The K2-3 system revisited: testing photoevaporation and core-powered mass loss with three small planets spanning the radius valley

Multi-planet systems orbiting M dwarfs provide valuable tests of theories of small planet formation and evolution. K2-3 is an early M dwarf hosting three small exoplanets (1.5-2.0 Earth radii) at distances of 0.07-0.20 AU. We measure the high-energy spectrum of K2-3 with HST/COS and XMM-Newton, and use empirically-driven estimates of Ly-alpha and extreme ultraviolet flux. We use EXOFASTv2 to jointly fit radial velocity, transit, and SED data. This constrains the K2-3 planet radii to 4% uncertainty and the masses of K2-3b and c to 13% and 30%, respectively; K2-3d is not detected in RV measurements. K2-3b and c are consistent with rocky cores surrounded by solar composition envelopes (mass fractions of 0.36% and 0.07%), H2O envelopes (55% and 16%), or a mixture of both. However, based on the high-energy output and estimated age of K2-3, it is unlikely that K2-3b and c retain solar composition atmospheres. We pass the planet parameters and high-energy stellar spectrum to atmospheric models. Dialing the high-energy spectrum up and down by a factor of 10 produces significant changes in trace molecule abundances, but not at a level detectable with transmission spectroscopy. Though the K2-3 planets span the small planet radius valley, the observed system architecture cannot be readily explained by photoevaporation or core-powered mass loss. We instead propose 1) the K2-3 planets are all volatile-rich, with K2-3d having a lower density than typical of super-Earths, and/or 2) the K2-3 planet architecture results from more stochastic processes such as planet formation, planet migration, and impact erosion.Comment: 15 pages, 7 figure, published in AJ, HLSPs at https://archive.stsci.edu/hlsp/mstarpanspe

Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters

IntroductionAntibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.MethodsTotal IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.ResultsThe IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.DiscussionThis study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Characterizing Ham and Loin Quality as Hot Carcass Weight Increases to an Average of 119 Kilograms

The objective was to characterize ham and loin quality of carcasses ranging from 78 to 145 kg (average ∼119 kg). Hot carcass weight (HCW), back fat depth, and loin depth was measured on 666 carcasses. Loin pH, instrumental and visual color and iodine value of clear plate fat (all 3 layers) was measured on approximately 90% of the population. Quality measurements of the ham, 14 d aged loin and chop, and loin chop shear force (SSF) were evaluated on approximately 30% of the population. Myosin heavy chain fiber type determination was completed on 49 carcasses. Slopes of regression lines and coefficients of determination between HCW and quality traits were calculated using the REG procedure in SAS and considered significantly different from 0 at P ≤ 0.05. As HCW increased, loin depth (b1 = 0.2496, P 0.15) and did not explain more than 1% (R2 ≤ 0.01) of the variation in 1 d loin color or pH. Loins from heavier carcasses were more tender (decreased SSF; b1 = –0.0674, P 0.22) muscle fiber type percentage or area. These results suggest that increasing HCW to an average of 119 kg did not compromise pork quality