SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET.

Targeting the interaction between the SARS-CoV-2 spike protein and human ACE2, its primary cell membrane receptor, is a promising therapeutic strategy to prevent viral entry. Recent in vitro studies revealed that the receptor binding domain (RBD) of the spike protein plays a prominent role in ACE2 binding, yet a simple and quantitative assay for monitoring this interaction in a cellular environment is lacking. Here, we developed an RBD-ACE2 binding assay that is based on time-resolved FRET, which reliably monitors the interaction in a physiologically relevant and cellular context.

Engagement and social acceptance in genome editing for human benefit: Reflections on research and practice in a global context.

While there are both practical and ethical reasons for public engagement in science and innovation, real-world detailed examples of engagement practice and the lessons to come from these are still hard to find. This paper showcases three contextually diverse case studies of engagement practice. Case 1 recounts the experiences of a government-funded initiative to involve scientists and policy makers as science communicators for the purpose of engaging the Argentine public on gene editing.

Qualification of ELISA and neutralization methodologies to measure SARS-CoV-2 humoral immunity using human clinical samples.

In response to the SARS-CoV-2 pandemic many vaccines have been developed and evaluated in human clinical trials. The humoral immune response magnitude, composition and efficacy of neutralizing SARS-CoV-2 are essential endpoints for these trials. Robust assays that are reproducibly precise, linear, and specific for SARS-CoV-2 antigens would be beneficial for the vaccine pipeline.

Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.

Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to have a global impact. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 spike receptor-binding domain. Here, we investigated the capacity of modified versions of one lead miniprotein, LCB1, to protect against SARS-CoV-2-mediated lung disease in mice.

Detection of antibodies neutralizing historical and emerging SARS-CoV-2 strains using a thermodynamically coupled de novo biosensor system.

With global vaccination efforts against SARS-CoV-2 underway, there is a need for rapid quantification methods for neutralizing antibodies elicited by vaccination and characterization of their strain dependence. Here, we describe a designed protein biosensor that enables sensitive and rapid detection of neutralizing antibodies against wild type and variant SARS-CoV-2 in serum samples. More generally, our thermodynamic coupling approach can better distinguish sample to sample differences in analyte binding affinity and abundance than traditional competition based assays.

Endoscopic Placement of Fourth Ventricular Catheter Using Seldinger Technique: Description of Technique and Case Series.

Background: Neonatal intraventricular hemorrhage remains a significant source of morbidity in premature and low-weight patients. Approximately 15% of patients who require cerebrospinal fluid shunting develop trapped fourth ventricle (TFV). Surgical treatment presents challenges with short- and long-term complications.

Dynamic Occlusion of Distal Ventriculoperitoneal Shunt Catheter after Infusion Port Placement: A New Shunt Malfunction.

Shunt failure requiring reintervention remains a common complication of hydrocephalus treatment. Here, we report a novel cause of mechanical shunt obstruction in an adult patient: position-dependent intermittent occlusion via an infusion port catheter. A 51-year-old woman with a grade II oligodendroglioma presented in a delayed fashion following surgery with a pseudomeningocele.

Neural G0: a quiescent-like state found in neuroepithelial-derived cells and glioma.

Single-cell RNA sequencing has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA-seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From these data, we constructed a cell cycle classifier that identifies traditional cell cycle phases and a putative quiescent-like state in neuroepithelial-derived cell types during mammalian neurogenesis and in gliomas.

Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials.

TARGET (tumour characterisation to guide experimental targeted therapy) is a cancer precision medicine programme focused on molecular characterisation of patients entering early phase clinical trials. Performance status (PS) measures a patient's ability to perform a variety of activities. However, the quality of present algorithms to assess PS is limited and based on qualitative clinician assessment.

Visualizing 3D imagery by mouth using candy-like models.

Handheld models help students visualize three-dimensional (3D) objects, especially students with blindness who use large 3D models to visualize imagery by hand. The mouth has finer tactile sensors than hand, which could improve visualization using microscopic models that are portable, inexpensive, and disposable. The mouth remains unused in tactile learning.

Digital Technology Needs in Maternal Mental Health: A Qualitative Inquiry.

Digital technologies offer many opportunities to improve mental healthcare management for women seeking pre- and-postnatal care. They provide a discrete, practical medium that is well-suited for the sensitive nature of mental health. Women who are more prone to experiencing peripartum depression (PPD), such as those of low-socioeconomic background or in high-risk pregnancies, can benefit the most from such technologies.

Transcriptional heterogeneity of stemness phenotypes in the ovarian epithelium.

The ovarian surface epithelium (OSE) is a monolayer of epithelial cells surrounding the ovary that ruptures during each ovulation to allow release of the oocyte. This wound is quickly repaired, but mechanisms promoting repair are poorly understood. The contribution of tissue-resident stem cells in the homeostasis of several epithelial tissues is widely accepted, but their involvement in OSE is unclear.

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum.

Patient Size-Dependent Dosimetry Methodology Applied to F-FDG Using New ICRP Mesh Phantoms.

Despite the known influence of anatomic variability on internal dosimetry, dosimetry for F-FDG and other diagnostic radiopharmaceuticals is routinely derived using reference phantoms, which embody population-averaged morphometry for a given age and sex. Moreover, phantom format affects dosimetry estimates to varying extent. Here, we applied newly developed mesh format reference phantoms and a patient-dependent phantom library to assess the impact of height, weight, and body contour variation on dosimetry of F-FDG.

Highly Accurate Chip-Based Resequencing of SARS-CoV-2 Clinical Samples.

SARS-CoV-2 has infected over 128 million people worldwide, and until a vaccine is developed and widely disseminated, vigilant testing and contact tracing are the most effective ways to slow the spread of COVID-19. Typical clinical testing only confirms the presence or absence of the virus, but rather, a simple and rapid testing procedure that sequences the entire genome would be impactful and allow for tracing the spread of the virus and variants, as well as the appearance of new variants. However, traditional short read sequencing methods are time consuming and expensive.

Engineered Cells as a Test Platform for Radiohaptens in Pretargeted Imaging and Radioimmunotherapy Applications.

Pretargeted imaging and radioimmunotherapy approaches are designed to have superior targeting properties over directly targeted antibodies but impose more complex pharmacology, which hinders efforts to optimize the ligands prior to human applications. Human embryonic kidney 293T cells expressing the humanized single-chain variable fragment (scFv) C825 (huC825) with high-affinity for DOTA-haptens (293T-huC825) in a transmembrane-anchored format eliminated the requirement to use other pretargeting reagents and provided a simplified, accelerated assay of radiohapten capture while offering normalized cell surface expression of the molecular target of interest. Using binding assays, biodistribution, and imaging, we demonstrated that radiohaptens based on benzyl-DOTA and a second generation "Proteus" DOTA-platform effectively and specifically engaged membrane-bound huC825, achieving favorable tumor-to-normal tissue uptake ratios in mice.

Developmental trajectories of ADHD symptoms in a large population-representative longitudinal study.

Background: Previous research has suggested that there is substantial heterogeneity in the developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms. Sometimes, qualitative distinctions between trajectories with different ages of onset and/or patterns of remission are made; however, little is known about the predictors and broader clinical meaningfulness of these candidate 'developmental subtypes' of ADHD symptoms.

Methods: We applied latent class growth analysis to data from the UK Millennium Cohort Study (MCS; N = 11 316; ages 3, 5, 7, 11 and 14) to evaluate whether developmental trajectories of ADHD symptoms differing in early life predictors could be identified.

Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.

Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies.

Ultrapotent miniproteins targeting the receptor-binding domain protect against SARS-CoV-2 infection and disease in mice.

Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to rise. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 receptor binding domain. Here, we investigated the capacity of modified versions of one lead binder, LCB1, to protect against SARS-CoV-2-mediated lung disease in human ACE2-expressing transgenic mice.