Documentation of Shared Decisionmaking in the Emergency Department.

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.

Infection dynamics of Bonamia exitiosa on intertidal Ostrea angasi farms.

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.

Rapid transmission of Bonamia exitiosa by cohabitation causes mortality in Ostrea angasi.

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.

Baseline characterization of aerobic hydrocarbon degrading microbial communities in deep-sea sediments of the Great Australian Bight, Australia.

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.

The role of sponge-bacteria interactions: the sponge Aplysilla rosea challenged by its associated bacterium Streptomyces ACT-52A in a controlled aquarium system.

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.

Extensive scalp angioedema following high-dose diphenylcyclopropenone for alopecia areata.

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.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA and viable virus contamination of hospital emergency department surfaces and association with patient coronavirus disease 2019 (COVID-19) status and aerosol-generating procedures.

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.

The peritoneal cavity B-2 antibody repertoire appears to reflect many of the same selective pressures that shape the B-1a and B-1b repertoires.

To assess the extent and nature of somatic categorical selection of CDR-3 of the Ig H chain (CDR-H3) content in peritoneal cavity (PerC) B cells, we analyzed the composition of V(H)7183DJCµ transcripts derived from sorted PerC B-1a, B-1b, and B-2 cells. We divided these sequences into those that contained N nucleotides (N(+)) and those that did not (N(-)) and then compared them with sequences cloned from sorted IgM(+)IgD(+) B cells from neonatal liver and both wild-type and TdT-deficient adult bone marrow. We found that the PerC B-1a N(-) repertoire is enriched for the signatures of CDR-H3 sequences present in neonatal liver and shares many features with the B-1b N(-) repertoire, whereas the PerC B-1a N(+), B-1b N(+), and B-2 N(+) repertoires are enriched for adult bone marrow sequence signatures. However, we also found several sequence signatures that were not shared with other mature perinatal or adult B cell subsets but were either unique or variably shared between the two or even among all three of the PerC subsets that we examined. These signatures included more sequences lacking N nucleotides in the B-2 population and an increased use of D(H) reading frame 2, which created CDR-H3s of greater average hydrophobicity. These findings provide support for both ontogenetic origin and shared Ag receptor-influenced selection as the mechanisms that shape the unique composition of the B-1a, B-1b, and B-2 repertoires. The PerC may thus serve as a general reservoir for B cells with Ag binding specificities that are uncommon in other mature compartments.

Coral community data Heron Island Great Barrier Reef 1962-2016.

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.

Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressure.

Impaired insulin signaling via phosphatidylinositol 3-kinase/Akt to endothelial nitric oxide synthase (eNOS) in the vasculature has been postulated to lead to arterial dysfunction and hypertension in obesity and other insulin resistant states. To investigate this, we compared insulin signaling in the vasculature, endothelial function, and systemic blood pressure in mice fed a high-fat (HF) diet to mice with genetic ablation of insulin receptors in all vascular tissues (TTr-IR(-/-)) or mice with genetic ablation of Akt1 (Akt1-/-). HF mice developed obesity, impaired glucose tolerance, and elevated free fatty acids that was associated with endothelial dysfunction and hypertension. Basal and insulin-mediated phosphorylation of extracellular signal-regulated kinase 1/2 and Akt in the vasculature was preserved, but basal and insulin-stimulated eNOS phosphorylation was abolished in vessels from HF versus lean mice. In contrast, basal vascular eNOS phosphorylation, endothelial function, and blood pressure were normal despite absent insulin-mediated eNOS phosphorylation in TTr-IR(-/-) mice and absent insulin-mediated eNOS phosphorylation via Akt1 in Akt1-/- mice. In cultured endothelial cells, 6 hours of incubation with palmitate attenuated basal and insulin-stimulated eNOS phosphorylation and NO production despite normal activation of extracellular signal-regulated kinase 1/2 and Akt. Moreover, incubation of isolated arteries with palmitate impaired endothelium-dependent but not vascular smooth muscle function. Collectively, these results indicate that lower arterial eNOS phosphorylation, hypertension, and vascular dysfunction following HF feeding do not result from defective upstream signaling via Akt, but from free fatty acid-mediated impairment of eNOS phosphorylation.

Chromatin profiling reveals relocalization of lysine-specific demethylase 1 by an oncogenic fusion protein.

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.

Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier.

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.

Endothelial nitric oxide synthase phosphorylation in treadmill-running mice: role of vascular signalling kinases.

The intracellular signalling kinases Akt/protein kinase B (Akt), protein kinase A (PKA) and adenosine monophosphate-activated protein kinase (AMPK) are phosphorylated in response to increased mechanical force or perfusion rate in cultured endothelial cells or isolated blood vessels. All three kinases phosphorylate endothelial nitric oxide synthase (eNOS) on serine (S) 1177, while Akt and PKA additionally phosphorylate eNOS on S617 and S635 respectively. Although these kinases might contribute to subsequent activation of eNOS during dynamic exercise, the specific mediators of exercise-induced eNOS phosphorylation and activation in vivo are unknown. We determined the impact of 50 min of treadmill running on the phosphorylation of Akt, AMPK, cyclic adenosine monophosphate response element binding protein (CREB - a target of PKA) and eNOS (S 1177, 635 and 617 and threonine (T) 495) in the presence or absence of pharmacological inhibition of PI3 kinase (PI3K) and Akt signalling using wortmannin. Compared to arteries from sedentary mice, eNOS enzyme activity was greater in vessels from treadmill-running animals and was associated with increased phosphorylation of Akt (S473), CREB (S133), AMPK (T172), and eNOS at S1177 and S617 but not at S635 or T495. These data suggest that Akt signalling is a major mediator of eNOS activation. To confirm this, treadmill-running was performed in the presence of vehicle (DMSO) or PI3K inhibition. Compared to results from sedentary mice, vascular Akt phosphorylation and eNOS phosphorylation at S617 during treadmill-running were prevented by wortmannin but not vehicle treatment, whereas exercise-related increases in AMPK and CREB phosphorylation were similar between groups. Arterial eNOS phosphorylation at S1177 increased during exercise after wortmannin treatment relative to values obtained from sedentary animals, but the elevation was blunted by approximately 50% compared to results from vehicle-treated mice. These findings indicate that Akt and AMPK contribute importantly to vascular eNOS S1177 phosphorylation during treadmill-running, and that AMPK is sufficient to activate p-eNOS S1177 in the presence of PI3K inhibition.

Community-level density dependence: an example from a shallow coral assemblage.

While density dependence is a popular topic of research in population ecology, it has received much less attention at the community level. Using 27 years of data from Heron Island, on Australia's Great Barrier Reef, we develop a matrix model of coral community dynamics that shows that community-level density dependence does occur and that it is fairly common, being found in 38% of the model parameters for which it was tested. In particular, colonization of free space (through either recruitment or growth of existing colonies) was nearly always density dependent. There were no consistent patterns in the results for mortality, persistence, or species interactions. Most transitions were found to be dependent on the cover of the incoming species group, with only a few dependent on that of the outgoing species group. In addition, few of the transitions representing species interactions were dependent on the amount of free space present, suggesting that the cover of other species does not influence encounters. When these results were combined into a model of community dynamics, it was found that density dependence resulted in a moderate increase in coral cover, which was spread over most species groups. The dynamics of the density-dependent assemblage were also a lot noisier than those of an assemblage without density dependence. Sensitivity analysis indicated that it was density dependence in the colonization probabilities, particularly of encrusting acroporids, bushy Acropora and staghorn Acropora, which had the main influence on the model, although persistence of free space was also important. Transitions representing mortality were only of minor importance, and those representing species interactions were of no importance.

Lotka-Volterra competition models for sessile organisms.

Markov models are widely used to describe the dynamics of communities of sessile organisms, because they are easily fitted to field data and provide a rich set of analytical tools. In typical ecological applications, at any point in time, each point in space is in one of a finite set of states (e.g., species, empty space). The models aim to describe the probabilities of transitions between states. In most Markov models for communities, these transition probabilities are assumed to be independent of state abundances. This assumption is often suspected to be false and is rarely justified explicitly. Here, we start with simple assumptions about the interactions among sessile organisms and derive a model in which transition probabilities depend on the abundance of destination states. This model is formulated in continuous time and is equivalent to a Lotka-Volterra competition model. We fit this model and a variety of alternatives in which transition probabilities do not depend on state abundances to a long-term coral reef data set. The Lotka-Volterra model describes the data much better than all models we consider other than a saturated model (a model with a separate parameter for each transition at each time interval, which by definition fits the data perfectly). Our approach provides a basis for further development of stochastic models of sessile communities, and many of the methods we use are relevant to other types of community. We discuss possible extensions to spatially explicit models.

Benthic biogeographic patterns in the southern Australian deep sea: Do historical museum records accord with recent systematic, but spatially limited, survey data?

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.

A controlled aquarium system and approach to study the role of sponge-bacteria interactions using Aplysilla rosea and Vibrio natriegens.

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.

EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma.

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.

Identifying knowledge gaps in seagrass research and management: An Australian perspective.

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.

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

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.