CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18.

Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli.

Age and sex-related decline of muscle strength across the adult lifespan: a scoping review of aggregated data.

Muscle strength is sex-related and declines with advancing age; yet, a comprehensive comparative evaluation of age-related strength loss in human females and males has not been undertaken. To do so, segmented piecewise regression analysis was performed on aggregated data from studies published from 1990 to 2018 and are available in CINAHL, EMBASE, MEDLINE, and PsycINFO databases. The search identified 5613 articles that were reviewed for physical assessment results stratified by sex and age. Maximal isometric and isokinetic 60°·s-1 knee extension (KE) and knee flexion (KF) contractions from 57 studies and 15 283 subjects (N = 7918 females) had sufficient data reported on females and males for meaningful statistical evaluation to be undertaken. The analysis revealed that isometric KE and KF strength undergo similar rapid declines in both sexes late in the sixth decade of life. Yet, there is an abrupt age-related decline in KE 60°·s-1 peak torque earlier in females (aged 41.8 years) than males (aged 66.7 years). In the assessment of KF peak torque, an age-related acceleration in strength loss was only identified in males (aged 49.3 years). The results suggest that age-related isometric strength loss is similar between sexes while the characteristics of KE and KF peak torque decline are sex-related, which likely explains the differential rate of age-related functional decline. Novelty Inclusion of muscle strength and torque of KE and KF data from >15 000 subjects. Isometric KE and KF strength loss are similar between sexes. Isokinetic 60°·s-1 KE torque decline accelerates 25 years earlier in females and female age-related KF peak torque decline does not accelerate with age.

Novel protein pathways in development and progression of pulmonary sarcoidosis.

Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.

A test of models of personality disorder configuration.

In this study, the authors examined the degrees to which various models of personality disorder (PD) configuration are consistent with the primary data sets from clinical and community samples reported in the recent literature. Factor analyses were conducted on PD intercorrelation matrices, and the loading matrices were rotated to maximum possible fit with target matrices representing the PD configuration models. There was little support for the interpersonal circle or other circular orderings of PDs, or for T. Millon's (1990, 1996) biosocial learning theory. There was moderate support for the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994) dimensions, for C. R. Cloninger's (1987) tridimensional theory, and for S. Torgersen and R. Alnaes's (1989) decision tree. There was consistent, stronger support for the 5-factor model (T. A. Widiger, T. J. Trull, J. F. Clarkin, C. Sanderson, & P. T. Costa, 1994) and for an empirically derived 7-factor model by C. R. Cloninger and D. M. Svrakic (1994).

Rigid and extreme: a geometric representation of personality disorders in five-factor model space.

Personality disorder rigidity and extremity can be geometrically defined and operationalized within the 5-factor model (FFM) of personality. A series of geometric and substantive assumptions were derived and then tested in samples of college students (N = 1,323) and psychiatric patients (N = 86). Normal and disordered personalities were found to coexist in a variety of regions of the FFM multivariate space. Within regions, the profiles of normal and disordered personalities were very similar in characteristic configuration but notably different in profile variability. Personality-disordered individuals tended to be located in the perimeters or outer regions of the FFM space, as indicated by their longer vector lengths. These findings generalized across 2 measures of personality disorders and across 2 measures of normal personality traits.

Perceptions of baby talk, frequency of receiving baby talk, and self-esteem among community and nursing home residents.

Community-living seniors (n = 113) and nursing home residents (n = 43) provided their impressions of baby-talk and neutral-talk scenarios and completed measures of functional health, need for succorance, and self-esteem. Two orthogonal dimensions were found in perceptions of baby talk: Warmth and Superiority. The personality trait of need for succorance was consistently associated with perceptions of warmth in baby talk, whereas functional health, age, and institutionalization were associated with perceptions of superiority. Significant interactions were found between perceptions of baby talk and frequency of receiving baby talk in the prediction of self-esteem, providing suggestive evidence for previously expressed concerns about potentially harmful effects of receiving baby talk on self-esteem among seniors who have negative perceptions of baby talk. However, older persons with positive perceptions of baby talk reported higher self-esteem when they frequently received baby talk, in accordance with person-environment theory. The self-esteem interaction for men occurred on the Superiority dimension, whereas the interaction for women occurred on the Warmth dimension.

Motivation, self-determination, and person-environment fit as predictors of psychological adjustment among nursing home residents.

In this report self-determination theory is applied to the regulation of everyday behavior in later life. Nursing home residents with more self-determined motivational orientations displayed higher levels of psychological adjustment. However, the effects of opportunities for self-determination available in the environment were less straightforward and were moderated by motivational styles. Specifically, residents with self-determined motivational styles were better adjusted when they lived in homes that provided opportunities for freedom and choice, whereas residents with less self-determined motivational styles were better adjusted when they lived in high constraint environments. The findings support person-environment fit models of adjustment in old age.

Psychological adjustment variables as predictors of mortality among nursing home residents.

Mortality over a 4-year period was examined in relation to self-esteem, depression, life satisfaction, and meaning in life in a nonclinical sample of 129 intermediate-care nursing home residents. Survival was associated with the psychological adjustment variables, and the effect persisted after statistically controlling for age, sex, and physical health. Self-evaluations (self-esteem and depression) were stronger predictors of mortality than were general life evaluations (life satisfaction and meaning in life). Comparisons with previous studies suggest conditions under which psychological variables are likely to be associated with mortality.

Personality disorders and the five-factor model: a test of facet-level predictions.

We tested predicted relationships (Widiger, 1993; Widiger, Trull, Clarkin, Sanderson, & Costa, 1994) between personality disorder scores and facets of the five-factor model, and evaluated the relative benefits of facet-level analyses over domain-level analyses. Data from 614 undergraduates indicated: (a) 63% of the predicted facet relationships were significant, although many unpredicted relationships also emerged; (b) facet-level analyses did not yield substantially stronger effect sizes than domain-level analyses; but (c) facet-level analyses provided much better discrimination between personality disorders than domain-level analyses. Facets of the openness to experience domain also helped discriminate between personality disorders, which is in contrast to previous domain-level findings that openness is not important.

Abnormal modelling of trabecular bone in calves.

Lesions due to abnormal modelling of trabecular bone were identified in the femurs of 26 of 55 prenatal and neonatal calves at postmortem examination. Abnormalities included growth retardation lines and lattices, focal retention of primary spongiosa and persistence of secondary spongiosa. The possible cause and pathogenesis of these lesions is discussed. The normal radiographic and histological appearance of the developing bovine femur, during the last four months of gestation, is also described.

Religious motivation in the elderly: a French-Canadian replication and an extension.

To clarify further the relationship between religiosity and personal adjustment, four kinds of religious motivation were distinguished: intrinsic, self-determined extrinsic, non-self-determined extrinsic, and amotivation. A study of 176 French-Canadian elderly people found that these four kinds of religious motivation can be reliably measured, that they display a pattern of intercorrelations consistent with theoretical predictions, and that they are related to other important aspects of the lives of these elderly people in a theoretically meaningful manner.

How a relationship between thinking and feeling may give rise to a variety of human behaviors.

In this study, it is proposed that, as a result of evolution and natural selection, human beings experience positive feelings when they succeed in comprehending some aspect of reality and negative feelings when they fail. It is also shown how the relationship between thinking and feeling may give rise to competence and intrinsic motivation, the need for perceived control, the need to believe in a just world, the need for cognitive consistency, the need for self-esteem, and the need for meaning. The proposal can also account for the motivation behind autotelic activities; can specify the conditions under which self-esteem and self-consistency motivations will operate; and is consistent with theory and research on adaptation to stressful life events and with views on the causes and treatment of psychopathology.

SPSS and SAS programs for determining the number of components using parallel analysis and velicer's MAP test.

Popular statistical software packages do not have the proper procedures for determining the number of components in factor and principal components analyses. Parallel analysis and Velicer's minimum average partial (MAP) test are validated procedures, recommended widely by statisticians. However, many researchers continue to use alternative, simpler, but flawed procedures, such as the eigenvalues-greater-than-one rule. Use of the proper procedures might be increased if these procedures could be conducted within familiar software environments. This paper describes brief and efficient programs for using SPSS and SAS to conduct parallel analyses and the MAP test.

Family and friend relationships among older and younger adults: interaction motivation, mood, and quality.

This research examined relationships and life satisfaction among older and younger adults. Eighty-two independently-living older adults and ninety-one younger adults completed a variety of measures of their relationships with family and friends. For both groups the quality of relationships was a stronger predictor of life satisfaction than frequency of contact. For elderly people the quality of their relationships with friends was more important to life satisfaction than the quality of their relationships with children. However, in contrast to a common assumption in the literature, relationships with friends were not perceived to be more positive or intrinsically motivated than relationships with children. It was also found that experiences of criticism and intrusion are particularly important to the family relationships of both older and younger adults. The discussion focuses on how elderly people may have overly positive perceptions of their family relationships.

Simple and flexible SAS and SPSS programs for analyzing lag-sequential categorical data.

This paper describes simple and flexible programs for analyzing lag-sequential categorical data, using SAS and SPSS. The programs read a stream of codes and produce a variety of lag-sequential statistics, including transitional frequencies, expected transitional frequencies, transitional probabilities, adjusted residuals, z values, Yule's Q values, likelihood ratio tests of stationarity across time and homogeneity across groups or segments, transformed kappas for unidirectional dependence, bidirectional dependence, parallel and nonparallel dominance, and significance levels based on both parametric and randomization tests.

Identity development and formal operations as sources of adolescent egocentrism.

The self-concerns and social expectations that are part of the identity development process may lead adolescents to think that others survey them for signs of individuality. The novelty of identity development may also lead to feelings of uniqueness and invulnerability. The imaginary audience and personal fable may therefore stem from identity development and not from the emergence of formal operations. In this study high school and first-year university students (N=255) completed measures of adolescent egocentrism, identity development, and formal operations. Egocentrism was moderately associated with higher scores on identity crisis and identity achievement, and with lower scores on identity diffusion. There was no significant relationship between egocentrism and the emergence of formal operations.

Perceived control and acceptance of the decision to enter a nursing home as predictors of adjustment.

A longitudinal study of newly admitted nursing home residents examined the effects of perceived control over the relocation decision and acceptance of the relocation in general as determinants of changes in functional health and morale. Perceived control had positive effects on health during the first month of residency but negative effects on health and morale between the second and fourth months. On the other hand, acceptance had positive effects on both health and morale between the second and fourth months. Perceived control over the relocation process appears to have short-term benefits but long-term costs, whereas acceptance appears to be a separate and important coping function.

Motivation in later life: theory and assessment.

A framework that has been found useful in research on young adults, Deci and Ryan's self-determination theory [1, 2], is suggested as a promising direction for research on motivation in later life. The theory proposes the existence of four types of motivation (intrinsic, self-determined extrinsic, nonself-determined extrinsic, and amotivation) which are assumed to have varying consequences for adaptation and well-being. A previously published French measure of motivational styles which is known to be reliable and valid was translated into English and was tested on seventy-seven nursing home residents (aged 60 to 98 years). It was found that the four motivational styles can be reliably measured; that the intercorrelations between the motivational styles are consistent with theoretical predictions; and that the four types of motivation are related to other important aspects of the lives of elderly people in a theoretically meaningful manner. Suggestions are made for further research using self-determination theory and the present scales.