Protein phosphatases regulate the formation of Müller glia-derived progenitor cells in the chick retina.

Different kinase-dependent cell signaling pathways are known to play important roles in glia-mediated neuroprotection and reprogramming of Müller glia (MG) into Müller glia-derived progenitor cells (MGPCs) in the retina. However, very little is known about the phosphatases that regulate kinase-dependent signaling in MG. Using single-cell RNA-sequencing (scRNA-seq) databases, we investigated patterns of expression of Dual Specificity Phosphatases (DUSP1/6) and other protein phosphatases in normal and damaged chick retinas. We found that DUSP1, DUSP6, PPP3CB, PPP3R1 and PPPM1A/B/D/E/G are widely expressed by many types of retinal neurons and are dynamically expressed by MG and MGPCs in retinas during the process of reprogramming. We find that inhibition of DUSP1/6 and PP2C phosphatases enhances the formation of proliferating MGPCs in damaged retinas and in retinas treated with insulin and FGF2 in the absence of damage. By contrast, inhibition of PP2B phosphatases suppressed the formation of proliferating MGPCs, but increased numbers of proliferating MGPCs in undamaged retinas treated with insulin and FGF2. In damaged retinas, inhibition of DUSP1/6 increased levels of pERK1/2 and cFos in MG whereas inhibition of PP2B's decreased levels of pStat3 and pS6 in MG. Analyses of scRNA-seq libraries identified numerous differentially activated gene modules in MG in damaged retinas versus MG in retinas treated with insulin+FGF2 suggesting significant differences in kinase-dependent signaling pathways that converge on the formation of MGPCs. Inhibition of phosphatases had no significant effects upon numbers of dying cells in damaged retinas. We conclude that the activity of different protein phosphatases acting through retinal neurons and MG "fine-tune" the cell signaling responses of MG in damaged retinas and during the reprogramming of MG into MGPCs.

Protein phosphatases regulate the formation of Müller glia-derived progenitor cells in the chick retina.

Different kinase-dependent cell signaling pathways are known to play important roles in glia-mediated neuroprotection and reprogramming of Müller glia (MG) into Müller glia-derived progenitor cells (MGPCs) in the retina. However, very little is known about the phosphatases that regulate kinase-dependent signaling in MG. Using single-cell RNA-sequencing (scRNA-seq) databases, we investigated patterns of expression of Dual Specificity Phosphatases (DUSP1/6) and other protein phosphatases in normal and damaged chick retinas. We found that DUSP1, DUSP6, PPP3CB, PPP3R1 and PPPM1A/B/D/E/G are dynamically expressed by MG and MGPCs in retinas during the process of reprogramming. We find that inhibition of DUSP1/6 and PP2C phosphatases enhances the formation of proliferating MGPCs in damaged retinas and in retinas treated with insulin in FGF2 in the absence of damage. By contrast, inhibition of PP2B phosphatases suppressed the formation of proliferating MGPCs, but increased numbers of proliferating MGPCs in undamaged retinas treated with insulin and FGF2. In damaged retinas, inhibition of DUSP1/6 increased levels of pERK1/2 and cFos in MG whereas inhibition of PP2B's decreased levels of pStat3 and pS6 in MG. Analyses of scRNA-seq libraries identified numerous differentially activated gene modules in MG in damaged retinas versus MG in retinas treated with insulin+FGF2 suggesting significant differences in kinase-dependent signaling pathways that converge on the formation of MGPCs. Inhibition of phosphatases had no significant effects upon numbers of dying cells in damaged retinas. We conclude that the activity of different protein phosphatases "fine-tune" the cell signaling responses of MG in damaged retinas and during the reprogramming of MG into MGPCs.

Personality and electrodermal response lability: an interpretation.

Electrodermal response (EDR) lability is a psychophysiological trait reflecting stable individual differences in electrodermal activation as indexed by frequency measures of phasic EDR activity. There is no consistent evidence that EDR lability reflects dispositional or clinical anxiety. However, EDR lability appears to be related to individual differences in the overt expression of emotional and antagonistic impulses. Greater EDR lability is associated with a relatively undemonstrative and agreeable disposition, whereas greater EDR stability is associated with a relatively expressive and antagonistic disposition. The inverse relationship between EDR lability and the expression of emotional and antagonistic impulses suggests that EDR lability may reflect individual differences in the effortful control of such expression. This hypothesis is consistent with cognitive effort interpretations of phasic EDR activity, with evidence of the sensitivity of phasic EDR activity to capacity-demanding tasks, and with evidence of reduced spare capacity among EDR labile individuals under cognitive challenge. Individual differences in effortful self-control may explain the association of greater EDR lability with essential hypertension and greater EDR stability with forms of antisocial behavior.

Storage and executive components of working memory: integrating cognitive psychology and behavior genetics in the study of aging.

We combined experimental cognitive and behavior genetic methods to investigate storage and executive components of working memory in 663 middle-aged male twins. A single latent factor model indicated that digits forward (storage) and two-digit transformation (executive + storage) scores were influenced by the same genes. Additional executive demands in digit transformation appeared to increase the variance of individual genetic differences from 25% for digits forward to 48% and 53% for the digit transformation scores. Although it was not the best model, a two-factor model also provided a good fit to the data. This model suggested the possibility of a second set of genes specifically influencing the executive component. We discuss the findings in the context of research suggesting that new genetic influences come into play if demand continues to increase beyond a certain threshold, a threshold that may change with task difficulty and with age.

Efficacy of biofeedback-based treatments for temporomandibular disorders.

Bibliographic searches identified 14 controlled and uncontrolled outcome evaluations of biofeedback-based treatments for temporomandibular disorders published since 1978. This literature includes two randomized controlled trials (RCTs) of each of three types of biofeedback treatment: (1) surface electromyographic (SEMG) training of the masticatory muscles, (2) SEMG training combined with adjunctive cognitive-behavioral therapy (CBT) techniques, and (3) biofeedback-assisted relaxation training (BART). A detailed review of these six RCTs, supplemented with information from non-RCT findings, was conducted to determine the extent to which each type of intervention met treatment efficacy criteria promulgated by the Association for Applied Psychophysiology and Biofeedback (AAPB). We conclude that SEMG training with adjunctive CBT is an efficacious treatment for temporomandibular disorders and that both SEMG training as the sole intervention and BART are probably efficacious treatments. We discuss guidelines for designing and reporting research in this area and suggest possible directions for future studies.

Stability, consistency, and heritability of electrodermal response lability in middle-aged male twins.

We examined individual differences in nonspecific electrodermal response (EDR) lability in terms of retest stability, cross-situational consistency, and heritability in a sample of 345 adult monozygotic and dizygotic twin pairs. We also examined the phenotypic and genetic relationships between EDR lability and speed of habituation of the specific EDR to a nonsignal stimulus. Individual variation in EDR lability showed substantial retest stability and cross-situational consistency and also predicted resistance to specific EDR habituation. Structural equation modeling showed that the covariation among EDR lability measures and resistance to specific EDR habituation operated through a single latent phenotype, which was influenced in approximately equal measure by genetic and unique environmental factors. We discuss these findings in terms of an information processing account of individual differences in phasic EDR activation.