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Heat shock protein 90 plays critical roles in client protein maturation, signal transduction, protein folding and degradation, and morphological evolution; however, its function in human sperm is not fully understood. Therefore, our objective in this study was to elucidate the mechanism by which heat shock protein 90 exerts its effects on human sperm function. By performing indirect immunofluorescence staining, we found that heat shock protein 90 was localized primarily in the neck, midpiece, and tail regions of human sperm, and that its expression increased with increasing incubation time under capacitation conditions. Geldanamycin, a specific inhibitor of heat shock protein 90, was shown to inhibit this increase in heat shock protein 90 expression in western blotting analyses. Using a multifunctional microplate reader to examine Fluo-3 AM-loaded sperm, we observed for the first time that inhibition of heat shock protein 90 by using geldanamycin significantly decreased intracellular calcium concentrations during capacitation. Moreover, western blot analysis showed that geldanamycin enhanced tyrosine phosphorylation of several proteins, including heat shock protein 90, in a dose-dependent manner. The effects of geldanamycin on human sperm function in the absence or presence of progesterone was evaluated by performing chlortetracycline staining and by using a computer-assisted sperm analyzer. We found that geldanamycin alone did not affect sperm capacitation, hyperactivation, and motility, but did so in the presence of progesterone. Taken together, these data suggest that heat shock protein 90, which increases in expression in human sperm during capacitation, has roles in intracellular calcium homeostasis, protein tyrosine phosphorylation regulation, and progesterone-stimulated sperm function. In this study, we provide new insights into the roles of heat shock protein 90 in sperm function.

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SummaryProgranulin (PGRN) is a multi-functional protein known to be involved in inflammation. Recent studies have found that PGRN has dual roles in inflammation and exerts anti-inflammatory and pro-inflammatory function in different diseases. However, the role of PGRN in psoriasis has not been fully elucidated. Here, we detected preferential expression of PGRN in human psoriatic lesions and serum. Moreover, serum PGRN/tumour necrosis factor-a ratio was negatively correlated with disease severity. To investigate the role of PGRN in the pathogenesis of psoriasis, we used wild-type (WT) and PGRN À/À mice in a model of 12-O-tetradecanoylphorbol 13-acetate (TPA) -induced psoriasis-like inflammation. We demonstrated that PGRN expression was dramatically enhanced in the psoriasis-like lesions of TPA-treated WT mice, in accordance with human psoriatic lesions. Surprisingly, PGRN À/À mice were more sensitive to the development of TPA-induced psoriasis-like inflammation. The mechanism underlying this increased sensitivity of PGRN À/À mice to TPA-induced psoriasis-like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in WT mice, PGRN promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis-like inflammatory response.

Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive lymphadenopathy, is a rare disease. Cutaneous RDD (CRDD) is an extremely rare form of RDD, which is limited to the skin. The present study examined a case of purely CRDD in a 25-year-old female patient who presented with a two-month history of red plaques on her face. In addition, a review of the literature was conducted, where the etiology, pathology, clinical characteristics and treatment of the disease were discussed. From a dermatological perspective, the current study aimed to emphasize the histological features and clinical morphology of cutaneous RDD. Clinicians should have sufficient knowledge to be able to recognize and manage this rare condition. The present study found that the presence of reddish-yellow nodules on the face without any particular sensitivity may be useful in the diagnosis of CRDD. Treatment with topical steroids was found to be beneficial in alleviating CRDD.

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BackgroundSkin cancer is the most common cancer in the United States, and ultraviolet B (UVB) radiation-induced DNA damage is the major environmental factor underlying skin cancer development. p21, a p53-inducible protein, plays a key role in the cellular response to UVB-induced DNA damage.Material/MethodsThrough p21 silencing and overexpression, we investigated the role of p21 in apoptosis, proliferation, cell cycle arrest, and oxidative stress in UVB-irradiated HaCaT keratinocytes.ResultsWe found that UVB exposure induced significant p21 downregulation (p<0.05) and was associated with significantly increased apoptosis, significantly decreased proliferation, and significantly increased G2 phase arrest (p<0.05) in UVB-irradiated HaCaT keratinocytes. p21 silencing significantly promoted apoptosis, significantly inhibited G2 phase arrest, and significantly inhibited proliferation (p<0.05), but after UVB irradiation, p21 silencing demonstrated a less significant pro-apoptotic effect and a more significant inhibition of G2 phase arrest (p<0.05), which was reflected in significantly higher proliferative activity (p<0.05). p21 overexpression acted in an anti-apoptotic manner in the absence of UVB-induced DNA damage but acted in a pro-apoptotic manner in the presence of UVB-induced DNA damage, displaying an “antagonistic duality” similar to other growth-promoting oncoproteins. p53 expression mirrored p21 expression, suggesting a regulatory feedback mechanism between p21 and p53 expression. p21 overexpression significantly downregulated glutathione peroxidase and superoxide dismutase antioxidant activity (p<0.05) while significantly upregulating hydrogen peroxide and malondialdehyde content (p<0.05), suggesting a role in decreasing antioxidant defense capabilities in UVB-irradiated HaCaT keratinocytes.ConclusionsThese findings reveal that p21 may play a key role in HaCaT keratinocytes’ response to UVB exposure.

SUMMARYGeospatial science is the science and art of acquiring, archiving, manipulating, analyzing, communicating, modeling with, and utilizing spatially explicit data for understanding physical, chemical, biological, and social systems on the Earth's surface or near the surface. In order to share distributed geospatial resources and facilitate the interoperability, the Open Geospatial Consortium (OGC), an industry-governmentacademia consortium, has developed a set of widely accepted Web-based interoperability standards and protocols. Grid is the technology enabling resource sharing and coordinated problem solving in dynamic, multi-institutional virtual organizations. Geospatial Grid is an extension and application of Grid technology in the geospatial discipline. This paper discusses problems associated with directly using Globus-based Grid technology in the geospatial disciplines, the needs for geospatial Grids, and the features of geospatial Grids. Then, the paper presents a research project that develops and deploys a geospatial Grid through integrating Web-based geospatial interoperability standards and technology developed by OGC with Globus-based Grid technology. The geospatial Grid technology developed by this project makes the interoperable, personalized, on-demand data access and services a reality at large geospatial data archives. Such a technology can significantly reduce problems associated with archiving, manipulating, analyzing,