Translational neuroscience measures of fear conditioning across development: applications to high-risk children and adolescents

Several mental illnesses, including anxiety, can manifest during development, with onsets in late childhood. Understanding the neurobiological underpinnings of risk for anxiety is of crucial importance for early prevention and intervention approaches. Translational neuroscience offers tools to investigate such mechanisms in human and animal models. The current review describes paradigms derived from neuroscience, such as fear conditioning and extinction and overviews studies that have used these paradigms in animals and humans across development. The review also briefly discusses developmental trajectories of the relevant neural circuits and the emergence of clinical anxiety. Future studies should focus on developmental changes in these paradigms, paying close attention to neurobiological and hormonal changes associated with childhood and adolescence

A New Spontaneously Transformed Syngeneic Model of High-Grade Serous Ovarian Cancer with a Tumor-Initiating Cell Population

Improving screening and treatment options for patients with epithelial ovarian cancer has been a major challenge in cancer research. Development of novel diagnostic and therapeutic approaches, particularly for the most common subtype, high-grade serous ovarian cancer (HGSC), has been hampered by controversies over the origin of the disease and a lack of spontaneous HGSC models to resolve this controversy. Over long-term culture in our laboratory, an ovarian surface epithelial (OSE) cell line spontaneously transformed OSE (STOSE). The objective of this study was to determine if the STOSE cell line is a good model of HGSC. STOSE cells grow faster than early passage parental M0505 cells with a doubling time of 13 and 48 h, respectively. STOSE cells form colonies in soft agar, an activity for which M0505 cells have negligible capacity. Microarray analysis identified 1755 down-regulated genes and 1203 up-regulated genes in STOSE compared to M0505 cells, many associated with aberrant Wnt/β-catenin and Nf-κB signaling. Upregulation of Ccnd1 and loss of Cdkn2a in STOSE tumors is consistent with changes identified in human ovarian cancers by The Cancer Genome Atlas. Intraperitoneal injection of STOSE cells into severe combined immunodeficient and syngeneic FVB/N mice produced cytokeratin+, WT1+, inhibin−, and PAX8+ tumors, a histotype resembling human HGSC. Based on evidence that a SCA1+ stem cell-like population exists in M0505 cells, we examined a subpopulation of SCA1+ cells that is present in STOSE cells. Compared to SCA1− cells, SCA1+ STOSE cells have increased colony-forming capacity and form palpable tumors 8 days faster after intrabursal injection into FVB/N mice. This study has identified the STOSE cells as the first spontaneous murine model of HGSC and provides evidence for the OSE as a possible origin of HGSC. Furthermore, this model provides a novel opportunity to study how normal stem-like OSE cells may transform into tumor-initiating cells

Remarks on the Concept of Critique in Habermasian Thought

The main purpose of this paper is to examine the concept of critique in Habermasian thought. Given that the concept of critique is a central theoretical category in the work of the Frankfurt School, it comes as a surprise that little in the way of a systematic account which sheds light on the multifaceted meanings of the concept of critique in Habermas’s oeuvre can be found in the literature. This paper aims to fill this gap by exploring the various meanings that Habermas attributes to the concept of critique in 10 key thematic areas of his writings: (1) the public sphere, (2) knowledge, (3) language, (4) morality, (5) ethics, (6) evolution, (7) legitimation, (8) democracy, (9) religion, and (10) modernity. On the basis of a detailed analysis of Habermas’s multifaceted concerns with the nature and function of critique, the study seeks to demonstrate that the concept of critique can be considered not only as a constitutive element but also as a normative cornerstone of Habermasian thought. The paper draws to a close by reflecting on some of the limitations of Habermas’s conception of critique, arguing that in order to be truly critical in the Habermasian sense we need to turn the subject of critique into an object of critique