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Princess I Division

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Mature Bent

Mature Bent >>>

Mature Bent

Utku Goreke, Erdem Kucukal, Fang Wang, Ran An, Nicole Arnold, Erina Quinn, Charlotte Yuan, Allison Bode, Ailis Hill, Yuncheng Man, Bryan C. Hambley, Robert Schilz, Mahazarin Ginwalla, Jane Little, Umut A Gurkan; Membrane bending and sphingomyelinase associated sulfatide dependent hypoxic adhesion of sickle mature erythrocytes. Blood Adv 2023; bloodadvances.2022008392. doi:

Abnormal erythrocyte adhesion due to polymerization of sickle hemoglobin is central to the pathophysiology of sickle cell disease (SCD). Mature erythrocytes constitute >80% of all erythrocytes in SCD, and the relative contributions made by erythrocytes to acute and chronic vasculopathy in SCD are not well understood. Here, we show that the bending stress exerted on the erythrocyte plasma membrane by the sickle hemoglobin polymerization under hypoxia enhances sulfatide-mediated abnormal mature erythrocyte adhesion. We hypothesized that sphingomyelinase activity that is upregulated by accumulated bending energy leads to elevated membrane sulfatide availability and thus hypoxic mature erythrocyte adhesion. We found that mature erythrocyte adhesion to laminin in controlled microfluidic experiments is significantly greater under hypoxia than under normoxia (1856481 vs. 7823, meanSEM), while sickle reticulocyte (early erythrocyte) adhesion, high to begin with, does not change (1281 299 vs. 1258328, meanSEM). We show that greater mean accumulated bending energy of adhered mature erythrocytes is associated with higher acid SMase activity and increased mature erythrocyte adhesion (p=0.022, for the acid SMase activity and p=0.002 for the increase in mature erythrocyte adhesion with hypoxia, N=5). In addition, hypoxia results in sulfatide exposure on the erythrocyte membrane, and sphingomyelinase increases while anti-sulfatide inhibits the enhanced adhesion of erythrocytes. These results suggest that lipid components of the plasma membrane contribute to the complications in SCD. Therefore, sulfatide and the components of its upregulation pathway, particularly sphingomyelinase should be further explored as potential therapeutic targets to inhibit sickle erythrocyte adhesion.

Five 40-year-old Pinus taeda trees growing in Tochigi, Japan, were used to evaluate juvenile wood (JW) and mature wood (MW) properties and the bending properties of lumber. The boundary between JW and MW existed from the 14th to the 19th ring from pith in the sample trees. There were obvious differences in wood properties between the JW and MW: the MW had higher values in the latewood percentage and basic density and lower values in the microfibril angle. The microfibril angle and the air-dry density were closely related to the bending properties of the JW lumber and the MW lumber, respectively.

In softwoods, it is known that there is a problem with using the juvenile wood as structural lumber and pulp because it has a lower density, shorter cell length, larger microfibril angle (MFA) of the S2 layer, and poor mechanical properties compared with mature wood (Shiokura 1982, Bendtsen and Senft 1986, Clark and Saucier 1989, Zobel and van Buijtenen 1989). It has been shown that the effects of the wood properties, such as the MFA and wood density, on the strength properties differ between juvenile and mature wood. For example, in Japanese cedar (Cryptomeria japonica), Ishiguri et al. (2009) pointed out that the MFA influenced mainly the bending properties of juvenile wood, whereas the air-dry density (AD) influenced mainly the bending properties of mature wood. Matsumura et al. (2012) examined the influence of the lumber positions (center [near the pith], inner, and outer [near the bark]) in large-diameter Japanese cedar logs on variations in the dynamic modulus of elasticity (DMOE) of the lumber. The results showed that the mean values of the DMOE of the lumber obtained from the center, inner, and outer positions were 4.64, 5.44, and 6.48 GPa, respectively. These differences in


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