Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

Genetic Rodent Models of Huntington Disease.

The monogenic nature of Huntington disease (HD) has led to the development of a spectrum of useful genetically modified models. In particular, rodents have pioneered as the first HD model being generated and have since been the most widely used animal model for HD in both basic research and preclinical therapeutic studies. Based on the generation strategies, these rodent models can be classified into 3 major groups, the transgenic fragment models, the transgenic full-length models and the knock-in models. These models display a range of HD-like characteristics which resemble the clinical symptoms of HD patients. Their applications in research are thus regarded as an invaluable approach to speeding up the unraveling of the underlying pathological mechanisms of HD and for finding a disease-modifying treatment for this devastating disease. In this chapter, the similarities and differences of the most commonly used rodent HD models and their relevance to human HD will be compared and discussed. This also serves to guide the selection of an appropriate rodent HD model according to the nature of investigation.

Shape control and compartmentalization in active colloidal cells.

Small autonomous machines like biological cells or soft robots can convert energy input into control of function and form. It is desired that this behavior emerges spontaneously and can be easily switched over time. For this purpose we introduce an active matter system that is loosely inspired by biology and which we term an active colloidal cell. The active colloidal cell consists of a boundary and a fluid interior, both of which are built from identical rotating spinners whose activity creates convective flows. Similarly to biological cell motility, which is driven by cytoskeletal components spread throughout the entire volume of the cell, active colloidal cells are characterized by highly distributed energy conversion. We demonstrate that we can control the shape of the active colloidal cell and drive compartmentalization by varying the details of the boundary (hard vs. flexible) and the character of the spinners (passive vs. active). We report buckling of the boundary controlled by the pattern of boundary activity, as well as formation of core-shell and inverted Janus phase-separated configurations within the active cell interior. As the cell size is increased, the inverted Janus configuration spontaneously breaks its mirror symmetry. The result is a bubble-crescent configuration, which alternates between two degenerate states over time and exhibits collective migration of the fluid along the boundary. Our results are obtained using microscopic, non-momentum-conserving Langevin dynamics simulations and verified via a phase-field continuum model coupled to a Navier-Stokes equation.

Molecular insight into the viral biology and clinical features of trichodysplasia spinulosa.

Trichodysplasia spinulosa (TS) is a disfiguring skin disease that occurs most frequently in patients receiving immunosuppressive therapies, and is thus frequently associated with organ transplantation. TS is characterized clinically by folliculocentric papular eruption, keratin spine formation and development of leonine face; and histologically by expansion of the inner root sheath epithelium and high expression of the proliferative marker Ki-67. Recent discovery of the TS-associated polyomavirus (TSPyV) and emerging studies demonstrating the role of TSPyV tumour antigens in cell proliferation pathways have opened a new corridor for research on TS. In this brief review, we summarize the clinical and histological features of TS and evaluate the current options for therapy. Furthermore, we address the viral aetiology of the disease and explore the mechanisms by which TSPyV may influence TS development and progression. As reports of TS continue to rise, clinician recognition of TS, as well as accompanying research on its underlying pathogenesis and therapeutic options, is becoming increasingly important. It is our hope that heightened clinical suspicion for TS will increase rates of diagnosis and will galvanize both molecular and clinical interest in this disease.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

Alternating-Current InGaN/GaN Tunnel Junction Nanowire White-Light Emitting Diodes.

The current LED lighting technology relies on the use of a driver to convert alternating current (AC) to low-voltage direct current (DC) power, a resistive p-GaN contact layer to inject positive charge carriers (holes) for blue light emission, and rare-earth doped phosphors to down-convert blue photons into green/red light, which have been identified as some of the major factors limiting the device efficiency, light quality, and cost. Here, we show that multiple-active region phosphor-free InGaN nanowire white LEDs connected through a polarization engineered tunnel junction can fundamentally address the afore-described challenges. Such a p-GaN contact-free LED offers the benefit of carrier regeneration, leading to enhanced light intensity and reduced efficiency droop. Moreover, through the monolithic integration of p-GaN up and p-GaN down nanowire LED structures on the same substrate, we have demonstrated, for the first time, AC operated LEDs on a Si platform, which can operate efficiently in both polarities (positive and negative) of applied voltage.

Sugar Sag: Glycation and the Role of Diet in Aging Skin.

First described in the context of diabetes, advanced glycation end products (AGEs) are formed through a type of non-enzymatic reaction called glycation. Increased accumulation of AGEs in human tissue has now been associated with end stage renal disease, chronic obstructive pulmonary disease, and, recently, skin aging. Characteristic findings of aging skin, including decreased resistance to mechanical stress, impaired wound healing, and distorted dermal vasculature, can be in part attributable to glycation. Multiple factors mediate cutaneous senescence, and these factors are generally characterized as endogenous (e.g., telomere shortening) or exogenous (e.g., ultraviolet radiation exposure). Interestingly, AGEs exert their pathophysiological effects from both endogenous and exogenous routes. The former entails the consumption of sugar in the diet, which then covalently binds an electron from a donor molecule to form an AGE. The latter process mostly refers to the formation of AGEs through cooking. Recent studies have revealed that certain methods of food preparation (i.e., grilling, frying, and roasting) produce much higher levels of AGEs than water-based cooking methods such as boiling and steaming. Moreover, several dietary compounds have emerged as promising candidates for the inhibition of glycation-mediated aging. In this review, we summarize the evidence supporting the critical role of glycation in skin aging and highlight preliminary studies on dietary strategies that may be able to combat this process.

Emergent collective phenomena in a mixture of hard shapes through active rotation.

We investigate collective phenomena with rotationally driven spinners of concave shape. Each spinner experiences a constant internal torque in either a clockwise or counterclockwise direction. Although the spinners are modeled as hard, otherwise noninteracting rigid bodies, their active motion induces an effective interaction that favors rotation in the same direction. With increasing density and activity, phase separation occurs via spinodal decomposition, as well as self-organization into rotating crystals. We observe the emergence of cooperative, superdiffusive motion along interfaces, which can transport inactive test particles. Our results demonstrate novel phase behavior of actively rotated particles that is not possible with linear propulsion or in nondriven, equilibrium systems of identical hard particles.

Phase behavior of Janus colloids determined by sedimentation equilibrium.

We investigate the phase behavior of short-range interacting isotropic particles and single-patch Janus particles via simulations of sedimentation equilibrium, which allows for a rapid assessment of the equation of state and phase behavior directly from simulation. The methodology is tested against results by traditional methods and is found to yield good agreement for isotropic interactions. The method is then used to study single-patch Janus particles with different interaction strengths and patch sizes with particle area coverage greater than ∼0.63. Our results show an interplay between translational and orientational order. We observe a lamellar phase, a fluid phase and a rotator close-packed structure. The lamellar phase is shown to have a different range of stability than previously observed in simulation studies for systems of similar and longer-ranged interactions.

Improvement of the emission properties from InGaN/GaN dot-in-a-wire nanostructures after treatment in the flowing afterglow of a microwave N2 plasma.

Nominally pure GaN nanowires (NWs) and InGaN/GaN dot-in-a-wire heterostructures were exposed to the flowing afterglow of a N2 microwave plasma and characterized by photoluminescence (PL) spectroscopy. While the band-edge emission from GaN NWs and the GaN matrix of the InGaN/GaN NWs strongly decreased due to the creation of non-radiative recombination centers in the near-surface region, the emission from the InGaN dots strongly increased. PL excitation measurements indicate that such an increase cannot be explained by a plasma-induced shift of the GaN absorption edge. It is rather ascribed to the passivation of grown-in defects and dynamic annealing due to the presence of plasma-generated N atoms and N2 metastables without excessive introduction of ion-induced damage.

Recent approval of Xerese in Canada: 5% acyclovir and 1% hydrocortisone topical cream in the treatment of herpes labialis.

Herpes labialis is a frequently occurring viral infection of the lips and oral mucosa. Recurring lesions are induced by viral reactivation and replication, but the symptoms leading to morbidity, such as pain and inflammation, are immune-mediated. The introduction of 5% acyclovir/1% hydrocortisone in a topical cream (Xerese™) represents a therapeutic strategy directed at both of these pathogenic processes. Applied at the onset of prodromal symptoms, this combination treatment has a good safety profile and is more effective in reducing healing time than antiviral or anti-inflammatory agents alone. Although it was US FDA-approved for herpes labialis in 2009, Xerese™ has only recently been approved for use in Canada in October 2013. Herein, we review the basic science and clinical studies that support the efficacy of this topical combination acyclovir-hydrocortisone product in treating herpes labialis and examine its safety profile, as well as touch upon other therapies that have been shown to be effective in treating this common viral condition.

Highly stable photoelectrochemical water splitting and hydrogen generation using a double-band InGaN/GaN core/shell nanowire photoanode.

We report on the first demonstration of stable photoelectrochemical water splitting and hydrogen generation on a double-band photoanode in acidic solution (hydrogen bromide), which is achieved by InGaN/GaN core/shell nanowire arrays grown on Si substrate using catalyst-free molecular beam epitaxy. The nanowires are doped n-type using Si to reduce the surface depletion region and increase current conduction. Relatively high incident-photon-to-current-conversion efficiency (up to ~27%) is measured under ultraviolet and visible light irradiation. Under simulated sunlight illumination, steady evolution of molecular hydrogen is further demonstrated.

High efficiency photoelectrochemical water splitting and hydrogen generation using GaN nanowire photoelectrode.

We have studied the photoelectrochemical properties of both undoped and Si-doped GaN nanowire arrays in 1 mol l(-1) solutions of hydrogen bromide and potassium bromide, which were used separately as electrolytes. It is observed that variations of the photocurrent with bias voltage depend strongly on the n-type doping in GaN nanowires in both electrolytes, which are analyzed in the context of GaN surface band bending and its variation with the incorporation of Si-doping. Maximum incident-photon-to-current-conversion efficiencies of ~15% and 18% are measured for undoped and Si-doped GaN nanowires under ~350 nm light illumination, respectively. Stable hydrogen generation is also observed at a zero bias potential versus the counter-electrode.

Highly efficient, spectrally pure 340 nm ultraviolet emission from AlxGa1-xN nanowire based light emitting diodes.

High crystal quality, vertically aligned AlxGa1-xN nanowire based double heterojunction light emitting diodes (LEDs) are grown on Si substrate by molecular beam epitaxy. Such AlxGa1-xN nanowires exhibit unique core-shell structures, which can significantly suppress surface nonradiative recombination. We successfully demonstrate highly efficient AlxGa1-xN nanowire array based LEDs operating at ∼340 nm. Such nanowire devices exhibit superior electrical and optical performance, including an internal quantum efficiency of ∼59% at room temperature, a relatively small series resistance, highly stable emission characteristics, and the absence of efficiency droop under pulsed biasing conditions.

Recombination dynamics in InGaN/GaN nanowire heterostructures on Si(111).

We have performed room-temperature time-resolved photoluminescence measurements on samples that comprise InGaN insertions embedded in GaN nanowires. The decay curves reveal non-exponential recombination dynamics that evolve into a power law at long times. We find that the characteristic power-law exponent increases with emission photon energy. The data are analyzed in terms of a model that involves an interplay between a radiative state and a metastable charge-separated state. The agreement between our results and the model points towards an emission dominated by carriers localized on In-rich nanoclusters that form spontaneously inside the InGaN insertions.

p-Type modulation doped InGaN/GaN dot-in-a-wire white-light-emitting diodes monolithically grown on Si(111).

Full-color, catalyst-free InGaN/GaN dot-in-a-wire light-emitting diodes (LEDs) were monolithically grown on Si(111) by molecular beam epitaxy, with the emission characteristics controlled by the dot properties in a single epitaxial growth step. With the use of p-type modulation doping in the dot-in-a-wire heterostructures, we have demonstrated the most efficient phosphor-free white LEDs ever reported, which exhibit an internal quantum efficiency of ∼56.8%, nearly unaltered CIE chromaticity coordinates with increasing injection current, and virtually zero efficiency droop at current densities up to ∼640 A/cm(2). The remarkable performance is attributed to the superior three-dimensional carrier confinement provided by the electronically coupled dot-in-a-wire heterostructures, the nearly defect- and strain-free GaN nanowires, and the significantly enhanced hole transport due to the p-type modulation doping.