Yao Huang

Background: Pulsed dye laser is a commonly utilized treatment for port wine stain birthmarks in the United States; however, results are variable and few patients achieve complete removal. Photodynamic therapy is commonly used in China, but treatment associated photosensitivity lasts several weeks and scarring may occur. We propose an alternative treatment option, combined PDT + PDL and performed a proof-of-concept preliminary clinical trial. Methods: Subjects with non-facial PWS were studied. Each subject had four test sites: control, PDL alone, PDT alone, and PDT + PDL. Radiant exposure time for PDT was increased in increments of 15 J/cm2. Authors evaluated photographs and chromametric measurements before and 12 weeks post-treatment. Results: No serious adverse events were reported; epidermal changes were mild and self-limited. No clinical blanching was noted in control or PDT-alone sites. At PDT radiant exposures of 15 and 30 J/cm2, equivalent purpura and blanching was observed at PDL and PDT + PDL sites. At PDT radiant exposures over 30 J/cm2, greater purpura was noted at PDT + PDL sites as compared to PDL alone. Starting at 75 J/cm2, improved blanching was noted at PDT + PDL sites. Conclusions: Preliminary results indicate that PDT + PDL is safe and may offer improved PWS treatment efficacy. Additional studies are warranted. © 2009 Elsevier B.V. All rights reserved.

Due to their unique properties, copper-based nanopesticides are emerging in the market. Thus, understanding their effect on crop plants is very important. Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. We selected maize and cucumber as model plants for exposure to different doses of Cu2 nanopesticide. GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. Results revealed significant differences in metabolite profile changes between maize and cucumber. Furthermore, the Cu2 nanopesticide induced metabolic reprogramming in both species, but in different manners. In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle were up-regulated, indicating the energy metabolism was activated. In addition, the levels of aromatic compounds and their precursors were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu2 nanopesticide. Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor.

To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data.We recovered a highly resolved tree that confirms previously controversial sister or close relationships.We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.

Apolipoprotein E4 is the major genetic risk factor for Alzheimer's disease. ApoE4 has sex-dependent effects, whereby the risk of developing AD is higher in apoE4-expressing females than males. However, the mechanism underlying the sex difference, in relation to apoE4, is unknown. Previous findings indicate that apoE4 causes age-dependent impairments of hilar GABAergic interneurons in female mice, leading to learning and memory deficits. Here, we investigate whether the detrimental effects of apoE4 on hilar GABAergic interneurons are sex-dependent using apoE knock-in mice across different ages. We found that in female apoE-KI mice, there was an age-dependent depletion of hilar GABAergic interneurons, whereby GAD67- or somatostatin-positive-but not NPY- or parvalbumin-positive-interneuron loss was exacerbated by apoE4. Loss of these neuronal populations was correlated with the severity of spatial learning deficits at 16 months of age in female apoE4-KI mice; however, this effect was not observed in female apoE3-KI mice. In contrast, we found an increase in the numbers of hilar GABAergic interneurons with advancing age in male apoE-KI mice, regardless of apoE genotype. Moreover, male apoE-KI mice showed a consistent ratio of hilar inhibitory GABAergic interneurons to excitatory mossy cells approximating 1.5 that is independent of apoE genotype and age, whereas female apoE-KI mice exhibited an age-dependent decrease in this ratio, which was exacerbated by apoE4. Interestingly, there are no apoE genotype effects on GABAergic interneurons in the CA1 and CA3 subregions of the hippocampus as well as the entorhinal and auditory cortexes. These findings suggest that the sex-dependent effects of apoE4 on developing AD is in part attributable to inherent sex-based differences in the numbers of hilar GABAergic interneurons, which is further modulated by apoE genotype. © 2012 Leung et al.

Apolipoprotein E4 is the leading genetic risk factor for Alzheimer's disease, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin and mushroom spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase -apoE4 and apoE4-knockin mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein -apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4. © 2013 Jain et al.

© 2016 American Chemical Society.Layered transition metal chalcogenides with large spin orbit coupling have recently sparked much interest due to their potential applications for electronic, optoelectronic, spintronics, and valleytronics. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS2 remains controversial. Here, using angle-resolved photoemission spectroscopy with submicron spatial resolution, we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS2, WS2, and WSe2, as well as the thickness dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications.

Background: Pulsed dye laser is the gold standard for treatment of port-wine stain birthmarks but multiple treatments are required and complete resolution is often not achieved. Posttreatment vessel recurrence is thought to be a factor that limits efficacy of PDL treatment of PWS. Imiquimod 5% cream is an immunomodulator with antiangiogenic effects. Objective: We sought to determine if application of imiquimod 5% cream after PDL improves treatment outcome. Methods: Healthy individuals with PWS were treated with PDL and then randomized to apply posttreatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements for 57 PWS sites were taken at baseline and compared with measurements taken 8 weeks posttreatment. The Δa and ΔE were measured to quantify treatment outcome. Results: Two patients developed minor skin irritation. Other adverse effects were not noted. Average a was 0.43 for PDL + placebo sites and 1.27 for PDL + imiquimod sites indicating a greater reduction in erythema with imiquimod. Average E was 2.59 for PDL + placebo and 4.08 for PDL + imiquimod, again indicating a greater color improvement with imiquimod. Limitations: Effects were evaluated after a single treatment and duration of effect is unknown. Conclusion: Combined selective photothermolysis and antiangiogenic therapy may enhance PWS treatment efficacy. © 2011 by the American Academy of Dermatology, Inc.

Background and Objective: During laser therapy of port wine stain birthmarks, regions of perfusionmay persist. We hypothesize that such regions are not readily observable even when laser surgery is performed by highly experienced clinicians. The objective of this study was to use objective feedback to assess the acute vascular response to laser therapy. Study Design/Materials and Methods: A clinic-friendly laser speckle imaging instrument was developed to provide the clinician with real-time images of blood flow during laser therapy. Images were acquired from patients undergoing laser therapy of PWS birthmarks at Scripps Clinic and the Beckman Laser Institute and Medical Clinic. Blood flow maps were extracted from the acquired imaging data. Histogram-based analysis was applied in grading the degree of heterogeneity present in the blood flow maps after laser therapy. Results: Collectively, two types of patient responses were observed in response to laser exposure: an immediate increase in perfusion within minutes after laser therapy; and an overall decrease in blood perfusion ∼1 hour after laser therapy, with distinct regions of persistent perfusion apparent in the majority of post-treatment blood-flow images. A comparison of blood flow in PWS and adjacent normal skin demonstrated that PWS blood flow can be greater than, or sometimes equivalent to, that of normal skin. Conclusion: In general, a decrease in skin perfusion is observed during pulsed laser therapy of PWS birthmarks. However, a heterogeneous perfusion map was frequently observed. These regions of persistent perfusion may be due to incomplete photocoagulation of the targeted vessels. We hypothesize that immediate retreatment of these regions identified with LSI, will result in enhanced removal of the PWS vasculature. © 2009 Wiley-Liss, Inc.