Analysing cylindromatosis and the associated defects in the CYLD gene is providing novel insights into the molecular principles of epithelial growth control and carcinogenesis in, and beyond, the skin. In this review, we summarize the histopathology and histogenesis of cylindromas, and the available genetic information on patients with these skin appendage tumors. Focusing on recent data concerning the normal functions and signaling interactions of the CYLD gene product, we explain how CYLD interferes with TNF‐α or TLR‐mediated signaling as well as (...) with JNK or NF‐κB‐dependent p65/50 signaling to limit inflammation. In addition, we delineate how CYLD interferes with activation of the proto‐oncogene Bcl3 and with cyclin D1 expression to limit tumorigenesis, and chart how tumor growth‐promoting agents or UV light and inflammatory mediators can activate CYLD. We argue that these recent insights into CYLD function and cylindroma pathogenesis may lead to the development of novel molecular strategies for cancer prevention and treatment. BioEssays 29:1203–1214, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

This article argues that public health campaigns have an ethical obligation to combat fat stigma, not mobilize it in the “war on obesity.” Fat stigma is conceptualized, and a review is undertaken of how pervasive fat stigma is across the world and across the lifespan. By reviewing the negative impacts of fat stigma on physical health, mental health, and health seeking behaviors, fat stigma is clearly identified as a social determinant of health. Considering the role of fat stigma in public (...) health, and the arguments made for using stigmatisation in public health campaigns to promote population health, it is concluded that it is a violation of public health ethics to use stigma as a tool in combatting fatness. The article concludes by making recommendations of how public health in New Zealand can combat, rather than reinforce, fat stigma. (shrink)

Interleukin‐15 (IL‐15) is a pleiotropic cytokine of the 4 α‐helix bundle family, which binds to a receptor complex that displays common elements with the IL‐2 receptor and a unique high‐affinity α chain. This review focuses on juxtacrine and reverse signaling levels in the IL‐15/IL‐15R system. Specifically, we discuss how agonistic stimulation of membrane‐bound IL‐15 induces phosphorylation of members of the MAP kinase family and of focal adhesion kinase (FAK), thereby upregulating processes including cytokine secretion, cell adhesion and migration. In addition, (...) we explore IL‐15 trans‐presentation and intracellular signaling, and define promising molecular targets for future pharmacological intervention in infectious diseases and immunological disorders. These frontiers in IL‐15/IL‐15Rα research serve as highly instructive examples for key concepts, unsolved problems and therapeutic opportunities in juxtacrine and reverse signaling in general. BioEssays 28: 362–377, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In this issue of Narrative Inquiries in Bioethics, fat individuals share their healthcare experiences. Through reading the narratives, it becomes clear that access to proper healthcare is often blocked for fat patients by a variety of things, including shame and fat stigma. From physical spaces in which they do not fit, to doctors who diagnose all of their problems as ‘fat’, similar themes are echoed across the stories. And common are the refrains for better treatment, less shame, and access to (...) evidenced based care from educated providers. In this manuscript, I highlight common themes from the stories and integrate them with themes from the literature. I allow the two dissenting narratives to suggest other ways of thinking about fatness and well–being. And I conclude by suggesting ways to provide better access to quality healthcare for fat individuals. (shrink)

This study examines how evidence is used differently in argumentative discourse compared to individual arguments. Applying a 1×2 crossover study design, 37 secondary school students were asked either to discuss a social issue with their partner before individually writing an essay outlining their opinion or, vice versa, first to discuss and then to write. As background information, they were provided with pieces of evidence with different levels of quality. Dialogs and essays were analyzed regarding (a) the type of evidence and (...) (b) the way evidence was used. Results showed that in their essays students referred more often to the pieces of evidence provided to them (shared evidence). In contrast, they used evidence more often to address the opposing viewpoint in dialogs by incorporating it in a more elaborated (clearer) line of reasoning. Findings suggest that dialogues are a more effective tool than individual writing production, and the study provides first hints regarding how to design curricula that will encourage students to use evidence in a more sophisticated way in their argumentation. (shrink)

Erythropoietin (EPO), long appreciated as the chief endocrine regulator of red blood cell formation, is now recognized to exert many additional functions outside the bone marrow. Thus, the quest is on to define the full range of EPO functions in the physiology and pathology of non‐hematopoietic tissues. Two recent studies in man and mice have highlighted the importance of the mammalian skin as one peripheral tissue with a previously unsuspected role in EPO biology; both, as a target and as a (...) source of EPO. In addition, the skin has been proposed to function as an oxygen sensor. The present hypothesis essay critically reviews the currently available evidence for this and provides a unifying theoretical scenario for intracutaneous EPO functions and for a potential role of the skin in the control of EPO production. Mainly, we propose that the skin itself directly contributes to the up‐regulation of EPO plasma levels in response to hypoxia. (shrink)

The study presented here examines how interacting with a more capable interlocutor influences use of argumentation strategies in electronic discourse. To address this question, 54 young adolescents participating in an intervention centered on electronic peer dialogs were randomly assigned to either an experimental or control condition. In both conditions, pairs who held the same position on a social issue engaged in a series of electronic dialogs with pairs who held an opposing position. In the experimental condition, in some dialogs, unbeknownst (...) to them (because dialog took place electronically), the opponent was a more capable (“expert”) adult. Dialogs in the control condition were only with peers. Argumentation strategies of the experimental group who argued with the “expert” showed immediate strategy improvements in their subsequent peer dialogs, improvement absent in the control group (Cohen's d = 1.12). In particular, the experimental group showed greater use of counterargument in general and advanced forms of counterargument (undermining) that challenges the deeper premises or reasoning on which an argument is based. Implications with respect to mechanisms of change in the development of argumentation skills are considered. (shrink)

This paper is aimed at combining the advances in argumentation theory with the models used in the field of education to address the issue of improving students’ argumentative behavior by interacting with an expert. The concept of deeper or more sophisticated argumentative strategy is theoretically defined and used to advance two new coding schemes, based on the advances in the argumentation studies and aimed at capturing the dialectical, or structural, behavior, and the argumentative content of each dialogue unit. These coding (...) schemes are then applied for a qualitative analysis of a study designed to investigate how students’ argumentative behavior can be influenced by the interaction with an expert, who used specific types of attacks to the interlocutors’ positions. The twofold coding shows at which dialogical level expert–peer interactions can directly and more stably affect students’ argumentative behavior, and what effects such more sophisticated strategies can have on the discussion and the analysis of disagreements. In particular, this paper shows how a specific type of deep-level attack, the underminer, can open dialogues of a different level, focused on unveiling and debating background beliefs underlying a specific position. (shrink)

Many urgent problems that societies currently face—from climate change to a global pandemic—require citizens to engage with scientific information as members of democratic societies as well as to solve problems in their personal lives. Most often, to solve their epistemic aims (aims directed at achieving knowledge and understanding) regarding such socio-scientific issues, individuals search for information online, where there exists a multitude of possibly relevant and highly interconnected sources of different perspectives, sometimes providing conflicting information. The paper provides a review (...) of the literature aimed at identifying (a) constraints and affordances that scientific knowledge and the online information environment entail and (b) individuals' cognitive and motivational processes that have been found to hinder, or conversely, support practices of engagement (such as critical information evaluation or two-sided dialogue). Doing this, a conceptual framework for understanding and fostering what we callonline engagement with scientific informationis introduced, which is conceived as consisting of individual engagement (engaging on one's own in the search, selection, evaluation, and integration of information) and dialogic engagement (engaging in discourse with others to interpret, articulate and critically examine scientific information). In turn, this paper identifies individual and contextual conditions for individuals' goal-directed and effortful online engagement with scientific information. (shrink)

Keratins are a family of intermediate filaments that serve various crucial roles in skin physiology. For mammalian skin to function properly, and to produce epidermal and hair keratins that are optimally adapted for their environment, it is critical that keratin gene and protein expression are stringently controlled. Given that the skin is not only targeted by multiple hormones, but also constitutes a veritable peripheral endocrine organ, it is not surprizing that intracutaneous keratin expression is underlined by tight endocrine controls. These (...) controls encompass thyroid hormones, steroid hormones such as glucocorticoids (GCs), retinoic acid (RA) and vitamin D, and several neuroendocrine mediators. Here, we review why a better understanding of the endocrine controls of keratin expression is not only required for an improved insight into normal human skin and hair function, but may also open new therapeutic avenues in a wide range of skin and hair diseases. (shrink)

Human skin produces numerous neurohormones and neuropeptides. Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin‐releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1‐ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ. Since selected keratins are now understood to exert important regulatory functions beyond mechanical stability, we argue that neuroendocrine pathways of keratin regulation are (...) important for maintaining skin and hair follicle homeostasis. This invites innovative neuroendocrine therapeutic interventions for skin disorders characterized by abnormal keratin expression, ranging from psoriasis to genodermatoses, and for promoting skin wound healing and hair growth. This strategy can be probed in simple, but instructive and readily available human skin and hair follicle organ culture assays as ideal models for exploring this new neuroendocrine frontier in translational epithelial biology. (shrink)

Stem cell self renewal, maintenance and differentiation are influenced by the convergence of intrinsic cellular signals and extrinsic microenvironmental cues from the surrounding stem cell niche. However, the specific signals involved are often still poorly understood. This is also true for skin epithelial stem cells. Recently, by transcriptionally profiling of embryonic hair progenitors in mice, Rhee et al.1 have managed to define how murine hair follicle epithelial stem cells are specified and maintained in an undifferentiated state. These authors have identified (...) Lhx2 as a transcription factor functionally positioned downstream of signals necessary to specify hair follicle stem cells such as p63 or NFκB, but upstream of signals like Wnt/β‐catenin, Bmp or Shh that are required to drive activated stem cells via the production of transient amplifying cells into terminal differentiation. BioEssays 28: 1157–1160, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Skin is a comparatively accessible organ possessing many conserved regulatory and signaling pathways, drawing researchers from varied fields toward its study. Hair follicle (HF) biology in particular has expanded rapidly over the preceding decade, helping to shape and develop scientific knowledge across diverse areas of biomedical research, beyond the skin. The hope in compiling this review is to inspire more researchers to utilize the HF as an instructive biological model, bringing with them fresh perspectives and experience from differing fields of (...) study. The authors also wish to further motivate seasoned hair researchers to explore the further reaches of their understanding and the discoveries yet to be made. For this reason, the authors have endeavored to collate an eclectic mix of some of the most thought‐provoking and scientifically intriguing articles associated with the field of HF research, published in the preceding two years. (shrink)

Since the spectrum of possibilities in linguistic theory construction is much broader and more variegated than students of linguistics have perhaps been led to believe, the Current Issues in Linguistic Theory series has been established in order to provide a forum for the presentation and discussion of linguistic opinions of scholars who do not necessarily accept the prevailing mode of thought in linguistic science. CILT is a theory-oriented series which welcomes contributions from scholars who have significant proposals to make towards (...) the advancement of our understanding of language, its structure, functioning, and development. Current Issues in Linguistic Theory is especially designed, by offering an alternative outlet for meaningful contributions to the current linguistic debate, to furnish the community of linguists the diversity of opinion which a healthy discipline must have. (shrink)

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under‐investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immune‐modulatory properties, including the creation of an immunoinhibitory, immune‐privileged milieu, we propose a novel hypothesis taking into account the role of the hair follicle. We hypothesize that the changes and imbalance of (...) yeast and bacterial species, along with increasing proinflammatory sebum by‐products, leads to the activation of immune response and inflammation. Hair follicle keratinocytes may then detect these changes in scalp microbiota resulting in the recruitment of leukocytes to the inflammation site. These changes in the scalp skin immune‐microenvironment may impact hair follicle immune privilege status, which opens new avenues into exploring the role of the hair follicle in dandruff pathogenesis. Also see the video abstract here: https://youtu.be/mEZEznCYtNs. (shrink)

Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current (...) concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber‐EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology. (shrink)

From four countries (Canada, England, New Zealand and the United States of America) and five disciplines (Counselling & Guidance, Adult Education, Early Years Education, Indigenous Education and Human Development), five feminists in academia come together to share how feminism affects their practice. Ranging in reflections on teaching, research, service and scholarship, this article describes a cooperative enquiry into feminism in action in Aotearoa, New Zealand.

The microbiome of human hair follicles (HFs) has emerged as an important player in different HF and skin pathologies, yet awaits in‐depth exploration. This raises questions regarding the tightly linked interactions between host environment, nutrient dependency of host‐associated microbes, microbial metabolism, microbe‐microbe interactions and host immunity. The use of simple model systems facilitates addressing generally important questions and testing overarching, therapeutically relevant principles that likely transcend obvious interspecies differences. Here, we evaluate the potential of the freshwater polyp Hydra, to dissect (...) fundamental principles of microbiome regulation by the host, that is the human HF. In particular, we focus on therapeutically targetable host‐microbiome interactions, such as nutrient dependency, microbial interactions and host defence. Offering a new lens into the study of HF – microbiota interactions, we argue that general principles of how Hydra manages its microbiota can inform the development of novel, microbiome‐targeting therapeutic interventions in human skin disease. (shrink)

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub (...) that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. (shrink)

As crucial interface organs gut and skin have much in common. Therefore it is unsurprising that several gut pathologies have skin co‐morbidities. Nevertheless, the reason for this remains ill explored, and neither mainstream gastroenterology nor dermatology research have systematically investigated the ‘gut‐skin axis'. Here, in reviewing the field, we propose several mechanistic levels on which gut and skin may interact under physiological and pathological circumstances. We focus on the gut microbiota, with its huge metabolic capacity, and the role of dietary (...) components as potential principle actors along the gut‐skin axis. We suggest that metabolites from either the diet or the microbiota are skin accessible. After defining open key questions around the nature of these metabolites, how they are sensed, and which cutaneous changes they can induce, we propose that understanding of these pathways will lead to novel therapeutic strategies based on targeting one organ to improve the health of the other. (shrink)

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging ] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development study. Higher levels of psychopathology and lower (...) levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally—across the cerebral cortex—the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition. (shrink)

Widespread expression of the transcription factor, nuclear factor (erythroid‐derived 2)‐like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy‐induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide‐induced hair growth inhibition. Multiple parameters can increase the levels of reactive (...) oxygen species in the HF, for example melanogenesis, depilation‐induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging‐associated mitochondrial dysfunction. In this review, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox‐associated HF disorders are therefore discussed. (shrink)