Evaluating Student Learning: Community-Based Nursing Education as Action to Address Inequities.

BACKGROUND: This study evaluated nursing students' learning at a nurse-led, faculty-organized, drop-in health care center that provided basic care to marginalized communities. Nursing students have engaged in practicum and coursework at this site for more than 30 years; thus, a review of learning outcomes was needed. METHOD: Using grounded theory as outlined by Strauss and Corbin, data were collected and then analyzed for patterns and themes to inform the research purpose. RESULTS: Four main themes were identified from the data analysis regarding what students learned during their practicum at the community health care center. The themes included: connecting on a human scale, using self-reflection, building relationships with marginalized individuals, and developing skills to make needed changes. CONCLUSION: The findings supported the continuation of this educational opportunity to provide learning experiences that addressed health inequities and social determinants of health for nursing students. [J Nurs Educ. 2022;61(9):525-527.].

A TCF7L2-responsive suppression of both homeostatic and compensatory remyelination in Huntington disease mice.

Huntington's disease (HD) is characterized by defective oligodendroglial differentiation and white matter disease. Here, we investigate the role of oligodendrocyte progenitor cell (OPC) dysfunction in adult myelin maintenance in HD. We first note a progressive, age-related loss of myelin in both R6/2 and zQ175 HD mice compared with wild-type controls. Adult R6/2 mice then manifest a significant delay in remyelination following cuprizone demyelination. RNA-sequencing and proteomic analysis of callosal white matter and OPCs isolated from both R6/2 and zQ175 mice reveals a systematic downregulation of genes associated with oligodendrocyte differentiation and myelinogenesis. Gene co-expression and network analysis predicts repressed Tcf7l2 signaling as a major driver of this expression pattern. In vivo Tcf7l2 overexpression restores both myelin gene expression and remyelination in demyelinated R6/2 mice. These data causally link impaired TCF7L2-dependent transcription to the poor development and homeostatic retention of myelin in HD and provide a mechanism for its therapeutic restoration.

Caring in the Margins: A Scholarship of Accompaniment for Advanced Transcultural Nursing Practice.

Nurses must learn essential skills based in transcultural nursing to address issues of equity and social justice. The development of a model for nursing practice for an urban nurse-led drop-in center for individuals experiencing marginalization provides an opportunity for student nurses to learn transcultural nursing skills that shifts care from acknowledging the need of others to accompanying others on their health journey. The practice model provides the opportunity for undergraduate and graduate nursing students at Augsburg University to de-emphasize tasks and build relationships. Students learn to listen to others' stories and acknowledge their struggles in the margins. Four stages of nursing practice skills, acknowledging others' needs, attending to their struggles, affirming strengths, and ultimately accompanying others, are taught and experienced. At the core of the nursing practice model is the concept of "hospitality." The nursing practice model serves as guide for student nurses to learn to suspend disbeliefs, withhold judgment, and ultimately reduce stereotypes and stigma to offer a safe space for individuals living in the margins seeking care. The future of nursing requires essential knowledge, skills, and attitudes that shift care from need-based care to accompaniment to address health inequities and provide culturally appropriate care.

The Citizen Nurse: An Educational Innovation for Change.

BACKGROUND: Nursing education needs to provide the necessary tools for students to develop leadership skills and to practice civic agency to create meaningful change in the shifting health care field. This article focuses on facilitating a student's role in becoming a citizen nurse through curricular modifications. METHOD: Through an ongoing partnership, nursing faculty and community organizers implemented a year-long pilot project to discover the deeper insights into the role of a citizen nurse and to analyze the skills students need to be effective agents of change. Pilot lectures and workshops were held throughout the academic year, and curricular changes were implemented. RESULTS: Based on input from pilot class experiences, student reflections, and faculty workshop feedback, the decision to implement ongoing curricular changes was made by the department. CONCLUSION: The development of citizen nurses in nursing education will pave the way for praxis embedded in meaningful work with just solutions, enhancing the agency of all involved in promoting health and well-being. [J Nurs Educ. 2017;56(4):247-250.].

Human CaaX protease ZMPSTE24 expressed in yeast: Structure and inhibition by HIV protease inhibitors.

The function and localization of proteins and peptides containing C-terminal "CaaX" (Cys-aliphatic-aliphatic-anything) sequence motifs are modulated by post-translational attachment of isoprenyl groups to the cysteine sulfhydryl, followed by proteolytic cleavage of the aaX amino acids. The zinc metalloprotease ZMPSTE24 is one of two enzymes known to catalyze this cleavage. The only identified target of mammalian ZMPSTE24 is prelamin A, the precursor to the nuclear scaffold protein lamin A. ZMPSTE24 also cleaves prelamin A at a second site 15 residues upstream from the CaaX site. Mutations in ZMPSTE24 result in premature-aging diseases and inhibition of ZMPSTE24 activity has been reported to be an off-target effect of HIV protease inhibitors. We report here the expression (in yeast), purification, and crystallization of human ZMPSTE24 allowing determination of the structure to 2.0 Å resolution. Compared to previous lower resolution structures, the enhanced resolution provides: (1) a detailed view of the active site of ZMPSTE24, including water coordinating the catalytic zinc; (2) enhanced visualization of fenestrations providing access from the exterior to the interior cavity of the protein; (3) a view of the C-terminus extending away from the main body of the protein; (4) localization of ordered lipid and detergent molecules at internal and external surfaces and also projecting through fenestrations; (5) identification of water molecules associated with the surface of the internal cavity. We also used a fluorogenic assay of the activity of purified ZMPSTE24 to demonstrate that HIV protease inhibitors directly inhibit the human enzyme in a manner indicative of a competitive mechanism.

Structure of the integral membrane protein CAAX protease Ste24p.

Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a-factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.

The effects of verbal operant training and response interruption and redirection on appropriate and inappropriate vocalizations.

Past research has shown that response interruption and redirection (RIRD) can effectively decrease automatically reinforced motor behavior (Hagopian & Adelinis, 2001). Ahearn, Clark, MacDonald, and Chung (2007) found that a procedural adaptation of RIRD reduced vocal stereotypy and increased appropriate vocalizations for some children, although appropriate vocalizations were not targeted directly. The purpose of the current study was to examine the effects of directly targeting appropriate language (i.e., verbal operant training) on vocal stereotypy and appropriate speech in 3 children with an autism spectrum disorder. The effects of verbal operant (i.e., tact) training were evaluated in a nonconcurrent multiple baseline design across participants. In addition, RIRD was implemented with 2 of the 3 participants to further decrease levels of vocal stereotypy. Verbal operant training alone produced slightly lower levels of stereotypy and increased appropriate vocalizations for all 3 participants; however, RIRD was required to produce acceptably low levels of stereotypy for 2 of the 3 participants.

Purification of transmembrane proteins from Saccharomyces cerevisiae for X-ray crystallography.

To enhance the quantity and quality of eukaryotic transmembrane proteins (TMPs) available for structure determination by X-ray crystallography, we have optimized protocols for purification of TMPs expressed in the yeast Saccharomyces cerevisiae. We focused on a set of the highest-expressing endogenous yeast TMPs for which there are established biochemical assays. Genes encoding the target TMPs are transferred via ligation-independent cloning to a series of vectors that allow expression of reading frames fused to C-terminal His10 and ZZ (IgG-binding) domains that are separated from the reading frame by a cleavage site for rhinovirus 3C protease. Several TMP targets expressed from these vectors have been purified via affinity chromatography and gel filtration chromatography at levels and purities sufficient for ongoing crystallization trials. Initial purifications were based on expression of the genes under control of a galactose-inducible promoter, but higher cell densities and improved expression have been obtained through use of the yeast ADH2 promoter. Wide variations have been observed in the behavior of different TMP targets during purification; some can be readily purified, while others do not bind efficiently to affinity matrices, are not efficiently cleaved from the matrices, or remain tightly associated with the matrices even after cleavage of the affinity tags. The size, oligomeric state, and composition of purified protein-detergent complexes purified under different conditions were analyzed using a colorimetric assay of detergent concentrations and by analytical size-exclusion chromatography using static light scattering, refractive index, and UV absorption detection to monitor the elution profiles. Effective procedures were developed for obtaining high concentrations of purified TMPs without excessively concentrating detergents.

Characteristics affecting expression and solubilization of yeast membrane proteins.

Biochemical and structural analysis of membrane proteins often critically depends on the ability to overexpress and solubilize them. To identify properties of eukaryotic membrane proteins that may be predictive of successful overexpression, we analyzed expression levels of the genomic complement of over 1000 predicted membrane proteins in a recently completed Saccharomyces cerevisiae protein expression library. We detected statistically significant positive and negative correlations between high membrane protein expression and protein properties such as size, overall hydrophobicity, number of transmembrane helices, and amino acid composition of transmembrane segments. Although expression levels of membrane and soluble proteins exhibited similar negative correlations with overall hydrophobicity, high-level membrane protein expression was positively correlated with the hydrophobicity of predicted transmembrane segments. To further characterize yeast membrane proteins as potential targets for structure determination, we tested the solubility of 122 of the highest expressed yeast membrane proteins in six commonly used detergents. Almost all the proteins tested could be solubilized using a small number of detergents. Solubility in some detergents depended on protein size, number of transmembrane segments, and hydrophobicity of predicted transmembrane segments. These results suggest that bioinformatic approaches may be capable of identifying membrane proteins that are most amenable to overexpression and detergent solubilization for structural and biochemical analyses. Bioinformatic approaches could also be used in the redesign of proteins that are not intrinsically well-adapted to such studies.

Endoplasmic reticulum retention signal-dependent glycylation of the Hsp70/Grp170-related Pgp1p in Tetrahymena.

Glycylation is an uncommon posttranslational modification. It has been found that tubulin glycylation is essential for cell survival in Tetrahymena. Here we describe PGP1, a Tetrahymena gene encoding an Hsp70 homologue that is a novel glycylated protein. Pgp1p is a conserved glycoprotein that localizes within the lumen of the endoplasmic reticulum (ER). We demonstrate that PGP1 is essential for viability and present evidence that both glycosylation and ER retention are necessary but not sufficient for glycylation.

Longevity following the experience of parental divorce.

An archival prospective design was used to study mediating and moderating variables for the association between parental divorce and increased mortality risk, using a sub-group (n = 1183) of individuals from the US Terman Life Cycle Study covering the period 1921-2000. In childhood, both socioeconomic status (SES) and family psychosocial environment were related to parental divorce but did little to explain its effects. The higher mortality risk associated with experiencing parental divorce was ameliorated among individuals (especially men) who achieved a sense of personal satisfaction by mid-life. Behaviorally, smoking was the strongest mediator of the divorce-mortality link. This study extends previous work on the long-term effects of parental divorce and reveals some reasons why the stress of parental divorce in childhood need not necessarily lead to negative later-life outcomes.

Comparison of two procedures for teaching dictated-word/symbol relations to learners with autism.

The efficacy of exclusion and delayed-cue procedures for establishing novel dictated-word/symbol relations with 2 boys with autism was compared using computerized match-to-sample procedures. Acquisition of the relations under the two training conditions was compared via an alternating treatments design. The delayed-cue procedure was more efficacious than the exclusion procedure in four of five comparisons across participants.

Age-related changes in the associations of social network ties with mortality risk.

Age-related changes in the associations of social network ties with mortality risk were investigated using data from the Terman Life-Cycle Study (L. M. Terman, 1925; L. M. Terman & M. H. Oden, 1947, 1959). Marital status, number of living children, number of living siblings, and number of group memberships in 1940, 1950, 1960, and 1977 were reported across middle adulthood by 697 men and 544 women, with mortality follow-up as of 1991. Initial analyses confirmed previous work indicating that marital history (men only), number of children (both genders), and organizational memberships (both genders) are predictive of mortality risk. Further analyses compared the associations between these social ties and mortality prior to age 70 and at age 70 and older. Results indicated that for men, experiencing marital dissolution and subsequently remarrying is a stronger predictor of mortality risk prior to age 70 (p = .05), whereas for women, number of children (p < .05) is a stronger predictor of mortality risk after age 70. Implications of these age-related changes in social ties and mortality risk are discussed.