Search

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

The retinae of treeshrew have never been evaluated by scanning electron microscopic studies. This work described the visual cells in the photoreceptor layer of the retinae of treeshrew (Tupaia belangeri chinensis) living on the high plateau of Yunnan, China, via scanning electron microscopy. Results indicated five different types of cones morphologically, in which two of those have shown oil droplet like structures in their inner segments. To our knowledge, no prior studies have reported oil droplets in the visual cells of higher mammals, only in lower vertebrate and primitive mammals. In addition, this study revealed one type of degenerative visual cell without outer segments. The findings signal the needs for additional studies to understand the physiological functions and phylogenetic relationships of the diversity of visual cells in this group of mammal. [ABSTRACT FROM AUTHOR]

We present multitracer dynamical models of the low-mass (M * ∼ 107), isolated dwarf irregular galaxy WLM in order to simultaneously constrain the inner slope of the dark matter (DM) halo density profile (γ) and flattening (q DM), and the stellar orbital anisotropy (β z , β r ). For the first time, we show how jointly constraining the mass distribution from the H  i gas rotation curve and solving the Jeans equations with discrete stellar kinematics lead to a factor of ∼2 reduction in the uncertainties on γ. The mass-anisotropy degeneracy is also partially broken, leading to reductions on uncertainty by |${\sim} 30{{\ \rm per\ cent}}$| on M vir (and |${\sim} 70{{\ \rm per\ cent}}$| at the half-light radius) and |${\sim} 25{{\ \rm per\ cent}}$| on anisotropy. Our inferred value of γ = 0.3 ± 0.1 is robust to the halo geometry, and in excellent agreement with predictions of stellar feedback-driven DM core creation. The derived prolate geometry of the DM halo with q DM = 2 ± 1 is consistent with Lambda cold dark matter simulations of dwarf galaxy haloes. While self-interacting DM (SIDM) models with σ/ m X ∼ 0.6 can reproduce this cored DM profile, the interaction events may sphericalize the halo. The simultaneously cored and prolate DM halo may therefore present a challenge for SIDM. Finally, we find that the radial profile of stellar anisotropy in WLM (β r ) follows a nearly identical trend of increasing tangential anisotropy to the classical dwarf spheroidals, Fornax and Sculptor. Given WLM's orbital history, this result may call into question whether such anisotropy is a consequence of tidal stripping in only one pericentric passage or if it instead is a feature of the largely self-similar formation and evolutionary pathways for some dwarf galaxies. [ABSTRACT FROM AUTHOR]

The five globular clusters (GCs) of the Fornax dwarf spheroidal galaxy are puzzling for two reasons; the mass in GCs is high with respect to the galaxy's old stellar mass and their survival and large distance (>1 kpc) is at odds with naive expectations of dynamical friction. We present here a semi-analytic model, simultaneously addressing both problems in a comprehensive evolutionary framework for Fornax. Key to the model is inclusion of: (1) hydrodynamical constraints on the GC formation locations, (2) self-consistent velocity distribution functions in the dynamical friction calculations, and (3) expansion of GC orbits due to a past dwarf–dwarf merger in the orbit integrations. The latter is crucial for reconciling the dynamical survival of the clusters and their chemical properties with respect to the Fornax field stars. We find that in order for four of the GCs to survive at their observed projected location, a dark matter core of size r c > 1.5 kpc and a dwarf merger with dynamical mass ratio of 1:5 ≤ η ≤ 1:2 with Fornax is required. We support the merger scenario by showing that aspects of the field star metallicity distribution function and anomalous chemical properties of GC5, are representative of a merging galaxy which is ∼1/3 less massive than Fornax. Together the chemical and dynamical models suggest a scenario where three in situ GCs in proto-Fornax were ejected to the outskirts during the merger, a GC4 formed during the merger at about 10 Gyr ago, with GC5 being brought in by the merging galaxy to Fornax. [ABSTRACT FROM AUTHOR]

The Time Inference with MUSE in Extragalactic Rings (TIMER) project is a survey with the VLT–MUSE integral-field spectrograph of 24 nearby barred galaxies with prominent central structures (e.g. nuclear rings or inner discs). The main goals of the project are: (i) estimating the cosmic epoch when discs of galaxies settle, leading to the formation of bars; (ii) testing the hypothesis whereby discs in more massive galaxies are assembled first; and (iii) characterizing the history of external gas accretion in disc galaxies. We present details on the sample selection, observations, data reduction, and derivation of high-level data products, including stellar kinematics, ages, and metallicities. We also derive star formation histories and physical properties and kinematics of ionized gas. We illustrate how this data set can be used for a plethora of scientific applications, e.g. stellar feedback, outflows, nuclear and primary bars, stellar migration and chemical enrichment, and the gaseous and stellar dynamics of nuclear spiral arms, barlenses, box/peanuts, and bulges. Amongst our first results – based on a few selected galaxies – we show that the dynamics of nuclear rings and inner discs is consistent with the picture in which they are formed by bars, that the central few hundred parsecs in massive disc galaxies tend to show a pronounced peak in stellar metallicity, and that nuclear rings can efficiently prevent star formation in this region. Finally, we present evidence that starbursting nuclear rings can be fed with low-metallicity gas from low-mass companions. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a common autoimmune disorder affecting millions of people worldwide, which manifests as a sudden, non-scarring hair loss. The expression of a pro-inflammatory cytokine, interferon-gamma (INF-γ), has been well established to be involved in the development of AA. As IFN-γ and other cytokines are also known to up-regulate programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), which both negatively control immune responses, we asked whether or not a high number of infiltrated T cells, seen in AA lesions, can modulate the expression of PD-L1 and PD-L2 in skin cells. From a series of experiments, we showed that a significantly higher number of PD-L1 or PD-L2 positive cells affect the skin in AA mice, compared to the skin of non-AA mice. The number of PD-L1 positive cells was well correlated with the number of infiltrated T cells, especially CD8+ T cells. We also found that the expression of PD-L1 and PD-L2 was co-localized with type 1 pro-collagen, CD90 and vimentin, which are biomarkers for dermal fibroblasts. Further studies revealed that releasable factors from activated, but not inactivated, lymphocytes significantly increase the expressions of both PD-L1 and PD-L2 in cultured dermal fibroblasts. In conclusion, our findings suggest that the expression of PD-L1 and PD-L2 in dermal fibroblasts is up-regulated by activated T cells in AA-affected skin, and as such, these regulatory molecules may not exert a negative control of the immune activation seen in AA lesions. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on the alterations in immune privilege-associated gene expression in advance of hair loss from hair follicles among alopecia areata patients in the July 8, 2010 issue.

Aim: To investigate if increased dietary fiber, in terms of kiwifruit, is effective in Chinese constipated patients., Methods: 33 constipated patients and 20 healthy volunteers were recruited for a 4-wk treatment of kiwi fruit twice daily. Response during wk 1-4 was defined as an increase in complete spontaneous bowl, motion (CSBM) > or = 1/wk. Secondary efficacy included response during wk 1-4, individual symptoms and scores of bowel habits and constipation. Responses were compared with the baseline run-in period. Colonic transit time and anorectal manometry were performed before and after treatment., Results: Responder rate was 54.5% in the constipated group. The mean CSBM increased after treatment (2.2 +/- 2.6 vs 4.4 +/- 4.6, P = 0.013). There was also improvement in the scores for bothersomeness of constipation (P = 0.02), and satisfaction of bowel habit (P = 0.001), and decreased in days of laxative used (P = 0.003). There was also improvement in transit time (P = 0.003) and rectal sensation (P < 0.05). However, there was no change in the bowel symptoms or anorectal physiology in the healthy subjects., Conclusion: Increasing dietary fiber intake is effective in relieving chronic constipation in Chinese population.