Identification of Hyaloperonospora arabidopsidis Transcript Sequences Expressed during Infection Reveals Isolate-Specific Effectors

Biotrophic plant pathogens secrete effector proteins that are important for infection of the host. The aim of this study was to identify effectors of the downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) that are expressed during infection of its natural host Arabidopsis thaliana. Infection-related transcripts were identified from Expressed Sequence Tags (ESTs) derived from leaves of the susceptible Arabidopsis Ws eds1-1 mutant inoculated with the highly virulent Hpa isolate Waco9. Assembly of 6364 ESTs yielded 3729 unigenes, of which 2164 were Hpa-derived. From the translated Hpa unigenes, 198 predicted secreted proteins were identified. Of these, 75 were found to be Hpa-specific and six isolate Waco9-specific. Among 42 putative effectors identified there were three Elicitin-like proteins, 16 Cysteine-rich proteins and 18 host-translocated RXLR effectors. Sequencing of alleles in different Hpa isolates revealed that five RXLR genes show signatures of diversifying selection. Thus, EST analysis of Hpa-infected Arabidopsis is proving to be a powerful method for identifying pathogen effector candidates expressed during infection. Delivery of the Waco9-specific protein RXLR29 in planta revealed that this effector can suppress PAMP-triggered immunity and enhance disease susceptibility. We propose that differences in host colonization can be conditioned by isolate-specific effectors

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

As shown by analysis of mice and humans bearing DOCK8-inactivating mutations, DOCK8 plays a cell-autonomous role in survival of naive CD8 T cells, LFA-1 polarization toward the immune synapse, and CD8 T cell memory and recall responses following viral infection

Habitat and Scale Shape the Demographic Fate of the Keystone Sea Urchin Paracentrotus lividus in Mediterranean Macrophyte Communities

Demographic processes exert different degrees of control as individuals grow, and in species that span several habitats and spatial scales, this can influence our ability to predict their population at a particular life-history stage given the previous life stage. In particular, when keystone species are involved, this relative coupling between demographic stages can have significant implications for the functioning of ecosystems. We examined benthic and pelagic abundances of the sea urchin Paracentrotus lividus in order to: 1) understand the main life-history bottlenecks by observing the degree of coupling between demographic stages; and 2) explore the processes driving these linkages. P. lividus is the dominant invertebrate herbivore in the Mediterranean Sea, and has been repeatedly observed to overgraze shallow beds of the seagrass Posidonia oceanica and rocky macroalgal communities. We used a hierarchical sampling design at different spatial scales (100 s, 10 s and <1 km) and habitats (seagrass and rocky macroalgae) to describe the spatial patterns in the abundance of different demographic stages (larvae, settlers, recruits and adults). Our results indicate that large-scale factors (potentially currents, nutrients, temperature, etc.) determine larval availability and settlement in the pelagic stages of urchin life history. In rocky macroalgal habitats, benthic processes (like predation) acting at large or medium scales drive adult abundances. In contrast, adult numbers in seagrass meadows are most likely influenced by factors like local migration (from adjoining rocky habitats) functioning at much smaller scales. The complexity of spatial and habitat-dependent processes shaping urchin populations demands a multiplicity of approaches when addressing habitat conservation actions, yet such actions are currently mostly aimed at managing predation processes and fish numbers. We argue that a more holistic ecosystem management also needs to incorporate the landscape and habitat-quality level processes (eutrophication, fragmentation, etc.) that together regulate the populations of this keystone herbivore

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

“Choosing Wisely” Imaging Recommendations: Initial Implementation in New England Emergency Departments

Introduction: In June 2016, the American College of Emergency Physicians (ACEP) Emergency Quality Network began its Reduce Avoidable Imaging Initiative, designed to “reduce testing and imaging with low risk patients through the implementation of Choosing Wisely recommendations.” However, it is unknown whether New England emergency departments (ED) have already implemented evidence-based interventions to improve adherence to ACEP Choosing Wisely recommendations related to imaging after their initial release in 2013. Our objective was to determine this, as well as whether provider-specific audit and feedback for imaging had been implemented in these EDs. Methods: This survey study was exempt from institutional review board review. In 2015, we mailed surveys to 195 hospital-affiliated EDs in all six New England states to determine whether they had implemented Choosing Wisely-focused interventions in 2014. Initial mailings included cover letters denoting the endorsement of each state’s ACEP chapter, and we followed up twice with repeat mailings to non-responders. Data analysis included descriptive statistics and a comparison of state differences using Fisher’s exact test. Results: A total of 169/195 (87%) of New England EDs responded, with all individual state response rates >80%. Overall, 101 (60%) of responding EDs had implemented an intervention for at least one Choosing Wisely imaging scenario; 57% reported implementing a specific guideline/policy/clinical pathway and 28% reported implementing a computerized decision support system. The most common interventions were for chest computed tomography (CT) in patients at low risk of pulmonary embolism (47% of EDs) and head CT in patients with minor trauma (45% of EDs). In addition, 40% of EDs had implemented provider-specific audit and feedback, without significant interstate variation (range: 29–55%). Conclusion: One year after release of the ACEP Choosing Wisely recommendations, most New England EDs had a guideline/policy/clinical pathway related to at least one of the recommendations. However, only a minority of them were using provider-specific audit and feedback or computerized decision support. Few EDs have embraced the opportunity to implement the multiple evidence-based interventions likely to advance the national goals of improving patient-centered and resource-efficient care

Association of Guideline-concordant Acute Asthma Care in the Emergency Department With Shorter Hospital Length of Stay: A Multicenter Observational Study.

OBJECTIVES: The objectives were to determine whether guideline-concordant emergency department (ED) management of acute asthma is associated with a shorter hospital length of stay (LOS) among patients hospitalized for asthma. METHODS: A multicenter chart review study of patients aged 2-54 years who were hospitalized for acute asthma at one of the 25 U.S. hospitals during 2012-2013. Based on level A recommendations from national asthma guidelines, we derived four process measures of ED treatment before hospitalization: inhaled β-agonists, inhaled anticholinergic agents, systemic corticosteroids, and lack of methylxanthines. The outcome measure was hospital LOS. RESULTS: Among 854 ED patients subsequently hospitalized for acute asthma, 532 patients (62%) received care perfectly concordant with the four process measures in the ED. Overall, the median hospital LOS was 2 days (interquartile range = 1-3 days). In the multivariable negative binomial model, patients who received perfectly concordant ED asthma care had a significantly shorter hospital LOS (-17%, 95% confidence interval [CI] = -27% to -5%, p = 0.006), compared to other patients. In the mediation analysis, the direct effect of guideline-concordant ED asthma care on hospital LOS was similar to that of primary analysis (-16%, 95% CI = -27% to -5%, p = 0.005). By contrast, the indirect effect mediated by quality of inpatient asthma care was not significant, indicating that the effect of ED asthma care on hospital LOS was mediated through pathways other than quality of inpatient care. CONCLUSION: In this multicenter observational study, patients who received perfectly concordant asthma care in the ED had a shorter hospital LOS. Our findings encourage further adoption of guideline-recommended emergency asthma care to improve patient outcomes

Impact of community intervention to reduce patient delay time on use of reperfusion therapy for acute myocardial infarction: rapid early action for coronary treatment (REACT) trial. REACT Study Group

BACKGROUND: Reperfusion therapy for acute myocardial infarction (AMI) is a time-dependent intervention that can reduce infarct-related morbidity and mortality. Out-of-hospital patient delay from symptom onset until emergency department (ED) presentation may reduce the expected benefit of reperfusion therapy. OBJECTIVE: To determine the impact of a community educational intervention to reduce patient delay time on the use of reperfusion therapy for AMI. METHODS: This was a randomized, controlled community-based trial to enhance patient recognition of AMI symptoms and encourage early ED presentation with resultant increased reperfusion therapy rates for AMI. The study took place in 44 hospitals in 20 pair-matched communities in five U.S. geographic regions. Eligible study subjects were non-institutionalized patients without chest injury (aged \u3e or =30 years) who were admitted to participating hospitals and who received a hospital discharge diagnosis of AMI (ICD 410); n = 4,885. For outcome assessment, patients were excluded if they were without survival data (n = 402), enrolled in thrombolytic trials (n = 61), receiving reperfusion therapy \u3e12 hours after ED arrival (n = 628), or missing symptom onset or reperfusion times (n = 781). The applied intervention was an educational program targeting community organizations and the general public, high-risk patients, and health professionals in target communities. The primary outcome was a change in the proportion of AMI patients receiving early reperfusion therapy (i.e., within one hour of ED arrival or within six hours of symptom onset). Trends in reperfusion therapy rates were determined after adjustment for patient demographics, presenting blood pressure, cardiac history, and insurance status. Four-month baseline was compared with the 18-month intervention period. RESULTS: Of 3,013 selected AMI patients, 40% received reperfusion therapy. Eighteen percent received therapy within one hour of ED arrival (46% of treated patients), and 32% within six hours of symptom onset (80% of treated patients). No significant difference in the trends in reperfusion therapy rates was attributable to the intervention, although increases in early reperfusion therapy rates were noted during the first six months of the intervention. A significant association of early reperfusion therapy use with ambulance use was identified. CONCLUSIONS: Community-wide educational efforts to enhance patient response to AMI symptoms may not translate into sustained changes in reperfusion practices. However, an increased odds for early reperfusion therapy use during the initiation of the intervention and the association of early therapy with ambulance use suggest that reperfusion therapy rates can be enhanced