Lifeboat Foundation: Safeguarding Humanity
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Human natural killer (NK) cells are cytotoxic effector cells that are increasingly harnessed in cancer immunotherapy. NKG2A/CD94 is an inhibitory receptor on NK cells that has established regulatory functions in the direct interaction with target cells when engaged with its ligand, the non-classical HLA class I molecule HLA-E. Here, we confirmed NKG2A as a checkpoint molecule in primary human NK cells and identified a novel role for NKG2A in maintaining NK cell expansion capacity by dampening both proliferative activity and excessive activation-induced cell death. Maintenance of NK cell expansion capacity might contribute to the preferential accumulation of human NKG2A+ NK cells after hematopoietic cell transplantation and enrichment of functionally impaired NK cells in human cancers. Functional silencing of NKG2A for cancer immunotherapy is highly attractive but will need to consider that this might also lead to a reduced survival by driving activation-induced cell death in targeted NK cells.

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Reversal of fetal hemoglobin (HbF) silencing can ameliorate the effects of sickle cell anemia. Despite available gene therapy and stem cell transplantation modalities, the majority of affected patients worldwide will not have access to these in the near future. Thus, there is a need for safe and effective small-molecule therapeutics. We report here that stable occupancy of a major HbF silencing complex containing BCL11A, MBD2a–NURD, and PRMT5 and exclusion of the transcriptional activator NF-Y at the γ-globin gene promoter require specific features of MBD2a. These results provide a unified model for the relationships between the previously reported HbF silencers MBD2–NuRD, BCL11A, DNA methylation, and PRMT5 that may facilitate development of therapeutic agents to reverse HbF silencing.

During human development, there is a switch in the erythroid compartment at birth that results in silencing of expression of fetal hemoglobin (HbF). Reversal of this silencing has been shown to be effective in overcoming the pathophysiologic defect in sickle cell anemia. Among the many transcription factors and epigenetic effectors that are known to mediate HbF silencing, two of the most potent are BCL11A and MBD2–NuRD. In this report, we present direct evidence that MBD2–NuRD occupies the γ-globin gene promoter in adult erythroid cells and positions a nucleosome there that results in a closed chromatin conformation that prevents binding of the transcriptional activator, NF-Y. We show that the specific isoform, MBD2a, is required for the formation and stable occupancy of this repressor complex that includes BCL11A, MBD2a–NuRD, and the arginine methyltransferase, PRMT5. The methyl cytosine binding preference and the arginine-rich (GR) domain of MBD2a are required for high affinity binding to methylated γ-globin gene proximal promoter DNA sequences. Mutation of the methyl cytosine–binding domain (MBD) of MBD2 results in a variable but consistent loss of γ-globin gene silencing, in support of the importance of promoter methylation. The GR domain of MBD2a is also required for recruitment of PRMT5, which in turn results in placement of the repressive chromatin mark H3K8me2s at the promoter. These findings support a unified model that integrates the respective roles of BCL11A, MBD2a–NuRD, PRMT5, and DNA methylation in HbF silencing.

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It found that consciousness may emerge from a grid-like interconnection of neurons at the back of the head.

Launched in 2019, the $20 million project, COGITATE, sought to explore an age-old question: how does consciousness arise? The “outlandish” project threw the field into a tizzy for its audacity. But it set up a fair fight: the teams collaborated on specific experiment designs, published them online, and pre-registered predicted results based on each of their championed theories.

Human brain scan data was then collected from six theory-neutral labs around the world, with the results judged by three experts with no money in the game to see how well the measured results matched predicted ones.

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Having undergone two aneurysm surgeries, Sandi Rodoni thought she understood everything about the procedure. But when it came time for her third surgery, the Watsonville, California, resident was treated to a virtual reality trip inside her own brain.

Stanford Medicine is using a new software system that combines imaging from MRIs, CT scans and angiograms to create a three-dimensional model that physicians and patients can see and manipulate — just like a virtual reality game.

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Virgin Galactic successfully flew its first paying customers to the final frontier Thursday, a long-awaited achievement that puts it back on track in the emerging private spaceflight sector.

Italian Air Force officers unfurled their nation’s flag and peered out windows at the curve of Earth while enjoying a few minutes of weightlessness at 52.9 miles (85.1 kilometers) above sea level.

“It was a beautiful ride,” Colonel Walter Villadei told reporters at a press conference, adding that his favorite moment was seeing the contrast between the black of space and the planet beneath.

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Quantum physics governs the world of the very small and that of the very cold. Your dog cannot quantum-tunnel her way through the fence, nor will you see your cat exhibit wave-like properties. But physics is funny, and it is continually surprising us. Quantum physics is starting to show up in unexpected places. Indeed, it is at work in animals, plants, and our own bodies.

We once thought that biological systems are too warm, too wet, and too chaotic for quantum physics to play any part in how they work. But it now seems that life is employing feats of quantum physics every day in messy, real-world systems, including quantum tunneling, wave-particle duality, and even entanglement. To see how it all works, we can start by looking right inside our own noses.

The human nose can distinguish over one trillion smells. But how exactly the sense of smell works is still a mystery. When a molecule referred to as an odorant enters our nose, it binds to receptors. Initially, the prevailing theory held that these receptors used the shape of the odorants to differentiate smells. The so-called lock and key model suggests that when an odorant finds the right receptor, it fits into it and triggers a specific smell. But the lock and key model ran into trouble when tested. Subjects were able to tell two scents apart, even when the odorant molecules were identical in shape. Some other process must be at work.

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