The Robetta server (http://robetta.bakerlab.org) provides automated tools for protein structure prediction and analysis. For structure prediction, sequences submitted to the server are parsed into ...putative domains and structural models are generated using either comparative modeling or de novo structure prediction methods. If a confident match to a protein of known structure is found using BLAST, PSI-BLAST, FFAS03 or 3D-Jury, it is used as a template for comparative modeling. If no match is found, structure predictions are made using the de novo Rosetta fragment insertion method. Experimental nuclear magnetic resonance (NMR) constraints data can also be submitted with a query sequence for RosettaNMR de novo structure determination. Other current capabilities include the prediction of the effects of mutations on protein–protein interactions using computational interface alanine scanning. The Rosetta protein design and protein–protein docking methodologies will soon be available through the server as well.
: The accurate assessment of sleep is critical to better understand and evaluate its role in health and disease. The boom in wearable technology is part of the digital health revolution and is ...producing many novel, highly sophisticated and relatively inexpensive consumer devices collecting data from multiple sensors and claiming to extract information about users' behaviors, including sleep. These devices are now able to capture different biosignals for determining, for example, HR and its variability, skin conductance, and temperature, in addition to activity. They perform 24/7, generating overwhelmingly large data sets (big data), with the potential of offering an unprecedented window on users' health. Unfortunately, little guidance exists within and outside the scientific sleep community for their use, leading to confusion and controversy about their validity and application. The current state-of-the-art review aims to highlight use, validation and utility of consumer wearable sleep-trackers in clinical practice and research. Guidelines for a standardized assessment of device performance is deemed necessary, and several critical factors (proprietary algorithms, device malfunction, firmware updates) need to be considered before using these devices in clinical and sleep research protocols. Ultimately, wearable sleep technology holds promise for advancing understanding of sleep health; however, a careful path forward needs to be navigated, understanding the benefits and pitfalls of this technology as applied in sleep research and clinical sleep medicine.
Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey ...populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat⁻¹ year⁻¹ but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners.
The SARS-CoV-2 Omicron BA.1 variant emerged in 2021
and has multiple mutations in its spike protein
. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with ...Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways
demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 ...healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.
Hematopoietic stem cell transplantation (HSCT) is increasingly used to treat multiple malignant and nonmalignant conditions. The risk for cardiovascular disease after the procedure has not been ...well-described.
To compare rates and hazards of cardiovascular-related hospitalization and death among persons who were still alive at least 2 years after HSCT with those in a population-based sample.
Retrospective cohort study.
Comprehensive cancer center.
1491 patients who had survived 2 years or longer after HSCT received between 1985 and 2006, and frequency-matched persons who were randomly selected from drivers' license files in the state of Washington.
Cardiovascular hospitalizations and death, as determined from statewide hospital discharge records and death registries in Washington.
Compared with the general population, transplant recipients experienced increased cardiovascular death (adjusted incidence rate difference, 3.6 per 1000 person-years 95% CI, 1.7 to 5.5). Recipients also had an increased cumulative incidence of ischemic heart disease, cardiomyopathy or heart failure, stroke, vascular diseases, and rhythm disorders and an increased incidence of related conditions that predispose toward more serious cardiovascular disease (hypertension, renal disease, dyslipidemia, and diabetes). No consistent differences in hazards were observed after total-body irradiation or receipt of an allogeneic versus an autologous graft, aside from an increased rate of hypertension among recipients of allogeneic grafts. Disease relapse after transplantation was associated with an increased hazard of cardiovascular death (hazard ratio, 2.3 CI, 1.1 to 4.8).
All patients received HSCT at a single institution, and no information was available on pretransplantation treatment and lifestyle factors that may influence risk for cardiovascular disease.
Increased rates of cardiovascular disease should be taken into account when caring for patients who have received HSCT. Future efforts should be directed toward improved screening and controlling of factors that predispose toward cardiovascular disease.
The American Society for Blood and Marrow Transplantation, the Leukemia and Lymphoma Society, and the Seattle Children's Research Institute.
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