Myosin flexibility: Structural domains and collective vibrations

International audienceThe movement of the myosin motor along an actin filament involves a directed conformational change within the cross-bridge formed between the protein and the filament. Despite the structural data that has been obtained on this system, little is known of the mechanics of this conformational change. We have used existing crystallographic structures of three conformations of the myosin head, containing the motor domain and the lever arm, for structural comparisons and mechanical studies with a coarse-grained elastic network model. The results enable us to define structurally conserved domains within the protein and to better understand myosin flexibility. Notably they point to the role of the light chains in rigidifying the lever arm and to changes in flexibility as a consequence of nucleotide binding

Important fluctuation dynamics of large protein structures are preserved upon coarse-grained renormalization

International audienceThe fluctuations and important motions of three large proteins--hemaglutinin, xanthine dehydrogenase, and β-galactosidase--have been considered with a range of models having various levels of detail to represent the structures. Because the slowest modes of motion are the largest contributors to the total motions, and because these motions depend mainly on the shapes of the structures rather than their details, it is possible to replace the real structures with significantly fewer points and still retain the essential features of the structure for these modes of motion. We obtain excellent results, both for the magnitudes of the individual motions as well as for the molecular changes occurring during these motions. Similar results are obtained with another completely different approach where the coarse graining is based on invariant regions of structure found by comparing two structures of the same protein, given as an example here for myosin. Results confirm the important coupling of local functional motions with the large-scale motions, implying important functional roles for the entire protein structure

Hurricane Risk Perceptions and Evacuation Decision-Making in the Age of COVID-19

The COVID-19 pandemic increases the complexity of planning for hurricanes as social distancing is in direct conflict with human mobility and congregation. COVID-19 presents not only urgent challenges for this hurricane season due to the likeliness of continued or heightened COVID-19 threat, but also challenges with the next hurricane season with additional waves of the pandemic. There is severe urgency to understand the impact of COVID-19 risk perceptions and the extent people are willing to risk their lives by sheltering in place rather than evacuating during severe hurricanes. In June 2020, a survey (in both English and Spanish) of 40 questions was disseminated through regional planning councils, emergency management, and the media to Florida residents. A total of 7,072 people responded from over 50 counties. Most data obtained were ordinal or categorical in nature, encouraging usage of nonparametric analysis and chi-square tests. Almost half the respondents view themselves as vulnerable to COVID-19 due to preexisting health conditions, and 74.3% of individuals viewed the risk of being in a shelter during the COVID-19 pandemic as more dangerous than enduring hurricane hazards. Additionally, there was a significant number of individuals who would choose to not utilize a public shelter during COVID-19 when they would have previously. Officials can use the results of this study regarding how household evacuation plans change with social distancing to better inform strategies of shelter preparedness and COVID-19 risk mitigation to minimize risk to those in harm’s way of storm surge and other hurricane effects during a mandatory evacuation order

An Analysis of Virtual Research Experiences for Undergraduates Programs in Light of the COVID-19 Pandemic

With the continued social distancing requirements of the novel COVID-19 pandemic, many in-person educational programs were halted in 2020, including specialty education and research experiences for undergraduates. However, some Research Experiences for Undergraduates (REUs) progressed in summer 2020 in a fully virtual format. The importance of understanding how these practical STEM skills translated in a virtual REU format, in addition to areas of improvement going forward, are critical to the development of effective online STEM learning through REUs. Two survey instruments were designed to capture data from both the REU mentors (including the PIs) and the students in the programs. Questions included information on the REU they participated in, their perceptions of the best and worst aspects, their overall satisfaction with the experience, and their likelihood to seek out virtual REUs in the future. Overall, both students and faculty involved in virtual REUs were glad to have had the experience and were satisfied with it. The benefits of flexibility, the ease of communication and scheduling, and the increased access to online resources were echoed as the strengths of the virtual format. However, many believe that an in-person REU had benefits that could not be replicated in a virtual environment, including community building and hands-on experiences. Several were bogged down by technical difficulties. With more effort made to include community building to a greater extent, as well as considerations and planning for technical demands, the future of widely accessible online REU experiences is a bright one

Hurricanes Laura and Sally: A Case Study of Evacuation Decision-Making in the Age of COVID-19

This study examines risk perceptions and evacuation planning for those residents affected by Hurricane Laura–the first major hurricane evacuation during the COVID-19 pandemic–and Hurricane Sally, prior to the widespread availability of vaccines. Research on hurricane evacuation behavior and risk perceptions during a pandemic is critical for quantifying the intersect of these compounding threats. Analyses captured how people perceive public shelters and whether evacuation choices changed in light of the pandemic. Many study participants considered themselves vulnerable to COVID-19 (39.4%) and two-thirds believed it would be “very serious” if they or their loved ones contracted COVID-19, but this had no impact on their actual evacuation decision-making. Approximately 75% of the sample stayed at home during Hurricanes Laura or Sally, and of these, just over 80% indicated that COVID-19 was a somewhat important deciding factor. This reflects the partial role that COVID-19 played in balancing individual and household protective action decision-making during complex disasters. Whereas 15.5% wanted to evacuate but waited until it was too late. For those who evacuated to a hotel, many found that staff and guests wore masks and socially distanced in common spaces. Of particular interest is that individuals have a continued negative perception of public shelters’ ability to safeguard against COVID-19 which was coupled with a significant decrease in the number of respondents that would potentially use shelters in 2020 compared to before the COVID-19 pandemic. These results have and will inform future hazard mitigation planning during the current or future pandemic, or infectious disease outbreaks

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

ImportanceThe prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.ObservationsWe describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.Conclusions and relevanceRECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.Clinical trials.gov identifierClinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011