Lipoxygenase (LOX)-catalyzed oxidation of the essential fatty acid, linoleate, represents a vital step in construction of the mammalian epidermal permeability barrier. Analysis of epidermal lipids indicates that linoleate is converted to a trihydroxy derivative by hydrolysis of an epoxy-hydroxy precursor. We evaluated different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and compared the products to those of acid-catalyzed hydrolysis. In the absence of enzyme, exposure to pH 5 or pH 6 at 37°C for 30 min hydrolyzed fatty acid allylic epoxyalcohols to four trihydroxy products. By contrast, human soluble EH [sEH (EPHX2)] and human or murine epoxide hydrolase-3 [EH3 (EPHX3)] hydrolyzed cis or trans allylic epoxides to single diastereomers, identical to the major isomers detected in epidermis. Microsomal EH [mEH (EPHX1)] was inactive with these substrates. At low substrate concentrations (<10 μM), EPHX2 hydrolyzed 14,15-epoxyeicosatrienoic acid (EET) at twice the rate of the epidermal epoxyalcohol, 9R,10R-trans-epoxy-11E-13R-hydroxy-octadecenoic acid, whereas human or murine EPHX3 hydrolyzed the allylic epoxyalcohol at 31-fold and 39-fold higher rates, respectively. These data implicate the activities of EPHX2 and EPHX3 in production of the linoleate triols detected as end products of the 12R-LOX pathway in the epidermis and implicate their functioning in formation of the mammalian water permeability barrier.

The corneocyte lipid envelope (CLE), a monolayer of ω-hydroxyceramides whose function(s) remain(s) uncertain, is absent in patients with autosomal recessive congenital ichthyoses with mutations in enzymes that regulate epidermal lipid synthesis. Secreted lipids fail to transform into lamellar membranes in certain autosomal recessive congenital ichthyosis epidermis, suggesting the CLE provides a scaffold for the extracellular lamellae. However, because cornified envelopes are attenuated in these autosomal recessive congenital ichthyoses, the CLE may also provide a scaffold for subjacent cornified envelope formation, evidenced by restoration of cornified envelopes after CLE rescue. We provide multiple lines of evidence that the CLE originates as lamellar body-limiting membranes fuse with the plasma membrane: (i) ABCA12 patients and Abca12^-/- mice display normal CLEs; (ii) CLEs are normal in Netherton syndrome, despite destruction of secreted LB contents; (iii) CLEs are absent in VSP33B-negative patients; (iv) limiting membranes of lamellar bodies are defective in lipid-synthetic autosomal recessive congenital ichthyoses; and (v) lipoxygenases, lipase activity, and LIPN co-localize within putative lamellar bodies.

The corneocyte lipid envelope (CLE), a monolayer of ω-hydroxyceramides whose function(s) remain(s) uncertain, is absent in patients with autosomal recessive congenital ichthyoses with mutations in enzymes that regulate epidermal lipid synthesis. Secreted lipids fail to transform into lamellar membranes in certain autosomal recessive congenital ichthyosis epidermis, suggesting the CLE provides a scaffold for the extracellular lamellae. However, because cornified envelopes are attenuated in these autosomal recessive congenital ichthyoses, the CLE may also provide a scaffold for subjacent cornified envelope formation, evidenced by restoration of cornified envelopes after CLE rescue. We provide multiple lines of evidence that the CLE originates as lamellar body-limiting membranes fuse with the plasma membrane: (i) ABCA12 patients and Abca12^-/- mice display normal CLEs; (ii) CLEs are normal in Netherton syndrome, despite destruction of secreted LB contents; (iii) CLEs are absent in VSP33B-negative patients; (iv) limiting membranes of lamellar bodies are defective in lipid-synthetic autosomal recessive congenital ichthyoses; and (v) lipoxygenases, lipase activity, and LIPN co-localize within putative lamellar bodies.

In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.

Background: Measurements of exclusive meson production are a useful tool in the study of hadronic structure. In particular, one can discern the relevant degrees of freedom at different distance scales through these studies. Purpose: To study the transition between nonperturbative and perturbative quantum chromodynamics as the square of four-momentum transfer to the struck proton, -t, is increased. Method: Cross sections for the H1(e,e′π+)n reaction were measured over the -t range of 0.272 to 2.127 GeV2 with limited azimuthal coverage at fixed beam energy of 4.709 GeV, Q2 of 2.4 GeV2, and W of 2.0 GeV at the Thomas Jefferson National Accelerator Facility (JLab) Hall C. Results: The -t dependence of the measured π+ electroproduction cross section generally agrees with prior data from JLab Halls B and C. The data are consistent with a Regge amplitude-based theoretical model but show poor agreement with a generalized parton distribution-based model. Conclusion: The agreement of cross sections with prior data implies small contribution from the interference terms, and the confirmation of the change in t slopes between the low- and high - t regions previously observed in photoproduction indicates the changing nature of the electroproduction reaction in our kinematic regime.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45  GeV^{2}, at W=2.21  GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45  GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

The H1(e,e′K+)Λ reaction was studied as a function of the Mandelstam variable -t using data from the E01-004 (FPI-2) and E93-018 experiments that were carried out in Hall C at the 6 GeV Jefferson Laboratory. The cross section was fully separated into longitudinal and transverse components, and two interference terms at four-momentum transfers Q2 of 1.00, 1.36, and 2.07GeV2. The kaon form factor was extracted from the longitudinal cross section using the Regge model by Vanderhaeghen et al. [Phys. Rev. C 57, 1454 (1998)PRVCAN0556-281310.1103/PhysRevC.57.1454]. The results establish the method, previously used successfully for pion analyses, for extracting the kaon form factor. Data from 12 GeV Jefferson Laboratory experiments are expected to have sufficient precision to distinguish between theoretical predictions, for example, recent perturbative QCD calculations with modern parton distribution amplitudes. The leading-twist behavior for light mesons is predicted to set in for values of Q2 between 5 and 10GeV2, which makes data in the few-GeV regime particularly interesting. The Q2 dependence at fixed x and -t of the longitudinal cross section that we extracted seems consistent with the QCD factorization prediction within the experimental uncertainty.

The GEp-III and GEp-2γ experiments, carried out in Jefferson Lab's Hall C from 2007–2008, consisted of measurements of polarization transfer in elastic electron–proton scattering at momentum transfers of Q2=2.5,5.2,6.8, and 8.54 GeV 2. These measurements were carried out to improve knowledge of the proton electromagnetic form factor ratio R=μpGEp∕GMp at large values of Q2 and to search for effects beyond the Born approximation in polarization transfer observables at Q2=2.5GeV2. The final results of both experiments were reported in a recent archival publication. A full reanalysis of the data from both experiments was carried out in order to reduce the systematic and, for the GEp-2γ experiment, statistical uncertainties. This technical note provides additional details of the final analysis omitted from the main publication, including the final evaluation of the systematic uncertainties.