The goals of a gestational surrogacy relationship are to have a healthy baby for the intended parents while maintaining the medical and psychological well-being of the gestational carrier. A ...successful gestational surrogacy relationship will result also in good psychosocial outcomes for the gestational carrier, intended parents, and child. Finding a gestational carrier who will achieve these goals would be the ideal. This article focuses on key medical, reproductive, and ethical considerations to optimize clinical outcomes in gestational carrier cycles. Recommendations from available clinical guidelines regarding gestational surrogacy are reviewed, along with updates from current literature.
A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1) vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs). One approach to the ...problem is to create trimeric mimics of the native envelope glycoprotein (Env) spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs). Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM). We used several techniques, including ELISA and surface plasmon resonance (SPR), to determine the relationship between the ability of monoclonal antibodies (MAbs) to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145). Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits). Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens.
The global temperature has been increasing resulting in climate change. This negatively impacts planetary health that disproportionately affects the most vulnerable among us, especially children. ...Extreme weather events, such as hurricanes, tornadoes, wildfires, flooding, and heatwaves, are becoming more frequent and severe, posing a significant threat to our patients’ health, safety, and security. Concurrently, shifts in environmental exposures, including air pollution, allergens, pathogenic vectors, and microplastics, further exacerbate the risks faced by children. In this paper, we provide an overview of pediatric illnesses that are becoming more prevalent and severe because of extreme weather events, global temperature increases, and shifts in environmental exposures. As members of pediatric health care teams, it is crucial for pediatric radiologists to be knowledgeable about the impacts of climate change on our patients, and continue to advocate for safe, healthier environments for our patients.
The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of ...broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121–123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans.
Display omitted
•Potent broadly neutralizing HIV antibody PGT124 contacts both glycan and protein•PGT124 contrasts with other family members by contacting only a single glycan•Inferred germline antibody incorporates features important for protein and glycan recognition•Antibody maturation diversifies modes of glycan recognition
Structural data reveal how a family of human antibodies has evolved diverse solutions to interact with and penetrate the HIV envelope glycan defensive shield so as to potently neutralize HIV.
PDF
