The orphan G protein-coupled receptor (GPCR) GPR161 plays a central role in development by suppressing Hedgehog signaling. The fundamental basis of how GPR161 is activated remains unclear. Here, we determined a cryogenic-electron microscopy structure of active human GPR161 bound to heterotrimeric G.
View Article and Find Full Text PDFS100 proteins are a subfamily of EF-hand calcium-binding proteins found primarily in vertebrate animals. They are distinguished by binding of transition metals and functioning in both the intracellular and extracellular milieu. S100A7 functions in the protection of the skin and mucous membranes and is a biomarker in inflammatory skin disease.
View Article and Find Full Text PDFThe orphan G protein-coupled receptor (GPCR) GPR161 is enriched in primary cilia, where it plays a central role in suppressing Hedgehog signaling. GPR161 mutations lead to developmental defects and cancers. The fundamental basis of how GPR161 is activated, including potential endogenous activators and pathway-relevant signal transducers, remains unclear.
View Article and Find Full Text PDFLaboratory models are critical to basic and translational microbiology research. Models serve multiple purposes, from providing tractable systems to study cell biology to allowing the investigation of inaccessible clinical and environmental ecosystems. Although there is a recognized need for improved model systems, there is a gap in rational approaches to accomplish this goal.
View Article and Find Full Text PDFNumerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers in Townsville (19.
View Article and Find Full Text PDFAustralia and New Zealand have the highest incidence of skin cancer. Sport is a fundamental part of Australasian culture, beginning in childhood, often with life-long participation. Participating in outdoor sports can contribute significantly to the lifetime ultraviolet radiation (UVR) dose individuals receive and their risk of developing skin cancer.
View Article and Find Full Text PDFSkin cancer, the most prevalent cancer in Caucasians residing at low latitudes, can primarily be prevented by avoiding overexposure to sunlight. Serial cross-sectional observations were conducted at an outdoor motorsport event held in Townsville, Queensland each July (Southern winter) to determine whether sun-protection habits changed over time. Most (71.
View Article and Find Full Text PDFNeisseria gonorrhoeae (Gc) must overcome the limitation of metals such as zinc to colonize mucosal surfaces in its obligate human host. While the zinc-binding nutritional immunity proteins calprotectin (S100A8/A9) and psoriasin (S100A7) are abundant in human cervicovaginal lavage fluid, Gc possesses TonB-dependent transporters TdfH and TdfJ that bind and extract zinc from the human version of these proteins, respectively. Here we investigated the contribution of zinc acquisition to Gc infection of epithelial cells of the female genital tract.
View Article and Find Full Text PDFTo combat nutritional immunity, N. gonorrhoeae has evolved systems to hijack zinc and other metals directly from host metal-binding proteins such as calprotectin (CP). Here, we report the 6.
View Article and Find Full Text PDFVibrio cholerae, the cause of human cholera, is an aquatic bacterium found in association with a variety of animals in the environment, including many teleost fish species. V. cholerae infection induces a proinflammatory response followed by a noninflammatory convalescent phase.
View Article and Find Full Text PDFThe human pathogen Acinetobacter baumannii produces and utilizes acinetobactin for iron assimilation. Although two isomeric structures of acinetobactin, one featuring an oxazoline (Oxa) and the other with an isoxazolidinone (Isox) at the core, have been identified, their differential roles as virulence factors for successful infection have yet to be established. This study provides direct evidence that Oxa supplies iron more efficiently than Isox, primarily owing to its specific recognition by the cognate outer membrane receptor, BauA.
View Article and Find Full Text PDFChromobacterium violaceum is a ubiquitous environmental bacterium that causes sporadic life-threatening infections in humans. How C. violaceum acquires zinc to colonize environmental and host niches is unknown.
View Article and Find Full Text PDFThis research compared personal sunlight exposure times monitored electronically within suburban Australian environments against self-report paper journals for determining the timing and total duration of individual exposure to daily solar radiation. A total of 90 Electronic Sun Journal (ESJ) daily readings and self-report timing and duration estimates of exposure for weekend and weekdays were compared. A Wilcoxon ranked sign test showed a significant difference (V = 157, P < 0.
View Article and Find Full Text PDFHaving numerous melanocytic nevi increases melanoma risk. Few studies have enumerated nevi in children and re-examined them as adults. We aimed to determine if childhood nevus-counts predict nevus-prone adults, and further explore the relevance of host-factors and sun-exposure.
View Article and Find Full Text PDF, responsible for the sexually transmitted infection gonorrhea, is an obligate human pathogen exquisitely adapted for survival on mucosal surfaces of humans. This host-pathogen relationship has resulted in evolution by of pathways that enable the use of host metalloproteins as required nutrients through the deployment of outer membrane-bound TonB-dependent transporters (TdTs). Recently, a TdT called TdfH was implicated in binding to calprotectin (CP) and in removal of the bound zinc (Zn), enabling gonococcal growth.
View Article and Find Full Text PDFSolar ultraviolet radiation (UVR) is the main environmental risk-factor for cancer of the skin. Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin and European and Australian standards for sun-protective clothing set minimum clothing coverage requirements. Body Surface Area Coverage by clothing (BSAC) is calculated by means of indirect or direct methods, which are laborious and do not support computer-based apparel design.
View Article and Find Full Text PDFAnimal and human studies show that exposure to solar-simulated UVR is immunomodulatory. Human studies that used natural sun exposure and controlled for confounding are rare. We immunized 217 healthy adults (age range = 18-40 years) with a T-cell-dependent antigen, keyhole limpet hemocyanin, and measured personal clothing-adjusted UVR exposure (for 5 days before and after immunization), lifetime cumulative UVR exposure, serum 25-hydroxyvitamin D concentration at immunization, and potential confounding factors.
View Article and Find Full Text PDFThe risk of keratinocyte skin cancer, malignant melanoma and ultraviolet radiation (UVR)-induced eye disease is disproportionately higher in Australia and New Zealand compared to equivalent northern hemisphere latitudes. While many teachers are aware of the importance of reinforcing sun safety messages to students, many may not be aware of the considerable personal exposure risk while performing outdoor duties in locations experiencing high to extreme ambient UVR year-round. Personal erythemally effective exposure of classroom teachers in tropical Townsville (19.
View Article and Find Full Text PDFKeratinocyte cancer is the most common malignancy in Caucasians. The aim of this study was to investigate risk-factors responsible for development of keratinocyte cancer in Australia. A case-control study was conducted, including 112 cases of squamous cell carcinoma (SCC), 95 cases of basal cell carcinoma (BCC) and 122 controls.
View Article and Find Full Text PDFMelanoma skin cancer rates in Queensland exceed the national Australian incidence rate, which together with New Zealand are recognized as the world's highest. Incidence is especially high among younger members of the population. In this study, the sun-protective behaviors of urban Queenslanders (n = 752) going about their day-to-day activities during a midweek noon time hourly period were observed on a summer's day in central Brisbane (27.
View Article and Find Full Text PDFTropical Ecuador presents a unique climate in which we study the relationship between the ambient levels of solar ultraviolet radiation and eye disease in the absence of a latitudinal gradient. The national distribution of surface ultraviolet, taking into account MODIS and OMI satellite observation of aerosol, ozone, surface albedo, local elevation and cloud fractions measured during 2011, was compared with the national pterygium (WHO ICD H11) and senile cataract (WHO ICD H25) incidence projected from the 2010 National Institute of Statistics and Census (Ecuador). Public Health Ministry projections for age categories 0 to 39, 40 to 59 and 60+ years were compared to surface ultraviolet irradiance data in 1040 parishes.
View Article and Find Full Text PDFAn observational study was conducted to examine the use of sun protective hats, clothing, and sunglasses of people attending an outdoor entertainment event in an area of high-to-extreme ultraviolet radiation in New South Wales, Australia. Armidale is unique, as it is a highly-elevated area, almost 1000 m above sea level, and temperatures are often mild with very high-to-extreme levels of ultraviolet radiation. Four trained data collectors observed attendees as they entered the event, and recorded their use of sun protective hats, clothing, and sunglasses.
View Article and Find Full Text PDFData on personal sun exposure over a period exceeding the immediate past days or weeks are typically self-reported in brief questionnaire items. The validity of such self-reporting of longer term personal sun exposure, for example over a year, including detail on variation across seasons, has not previously been investigated. In a volunteer sample (n = 331) of Australian adults aged 18 years and over, we assessed the 12-month reliability of sun exposure reported separately for each season, and its accuracy compared to a daily sun diary in the same season.
View Article and Find Full Text PDFSkin cancer is the most common cancer in humans and Australia (particularly in Queensland) has the highest incidence globally. Sunlight is a known skin carcinogen and reflects off water, exacerbating the risk of sunburn. In 1988, the "SunSmart Program" was developed to promote sun-protection to Australian children.
View Article and Find Full Text PDFBackground: Vitamin D status generally varies seasonally with changing solar UVB radiation, time in the sun, amount of skin exposed, and, possibly, diet. The Seasonal D Study was designed to quantify the amplitude and phase of seasonal variation in the serum concentration of 25-hydroxyvitamin D, (25OH)D)) and identify the determinants of the amplitude and phase and those of inter-individual variability in seasonal pattern.
Methods: The Seasonal D Study collected data 2-monthly for 12 months, including demographics, personal sun exposure using a diary and polysulphone dosimeters over 7 days, and blood for serum 25(OH)D concentration.