Beyond Shielding: The Roles of Glycans in the SARS-CoV‑2 Spike Protein

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 28,000,000 infections and 900,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viral fusion proteins, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of the glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the roles of glycans and on the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the "down" state. Additionally, end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of the SARS-CoV-2 S protein, which may be exploited in the therapeutic efforts targeting this molecular machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development

ToxoDB: an integrated Toxoplasma gondii database resource

ToxoDB (http://ToxoDB.org) is a genome and functional genomic database for the protozoan parasite Toxoplasma gondii. It incorporates the sequence and annotation of the T. gondii ME49 strain, as well as genome sequences for the GT1, VEG and RH (Chr Ia, Chr Ib) strains. Sequence information is integrated with various other genomic-scale data, including community annotation, ESTs, gene expression and proteomics data. ToxoDB has matured significantly since its initial release. Here we outline the numerous updates with respect to the data and increased functionality available on the website

GiardiaDB and TrichDB : integrated genomic resources for the eukaryotic protist pathogens Giardia lamblia and Trichomonas vaginalis

© 2008 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License. The definitive version was published in Nucleic Acids Research 37 (2009): D526-D530, doi:10.1093/nar/gkn631.GiardiaDB (http://GiardiaDB.org) and TrichDB (http://TrichDB.org) house the genome databases for Giardia lamblia and Trichomonas vaginalis, respectively, and represent the latest additions to the EuPathDB (http://EuPathDB.org) family of functional genomic databases. GiardiaDB and TrichDB employ the same framework as other EuPathDB sites (CryptoDB, PlasmoDB and ToxoDB), supporting fully integrated and searchable databases. Genomic-scale data available via these resources may be queried based on BLAST searches, annotation keywords and gene ID searches, GO terms, sequence motifs and other protein characteristics. Functional queries may also be formulated, based on transcript and protein expression data from a variety of platforms. Phylogenetic relationships may also be interrogated. The ability to combine the results from independent queries, and to store queries and query results for future use facilitates complex, genome-wide mining of functional genomic data.Federal funds from the National Institute of Allergy and Infectious Diseases; Department of Health and Human Services, National Institutes of Health (HHSN266200400037C). Funding for open access charge: National Institutes of Health (HHSN266200400037C)

Between-brain coherence during joint n-back task performance: a two-person functional near-infrared spectroscopy study

The present study aimed to step into two-person neuroscience by investigating the hemodynamic correlates of between-brain connectivity during joint task performance. To test this approach, wireless functional near-infrared spectroscopy (fNIRS) was used to record brain signals during performance of a dual n-back task simultaneously in paired players as compared to single players. Evaluating functional connectivity between the paired players' brains using wavelet transform coherence (WTC) analysis revealed (1) a significant increase in between-brain coherence during joint task performance as compared to baseline condition. These patterns were observed in two frequency bands, i.e. in the heart rate (HR) frequency and in low-frequency oscillations (LFOs). (2) Averaged hemodynamic responses revealed larger responses in total hemoglobin concentration changes [tHb] for the paired players as compared to the single players; in addition, within the paired players groups joint task performance revealed larger changes in [tHb] as compared to a rest period and to a baseline condition. (3) No increase in behavioral performance was found in the paired players as compared to the single players. Our findings designate fNIRS as suitable tool for monitoring interpersonal performances between two subjects. The results show that two-person performance leads to relevant and significant effects, which are detectable using between-brain connectivity analysis. Using this approach can provide additional insight into interpersonal activation patterns not detectable using typical one-person experiments. Our study demonstrates the potential of simultaneously assessing cerebral hemodynamic responses for various two-person experimental paradigms and research areas where interpersonal performances are involved

Umgang des Rettungsdienstes mit in der Präklinik verstorbenen Patienten

Both preservation of deceased person's dignity and immediate regaining of operational readiness are crucial for emergency medical services (EMS). In addition, investigations concerning circumstances and cause of death should not be affected by EMS actions. For cases of death before beginning of EMS transportation, legal regulations are well defined and EMS transportation of the corpse is basically prohibited. This article deals with death after onset and during ongoing EMS transportation. For this circumstance, there are no generally accepted practices in terms of law, ethics and organisation. Pragmatically continued resuscitation violates human dignity and falsifies time and place of death, and therefore must be rejected. Bavarian state law allows transport to the hospital for postmortem examination in case that the patient had deceased en route. In Saxonian state law, this procedure is even explicitly intended. Unloading the corpse without appropriate premises or in public could be considered as disturbing peace of the dead. To provide immediate restitution of EMS unit operational readiness, postmortem examination of any person deceased en route in the nearest eligible treatment facility should be generally rendered possible. However, this approach implies evolution of German state funeral laws. This article presents atransectoral conception for Bavaria and addresses the need to adapt German state laws to the needs of emergency medicine

Vorrichtung und Verfahren zum Erwaermen von Bauteilen aus mikrowellenabsorbierendem Kunststoff

EP 991136 A UPAB: 20000508 NOVELTY - A heater for plastics comprises a microwave generator, a waveguide and screened antenna, and has a safe and coaxial wave trap which is completely open for insertion of e.g. a plastic tube end, for concentrated, controlled, efficient local heating. DETAILED DESCRIPTION - An INDEPENDENT CLAIM is included for the method of heating components made of microwave-absorbing plastic. Preferred features: The screen projection beyond the antenna tip, is a quarter wavelength or more. The zone between the antenna tip and the screen is dimensioned in accordance with the size of the component to be heated. In one region it is especially narrow, to concentrate heating locally. The component inserted in the narrow region is heated there, in accordance with specific requirements. Between the antenna and screen, dielectric is included. The antenna tip is e.g. conical, a mandrel, a rod or a hook. Antenna tip and screen are coaxial. In the method, components are heated, to weld them together. A double version of the heater (illustrated in the disclosure) may be constructed to heat e.g. two tube ends simultaneously, to weld them together. Heating may precede permanent deformation. A conically-tipped antenna may be used for tube end flaring. Heating may induce crosslinking. USE - To heat plastic components, especially tube ends, using microwaves. ADVANTAGE - Despite being very compact for the duty, the head heats particularly uniformly. It is very simple to use. A striking feature is the containment of microwave radiation, a consequence of selecting dimensions in relation to the wavelength. Usefully, the screen is wide open at the end, yet blocks microwave release. The limited heating region ensures efficient use of energy; the microwave field may be concentrated for more intense local heating. Heating and deformation of pipe ends, suggests application as a pipeline joint welding machine

Changing pattern of brain hemorrhage during 12 years of computed axial tomography

We examined whether the pattern of cerebral hemorrhage changed after the introduction of computed tomography

Massive Rotator Cuff Tears With Short Tendon Length Can Be Successfully Repaired Using Synthetic Patch Augmentation.

BACKGROUND Choosing the optimal treatment for massive rotator cuff tears (MRCT) still poses a surgical problem. In MRCT with good muscle quality, but short tendon length, non-augmented repairs lead to high failure rates of up to 90%. AIM The aim of the study was to evaluate mid-term clinical and radiological outcomes of massive rotator cuff tears with good muscle quality, but short tendon length, which were repaired with synthetic patch augmentation. METHODS A retrospective study of patients who underwent arthroscopic or open rotator cuff repairs with patch augmentation between 2016 and 2019 was performed. We included patients older than 18 years, who presented with MRCT confirmed by an MRI arthrogram showing good muscle quality (Goutallier ≤II) and short tendon length (length <15mm). Constant-Murley score (CS), subjective shoulder value (SSV) and range of motion (ROM) were compared pre- and postoperatively. We excluded patients older than 75 years or with presence of rotator cuff arthropathy Hamada ≥ 2a. Patients were followed up for two years minimum. Clinical failures were defined by re-operation, forward flexion <120 or a relative CS < 70. Structural integrity of the repair was assessed using an MRI. Comparison between different variables and outcomes was performed using Wilcoxon-Mann-Whitney and Chi square tests. RESULTS Fifteen patients (mean age 57 years, 13 (86.7%) male, 9 (60%) right shoulders) were reevaluated with a mean follow-up of 43.8 months (27-55 months). There was a significant improvement in the absolute CS (from 33 to 81 points, p=0.03), the relative CS (from 41% to 88%, p=0.04), the SSV (from 31% to 93% p=0,007) and forward flexion (from 111° to 163°, p=0.004) but not in external rotation (from 37° to 38°, p=0.5). There were three clinical failures (one atraumatic, two traumatic) with re-operations (two reverse total shoulder arthroplasties and one refixation). Structurally, there were three Sugaya grade 4 and five Sugaya grade 5 re-ruptures resulting in a retear rate of 53%. The presence of a complete or partial re-rupture was not associated with inferior outcomes compared to intact cuff repairs. There were no correlations between the grade of retraction, muscle quality or rotator cuff tear configuration and re-rupture or functional outcomes. CONCLUSION Patch augmented cuff repair leads to a significant improvement of functional and structural outcomes. Partial re-ruptures were not associated with inferior functional outcomes. Prospective randomized trials are needed to confirm the results found in our study