Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.

Nonsense-mediated decay (NMD) is a major pathogenic mechanism underlying a diversity of genetic disorders. Nonsense variants tend to lead to more severe disease phenotypes and are often difficult targets for small molecule therapeutic development as a result of insufficient protein production. The treatment of cystic fibrosis (CF), an autosomal recessive disease caused by mutations in the CFTR gene, exemplifies the challenge of therapeutically addressing nonsense mutations in human disease. Therapeutic development in CF has led to multiple, highly successful protein modulatory interventions, yet no targeted therapies have been approved for nonsense mutations. Here, we have designed a CRISPR-Cas9-based strategy for the targeted prevention of NMD of CFTR transcripts containing the second most common nonsense variant listed in CFTR2, W1282X. By introducing a deletion of the downstream genic region following the premature stop codon, we demonstrate significantly increased protein expression of this mutant variant. Notably, in combination with protein modulators, genome editing significantly increases the potentiated channel activity of W1282X-CFTR in human bronchial epithelial cells. Furthermore, we show how the outlined approach can be modified to permit allele-specific editing. The described approach can be extended to other late-occurring nonsense mutations in the CFTR gene or applied as a generalized approach for gene-specific prevention of NMD in disorders where a truncated protein product retains full or partial functionality.

Histories of psychology after Stonewall: Introduction to the special issue.

This article introduces the special issue Fifty Years Since Stonewall: The Science and Politics of Sexual Orientation and Gender Diversity. Here, the commemoration of the 1969 Stonewall uprising frames our discussion of issues of representation that arise in commemorating events in general, and events in the history of psychology in particular. We describe how the articles in the special issue expand the existing narratives about the history of lesbian, gay, bisexual, and transgender psychology that are centered in the United States, focused primarily on sexual orientation and often end, rather than begin, in the time of Stonewall. The international scope of the special issue can suggest new ways to particularize histories of psychology since Stonewall that are centered on the United States. We describe the ideological context that shapes the doing of psychology since Stonewall, the telling of the histories of that psychology, and how "the problem of speaking for others" arises in contexts of power, including the curation of the special issue itself. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

"The difference being a woman made" Untold Lives in personal and intellectual context.

To mark the 30th anniversary of the publication of Scarborough and Furumoto's classic work Untold Lives, and to honor the intellectual legacy of Elizabeth Scarborough (1935-2015), we introduce this special issue devoted to the histories of women, gender, and feminism in psychology. We provide a short biographical sketch of Elizabeth, highlighting her own marriage-career dilemma, then contextualize the publication of Untold Lives within the historiography on women in psychology at that time. We conclude by discussing intersectionality as an analytic framework for the history of psychology as a way to extend and enrich this historiography.

"Making better use of U.S. women" Psychology, sex roles, and womanpower in post-WWII America.

The relationship between American psychology and gender ideologies in the two decades following World War II was complicated and multivalent. Although many psy-professionals publicly contributed to the cult of domesticity that valorized women's roles as wives and mothers, other psychologists, many of them women, reimagined traditional sex roles to accommodate and deproblematize the increasing numbers of women at work, especially working mothers. In this article, I excavate and highlight the contributions of several of these psychologists, embedding their efforts in the context of the paradoxical expectations for women that colored the postwar and increasingly Cold War landscape of the United States. By arguing that conflict was inherent in the lives of both women and men, that role conflict (when it did occur) was a cultural, not intrapsychic, phenomenon, and that maternal employment itself was not damaging to children or families, these psychologists connected the work of their first-wave, first-generation forebears with that of the explicitly feminist psychologists who would come after them.

B. F. Skinner and technology's nation: Technocracy, social engineering, and the good life in 20th-century America.

Psychologist B. F. Skinner developed and promoted a technology of behavior as the basis for widespread social reform over much of his career. In 1948, he published his behaviorally engineered vision of the good life in his utopian novel Walden Two (Skinner, 1948). Skinner's efforts were part of a much larger social engineering tradition that received one of its fullest expressions in the Technocracy Movement of the 1930s. Fifteen years before Skinner's Walden Two, at the height of the Technocracy Movement's public visibility in the United States, technocrat Harold Loeb (1933/1996) published his utopia, Life in a Technocracy: What It Might Be Like. In this article, I place the socially engineered visions of the good life promoted by the Technocracy Movement and by Skinner on an intellectual and ideological continuum to amplify and explore American attitudes toward psychology, technology, and social engineering during the middle decades of the 20th century. I argue that responses to both reveal the possibilities and limits of the social engineering enterprise, and suggest that historians of technology might consider how the history of psychology and other psy-disciplines can deepen conceptualizations of the relationships among the psychological, the social, and the technological in this period. (PsycINFO Database Record

Nancy Main Henley (1934-2016).

Presents an obituary for Nancy Main Henley who passed away on June 4, 2016, in Maryland. Henley was a feminist trailblazer who conducted influential work on gender, communication, and power. (PsycINFO Database Record

Naomi Weisstein (1939-2015).

This article memorializes Naomi Weisstein, who passed away on March 26, 2015 at Mount Sinai Hospital in New York City. In Chicago, Illinois, Weisstein began what would become a defining feature of her career and legacy-combining feminist political activism with both her academic and personal life pursuits. By the time she began her first faculty position at Loyola University in Chicago in 1966, Weisstein was an outspoken feminist. In 1968, she published her now classic article "Kirche, Kuche, Kinder as Scientific Law: Psychology Constructs the Female" (PCF; New England Free Press), wherein she criticized the field of psychology for failing to understand women because of its overreliance on essentialism and biologically based theories, while ignoring the importance of social context. Her critique laid the groundwork for others to explore the social construction of gender, and for second-wave feminism to take hold within the discipline of psychology. Despite all of her varied contributions, it is PCF that helped to define Weisstein's legacy in psychology. The article has been cited as a defining moment in second-wave feminism, and several psychologists have remembered the piece as a catalyst for their feminist awakening.

Feminism and/in/as psychology: The public sciences of sex and gender.

In our introduction to this special issue on the histories of feminism, gender, sexuality, and the psy-disciplines, we propose the tripartite framework of "feminism and/in/as psychology" to conceptualize the dynamics of their conjoined trajectories and relationship to gender and sexuality from the late 19th through the late 20th centuries. "Feminism and psychology" highlights the tensions between a political movement and a scientific discipline and the efforts of participants in each to problematize the other. "Feminism in psychology" refers to those historical moments when self-identified feminists intervened in psychology to alter its content, methodologies, and populations. We propose, as have others, that these interventions predate the 1970s, the period most commonly associated with the "founding" of feminist psychology. Finally, "feminism as psychology/psychology as feminism" explores the shared ground between psychology and feminism-the conceptual, methodological, and (more rarely) epistemological moments when psychology and feminism made common cause. We suggest that the traffic between feminism and psychology has been persistent, continuous, and productive, despite taking different historically and geographically contingent forms.

From seduction to sexism: Feminists challenge the ethics of therapist-client sexual relations in 1970s america.

Before the 1970s, psychologists and other mental health professionals who had sex with their patients committed no ethical violations. Indeed, the line between seduction and sexual exploitation in the therapy hour was extremely blurry to patients and therapists alike. This article is about how that changed. We focus on feminist psychologists' efforts, through the American Psychological Association Task Force on Sex Bias and Sex Role Stereotyping in Psychotherapeutic Practice, to document and reduce sexism in psychotherapy, including that involving therapist-client sexual relations. We contextualize these efforts within the larger feminist critique of the psy-disciplines that began in the late 1960s, highlighting how psychologists used several feminist strategies to recast seduction as sexism and revise the profession's ethical standards to specifically state that sexual intimacies with clients are unethical. As an example of a feminist intervention into psychology's-and society's-extant gender ideologies, this process highlights the mutually reinforcing entanglements of psychology and feminism, both methodologically and politically.

Maintaining Masculinity in Mid-Twentieth-Century American Psychology: Edwin Boring, Scientific Eminence, and the "Woman Problem".

Using mid-twentieth-century American psychology as my focus, I explore how scientific psychology was constructed as a distinctly masculine enterprise and was navigated by those who did not conform easily to this masculine ideal. I show how women emerged as problems for science through the vigorous gatekeeping activities and personal and professional writings of disciplinary figurehead Edwin G. Boring. I trace Boring's intellectual and professional socialization into masculine science and his efforts to understand women's apparent lack of scientific eminence, efforts that were clearly undergirded by preexisting and widely shared assumptions about men's and women's capacities and preferences.

Can't a mother sing the blues? Postpartum depression and the construction of motherhood in late 20th-century America.

Popular depictions of 20th-century American motherhood have typically emphasized the joy and fulfillment that a new mother can expect to experience on her child's arrival. But starting in the 1950s, discussions of the "baby blues" began to appear in the popular press. How did articles about the baby blues, and then postpartum depression, challenge these rosy depictions? In this article, we examine portrayals of postpartum distress in popular magazines and advice books during the second half of the 20th century to examine how the unsettling pairing of distress and motherhood was culturally negotiated in these decades. We show that these portrayals revealed a persistent reluctance to situate motherhood itself as the cause of serious emotional distress and a consistent focus on changing mothers to adapt to their role rather than changing the parameters of the role itself. Regardless of whether these messages actually helped or hindered new mothers themselves, we suggest that they reflected the rarely challenged assumption that motherhood and distress should not mix.

Problems of sex and the problem with nature: A commentary on "Beyond Kinsey".

In this commentary on the three articles in the special section "Beyond Kinsey: The Committee for Research in Problems of Sex and American Psychology," I focus on the implications of each author's analysis for understanding scientific constructions of sex and sexuality by examining the complex intersection of sex and nature. I show how each paper illuminates the ways nature was deployed by researchers investigating one of the most intimate yet most political aspects of being human. What did they count as "natural" when it came to sex and sexuality? What did they exclude or overlook? What political and moral work did the rhetoric of "the natural" do? (PsycINFO Database Record (c) 2012 APA, all rights reserved).

History's mysteries demystified: becoming a psychologist-historian.

More than 40 years ago, psychologist-historian Robert Watson argued that the study of history was of particular salience to psychology. In this article we explore the relationship between psychology and history and argue that the psychologist-historian plays a vital role in the discipline of psychology. We provide a brief overview of the emergence of the history of psychology as a professional subdiscipline, describe who psychologist-historians are, explain why they are needed, and detail how to join their ranks. We argue that increasing historical sophistication among psychologists will have beneficial effects on research and teaching, and we invite all psychologists to participate in the making of psychology's history.

The social control of behavior control: behavior modification, Individual Rights, and research ethics in America, 1971-1979.

In 1971, the U.S. Senate Subcommittee on Constitutional Rights began a three-year study to investigate the federal funding of all research involving behavior modification. During this period, operant programs of behavior change, particularly those implemented in closed institutions, were subjected to specific scrutiny. In this article, I outline a number of scientific and social factors that led to this investigation and discuss the study itself. I show how behavioral scientists, both individually and through their professional organizations, responded to this public scrutiny by (1) self-consciously altering their terminology and techniques; (2) considering the need to more effectively police their professional turf; and (3) confronting issues of ethics and values in their work. Finally, I link this episode to the formation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, whose recommendations resulted in changes to the ethical regulation of federally funded human subjects research that persist to the present day.

B. F. Skinner's technology of behavior in American life: from consumer culture to counterculture.

From the 1940s through the 1970s, articles in popular magazines and newspapers presented B. F. Skinner in a wide array of guises, from educational revolutionary and utopian to totalitarian and fascist. Understanding these diverse, and often contradictory, portrayals requires a consideration of the social and political discourses in which they were embedded. In this paper, I suggest that reports of Skinner's work were influenced by a number of cultural categories, from the better living campaign of the 1950s, to the counterculture crusade of the late 1960s. Through this examination, a multifaceted rendering of Skinner's public image that takes into account the nature of his work, the context in which it was produced, and the culture in which it was received is revealed. I propose that the received view of Skinner as maligned behaviorist actually obscures the complexity of his relationship with psychology's public throughout this period.

Skinner boxes for psychotics: operant conditioning at Metropolitan State Hospital.

Between 1953 and 1965, Ogden Lindsley and his associates conducted free-operant research with psychiatric inpatients and normal volunteers at Metropolitan State Hospital in Waltham, Massachusetts. Their project, originally named "Studies in Behavior Therapy," was renamed "Harvard Medical School Behavior Research Laboratory" in 1955. This name change and its implications were significant. The role of the laboratory in the history of the relationship between the experimental analysis of behavior and applied behavior analysis is discussed. A case is made for viewing Lindsley's early work as foundational for the subfield of the experimental analysis of human behavior that formally coalesced in the early 1980s. The laboratory's work is also contextualized with reference to the psychopharmacological revolution of the 1950s. Finally, a four-stage framework for studying the historical and conceptual development of behavior analysis is proposed.

B.F. Skinner and the auditory inkblot: The rise and fall of the verbal summator as a projective technique.

Behaviorist B.F. Skinner is not typically associated with the fields of personality assessment or projective testing. However, early in his career Skinner developed an instrument he named the verbal summator, which, at one point, he referred to as a device for "snaring out complexes," much like an auditory analogue of the Rorschach inkblots. Skinner's interest in the projective potential of his technique was relatively short lived, but whereas he used the verbal summator to generate experimental data for his theory of verbal behavior, several other clinicians and researchers exploited this potential and adapted the verbal summator technique for both research and applied purposes. The idea of an auditory inkblot struck many as a useful innovation, and the verbal summator spawned the tautophone test, the auditory apperception test, and the Azzageddi test, among others. This article traces the origin, development, and eventual demise of the verbal summator as an auditory projective technique.