Z-shaped polycyclic aromatic hydrocarbons with embedded five-membered rings and their application in organic thin-film transistors

Z-shaped polycyclic hydrocarbons with embedded five-membered rings as well as their diaza-analogues have been synthesized. Soluble congeners were obtained by the introduction of mesityl substituents and studied by cyclo- as well as differential pulse voltammetry revealing an amphoteric redox behavior. Unsubstituted congeners showed close π-stacking in single crystal X-ray diffraction analyses and thus promising characteristics for the application as semiconducting materials in p-channel thin-film transistors (TFTs). The hole transport characteristics of the corresponding devices were investigated by GIWAXS

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts

Background: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86, 467) and EPA +DHA (n = 62, 265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13

Do Hair Bulb Melanocytes Undergo Apotosis During Hair Follicle Regression (Catagen)?

The fate of the hair follicle pigmentary unit during the cyclical involution of anagen hair follicles is unknown. Using the C57BL/6 mouse model for hair research, hair follicle melanocytes were examined during the anagen–catagen transformation, comparing spontaneous and pharmacologically induced catagen development. This study shows that both spontaneous catagen and dexamethasone-induced catagen display similar changes in the pigmentary unit. Catagen hair follicles exhibited pigment incontinence in the dermal papilla and in selected outer root sheath keratinocytes. Melanocytes deleted by apoptosis were detected in spontaneous catagen and, more commonly, in dexamethasone-induced catagen, and were identified using transmission electron microscopy by the presence of free premelanosomes in affected cells lacking epithelial specializations, and by the colocalization of TUNEL positivity and tyrosinase-related protein-1 immunoreactivity. By contrast, cyclophosphamide-induced catagen was characterized by the initial retention of melanogenic and dendritic melanocytes in the presence of widespread keratinocyte apoptosis. Melanocyte incontinence and the ectopic distribution of melanin were more severe than in the other forms of catagen. Whereas much of this melanin was extruded, via the hair canal, to the skin surface, hair follicle-derived pigment was also detected within the epidermis, probably derived from pigment-carrying migrating outer root sheath keratinocytes from the proximal hair follicle. Thus, apoptosis may account, at least in part, for the loss of melanogenic melanocytes during spontaneous catagen. Although dexamethasone-induced catagen may provide a useful model for general hair pigmentation research, catagen induced by cyclophosphamide offers an interesting model for studying the response, and relative resistance, of melanocytes to chemical injury

Indications for a brain‐hair follicle axis: inhibition of keratinocyte proliferation and up‐regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P

ABSTRACT It has long been suspected that stress can cause hair loss, although convincing evidence of this has been unavailable. Here, we show that in mice sonic stress significantly increased the number of hair follicles containing apoptotic cells and inhibited intrafollicular keratinocyte proliferation in situ. Sonic stress also significantly increased the number of activated perifollicular macrophage clusters and the number of degranulated mast cells, whereas it down‐regulated the number of intraepithelial γδ T lymphocytes. These stress‐induced immune changes could be mimicked by injection of the neuropeptide substance P in nonstressed mice and were abrogated by a selective substance P receptor antagonist in stressed mice. We conclude that stress can indeed inhibit hair growth in vivo, probably via a substance P‐dependent activation of macrophages and/or mast cells in the context of a brain‐hair follicle axis

Is there a 'gut-brain-skin axis'?

Emerging evidence arising from interdisciplinary research supports the occurrence of communication axes between organs, such as the brain-gut or brain-skin axis. The latter is employed in response to stress challenge, along which neurogenic skin inflammation and hair growth inhibition is mediated. We now show that ingestion of a Lactobacillus strain in mice dampens stress-induced neurogenic skin inflammation and the hair growth inhibition. In conclusion, we are introducing a hypothesis, encouraged by our pilot observations and resting upon published prior evidence from the literature, which amalgamates previously proposed partial concepts into a new, unifying model, i.e. the gut-brain-skin axis. This concept suggests that modulation of the microbiome by deployment of probiotics can not only greatly reduce stress-induced neurogenic skin inflammation but even affect a very complex cutaneous phenomenon of (mini-) organ transformation, i.e. hair follicle cycling. These observations raise the intriguing prospect that feeding of just the right kind of bacteria can exert profound beneficial effects on skin homoeostasis, skin inflammation, hair growth and peripheral tissue responses to perceived stress

Probing the Effects of Stress Mediators on the Human Hair Follicle Substance P Holds Central Position

Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and β2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata

Generation and Cyclic Remodeling of the Hair Follicle Immune System in Mice

In this immunohistomorphometric study, we have defined basic characteristics of the hair follicle (HF) immune system during follicle morphogenesis and cycling in C57BL/6 mice, in relation to the skin immune system. Langerhans cells and γδ T cell receptor immunoreactive lymphocytes were the predominant intraepithelial hematopoietic cells in neonatal mouse skin. After their numeric increase in the epidermis, these cells migrated into the HF, although only when follicle morphogenesis was almost completed. In contrast to Langerhans cells, γδ T cell receptor immunoreactive lymphocytes entered the HF only via the epidermis. Throughout HF morphogenesis and cycling, both cell types remained strikingly restricted to the distal outer root sheath. On extremely rare occasions, CD4+ or CD8+αβTC were detected within the HF epithelium or the sebaceous gland. Major histocompatibility complex class II+, MAC-1+ cells of macrophage phenotype and numerous mast cells appeared very early on during HF development in the perifollicular dermis, and the percentage of degranulated mast cells significantly increased during the initiation of synchronized HF cycling (first catagen). During both depilation- and cyclosporine A-induced HF cycling, the numbers of intrafollicular Langerhans cells, γδ T cell receptor immunoreactive lymphocytes, and perifollicular dermal macrophages fluctuated significantly. Yet, no numeric increase of perifollicular macrophages was detectable during HF regression, questioning their proposed role in catagen induction. In summary, the HF immune system is generated fairly late during follicle development, shows striking differences to the extrafollicular skin immune system, and undergoes substantial hair cycle-associated remodeling. In addition, synchronized HF cycling is accompanied by profound alterations of the skin immune system