National Centers for Coastal Ocean Science Coastal Ecosystem Assessment Program: a manual of methods

Environmental managers strive to preserve natural resources for future generations but have limited decision-making tools to define ecosystem health. Many programs offer relevant broad-scale, environmental policy information on regional ecosystem health. These programs provide evidence of environmental condition and change, but lack connections between local impacts and direct effects on living resources. To address this need, the National Oceanic and Atmospheric Administration/National Ocean Service (NOAA/NOS) Cooperative Oxford Laboratory (COL), in cooperation with federal, state, and academic partners, implemented an integrated biotic ecosystem assessment on a sub-watershed 14-digit Hydrologic Unit Code (HUD) scale in Chesapeake Bay. The goals of this effort were to 1) establish a suite of bioindicators that are sensitive to ecosystem change, 2) establish the effects of varying land-use patterns on water quality and the subsequent health of living resources, 3) communicate these findings to local decision-makers, and 4) evaluate the success of management decisions in these systems. To establish indicators, three sub-watersheds were chosen based on statistical analysis of land-use patterns to represent a gradient from developed to agricultural. The Magothy (developed), Corsica (agricultural), and Rhode (reference) Rivers were identified. A random stratified design was developed based on depth (2m contour) and river mile. Sampling approaches were coordinated within this structure to allow for robust system comparisons. The sampling approach was hierarchal, with metrics chosen to represent a range from community to cellular level responses across multiple organisms. This approach allowed for the identification of sub-lethal stressors, and assessment of their impact on the organism and subsequently the population. Fish, crabs, clams, oysters, benthic organisms, and bacteria were targeted, as each occupies a separate ecological niche and may respond dissimilarly to environmental stressors. Particular attention was focused on the use of pathobiology as a tool for assessing environmental condition. By integrating the biotic component with water quality, sediment indices, and land- use information, this holistic evaluation of ecosystem health will provide management entities with information needed to inform local decision-making processes and establish benchmarks for future restoration efforts

Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes

The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/ Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between fulllength Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit a-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein- protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions

The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch\u27s APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch\u27s data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch\u27s analytic tools by developing a customized plugin for OpenAI\u27s ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

A multicenter study of ICU telemedicine reengineering of adult critical care

BACKGROUND: Few studies have evaluated both the overall effect of ICU telemedicine programs and the effect of individual components of the intervention on clinical outcomes. METHODS: The effects of nonrandomized ICU telemedicine interventions on crude and adjusted mortality and length of stay (LOS) were measured. Additionally, individual intervention components related to process and setting of care were evaluated for their association with mortality and LOS. RESULTS: Overall, 118,990 adult patients (11,558 control subjects, 107,432 intervention group patients) from 56 ICUs in 32 hospitals from 19 US health-care systems were included. After statistical adjustment, hospital (hazard ratio [HR]=0.84; 95% CI, 0.78-0.89; P \u3c .001) and ICU (HR=0.74; 95% CI, 0.68-0.79; P \u3c .001) mortality in the ICU telemedicine intervention group was significantly better than that of control subjects. Moreover, adjusted hospital LOS was reduced, on average, by 0.5 (95% CI, 0.4-0.5), 1.0 (95% CI, 0.7-1.3), and 3.6 (95% CI, 2.3-4.8) days, and adjusted ICU LOS was reduced by 1.1 (95% CI, 0.8-1.4), 2.5 (95% CI, 1.6-3.4), and 4.5 (95% CI, 1.5-7.2) days among those who stayed in the ICU for \u3e /=7, \u3e /=14, and \u3e /=30 days, respectively. Individual components of the interventions that were associated with lower mortality, reduced LOS, or both included (1) intensivist case review within 1 h of admission, (2) timely use of performance data, (3) adherence to ICU best practices, and (4) quicker alert response times. CONCLUSIONS: ICU telemedicine interventions, specifically interventions that increase early intensivist case involvement, improve adherence to ICU best practices, reduce response times to alarms, and encourage the use of performance data, were associated with lower mortality and LOS

Proteolytic activity of cultured Pseudoperkinsus tapetis extracellular products

8 páginas, 3 tablas, 2 figurasSeveral pathogenic protozoan release proteases are necessary for host invasion and initiation of infection. We have identified proteolytic activities in extracellular proteins secreted by the clam parasite Pseudoperkinsus tapetis ŽMesomycetozoa.in vitro. The protein concentration of the P. tapetis extracellular productsŽECP.increased only during the first week of culture. The appearance of new proteins of 10 and 157 kDa at the second week sample and of 12 kDa at the third week sample was shown by SDS-PAGE. The protease activity rapidly increased in the first 3 weeks of culture, and five clear bands of 23, 29, 60, 67 and 96 kDa with proteolytic activity were detected in the ECP on gelatin SDS-PAGE. Using inhibitors, the proteases were identified as members of the Ca2 dependent, serine protease family. Their optimum pH was higher than pH 9.4. The protease activity of the P. tapetis ECP was different than that described for Perkinsus marinus, an oyster pathogen very similar morphologically to the clam parasite and member of the genus in which P. tapetis had been initially included.M.C. Ordás thanks the Xunta de Galicia for financial assistance. The work was partially funded by the Fulbright Commission for Cultural, Educational and Scientific Exchange between the United States of America and Spain.Peer reviewe

Influenza A Virus Detected in Native Bivalves in Waterfowl Habitat of the Delmarva Peninsula, USA

We evaluated the prevalence of influenza A virus (IAV) in different species of bivalves inhabiting natural water bodies in waterfowl habitat along the Delmarva Peninsula and Chesapeake Bay in eastern Maryland. Bivalve tissue from clam and mussel specimens (Macoma balthica, Macoma phenax, Mulinia sp., Rangia cuneata, Mya arenaria, Guekensia demissa, and an undetermined mussel species) from five collection sites was analyzed for the presence of type A influenza virus by qPCR targeting the matrix gene. Of the 300 tissue samples analyzed, 13 samples (4.3%) tested positive for presence of influenza virus A matrix gene. To our knowledge, this is the first report of detection of IAV in the tissue of any bivalve mollusk from a natural water body

Observations of a new source of coral mortality along the Kenyan coast

In early 2002 coral mortality occurred along 600 km of coastline from Tanzania to Kenya. Astreopora, Echinopora, and Montipora species were severely affected, with Montipora being nearly eliminated from Kenyan reefs. Acropora, Platygyra, Goniopora, and massive Porites were also affected; however, Porites and Goniopora rarely died and often recovered, whereas death for most other species occurred within 2 weeks. In Echinopora and Montipora, a dull ashy tissue color and brittle skeletons characterized the early stages of this event with a mucus layer on the tissue surface in intermediate stages. Mucus and embedded debris then disappeared and surfaces were left covered in a white calcareous dust that sometimes capped a black layer. Astreopora tissues became dull and pale, and seldom produced mucus; eventually the skeleton became bare and white. Either a colorless translucent or brownish thin margin of tissue was visible between living tissue and bare skeleton, depending on species. Scanning electron micrographs of affected corals revealed the presence of fungi. Histology and staining showed that the fungi were mostly in the three genera that died from the syndrome and it may be that fungi invaded and killed corals weakened by another unidentified pathogen