Effect of ethacrynic acid on contractility and Ca flux of guinea pig taenia coli smooth muscle (author's transl)

The effects of ethacrynic acid (ETCA) which has been known as an -SH groups inhibitor on the contractility and the Ca flux of guinea pig taenia coli were investigated. The results obtained were as follow: 1) Contractures induced by 10(-4) M ACh, or the tonic component of 150 mM K-contractures were markedly suppressed by previous treatment with a low concentration (2 X 10(-4) M) of ETCA for 40 min. Conversely with the same treatment, the phasic component of this K-contracture was only slightly suppressed. The inhibitory effects of ETCA in both cases were reversed by the repetitive washing out of ETCA from taenia coli with normal tris-buffered solution. 2) ETCA, at concentrations higher than 10(-3) M, more markedly inhibited the ACh-, and the K-contractures. In this case these inhibitions were irreversible. 3) Cysteine in an equimolar concentration of ETCA prevented the inhibitory effects of ETCA on both contractures. 4) ETCA (10(-4) M) inhibited the ACh-contracture in Ca2+-free isotonic KCl solution to approximately the same degree as that in normal solution. 5) Inhibition of ACh-contracture by ETCA in Na+-free isotonic LiCl solution was less than that in normal solution. 6) ETCA (2 X 10(-4), or 10(-3) M) markedly stimulated 45Ca efflux from taenia coli in 20 mM Ca-EGTA tris-buffered solution. 7) 45Ca efflux acceleration by ETCA in Na+-free (replaced by Li+) 20 mM Ca-EGTA tris-buffered solution was less than that in 20 mM Ca-EGTA tris-buffered solution. These results may be explained by assuming that the inhibitory effect of ETCA on ACh-contracture can be attributed to the depletion of stored intracellular Ca and the acceleration of Ca efflux as a result of ETCA treatment.     

Contact with basement membrane heparan sulfate enhances the growth of transformed vascular endothelial cells, but suppresses normal cells.

Modulation of vascular endothelial cell growth by basement membrane heparan sulfate was investigated using four lines of normal and transformed cells. The growth of transformed endothelial cells, but not normal cells, on reconstituted basement membrane was severely suppressed when heparan sulfate, one of the components of the membrane, was specifically degraded by an enzyme, heparitinase. Similarly, when cells were grown on surfaces coated with heparan sulfate, as little as 60 pg/cm2 of heparan sulfate caused growth enhancement of transformed cells, but suppression of normal cells. These results together with our previous observations (IMAMURA, T and MITSUI, Y. (1987) Exp. Cell Res., 172: 92-100) argue that transformed cells have reversed a mechanism by which basement membrane heparan sulfate functions as a physiological suppressor for the growth of normal endothelial cells.     

Relationship between postural stability and fall risk in elderly people with lumbar spondylosis during local vibratory stimulation for proprioception: a retrospective study

Abstract

Purpose: Reduced proprioception affects fall risks in elderly people with lumbar spondylosis. The decrease in proprioception in the trunk or lower legs may contribute to a decline in postural stability. We aimed to investigate the association between proprioceptive postural stability and fall risks in elderly individuals with lumbar spondylosis.

Materials and Methods: In this retrospective study, the centre-of-pressure displacement was determined in elderly individuals with lumbar spondylosis during upright stance while standing on a Wii Balance Board with their eyes closed (fall-risk group, n?=?55; non-fall-risk group, n?=?60). Vibratory stimulations at 30?Hz were applied to the lumbar multifidus and gastrocnemius to evaluate the relative contributions of proprioceptive signals used in postural control (relative proprioceptive weighting ratio).

Results: Compared with the non-fall-risk group, the fall-risk group displayed a high relative proprioceptive weighting ratio (p?=?0.024). Relative proprioceptive weighting ratio (odds ratio, 1.1; 95% confidence interval: 1.004–1.109) was independently associated with fall risks after adjusting for confounding factors. Among variables related to fall risk, the relative proprioceptive weighting ratio was a significant factor (p?<?0.035).

Conclusion: The fall-risk group of elderly individuals with lumbar spondylosis was dependent on the ankle strategy. The fall risk in elderly people with lumbar spondylosis could be due to over-dependence on the input from muscle spindles in the gastrocnemius.     

Response thresholds alone cannot explain empirical patterns of division of labor in social insects

The effects of heterogeneity in group composition remain a major hurdle to our understanding of collective behavior across disciplines. In social insects, division of labor (DOL) is an emergent, colony-level trait thought to depend on colony composition. Theoretically, behavioral response threshold models have most commonly been employed to investigate the impact of heterogeneity on DOL. However, empirical studies that systematically test their predictions are lacking because they require control over colony composition and the ability to monitor individual behavior in groups, both of which are challenging. Here, we employ automated behavioral tracking in 120 colonies of the clonal raider ant with unparalleled control over genetic, morphological, and demographic composition. We find that each of these sources of variation in colony composition generates a distinct pattern of behavioral organization, ranging from the amplification to the dampening of inherent behavioral differences in heterogeneous colonies. Furthermore, larvae modulate interactions between adults, exacerbating the apparent complexity. Models based on threshold variation alone only partially recapitulate these empirical patterns. However, by incorporating the potential for variability in task efficiency among adults and task demand among larvae, we account for all the observed phenomena. Our findings highlight the significance of previously overlooked parameters pertaining to both larvae and workers, allow the formulation of theoretical predictions for increasing colony complexity, and suggest new avenues of empirical study.

This study uses automated tracking of clonal raider ants and mathematical modeling to reveal how previously overlooked traits of larvae and workers might shape social organization in heterogeneous ant colonies. By incorporating the potential for variability in task efficiency among adults and task demand among larvae, the authors were able to account for all empirically observed phenomena.     

Infection-induced 5′-half molecules of tRNAHisGUG activate Toll-like receptor 7

Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5′-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and accompanying surface TLR activation up-regulate the expression of 5′-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5′-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundance of EV-5′-tRNA^HisGUG half molecules is >200-fold higher than that of the most abundant EV-microRNA (miRNA). Sequence identification of the 5′-tRNA halves using cP-RNA-seq revealed abundant and selective packaging of specific 5′-tRNA half species into EVs. The EV-5′-tRNA^HisGUG half was experimentally demonstrated to be delivered into endosomes in recipient cells and to activate endosomal TLR7. Up-regulation of the 5′-tRNA half molecules was also observed in the plasma of patients infected with Mycobacterium tuberculosis. These results unveil a novel tRNA-engaged pathway in the innate immune response and assign the role of “immune activators” to 5′-tRNA half molecules.

Although Toll-like receptors (TLRs) play a crucial role in the innate immune response, their endogenous ligands have not been fully explored. This study identifies tRNA half-molecules as abundant TLR ligands which are upregulated upon infection by mycobacteria and activate TLR7.