Effects of amino acid mutations in the pore-forming domain of the hemolytic lectin CEL-III

The hemolytic lectin CEL-III forms transmembrane pores in the membranes of target cells. A study on the effect of site-directed mutation at Lys405 in domain 3 of CEL-III indicated that replacements of this residue by relatively smaller residues lead to a marked increase in hemolytic activity, suggesting that moderately destabilizing domain 3 facilitates formation of transmembrane pores through conformational changes

Dry swing training with a light bat increases bat speed

Baseball training usually includes dry swing training to improve batting ability. However, no consensus has been reached on the relationship between bat weight and the increase in post-dry swing training bat speed. We hypothesized that dry swing training with a light bat would increase post dry swing training bat speed. Therefore, the purpose of this study was to examine the effect of dry swing training with a light bat on post dry swing training bat speed by comparing a light bat group with a heavy bat group. A total of 34 healthy male students from a university baseball team were randomly divided into a light bat group (n = 17) and a heavy bat group (n = 17). Subjects performed 100 dry swings per day, twice a week for eight weeks. The light bat group performed dry swing training with a 10.6 oz bat and the heavy bat group with a 38.8 oz bat. Bat speed and muscle power were measured before and after the intervention. There was no interaction between the intervention and post dry swing training bat speed, knee extension strength, shoulder horizontal flexion, or hand grip strength. There was a main effect of the intervention on post dry swing training bat speed and shoulder horizontal flexion. Bat speed increased in both groups, but without significant group differences in intervention effects. Since light bat loads in this study were very low, dry swing training with a light bat may be more effective and less strenuous

SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

臓器チップ技術を用いて新型コロナウイルスが血管へ侵入するメカニズムを解明 --Claudin-5発現抑制による呼吸器の血管内皮バリア破壊--. 京都大学プレスリリース. 2022-09-22.A study using an organ-on-a-chip reveals a mechanism of SARS-CoV-2 invasion into blood vessels --Disruption of vascular endothelial barrier in respiratory organs by decreasing Claudin-5 expression--. 京都大学プレスリリース. 2022-09-27.In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin–mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2–induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2–induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19

Modelling credit grade migration in large portfolios using cumulative t-link transition models

For a credit portfolio, we are often interested in modelling the migration of accounts between credit grades over time. For a large retail portfolio, data on credit grade migration may be available only in the form of a series of (typically monthly) population transition matrices representing the gross flow of accounts between each pair of credit grades in the given time period. The challenge is to model the transition process on the basis of these aggregate flow matrices. Each row of an observed transition matrix represents a sample from an ordinal probability distribution. Following [Malik, M. and Thomas, L.C. (2012). Transition matrix models of consumer credit ratings. International Journal of Forecasting, 28, 261-272.], [Feng, D., Gourieroux, C. and Jasiak, J. (2008). The ordered qualitative model for credit rating transitions. Journal of Empirical Finance, 15, 111-130.] and [McNeil, A.J. and Wendin, J.P. (2006). Dependent credit migrations. Journal of Credit Risk, 2, 87-114.], we assume a cumulative link model for these ordinal distributions. Common choices of link function are based on the normal (probit link) or logistic distributions, but the fit to observed data can be poor. In this paper, we investigate the fit of alternative link specifications based on the t-distribution. Such distributions arise naturally when modelling data which arise through aggregating an inhomogeneous sample of obligors, by combining a simple structural-type model for credit migration at the obligor level, with a suitable mixing distribution to model the variability between obligors

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters.

A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior

Blood retention of hemoglobin-albumin clusters.

<p>Relative plasma concentrations of ¹²⁵I-labeled Hb-HSA_<i>3</i>, Hb-HSA_<i>4</i>, XLHb-HSA_<i>3</i>, and HSA after intravenous administration to rats. Each data point represents the mean ± SD (<i>n</i> = 6). **<i>p</i> < 0.01 vs. HSA.</p