Novel single-cell measurements suggest irreversibly sickled cells are neither dense nor dehydrated.

In sickle cell anemia, deoxygenation causes erythrocytes to distort, while reoxygenation permits them to recover a normal biconcave disk shape. Irreversibly sickled cells (ISCs) remain distorted when reoxygenated and have been thought to have among the highest intracellular hemoglobin concentrations of the sickle red cell population and therefore the greatest vulnerability to vasoocclusion. Using a new optical method, which we describe, we have made precise measurements of the intracellular hemoglobin concentration, and intracellular O saturation, of ISCs, as well as oxygenated sickle cells with a normal biconcave disc shape, and cells with shapes distorted by the sickle fibers they contain.

An α-chain modification rivals the effect of fetal hemoglobin in retarding the rate of sickle cell fiber formation.

Adults with sickle cell disease bear a mutation in the β-globin gene, leading to the expression of sickle hemoglobin (HbS; αβ). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, αγ); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ chain or introduce a gene encoding a modified β chain having γ-like character.

Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation.

The drug voxelotor (commercially known as Oxbryta) has been approved by the US Food and Drug Administration for the treatment of sickle cell disease. It is known to reduce disease-causing sickling by inhibiting the transformation of the non-polymerizing, high-oxygen-affinity R quaternary structure of sickle hemoglobin into its polymerizing, low-affinity T quaternary structure. It has not been established whether the binding of the drug has anti-sickling effects beyond restricting the change of quaternary structure.

Women, Mobility, and Education in Twentieth-century England and Wales: A New Analytical Approach.

The twentieth century saw substantial changes in the educational and occupational opportunities available to women in Britain. These may have been supposed to foster new patterns of female mobility. Yet studies of women's intergenerational mobility are rare and tend not to focus on education.

Omega-3 fatty acids promote neuroprotection, decreased apoptosis and reduced glial cell activation in the retina of a mouse model of OPA1-related autosomal dominant optic atrophy.

The purpose of this study was to evaluate the neuroprotective effects of omega-3 polyunsaturated fatty acid (ω3-PUFA) supplementation in a mouse model of OPA1-associated autosomal dominant optic atrophy (ADOA). The blood level of arachidonic acid (AA) and eicosapentaenoic acid (EPA) served to adjust the treatment dosage (AA/EPA = 1.0-1.