspect of overestimation of threat (OET) that has been associated with obsessive‐compulsive disorder/symptoms (OCD/OCS). During the COVID‐19 pandemic, UP may have played an important role in the course of OCD. To investigate the relationship, we conducted two longitudinal studies assuming that higher UP predicts an increase in OCS. METHOD: In Study 1, we investigated UP in the general population (N = 1,184) at the start of the pandemic asking about overall vulnerability to infection with SARS‐CoV‐2 and UP regarding infection and outcome of severe illness. Further, OCS status (OCS+/−) was assessed at the start of the pandemic and 3 months later. In Study 2, we investigated UP in individuals with OCD (N = 268) regarding the likelihood of getting infected, recovering, or dying from an infection with SARS‐CoV‐2 at the start of the pandemic and re‐assessed OCS 3 months later. RESULTS: In Study 1, UP was higher in the OCS+ compared to the OCS− group, and estimates of a higher overall vulnerability for an infection predicted a decrease in OCS over time. UP regarding severe illness predicted an increase in symptoms over time. In Study 2, UP was found for a recovery and death after an infection with SARS‐CoV‐2, but not for infection itself. CONCLUSIONS: Exaggeration of one’s personal vulnerability rather than OET per se seems pivotal in OCD, with UP being associated with OCD/OCS+ as well as a more negative course of symptomatology over the pandemic in a nonclinical sample. PRACTITIONER POINTS: Unrealistic optimism, a bias common in healthy individuals, is thought to be a coping mechanism promoting well‐being in the face of danger or uncertainty. The current study extends findings that its inversion, unrealistic pessimism, may play an important role in obsessive‐compulsive disorder and may also be involved in the development of the disorder. This study highlights the importance that prevention programs during a pandemic should include targeting unrealistic pessimism

Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes

In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. We present a model for the evolution of HCF-1 proteolysis by OGT

The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities

O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities. OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1 <sub>PRO</sub> repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1). Here, we probed the relationship between these distinct glycosylation and proteolytic activities. For proteolysis, the HCF-1 <sub>PRO</sub> repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region. We report that linkage of this HCF-1 <sub>PRO</sub> -repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor R <sub>p</sub> -αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates. Furthermore, it potentiated proteolysis of a non-HCF-1 <sub>PRO</sub> -repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue. Using serine- or glutamate-containing HCF-1 <sub>PRO</sub> -repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together. In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis. These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies

Inanspruchnahme des Rettungsdiensts bei Suizidversuchen im Verlauf der SARS-CoV-2-Pandemie

Hintergrund Die Pandemie hat zu Veränderungen in der Notfallversorgung mit atypischen Schwankungen der Einsatzzahlen geführt. Dies wurde u. a. mit dem veränderten Verhalten und einem gesteigerten Belastungsempfinden der Bevölkerung erklärt. Bestehende Untersuchungen geben Hinweise auf das gesteigerte Auftreten von psychischen Krankheitsbildern in der Notfallversorgung bei fortwährender Pandemie. Ziel In diesem Beitrag wird ein Zusammenhang zwischen der COVID-19-Pandemie und dem Auftreten von Einsatzstichworten im Kontext Suizid in sechs unterschiedlich strukturierten Rettungsdienstbereichen untersucht. Methodik Es handelt sich um eine retrospektive Querschnittstudie basierend auf der Routinedokumentation einer integrierten Leitstelle mit deskriptiver und explorativer Datenanalyse. Die Daten werden anhand siedlungsstruktureller Kreistypen aufgeschlüsselt und mit dem vom Robert-Koch-Institut (RKI) dokumentierten Wert der COVID-19-Krankheitsfälle der letzten 7 Tage/100.000 Einwohner und Pandemiephasen ins Verhältnis gesetzt. Ergebnisse Es zeigt sich in Phase 1 und 2a ein Absinken des Einsatzaufkommens während der Pandemie. Zudem stellt sich eine Verschiebung der Dispositionsfälle mit Suizidkontext nach Strukturtypen in Phase 3 dar. Einer gesunkenen Einsatzrate im dünn besiedelten ländlichen Kreis steht eine Steigerung in der Großstadt gegenüber. Die Umstellung des Leitstellensystems zum 16.03.2021 zeigt eine deutliche Steigerung der Einsatzstichworte im Kontext Suizid. Diskussion Die Ausprägung der Resilienz der Landbevölkerung erscheint in Phase 3 stärker ausgeprägt. Eine kontinuierliche „mental health surveillance“ unter Einbeziehung auch rettungsdienstlich erhobener Daten kann wertvolle Erkenntnisse liefern. Die Studie zeigt zudem die Notwendigkeit einer Standardisierung von Leitstellendaten auf.Background The pandemic has caused several changes in the emergency care system. The deployment figures in emergency medical services have shown atypical fluctuations. This has also been explained by changes in behavior and an increased sense of stress among the population. Existing research provides hints for the increased incidence of mental health symptoms in emergency care during ongoing pandemics. Objective In this context, this paper examines the occurrence of emergency medical services calls related to the keyword suicide in relation to total calls. Methods This is a retrospective cross-sectional study based on routine documentation from a fire and rescue dispatch center with descriptive and exploratory data analyses. The data are divided by settlement-structural county types and compared with incidences and pandemic phases. Results Phase 1 and 2a show a decrease in the number of dispatches during the pandemic. In addition, there is a shift in the number of dispatch cases with a context of suicide by structure types in phase 3. A decreased dispatch rate in the sparsely populated rural county is offset by an increase in the metropolitan area. Changes made to the control center system resulted in an increase in the number of dispatch cases in the context of suicide. Conclusion Continuous mental health surveillance, including data collected by emergency medical services, can provide valuable insight. The study also highlights the need for standardization of emergency dispatch center data.Peer Reviewe

Systemic application of bone-targeting peptidoglycan hydrolases as a novel treatment approach for staphylococcal bone infection

The rising prevalence of antimicrobial resistance in S. aureus has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria