Bone Morphogenetic Proteins and Their Antagonists in Skin and Hair Follicle Biology

Bone morphogenetic proteins (BMP) are members of the transforming growth factor-β superfamily regulating a large variety of biologic responses in many different cells and tissues during embryonic development and postnatal life. BMP exert their biologic effects via binding to two types of serine/threonine kinase BMP receptors, activation of which leads to phosphorylation and translocation into the nucleus of intracellular signaling molecules, including Smad1, Smad5, and Smad8 (“canonical” BMP signaling pathway). BMP effects are also mediated by activation of the mitogen-activated protein (MAP) kinase pathway (“noncanonical” BMP Signaling pathway). BMP activity is regulated by diffusible BMP antagonists that prevent BMP interactions with BMP receptors thus modulating BMP effects in tissues. During skin development, BMPs its receptors and antagonists show stringent spatiotemporal expressions patterns to achieve proper regulation of cell proliferation and differentiation in the epidermis and in the hair follicle. In normal postnatal skin, BMP are involved in the control of epidermal homeostasis, hair follicle growth, and melanogenesis. Furthermore, BMP are implicated in a variety of pathobiologic processes in skin, including wound healing, psoriasis, and carcinogenesis. Therefore, BMPs represent new important players in the molecular network regulating homeostasis in normal and diseased skin. Pharmacologic modulation of BMP signaling may be used as a new approach for managing skin and hair disorders

Edar Signaling in the Control of Hair Follicle Development

Ectodysplasin receptor Edar and its ligand Eda A1, as well as their related receptor Xedar and ligand Eda A2, are recently discovered members of the tumor necrosis factor superfamily that signal predominantly through the nuclear factor-κB and c-jun N-terminal kinases pathways. Mutations in genes that encode proteins involved in Edar signaling pathway cause hypohidrotic ectodermal displasias in humans and mice and characterized by severe defects in development of ectodermal appendages including hairs, teeth, and exocrine glands. Here, we summarize the current knowledge of molecular mechanisms underlying the involvement of Edar signaling pathway in controlling hair follicle (HF) development and cycling. Genetic and experimental studies suggest that Edar signaling is involved in the control of cell fate decision in embryonic epidermis, as well as in the regulation of cell differentiation programs in the HF. Loss or gain of Edar signaling affects the initiation of several HF types (guard and zig-zag HF), hair shaft formation, as well as sebaceous gland morphology. We also review data on the cross-talk between Edar and Wnt, transforming growth factor-β/bone morphogenic protein/activin, and Shh signaling pathways in the control of HF development and cycling

Second order Raman spectroscopy of the wurtzite form of GaN

We report on Raman scattering by phonon pairs in GaN films grown on sapphire substrates by plasma‐enhanced molecular beam epitaxy. The first order data are consistent with results obtained from GaN bulk crystals of the wurtzite structure. The A1 and the much weaker E2 symmetry components of the second order scattering have been identified. Two‐phonon spectra are dominated by contributions due to longitudinal optical phonons. © 1995 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70248/2/JAPIAU-77-11-6042-1.pd

Neural Mechanisms of Hair Growth Control

Clinical and experimental observations have long suggested that skin nerves have “trophic” functions in hair follicle development, growth and/or cycling, even though the molecular and cellular basis of the underlying neuroepithelial interactions has remained obscure. Here, we critically review currently available evidence arguing in favor of or against the existence of neural mechanisms of hair growth control, and outline why the murine hair cycle provides an excellent experimental system for characterizing and manipulating piloneural interactions. Summarizing relevant, recent data from the C57BL/6 mouse model, it is pointed out that the sensory and autonomic innervation of normal pelage hair follicles, the substance P skin content, and cutaneous mast cell-nerve contacts show striking changes during synchronized hair follicle cycling. Furthermore, the murine hair follicle appears to be both a source and a target of neurotrophins, whereas neuropharmacologic manipulations alter murine hair follicle cycling in vivo. For example, anagen is induced by substance P or adrenocorticotropin (ACTH), and by the experimentally triggered release of neuropeptides from sensory nerves and of neurotransmitters from adrenergic nerves. Taken together, this argues in favor of neuroepithelial interactions as regulatory elements in hair growth control and suggests that the study of piloneural interactions promises important insights into general principles of neuroepithelial communication, namely during epithelial morphogenesis and remodeling. We delineate a hypothetical working model of piloneural interactions and propose that targeted manipulations deserve systematic exploration as a novel strategy for managing hair growth disorders. Journal of Investigative Dermatology Symposium Proceedings 2:61–68, 199

Ground state of excitons and charged excitons in a quantum well

A variational calculation of the ground state of a neutral exciton and of positively and negatively charged excitons (trions) in single quantum well is presented. We study the dependance of the correlation energy and of the binding energy on the well width and on the hole mass. Our results are are compared with previous theoretical results and with avalaible experimental data.Comment: 8 pages, 5 figures presented to OECS

Hair-Cycle-Associated Remodeling of the Peptidergic Innervation of Murine Skin, and Hair Growth Modulation by Neuropeptides

As the neuropeptide substance P can manipulate murine hair growth in vivo, we here further studied the role of sensory neuropeptides in hair follicle biology by determining the distribution and hair-cycle-dependent remodeling of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-related peptide, substance P, and peptide histidine methionine (employed as vasoactive intestinal peptide marker) were identified by immunohistochemistry. All of these markers immunolocalized to bundles of nerve fibers and to single nerve fibers, with distinct distribution patterns and major hair-cycle-associated changes. In the epidermis and around the distal hair follicle and the arrector pili muscle, only calcitonin-gene-related peptide immunoreactive nerve fibers were visualized, whereas substance P and peptide histidine methionine immunoreactive nerve fibers were largely restricted to the dermis and subcutis. Compared to telogen skin, the number of calcitonin-gene-related peptide, substance P, and peptide histidine methionine immunoreactive single nerve fibers increased significantly (p < 0.01) during anagen, including around the bulge region (the seat of epithelial stem cells). Substance P significantly accelerated anagen progression in murine skin organ culture, whereas calcitonin-gene-related peptide and a substance-P-inhibitory peptide inhibited anagen (p < 0.05). The inhibitory effect of calcitonin-gene-related peptide could be antagonized by coadministrating substance P. In contrast to substance P, calcitonin-gene-related peptide failed to induce anagen when released from subcutaneous implants. This might reflect a differential functional assignment of the neuropeptides calcitonin-gene-related peptide and substance P in hair growth control, and invites the use of neuropeptide receptor agonists and antagonists as novel pharmacologic tools for therapeutic hair growth manipulation

Well-width dependence of the ground level emission of GaN/AlGaN quantum wells

We have performed a systematic investigation of GaN/AlGaN quantum wells grown on different buffer layers (either GaN or AlGaN) in order to clarify the role of strain, structural parameters, and built-in field in determining the well-width dependence of the ground level emission energy. We find that identical quantum wells grown on different buffer layers exhibit strong variation of the ground level energy but similar well-width dependence. The data are quantitatively explained by an analytic model based on the envelope function formalism which accounts for screening and built-in field, and by a full self-consistent tight binding model

Piezoelectric effects on the optical properties of GaN/AlxGa1−xN multiple quantum wells

Piezoelectric effects on the optical properties of GaN/AlGaN multiple quantum wells(MQWs) have been investigated by picosecond time-resolvedphotoluminescence(PL)measurements. For MQWs with well thicknesses 30 and 40 Å, the excitonic transition peak positions at 10 K in continuous wave (cw) spectra are redshifted with respect to the GaN epilayer by 13 and 45 meV, respectively. The time-resolvedPL spectra of the 30 and 40 Å well MQWs reveal that the excitonic transition is in fact blueshifted at early delay times due to quantum confinement of carriers. The spectral peak position shifts toward lower energies as the delay time increases and becomes redshifted at longer delay times. We have demonstrated that the results described above are due to the presence of the piezoelectric field in the GaN wells of GaN/AlGaN MQWs subject to elastic strain together with screening of the photoexcited carriers. By comparing experimental and calculation results, we conclude that the piezoelectric field strength in GaN/Al0.15Ga0.85NMQWs has a lower limit value of about 560 kV/cm. The electron and hole wave function distributions have also been obtained. The implication of our findings on the practical applications of GaN based optoelectronic devices is also discussed

Effect of Ammonia Flow Rate on Impurity incorporation and Material Properties of Si-Doped GaN Epitaxial Films Grown by Reactive Molecular Beam Epitaxy

Effect of ammonia flow rate on the impurity incorporation and material properties of Si-doped GaN films grown by reactive molecular beam epitaxy (RMBE) process is discussed. It appears that the ammonia flow rate has a marginal effect on the incorporation of impurities into the Si-doped GaN films except there was a little decrease in O and Si with increasing ammonia flow rate when the Si concentration in the film is higher than 1018 cm−3. Electron Hall mobility of Si-doped GaN films grown by RMBE varies with ammonia flow rate used during film growth. From deep level transient spectroscopy (DLTS) measurements for Schottky diodes grown with different ammonia flow rates, one deep trap (C1) particular to the RMBE films was found. The concentration of C1 trap was found to be the lowest in the sample grown with the condition leading to the highest electron Hall mobility within the scope of this experiment. In addition to the DLTS result, other characterization techniques used (x-ray diffraction, cross-sectional transmission electron microscopy, and low-temperature photoluminescence) also consistently show that the RMBE process requires certain value of ammonia flow rate (or V/III ratio if the Ga flux is fixed) to produce Si-doped GaN films with high quality

Plasma heating in highly excited GaN/AlGaN multiple quantum wells

Time-resolvedphotoluminescence(PL)spectroscopy was used to investigate carrier distributions in a GaN/AlGaN multiple quantum well(MQW) sample under high excitation intensities necessary to achieve lasing threshold. Room temperaturePL spectra showed optical transitions involving both confined and unconfined states in the quantum well structure. Analysis of the experimental results using a microscopic theory, indicates that at high excitation the carrier distributions are characterized by plasma temperatures which are significantly higher than the lattice temperature. The implications of our findings on GaN MQW laser design are also discussed