SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and \u3e30 spike variants. Together with quantitative cell biology approaches, the screen reveals an essential role for biophysical aspects of the membrane, particularly cholesterol-rich regions, in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings potentially provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses

Hong Kong

https://digitalcommons.library.umaine.edu/mmb-vp/4969/thumbnail.jp

Mathematical Views within a Lakota Community: Towards a Mathematics for Tribal Self-Determination

In this dissertation, I examined the impact of Indian educational self-determination on the teaching of mathematics at the local level in a Lakota community. I drew upon a framework created by Bishop (1991) which described mathematical activities found in all cultures to develop a Lakota mathematical framework from which to compare activities and content found within the middle-school and elementary mathematics classrooms to mathematical activities found in Lakota culture. These six universal mathematical activities included counting, measuring, locating, designing, playing and explaining. I also constructed a framework (also for comparison) around self-determination principles that have been formulated and implemented in curriculum in Indian Country over the last forty years. I used this to inform the language used in the descriptions of self-determination in this Lakota community as well as the implementation of these principles in the structure and curriculum at the local K-8 school. I argue that self-determination, as an educational philosophy in this Lakota community had no impact on the teaching of mathematics. I also argue that, self-determination, at the curriculum level, has much potential, not only in integrating Lakota culture and language into the teaching of mathematics but also integrating mathematics into the teaching of the Lakota language and culture

Diversity of microbial eukaryotes along the West Antarctic Peninsula in austral spring

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Grattepanche, J.-D., Jeffrey, W., Gast, R., & Sanders, R. Diversity of microbial eukaryotes along the West Antarctic Peninsula in austral spring. Frontiers in Microbiology, 13, (2022): 844856, https://doi.org/10.3389/fmicb.2022.844856.During a cruise from October to November 2019, along the West Antarctic Peninsula, between 64.32 and 68.37°S, we assessed the diversity and composition of the active microbial eukaryotic community within three size fractions: micro- (> 20 μm), nano- (20–5 μm), and pico-size fractions (5–0.2 μm). The communities and the environmental parameters displayed latitudinal gradients, and we observed a strong similarity in the microbial eukaryotic communities as well as the environmental parameters between the sub-surface and the deep chlorophyll maximum (DCM) depths. Chlorophyll concentrations were low, and the mixed layer was shallow for most of the 17 stations sampled. The richness of the microplankton was higher in Marguerite Bay (our southernmost stations), compared to more northern stations, while the diversity for the nano- and pico-plankton was relatively stable across latitude. The microplankton communities were dominated by autotrophs, mostly diatoms, while mixotrophs (phototrophs-consuming bacteria and kleptoplastidic ciliates, mostly alveolates, and cryptophytes) were the most abundant and active members of the nano- and picoplankton communities. While phototrophy was the dominant trophic mode, heterotrophy (mixotrophy, phagotrophy, and parasitism) tended to increase southward. The samples from Marguerite Bay showed a distinct community with a high diversity of nanoplankton predators, including spirotrich ciliates, and dinoflagellates, while cryptophytes were observed elsewhere. Some lineages were significantly related—either positively or negatively—to ice coverage (e.g., positive for Pelagophyceae, negative for Spirotrichea) and temperature (e.g., positive for Cryptophyceae, negative for Spirotrichea). This suggests that climate changes will have a strong impact on the microbial eukaryotic community.This work was supported by the National Science Foundation (Grant Nos. ANT 1744767 to RS, ANT 1744663 to RG, and ANT 1744638 to WJ). This research was based, in part, upon sequencing conducted using the Rhode Island Genomics and Sequencing Center, which was supported in part by the National Science Foundation (MRI Grant No. DBI-0215393 and EPSCoR Grant Nos. 0554548 and EPS-1004057), the US Department of Agriculture (Grant Nos. 2002-34438-12688 and 2003-34438-13111), and the University of Rhode Island. This research includes calculations carried out on Temple University HPC resources supported in part by the National Science Foundation through major research instrumentation (Grant No. 1625061) and by the US Army Research Laboratory under (Contract No. W911NF-16-2-0189)

Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

Self Reported Incidence and Morbidity of Acute Respiratory Illness among Deployed U.S. Military in Iraq and Afghanistan

BACKGROUND: Historically, respiratory infections have had a significant impact on U.S. military missions. Deployed troops are particularly at high risk due to close living conditions, stressful work environments and increased exposure to pathogens. To date, there are limited data available on acute respiratory illness (ARI) among troops deployed in support of ongoing military operations, specifically Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). METHODS: Using self-report data from two sources collected from troops deployed to Iraq, Afghanistan and the surrounding region, we analyzed incidence and risk factors for ARI. Military personnel on mid-deployment Rest & Recuperation (R&R) or during redeployment were eligible to participate in the voluntary self-report survey. RESULTS: Overall, 39.5% reported having at least one ARI. Of these, 18.5% sought medical care and 33.8% reported having decreased job performance. The rate of self-reported ARI was 15 episodes per 100 person-months among those taking the voluntary survey, and 24.7 episodes per 100 person-months among those taking the clinic health questionnaire. Negative binomial regression analysis found female sex, Navy branch of service and lack of flush toilets to be independently associated with increased rates of ARI. Deployment to OIF, increasing age and higher rank were also positively associated with ARI risk. CONCLUSIONS: The overall percentage of deployed military personnel reporting at least one acute respiratory illness decreased since earlier parts of OIF/OEF. However, the reported effect on job performance increased tremendously. The most important factors associated with increased respiratory infection are female sex, Navy branch of service, lack of improved latrine facilities, deployment to OIF, increasing age and higher rank

Dynamics of a Quantum Reference Frame

We analyze a quantum mechanical gyroscope which is modeled as a large spin and used as a reference against which to measure the angular momenta of spin-1/2 particles. These measurements induce a back-action on the reference which is the central focus of our study. We begin by deriving explicit expressions for the quantum channel representing the back-action. Then, we analyze the dynamics incurred by the reference when it is used to sequentially measure particles drawn from a fixed ensemble. We prove that the reference thermalizes with the measured particles and find that generically, the thermal state is reached in time which scales linearly with the size of the reference. This contrasts a recent conclusion of Bartlett et al. that this takes a quadratic amount of time when the particles are completely unpolarized. We now understand their result in terms of a simple physical principle based on symmetries and conservation laws. Finally, we initiate the study of the non-equilibrium dynamics of the reference. Here we find that a reference in a coherent state will essentially remain in one when measuring polarized particles, while rotating itself to ultimately align with the polarization of the particles

A rule-based expert system to decide on direction and speed of a powered wheelchair

Some rule based techniques are presented that can assist powered wheelchair drivers. The expert system decides on the direction and speed of their wheelchair. The system tends to avoid obstacles while having a tendency to turn and head in towards a desired destination. This is achieved by producing a new target angle as an extra input. Other inputs are from sensors and a joystick. Directions are recommended and mixed with user inputs from the joystick representing desired direction and desired speed. The rule-based system decides on an angle to turn the powered wheelchair and suggest it. Inputs from the joystick and sensors are mixed with the suggested angle from the Rule Based Expert System. A modified direction for the wheelchair is produced. The whole system helps disabled wheelchair users to drive their powered wheelchairs

Child Support Grant access and receipt among 12-week-old infants in an urban township setting in South Africa

BACKGROUND: Cash transfers (CTs) are increasingly used as a strategy to alleviate poverty and improve child health outcomes in low- and middle-income countries. The Child Support Grant (CSG) is the largest CT programme in South Africa, and on the continent, targeting poor children from birth until the age of 18 with a monthly sum of R300 (USD30). Evidence on the CSG shows that early receipt of the grant is associated with improved child health outcomes. Since its implementation, one of the major concerns about the grant has been take-up rates, particularly for younger children. This paper reports results on take-up rates for 12-week-old infants residing in an urban township in South Africa. METHODS: This is a descriptive study utilising data from a community-based, cluster-randomised trial which evaluated a programme providing pregnancy and post-natal home visits by community health workers to 3,494 mothers in Umlazi township, South Africa. RESULTS: At the 12-week visit, half (52%) of the mothers who had enrolled in the study had applied for the CSG on behalf of their children, while 85% of the mothers who had not applied were still planning to apply. Only 38% (1,327) of all children had received the CSG. CONCLUSIONS: In this study, many mothers had not applied for the CSG in the first few months after delivery, and only a third of children had accessed the grant. Further research is needed to understand what the current barriers are that prevent mothers from applying for this important form of social protection in the early months after delivery