Age-dependent changes in geometry, tissue composition and mechanical properties of fetal to adult cryopreserved human heart valves

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La trigonometría como herramienta para medir nuestro entorno

En esta experiencia de aula se presenta el trabajo de un grupo de estudiantes de grado décimo que realizaron una actividad en la clase de trigonometría en la que aplicaron conceptos trigonométricos para calcular las medidas de las instalaciones de la institución educativa a la cual pertenecen. El objetivo es mostrar un ejemplo de cómo se puede generar un ambiente de aprendizaje en el que los estudiantes puedan elaborar significados de objetos matemáticos como lo son las razones trigonométricas mediante una labor que permita la aplicación fundamental de la trigonometría realizando mediciones indirectas

A SARS-CoV-2 Wuhan spike virosome vaccine induces superior neutralization breadth compared to one using the Beta spike

Current SARS-CoV-2 vaccines are effective, but long-term protection is threatened by the emergence of virus variants. We generated a virosome vaccine containing the Beta spike protein and compared its immunogenicity in mice to a virosome vaccine containing the original Wuhan spike. Two administrations of the virosomes induced potent SARS-CoV-2 neutralizing antibodies in both vaccine groups. The level of autologous neutralization in Beta-vaccinated mice was similar to the level of autologous neutralization in Wuhan-vaccinated mice. However, heterologous neutralization to the Wuhan strain in Beta-vaccinated mice was 4.7-fold lower than autologous neutralization, whereas heterologous neutralization to the Beta strain in Wuhan-vaccinated mice was reduced by only 1.9-fold compared to autologous neutralization levels. In addition, neutralizing activity against the D614G, Alpha and Delta variants was also significantly lower after Beta spike vaccination than after Wuhan spike vaccination. Our results show that Beta spike vaccination induces inferior neutralization breadth. These results are informative for programs aimed to develop broadly active SARS-CoV-2 vaccines

A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern

The emergence of SARS-CoV-2 variants that are more resistant to antibody-mediated neutralization pose a new hurdle in combating the COVID-19 pandemic. Although vaccines based on the original Wuhan sequence have been shown to be effective at preventing COVID-19, their efficacy is likely to be decreased against more neutralization-resistant variants-of-concern (VOC), in particular, the Beta variant originating in South Africa. We assessed, in mice, rabbits, and non-human primates, whether a third vaccination with experimental Wuhan-based Spike vaccines could alleviate this problem. Our data show that a third immunization improves neutralizing antibody titers against the variants-of-concern, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). After three vaccinations, the level of neutralization against Beta was similar to the level of neutralization against the original strain after two vaccinations, suggesting that simply providing a third immunization could nullify the reduced activity of current vaccines against VOC

Averaged stress-strain curves, E-modulus at high strains, and extensibility obtained from biaxial tensile tests.

<p>Averaged stress-strain curves (A, B), E-modulus at high strains (C), and extensibility (D) obtained from biaxial tensile tests. The E-moduli (E) in both circumferential and radial direction increase with age in the aortic valve (p<0.05). In the pulmonary valve the E-modulus does not change with age. The leaflets of the 11 and 20-year-old donors are more extensible than the adult leaflets (F). In addition, in these young donors, the pulmonary leaflets were slightly more extensible than the aortic leaflets. As the data of the 8-month old donor could be considered as an outlier, we also performed linear regression analysis of the data set excluding the 8-month data and added the corresponding linear regression lines to Figs E and F. This reveals that after the age of 11, leaflet extensibility significantly decreases with age in circumferential (AV: p<0.01, PV: p<0.05) and radial direction (PV: p<0.01). AV: aortic valve, PV: pulmonary valve.</p

Representative histological and immunofluorescent stainings on aortic valves.

<p>Figures A-E represent the whole aortic valve (leaflet, hinge region, and wall, while in E-W a representative part of the leaflet is shown. (A, C-F, H-J) Verhoeff-Van Gieson staining for collagen (red) and elastin (black). (B, G) Elastin was observed in the fetal valve using immunofluorescence (red). (K-N) Collagen type I (red) was predominant in the fibrosa. (O-R) Safranin-O staining showed proteoglycan presence (red/orange) mainly in the spongiosa and the hinge region. (S-W) αSMA (immunofluorescence; green) with cell nuclei (in blue). In the leaflets of the fetal (S) and 8-month old donor (T) αSMA-positive cells were observed, while in the older leaflets almost no αSMA-positive cells were observed (U-W). Scale bar: 500 μm. l: leaflet; w: wall; f: fibrosa; s: spongiosa; v: ventricularis.</p

Changes in stiffness at low strains as measured with indentation tests.

<p>The stiffness was computed in the belly (A) and commisures (B) (left side: all data points used for correlation analysis with age; at the right side). In the aortic valve, the stiffness in the belly and commissures increase with age, whereas in the pulmonary valve only the commissural stiffness increases with age. In both valves, E-moduli show a steep increase from adolescence to adulthood. Significant differences between groups (p<0.05) are indicated by paired symbols. AV: aortic valve, PV: pulmonary valve.</p

Changes in DNA-, sGAG-, and hydroxyproline (HYP) content.

<p>Changes in DNA- (A), sGAG- (B), and hydroxyproline (HYP) content (C) in μg/mg dry weight (left side: all data points used for correlation analysis with age; right side: grouped data). DNA content is higher in children, especially in the first years of life (0–4 years), compared to the adolescents and adults. sGAG content decreases with age. Hydroxyproline content increases with age in the aortic valve. Differences between groups (p<0.05) are indicated by paired symbols. AV: aortic valve, PV: pulmonary valve.</p