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1.
Infect Control Hosp Epidemiol ; 45(2): 244-246, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37767709

ABSTRACT

Emergency departments are high-risk settings for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination. Environmental surface samples were obtained in rooms with patients suspected of having COVID-19 who did or did not undergo aerosol-generating procedures (AGPs). SARS-CoV-2 RNA surface contamination was most frequent in rooms occupied by coronavirus disease 2019 (COVID-19) patients who received no AGPs.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , RNA, Viral , Respiratory Aerosols and Droplets , Hospitals
2.
Sci Data ; 9(1): 617, 2022 10 12.
Article in English | MEDLINE | ID: mdl-36224212

ABSTRACT

Here we describe benthic composition data derived from benthic photoquadrats collected over 41 surveys between 1962 and 2016 at four sites on Heron reef, at the southern end of Australia's Great Barrier Reef, to assess change in coral composition over time. Surveys have often been annual, in a few years sub-annual, and the longest gap is six years. A subset of the data from two sites with the most complete records has been fully processed to allow the size of all individual colonies, and changes in species composition and cover, to be tracked over time. The taxonomy in these quadrats has been carefully checked for internal consistency, and is generally at the species level. A second subset has been processed, but has not been through full quality control, while a third subset exists as images only. This is the longest, 56 years, regular photographic record of coral cover in existence, and provides a valuable temporal contrast dating back in time to more recent studies of greater geographic extent and/or resolution.


Subject(s)
Anthozoa , Coral Reefs , Animals , Australia
3.
Ann Emerg Med ; 78(5): 637-649, 2021 11.
Article in English | MEDLINE | ID: mdl-34340873

ABSTRACT

STUDY OBJECTIVE: While patient-centered communication and shared decisionmaking are increasingly recognized as vital aspects of clinical practice, little is known about their characteristics in real-world emergency department (ED) settings. We constructed a natural language processing tool to identify patient-centered communication as documented in ED notes and to describe visit-level, site-level, and temporal patterns within a large health system. METHODS: This was a 2-part study involving (1) the development and validation of an natural language processing tool using regular expressions to identify shared decisionmaking and (2) a retrospective analysis using mixed effects logistic regression and trend analysis of shared decisionmaking and general patient discussion using the natural language processing tool to assess ED physician and advanced practice provider notes from 2013 to 2020. RESULTS: Compared to chart review of 600 ED notes, the accuracy rates of the natural language processing tool for identification of shared decisionmaking and general patient discussion were 96.7% (95% CI 94.9% to 97.9%) and 88.9% (95% confidence interval [CI] 86.1% to 91.3%), respectively. The natural language processing tool identified shared decisionmaking in 58,246 (2.2%) and general patient discussion in 590,933 (22%) notes. From 2013 to 2020, natural language processing-detected shared decisionmaking increased 300% and general patient discussion increased 50%. We observed higher odds of shared decisionmaking documentation among physicians versus advanced practice providers (odds ratio [OR] 1.14, 95% CI 1.07 to 1.23) and among female versus male patients (OR 1.13, 95% CI 1.11 to 1.15). Black patients had lower odds of shared decisionmaking (OR 0.8, 95% CI 0.84 to 0.88) compared with White patients. Shared decisionmaking and general patient discussion were also associated with higher levels of triage and commercial insurance status. CONCLUSION: In this study, we developed and validated an natural language processing tool using regular expressions to extract shared decisionmaking from ED notes and found multiple potential factors contributing to variation, including social, demographic, temporal, and presentation characteristics.


Subject(s)
Communication , Decision Making, Shared , Electronic Health Records , Emergency Medicine/standards , Natural Language Processing , Physician-Patient Relations , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Surveys and Questionnaires , Young Adult
4.
Epigenetics ; 16(4): 405-424, 2021 04.
Article in English | MEDLINE | ID: mdl-32842875

ABSTRACT

Paediatric cancers commonly harbour quiet mutational landscapes and are instead characterized by single driver events such as the mutation of critical chromatin regulators, expression of oncohistones, or expression of oncogenic fusion proteins. These events ultimately promote malignancy through disruption of normal gene regulation and development. The driver protein in Ewing sarcoma, EWS/FLI, is an oncogenic fusion and transcription factor that reshapes the enhancer landscape, resulting in widespread transcriptional dysregulation. Lysine-specific demethylase 1 (LSD1) is a critical functional partner for EWS/FLI as inhibition of LSD1 reverses the transcriptional activity of EWS/FLI. However, how LSD1 participates in fusion-directed epigenomic regulation and aberrant gene activation is unknown. We now show EWS/FLI causes dynamic rearrangement of LSD1 and we uncover a role for LSD1 in gene activation through colocalization at EWS/FLI binding sites throughout the genome. LSD1 is integral to the establishment of Ewing sarcoma super-enhancers at GGAA-microsatellites, which ubiquitously overlap non-microsatellite loci bound by EWS/FLI. Together, we show that EWS/FLI induces widespread changes to LSD1 distribution in a process that impacts the enhancer landscape throughout the genome.


Subject(s)
Chromatin , Lysine , Cell Line, Tumor , Child , DNA Methylation , Gene Expression Regulation, Neoplastic , Humans , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Protein c-fli-1/genetics , Proto-Oncogene Protein c-fli-1/metabolism , RNA-Binding Protein EWS/genetics , RNA-Binding Protein EWS/metabolism
5.
J Fish Dis ; 43(3): 359-369, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31918456

ABSTRACT

Bonamia spp. cause epizootics in oysters worldwide. In southern Australia, Bonamia exitiosa Hine, Cochennac and Berthe, 2001 threatens aquaculture of Ostrea angasi Sowerby, 1871. Bonamia spp. infections can display strong seasonality, but seasonal dynamics of B. exitiosa-O. angasi are unknown. Ostrea angasi naïve to B. exitiosa infection were stocked onto farms in three growing regions, and B. exitiosa was monitored seasonally for one year. Environmental parameters we measured did not correlate with B. exitiosa prevalence or infection intensities. Extreme temperatures suggest O. angasi culture systems need development. Bonamia exitiosa prevalence increased over time. After three months, O. angasi had B. exitiosa prevalence of 0.08-0.4, and after one year, the prevalence was 0.57-0.88. At some sites, O. angasi had >0.5 B. exitiosa prevalence in >6 months, but at other sites, >9 months passed before prevalence was >0.5. Bonamia exitiosa infection intensities were low with no seasonal pattern but were affected by the interaction of site, season and oyster meat:shell ratio. Understanding infection and initiating a breeding programme for resistance would provide benefits for O. angasi industry expansion.


Subject(s)
Aquaculture , Haplosporida/physiology , Ostrea/parasitology , Animals , South Australia
6.
J Fish Dis ; 43(2): 227-237, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31755142

ABSTRACT

The haplosporidian Bonamia was first detected in Australian shellfish in 1991. Australian isolates in Ostrea angasi Sowerby, 1871 were identified as Bonamia exitiosa Hine, Cochennac and Berthe, 2001, which threatens development of an O. angasi aquaculture industry. European field data suggest that Bonamia ostreae Pichot, Comps, Tigé, Grizel and Rabouin, 1980 infections in Ostrea edulis Linnaeus, 1758 build slowly, but infection dynamics of B. exitiosa in O. angasi are unknown. We investigated B. exitiosa infection in O. angasi by cohabiting uninfected juvenile O. angasi with adults infected with B. exitiosa. Oysters were sampled at 10, 21 and 40 days after cohabitation, and B. exitiosa prevalence and intensity were assessed. Bonamia exitiosa rapidly infected and caused disease in O. angasi. Mortalities began at 12 days, with ˜50% mortality by day 21 and >85% mortality by day 40. Mortalities displayed pathology consistent with clinical B. exitiosa infection. Time to first infection is likely influenced by a combination of parasite infectivity, host exposure and host immune capacity. Host death is not required for transmission, but probably facilitates release of parasites from decaying tissue. Understanding B. exitiosa transmission informs design and interpretation of field studies and aids development of management strategies for oyster aquaculture.


Subject(s)
Haplosporida/physiology , Host-Parasite Interactions , Ostrea/parasitology , Animals , Aquaculture , South Australia
7.
Cell Metab ; 31(2): 284-300.e7, 2020 02 04.
Article in English | MEDLINE | ID: mdl-31813825

ABSTRACT

Although metabolic adaptations have been demonstrated to be essential for tumor cell proliferation, the metabolic underpinnings of tumor initiation are poorly understood. We found that the earliest stages of colorectal cancer (CRC) initiation are marked by a glycolytic metabolic signature, including downregulation of the mitochondrial pyruvate carrier (MPC), which couples glycolysis and glucose oxidation through mitochondrial pyruvate import. Genetic studies in Drosophila suggest that this downregulation is required because hyperplasia caused by loss of the Apc or Notch tumor suppressors in intestinal stem cells can be completely blocked by MPC overexpression. Moreover, in two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. These data suggest that changes in cellular pyruvate metabolism are necessary and sufficient to promote cancer initiation.


Subject(s)
Adenoma/metabolism , Carcinogenesis/metabolism , Colorectal Neoplasms/metabolism , Mitochondria/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Pyruvic Acid/metabolism , Animals , Cell Transformation, Neoplastic/metabolism , Drosophila , Female , Male , Mice , Mice, Inbred C57BL
8.
Environ Microbiol ; 21(5): 1782-1797, 2019 05.
Article in English | MEDLINE | ID: mdl-30761716

ABSTRACT

Exploratory drilling for deep-sea oil and gas resources is planned for the Great Australian Bight (GAB). There is scant knowledge of the region's benthic ecosystems and no baseline information of the region's indigenous oil degrading bacteria. To address this knowledge gap, we used next generation sequencing (NGS) of three marker genes (alkB, c23o and pmoA) to detect and characterize the microbial communities capable of aerobic hydrocarbon degradation. Unique, highly novel microbial communities capable of degrading hydrocarbons occur in surface sediments at depths between 200 and 2800 m. Clustering at 97% demonstrated differences in community structure with depth, changing most markedly between 400 and 1000 m depth on the continental slope, and identified putative functional 'ecotypes' related to depth. Observed differences in community structure showed strong correlations with temperature, other physicochemical properties of the overlying water column and are further modulated by differences in sediment grain size. This study provides important baseline data on hydrocarbon degrading microbial communities prior to the start of petroleum resource extraction. Our data will inform future ecological monitoring of the GAB deep-sea ecosystem.


Subject(s)
Bacteria/metabolism , Geologic Sediments/microbiology , Hydrocarbons/metabolism , Aerobiosis , Australia , Bacteria/classification , Bacteria/genetics , Biodegradation, Environmental , Geologic Sediments/analysis , Microbiota , Petroleum/metabolism , Petroleum Pollution
9.
Sci Rep ; 8(1): 11801, 2018 08 07.
Article in English | MEDLINE | ID: mdl-30087404

ABSTRACT

Sponge-bacteria interactions are very important due to their ecological and biological significance. To understand the impact of interactions between sponges and bacteria (both associated with and external to sponges) on sponge-associated microbial diversity, sponge metabolite profiles and bioactivity, we used a controlled aquarium system and designed an experimental approach that allows the study of sponge-bacteria interactions in a well-defined manner. To test the feasibility of this approach, this system was used to study the interaction between a sponge Aplysilla rosea and a marine bacterium commonly found in seawater, Vibrio natriegens. Sponge explants were exposed to V. natriegens, at 5 × 106 cfu/ml, and changes were monitored for 48 hours. Pyro-sequencing revealed significant shifts in microbial communities associated with the sponges after 24 to 48 hours. Both the control (sponge only without added bacteria) and Vibrio-exposed sponges showed a distinct shift in bacterial diversity and abundance with time. Vibrio exposure significantly increased bacterial diversity, the abundance of a number of taxa compared to control sponges. The result experimentally supports the notion of dynamic and concerted responses by the sponge when interacting with a bacterium, and demonstrates the feasibility of using this controlled aquarium system for the study of sponge-bacteria interactions.


Subject(s)
Microbial Consortia/physiology , Porifera/microbiology , Vibrio/growth & development , Animals , Vibrio/classification
10.
Ecol Evol ; 8(23): 11423-11433, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30598746

ABSTRACT

AIM: To document biogeographic patterns in the deepwater benthic epifauna and demersal fishes of southern Australia, and determine whether museum records and systematic survey data provide matching results. LOCATION: Southern Australian (32-44oS) continental slope (200-3,000 m deep). TAXON: Marine benthic fauna (Arthropoda, Bryozoa, Cnidaria, Echinodermata, Mollusca, Porifera, Sipuncula, and fishes). METHODS: All available electronic records of fauna from the above taxa and ≥200 m depth off the southern Australian coastline, regardless of organism size, were collated from Australian museums and checked for geographic and taxonomic consistency. These records were then split into 40 geographic segments of roughly equal numbers, with each segment then treated as a sample in multivariate analyses of assemblage composition. Data from a recent (2015) systematic beam trawl survey along five north-south transects in the central Great Australian Bight were also included for comparison. MAIN CONCLUSIONS: The systematic survey data grouped with the associated geographic segments despite differences in sampling technique (single gear compared to multiple gears), with subsequent differences in taxonomic biases, and the use of a 25 mm mesh, which would undersample some smaller organisms present in the museum data. Thus, the museum data and the survey data provided the same results for the central Great Australian Bight at the level of the whole assemblage. The main biogeographic break occurred off southeastern Tasmania, with a second substantial break occurring at around the border between New South Wales and Victoria. This indicates the potential for unused museum data to describe biogeographic patterns over regional spatial scales, especially in the deep sea where the expense of collecting new data is relatively high.

11.
Nat Cell Biol ; 19(9): 1027-1036, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28812582

ABSTRACT

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells.


Subject(s)
Cell Proliferation , Drosophila melanogaster/metabolism , Glycolysis , Intestinal Mucosa/metabolism , Mitochondria/metabolism , Pyruvic Acid/metabolism , Stem Cells/metabolism , Acrylates/pharmacology , Animals , Anion Transport Proteins/antagonists & inhibitors , Anion Transport Proteins/genetics , Anion Transport Proteins/metabolism , Cell Differentiation , Cell Proliferation/drug effects , Cells, Cultured , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Genotype , Humans , Intestines/cytology , Intestines/drug effects , Lactic Acid/metabolism , Mice, Knockout , Mitochondria/drug effects , Mitochondrial Membrane Transport Proteins/antagonists & inhibitors , Mitochondrial Membrane Transport Proteins/genetics , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Proteins/metabolism , Monocarboxylic Acid Transporters , Phenotype , RNA Interference , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction , Stem Cells/drug effects , Time Factors , Tissue Culture Techniques , Transfection
12.
Mol Cancer Res ; 15(11): 1517-1530, 2017 11.
Article in English | MEDLINE | ID: mdl-28720588

ABSTRACT

Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology. Therefore, the metabolic effects of silencing EF in Ewing sarcoma cells were determined. Metabolomic analyses revealed distinct separation of metabolic profiles in EF-knockdown versus control-knockdown cells. Mitochondrial stress tests demonstrated that knockdown of EF increased respiratory as well as glycolytic functions. Enzymes and metabolites in several metabolic pathways were altered, including de novo serine synthesis and elements of one-carbon metabolism. Furthermore, phosphoglycerate dehydrogenase (PHGDH) was found to be highly expressed in Ewing sarcoma and correlated with worse patient survival. PHGDH knockdown or pharmacologic inhibition in vitro caused impaired proliferation and cell death. Interestingly, PHGDH modulation also led to elevated histone expression and methylation. These studies demonstrate that the translocation-derived fusion protein EF is a master regulator of metabolic reprogramming in Ewing sarcoma, diverting metabolites toward biosynthesis. As such, these data suggest that the metabolic aberrations induced by EF are important contributors to the oncogenic biology of these tumors.Implications: This previously unexplored role of EWS/FLI1-driven metabolic changes expands the understanding of Ewing sarcoma biology, and has potential to significantly inform development of therapeutic strategies. Mol Cancer Res; 15(11); 1517-30. ©2017 AACR.


Subject(s)
Bone Neoplasms/metabolism , Metabolomics/methods , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Protein c-fli-1/genetics , Proto-Oncogene Protein c-fli-1/metabolism , RNA-Binding Protein EWS/genetics , RNA-Binding Protein EWS/metabolism , Sarcoma, Ewing/metabolism , Bone Neoplasms/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Glycolysis , Humans , Metabolic Networks and Pathways , Phosphoglycerate Dehydrogenase/metabolism , Sarcoma, Ewing/genetics , Signal Transduction , Up-Regulation
13.
Mar Environ Res ; 127: 163-172, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27342125

ABSTRACT

Seagrass species form important marine and estuarine habitats providing valuable ecosystem services and functions. Coastal zones that are increasingly impacted by anthropogenic development have experienced substantial declines in seagrass abundance around the world. Australia, which has some of the world's largest seagrass meadows and is home to over half of the known species, is not immune to these losses. In 1999 a review of seagrass ecosystems knowledge was conducted in Australia and strategic research priorities were developed to provide research direction for future studies and management. Subsequent rapid evolution of seagrass research and scientific methods has led to more than 70% of peer reviewed seagrass literature being produced since that time. A workshop was held as part of the Australian Marine Sciences Association conference in July 2015 in Geelong, Victoria, to update and redefine strategic priorities in seagrass research. Participants identified 40 research questions from 10 research fields (taxonomy and systematics, physiology, population biology, sediment biogeochemistry and microbiology, ecosystem function, faunal habitats, threats, rehabilitation and restoration, mapping and monitoring, management tools) as priorities for future research on Australian seagrasses. Progress in research will rely on advances in areas such as remote sensing, genomic tools, microsensors, computer modeling, and statistical analyses. A more interdisciplinary approach will be needed to facilitate greater understanding of the complex interactions among seagrasses and their environment.


Subject(s)
Alismatales , Conservation of Natural Resources/methods , Ecosystem , Environmental Monitoring/methods , Australia
14.
Appl Microbiol Biotechnol ; 100(24): 10609-10626, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27717966

ABSTRACT

Sponge-associated bacteria play a critical role in sponge biology, metabolism and ecology, but how they interact with their host sponges and the role of these interactions are poorly understood. This study investigated the role of the interaction between the sponge Aplysilla rosea and its associated actinobacterium, Streptomyces ACT-52A, in modifying sponge microbial diversity, metabolite profile and bioactivity. A recently developed experimental approach that exposes sponges to bacteria of interest in a controlled aquarium system was improved by including the capture and analysis of secreted metabolites by the addition of an absorbent resin in the seawater. In a series of controlled aquaria, A. rosea was exposed to Streptomyces ACT-52A at 106 cfu/ml and monitored for up to 360 h. Shifts in microbial communities associated with the sponges occurred within 24 to 48 h after bacterial exposure and continued until 360 h, as revealed by TRFLP. The metabolite profiles of sponge tissues also changed substantially as the microbial community shifted. Control sponges (without added bacteria) and Streptomyces ACT-52A-exposed sponges released different metabolites into the seawater that was captured by the resin. The antibacterial activity of compounds collected from the seawater increased at 96 and 360 h of exposure for the treated sponges compared to the control group due to new compounds being produced and released. Increased antibacterial activity of metabolites from treated sponge tissue was observed only at 360 h, whereas that of control sponge tissue remained unchanged. The results demonstrate that the interaction between sponges and their associated bacteria plays an important role in regulating secondary metabolite production.


Subject(s)
Aquatic Organisms/microbiology , Aquatic Organisms/physiology , Porifera/microbiology , Porifera/physiology , Secondary Metabolism , Streptomyces/growth & development , Animals , Biota , Metabolome , Microbiota , Polymorphism, Restriction Fragment Length
15.
Dev Cell ; 36(5): 483-5, 2016 Mar 07.
Article in English | MEDLINE | ID: mdl-26954542

ABSTRACT

In this issue of Developmental Cell, Hosios et al. (2016) take a rigorous and quantitative approach to analyze metabolite acquisition and allocation in proliferating cultured mammalian cells. This work clarifies what we know while providing a new analytical framework to undergird future work on the metabolism of proliferating cells.


Subject(s)
Amino Acids/metabolism , Carbon/metabolism , Cell Proliferation/physiology , Glucose/metabolism , Glutamic Acid/metabolism , Animals , Humans
16.
PeerJ ; 3: e1238, 2015.
Article in English | MEDLINE | ID: mdl-26401452

ABSTRACT

The influence of sea-cage aquaculture on wildfish assemblages has received little attention outside of Europe. Sea-cage aquaculture of finfish is a major focus in South Australia, and while the main species farmed is southern bluefin tuna (Thunnus maccoyii), there is also an important yellowtail kingfish (Seriola lalandi) industry. Yellowtail kingfish aquaculture did not appear to have any local or regional effects on demersal assemblages (primarily fish, but also some crustaceans) surveyed by baited remote underwater video (BRUV) in Fitzgerald Bay. We did, however, detect small scale spatial variations in assemblages within the bay. The type of bait used strongly influenced the assemblage recorded, with significantly greater numbers of fish attracted to deployments where sardines were used as the bait to compared to those with no bait. The pelleted feed used by the aquaculture industry was just as attractive as sardines at one site, and intermediate between sardines and no bait at the other. There was significant temporal variability in assemblages at both farm sites and one control site, while the second control site was temporally stable (over the 9 weeks of the study). Overall, the results suggested that aquaculture was having little if any impact on the abundance and assemblage structure of the demersal macrofauna in Fitzgerald Bay.

17.
Hosp Pharm ; 49(1): 48-51, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24421563

ABSTRACT

OBJECTIVE: To describe a case of an unusual adverse drug reaction to diphenylcyclopropenone for the treatment of alopecia areata. CASE SUMMARY: A 31-year-old Caucasian male presented with extensive angioedema to the head with neck involvement 10 days following treatment with diphenylcyclopropenone 2% solution in acetone topically on his scalp to treat alopecia areata. Findings on patient presentation included edema of the soft tissues (deeper dermis and subcutaneous tissue) of the head and face with mild neck involvement, acute inflammatory changes from chemical-induced irritation, scalp erythema, and serous fluid drainage from inflamed and fissured edematous scalp. Acute treatments used for control of the reaction included intravenous steroids and antihistamines during hospitalization followed by oral steroids and antihistamines for maintenance during outpatient treatment of the resolving condition. DISCUSSION: The role of topical diphenylcyclopropenone in this case of alopecia areata is probable according to the Naranjo criteria, with a score of 8. Diphenylcyclopropenone is not approved by the US Food and Drug Administration, but it has been used by many clinicians for the treatment of alopecia areata. Diphenylcyclopropenone causes an allergic contact dermatitis in the area of hair loss. In general, diphenylcyclopropenone is applied at a high concentration of 2% once and then at lower concentrations once weekly after the sensitization dose. This patient applied the 2% concentration on multiple consecutive days. CONCLUSION: Frequent use of topical diphenylcyclopropenone 2% applied to the scalp may cause scalp angioedema.

18.
Mol Cell Biol ; 33(22): 4448-60, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24043308

ABSTRACT

Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Glioma-associated oncogene homolog 1 (GLI1) is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1 contributes to the transformed phenotype of Ewing sarcoma was unknown. In this work, we identify keratin 17 (KRT17) as a direct downstream target gene upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. Taken together, our data reveal previously unknown molecular functions for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI- and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing sarcoma.


Subject(s)
Bone Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Keratin-17/genetics , Keratin-17/metabolism , Sarcoma, Ewing/genetics , Animals , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Adhesion , Cell Line, Tumor , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Humans , Mice , Mice, Nude , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Protein c-fli-1/genetics , Proto-Oncogene Protein c-fli-1/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA-Binding Protein EWS/genetics , RNA-Binding Protein EWS/metabolism , Sarcoma, Ewing/metabolism , Sarcoma, Ewing/pathology , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism , Zinc Finger Protein GLI1
19.
Mar Pollut Bull ; 66(1-2): 176-84, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23154140

ABSTRACT

Assessing environmental condition is essential for the management of coasts and their resources, but better management decisions occur when large databases are simplified into more manageable units of information. Here we present the habitat structure index (HSI), which enables rapid assessment and direct comparison of seagrass habitat structure using scores of 0 (poor) to 100 (excellent) based on integrating five habitat variables: area, continuity, proximity, percentage cover, and species identity. Acquiring data to calculate the HSI can be done in situ or from video recordings, and requires relatively simple methodology of belt transects, estimating percentage cover, and basic taxonomy. Spatiotemporal comparisons can usefully identify locations and periods of seagrass habitat change, potentially providing an early warning indicator of habitat damage and decline in environmental quality. Overall, the integrative approach of the HSI represents a step toward simplifying the exchange of environmental information among researchers, coastal managers, and governing bodies.


Subject(s)
Alismatales/physiology , Ecosystem , Environmental Monitoring/methods , Alismatales/classification , Alismatales/growth & development , Aquatic Organisms/classification , Conservation of Natural Resources
20.
Diabetes ; 61(7): 1848-59, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22586587

ABSTRACT

Vascular dysfunction that accompanies obesity and insulin resistance may be mediated by lipid metabolites. We sought to determine if vascular ceramide leads to arterial dysfunction and to elucidate the underlying mechanisms. Pharmacological inhibition of de novo ceramide synthesis, using the Ser palmitoyl transferase inhibitor myriocin, and heterozygous deletion of dihydroceramide desaturase prevented vascular dysfunction and hypertension in mice after high-fat feeding. These findings were recapitulated in isolated arteries in vitro, confirming that ceramide impairs endothelium-dependent vasorelaxation in a tissue-autonomous manner. Studies in endothelial cells reveal that de novo ceramide biosynthesis induced protein phosphatase 2A (PP2A) association directly with the endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent with decreased basal and agonist-stimulated eNOS phosphorylation. PP2A attenuates eNOS phosphorylation by preventing phosphorylation of the pool of Akt that colocalizes with eNOS and by dephosphorylating eNOS. Ceramide decreased the association between PP2A and the predominantly cytosolic inhibitor 2 of PP2A. We conclude that ceramide mediates obesity-related vascular dysfunction by a mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling complex. These results provide important insight into a pathway that represents a novel target for reversing obesity-related vascular dysfunction.


Subject(s)
Ceramides/biosynthesis , Diet, High-Fat , HSP90 Heat-Shock Proteins/metabolism , Nitric Oxide Synthase Type III/metabolism , Obesity/enzymology , Protein Phosphatase 2/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Cattle , Endothelial Cells/drug effects , Endothelial Cells/enzymology , Enzyme Inhibitors/pharmacology , Fatty Acids, Monounsaturated/pharmacology , Hypertension/drug therapy , Hypertension/enzymology , Male , Mice , Mice, Inbred C57BL , Obesity/drug therapy , Oxidoreductases/genetics , Oxidoreductases/metabolism , Serine C-Palmitoyltransferase/antagonists & inhibitors , Vasodilation/drug effects , Vasodilation/physiology
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