As with all metazoans, the fly makes extensive use of selective programmed cell death (PCD) to remove excess cells and properly sculpt developing tissues. Several core components of the cell death machinery have been identified in flies, including caspases and an Apaf-1 ortholog [1] [2] [3] [4]. One missing component has been a member of the Bcl-2 family of proteins, which act either pro- or anti-apoptotically as upstream regulatory proteins. Here, we report the identification of Bcl-2 family members in Drosophila - dBorg-1 (Drosophila Bcl-2 ortholog), also identified by Igaki et al. [5], and dBorg-2. Removal of dBorg-1 function during Drosophila embryonic development resulted in excess glial cells, demonstrating its pro-apoptotic function. In cell culture assays, dBorg-1 efficiently induced apoptosis but, remarkably, also demonstrated protective activity when death stimuli were introduced. Finally, ectopic expression of dBorg-1 in the eye led to subtle defects that were strongly potentiated by ultra violet (UV) irradiation, resulting in a dramatic loss of retinal cells.

Abstract. In several human volunteers, photoacoustic microscopy (PAM) has been utilized for noninvasive cutaneous imaging of the skin microvasculature and a melanocytic nevus. Microvascular networks in both acral and nonacral skin were imaged, and multiple features within the skin have been identified, including the stratum corneum, epidermal-dermal junction, and subpapillary vascular plexus. Several vascular and structural differences between acral and nonacral skin were also observed in the photoacoustic images. In addition, a nevus was photoacoustically imaged, excised, and histologically analyzed. The photoacoustic images allowed for in vivo measurement of tumor thickness, depth, and microvasculature-values confirmed by histologic examination. The presented images demonstrate the potential of PAM to aid in the study and evaluation of cutaneous microcirculation and analysis of pigmented lesions. Through its ability to three-dimensionally image the structure and function of the microvasculature and pigmented lesions, PAM can have a clinical impact in diagnosis and assessment of systemic diseases that affect the microvasculature such as diabetes and cardiovascular disease, cutaneous malignancies such as melanoma, and potentially other skin disorders. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Ultraviolet (UV) light is absorbed by cellular proteins and DNA, promoting skin damage, aging and cancer. In this paper, we explore the UV response by cells of the Drosophila retina. We demonstrate that the retina enters a period of heightened UV sensitivity in the young developing pupa, a stage closely associated with its period of normal developmental programmed cell death. Injury to irradiated cells included morphology changes and apoptotic cell death; these defects could be completely accounted for by DNA damage. Cell death, but not morphological changes, was blocked by the caspase inhibitor P35. Utilizing genetic and microarray data, we provide evidence for the central role of Hid expression and for Diap1 protein stability in controlling the UV response. In contrast, we found that Reaper had no effect on UV sensitivity. Surprisingly, Dmp53 is required to protect cells from UV-mediated cell death, an effect attributed to its role in DNA repair. These in vivo results demonstrate that the cellular effects of DNA damage depend on the developmental status of the tissue.

Evidence is accumulating to suggest that our indigenous microbial communities (microbiota) may play a role in modulating allergic and immune disorders of the skin (Gallo and Nakatsuji, 2011; Macia et al., 2012). To examine the link between the microbiota and atopic dermatitis, we examined a mouse model of defective cutaneous barrier function with an atopic dermatitis-like disease due to loss of Notch signaling. Comparisons of conventionally-raised (CONV-R) and germ-free (GF) mice revealed a similar degree of allergic skin inflammation, systemic atopy, and airway hypersensitivity. GF mutant animals expressed significantly higher levels of thymic stromal lymphopoietin (TSLP), a major proinflammatory cytokine released by skin with defective barrier function, resulting in a more severe B-lymphoproliferative disorder that persisted into adulthood. These findings suggest a role for the microbiota in ameliorating stress signals released by keratinocytes in response to perturbation in cutaneous barrier function.

Scalability is a key feature of photoacoustic microscopy (PAM). Reports have shown that PAM systems can be designed to possess sub-micron resolution at shallow depths or penetrate centimeters deep at the expense of resolution while the number of resolved pixels in the depth direction remains high. This capability to readily tune the imaging parameters while maintaining the same inherent contrast could be extremely useful for a variety of biomedical applications. Human skin, with its layered vascular structure whose dimensions scale with depth, provides an ideal imaging target to illustrate this advantage. Here, we present results from in vivo human skin imaging experiments using two different PAM systems, an approach which enables better characterization of the cutaneous microvasculature throughout the imaging depth. Specifically, we show images from several distinct areas of skin: the palm and the forearm. For each region, the same area was imaged with both an optical-resolution PAM (OR-PAM) and an acoustic-resolution PAM (AR-PAM), and the subsequent images were combined into composite images. The OR-PAM provides less than 5 µm lateral resolution, capable of imaging the smallest capillary vessels, while the AR-PAM enables imaging at depths of several millimeters. Several structures are identifiable in the OR-PAM images which cannot be differentiated in AR-PAM images, namely thin epidermal and stratum corneum layers, undulations in the dermal papillae, and capillary loops. However, the AR-PAM provides images of larger vessels, deeper than the OR-PAM can penetrate. These results demonstrate how PAM's scalability can be utilized to more fully characterize cutaneous vasculature, potentially impacting the assessment of numerous cardiovascular related and cutaneous diseases.

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Buruli ulcer, the third most common mycobacterial disease worldwide, rarely affects travelers and is uncommon in the United States. We report a travel-associated case imported from Australia and review 3 previous cases diagnosed and treated in the United States. The differential diagnoses for unusual chronic cutaneous ulcers and those nonresponsive to conventional therapy should include Mycobacterium ulcerans infection.