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At a time when scientific knowledge is rapidly growing within a multitude of subspecialties, it is difficult to remain familiar with the language, techniques, and relevance of all available research approaches. Still, a common language is essential for successful translational and team research. Having recently moved to Amsterdam (The Netherlands), I am acutely aware that communicating effectively is not like riding a bicycle. That is, communicating successfully once does not guarantee mastery for all time.
In vivo cell reprogramming offers a way to ameliorate or correct genetic defects in tissues without the need for in vitro manipulation. Until now, most reprogramming methods have relied on viral transfection, with its associated safety concerns and other challenges. Gallego-Perez and colleagues reported a novel, non-viral, nano-transfection approach to topically reprogram tissues using a nanochannelled device. These investigators demonstrated that not only does tissue nano-transfection deliver reprogramming factors (Etv2, Foxc2, and Fli1) into the skin rapidly and non-invasively, but that this technique also can reprogram skin fibroblasts into neurons and endothelial cells.
The aim of this study was to explore the impact of wearing a melanoma tattoo on medical students’ understanding of patienthood and the attitudes towards patients with melanoma. To achieve this, 10 fourth-year medical students were recruited to a simulation. They wore a melanoma tattoo for 24 h and listened to a patient’s account of receiving their diagnosis. Data were captured using audio diaries and face-to-face interviews, transcribed and analysed using the template analysis method. Four themes emerged.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz— In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
Eigentler and colleagues reported the findings of a prospective study of risk factors for tumor-specific and overall survival in 1,434 patients diagnosed with cutaneous squamous cell carcinomas (SCC). The 3-year overall and disease-specific survival rates in this cohort were 65.7% and 95.3%, respectively. The investigators found that a tumor thicknesses of ≥6 mm, desmoplastic growth, and immunosuppressed status identified patients at risk for low SCC tumor-specific survival. These investigators recommended inclusion of these factors in the next revision of TNM classification for skin tumors.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz— In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
According to Malcolm Gladwell (2000), author of The Tipping Point, “Connectors [are] people with a special gift for bringing the world together….” We all know these people, and they just seem to initiate contacts among individuals or groups that build new, and oftentimes lasting social and professional networks. It is therefore fitting that one of the quintessential “Connectors” in investigative dermatology, Barbara Gilchrest, created the JID Connector at the beginning of her tenure as JID Editor on the 75th anniversary of the JID in 2012.
Classical biochemical techniques have contributed a great deal to our understanding of the mechanisms regulating fundamental biological processes. However, these approaches are typically end-point, population-based assays and are often insufficient in examining transient molecular events. Förster resonance energy transfer (FRET) microscopy is a powerful technique capable of investigating dynamic interactions between proteins and a plethora of biochemical signaling events based on the development of specific biosensors.
Deletion of late cornified envelope (LCE) genes LCE3B and LCE3C (LCE3B/C-del) is a psoriasis risk factor linked to the major psoriasis risk gene HLA-C*06. Niehues et al. demonstrate that LCE3B/C-del leads to increased keratinocyte LCE3A expression. They also show that LCE3A/B/C possess antimicrobial activity but do not obviously regulate epidermal barrier integrity. These findings implicate LCE proteins in psoriasis pathogenesis via a new functional role.
Using a novel mouse model of scleroderma induced by immunization with topoisomerase-I peptide-loaded dendritic cells, Mehta et al. found that early-life antibiotic exposure resulted in increased later-life fibrosis in the skin and lungs. These observations advance the novel concept that gut microbiome alterations caused by early-life exposures may contribute to scleroderma pathogenesis, and warrant in-depth characterization and validation in complementary disease models.
Through coordinated and reciprocal interactions between the epithelium and mesenchyme, diverse integumentary organs form and undergo cyclic renewal. The hair follicle has become the main model to understand this extraordinary regenerative behavior. At the core is the dermal papilla, the organizing center, and the epithelial stem cells that respond to dermal papilla signaling. Two recent papers by Telerman et al. and Yang et al. unravel new molecular landscapes within the dermal papilla.
Pemphigus vulgaris is an autoimmune blistering disease caused by anti-desmoglein 3 IgG autoantibodies. It is accepted that interactions between autoreactive B and T cells are key to humoral autoimmunity targeting desmoglein 3. This orchestrated process usually occurs in secondary lymphoid organs, including the spleen and lymph nodes. Thus, it seems likely that autoreactive B cells reside and produce autoantibodies in these tissues. Yuan et al. analyzed lymphocytes in the lesional skin of patients with pemphigus vulgaris using several experimental techniques and concluded that desmoglein 3-reactive B cells were present.
Sensing environmental temperature is a key factor allowing individuals to maintain thermal homeostasis via thermoregulatory mechanisms, including changes to skin blood flow. Among transient receptor potential (TRP) channels, TRPV3 is a heat-activated cation channel highly expressed in keratinocytes. However, the role of TRPV3 in triggering heat-evoked cutaneous vasodilation is unknown. Using a murine in vivo model of local acute environmental heat exposure in the skin, we show that TRPV3 is involved in the local thermoregulatory control of skin blood flow by initiating the release of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in response to local heating of the skin.
Nowadays, there is no available vaccine for human leishmaniasis. Animal experiments demonstrate that pre-exposure to sand fly saliva confers protection against leishmaniasis. Our preceding work in humans indicates that Phlebotomus (P) papatasi saliva, induce the production of IL-10 by CD8+ T lymphocytes. The neutralization of IL-10 enhanced the activation of a T cells CD4+ population producing IFN-γ. Herein, we used a biochemical and functional genomics approach to identify the sand fly salivary components that are responsible for the activation of the Th1 immune response in humans therefore constituting potential vaccine candidates against leishmaniasis.
Vitiligo repigmentation is a complex process in which the melanocyte-depleted interfollicular epidermis (IE) is repopulated by melanocyte precursors from hair follicle (HF) bulge that proliferate, migrate, and differentiate into mature melanocytes on their way to the epidermis. The strongest stimulus for vitiligo repigmentation is narrow band UVB (NBUVB), but how the HF melanocyte precursors are activated by UV light has not been extensively studied. To better understand this process, we developed an application that combined laser capture microdissection and subsequent whole transcriptome RNA sequencing of HF bulge melanocyte precursors, and compared their gene signature to that of regenerated mature epidermal melanocytes from the NBUVB-treated vitiligo skin.
The melanosome pattern was characterized systematically in keratinocytes in situ in highly, moderately and lightly pigmented human skin, classified according to their Individual Typological Angle (ITA), a colorimetric measure of skin color phenotype. Electron microscopy of skin samples revealed qualitatively and quantitatively that in highly pigmented skin, although melanosomes are mostly isolated and distributed throughout the entire epidermis, clusters are also observed in the basal layer. In moderately and lightly pigmented skin, melanosomes are concentrated in the first layer of the epidermis, isolated but for most of them, grouped as clusters of melanocores delimited by a single membrane.