SUMMARY Rising levels of atmospheric CO 2 lead to acidification of the ocean and alter seawater carbonate chemistry, which can negatively impact calcifying organisms, including mollusks. In estuaries, exposure to elevated CO 2 levels often co-occurs with other stressors, such as reduced salinity, which enhances the acidification trend, affects ion and acid–base regulation of estuarine calcifiers and modifies their response to ocean acidification. We studied the interactive effects of salinity and partial pressure of CO 2 ( P CO2 ) on biomineralization and energy homeostasis in juveniles of the eastern oyster, Crassostrea virginica , a common estuarine bivalve. Juveniles were exposed for 11 weeks to one of two environmentally relevant salinities (30 or 15 PSU) either at current atmospheric P CO2 (∼400 μatm, normocapnia) or P CO2 projected by moderate IPCC scenarios for the year 2100 (∼700–800 μatm, hypercapnia). Exposure of the juvenile oysters to elevated P CO2 and/or low salinity led to a significant increase in mortality, reduction of tissue energy stores (glycogen and lipid) and negative soft tissue growth, indicating energy deficiency. Interestingly, tissue ATP levels were not affected by exposure to changing salinity and P CO2 , suggesting that juvenile oysters maintain their cellular energy status at the expense of lipid and glycogen stores. At the same time, no compensatory upregulation of carbonic anhydrase activity was found under the conditions of low salinity and high P CO2 . Metabolic profiling using magnetic resonance spectroscopy revealed altered metabolite status following low salinity exposure; specifically, acetate levels were lower in hypercapnic than in normocapnic individuals at low salinity. Combined exposure to hypercapnia and low salinity negatively affected mechanical properties of shells of the juveniles, resulting in reduced hardness and fracture resistance. Thus, our data suggest that the combined effects of elevated P CO2 and fluctuating salinity may jeopardize the survival of eastern oysters because of weakening of their shells and increased energy consumption.

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Interactive effects of salinity and elevated CO2 levels on juvenile eastern oysters, Crassostrea virginica.

Synthesis, characterization, inhibition effects, and molecular docking studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors of novel benzenesulfonamides incorporating 1,3,5-triazine structural motifs

Objectives: To determine the serum levels of methylglyoxal (MG) and carbonic anhydrase (CA) activity in known cases of type-II diabetes mellitus with insulin resistance and to compare them with age-sex matched healthy controls. Methods: Eightysix participants were enrolled for the present case-controlled study with ages ranging from 25 to 44 years. The analytes measured were fasting blood glucose, serum insulin, methylglyoxal and carbonic anhydrase assay by standard procedures. Further carbonic anhydrase activities were measured in erythrocytes haemolysate and the effect of methylglyoxal on erythrocyte membrane was studied. The effects of methylglyoxal on erythrocyte carbonic anhydrase activity and insulin reactivity were also measured. Results: The mean serum levels of insulin, fasting blood glucose, carbonic anhydrase activity, methylglyoxal and body mass index (BMI) was significantly higher (p<0.001) in patients compared to the controls. The carbonic anhydrase activity was directly proportional to increasing blood glucose concentration. The haemolysate prepared from the erythrocytes of patients and controls also showed significantly higher carbonic anhydrase activities in patients than the controls. Increased carbonic anhydrase activity in a dose-dependent manner with methylglyoxal was also observed. Conclusion: Insulin resistance is accompanied by increased activity of carbonic anhydrase which is significantly related to increasing methylglyoxal levels.

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Study on the changes of carbonic anhydrase activity in insulin resistance and the effect of methylglyoxal.

Interactive effects of ocean acidification and multiple stressors on physiology of marine bivalves

Abstract The Illuminating the Druggable Genome (IDG) project aims to improve our understanding of understudied proteins and our ability to study them in the context of disease biology by perturbing them with small molecules, biologics, or other therapeutic modalities. Two main products from the IDG effort are the Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/), which curates and aggregates information, and Pharos (https://pharos.nih.gov/), a web interface for users to extract and visualize data from TCRD. Since the 2021 release, TCRD/Pharos has focused on developing visualization and analysis tools that help reveal higher-level patterns in the underlying data. The current iterations of TCRD and Pharos enable users to perform enrichment calculations based on subsets of targets, diseases, or ligands and to create interactive heat maps and UpSet charts of many types of annotations. Using several examples, we show how to address disease biology and drug discovery questions through enrichment calculations and UpSet charts.

Pharos 2023: an integrated resource for the understudied human proteome

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

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Database resources of the National Center for Biotechnology Information in 2023.

There are thousands of distinct disease entities and concepts, each of which are known by different and sometimes contradictory names. The lack of a unified system for managing these entities poses a major challenge for both machines and humans that need to harmonize information to better predict causes and treatments for disease. The Mondo Disease Ontology is an open, community-driven ontology that integrates key medical and biomedical terminologies, supporting disease data integration to improve diagnosis, treatment, and translational research. Mondo records the sources of all data and is continually updated, making it suitable for research and clinical applications that require up-to-date disease knowledge.

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Mondo: Unifying diseases for the world, by the world

A previous study from this laboratory showed that patients with diabetes mellitus type 2 (type 2 diabetes) have significantly lower values (P \\ 0.05) of carbonic anhydrase (CA) activity and its isozyme (CAI) concentration compared with their healthy counterparts. Furthermore, the values varied with the severity of the diabetes or insulin resistance (Gambhir et al. 2007). Kondo et al. (1975) reported contradictory results, however, as they found increased levels of both CAI and CAII in patients with diabetes. A study involving hypertensive human subjects reported 63% of hypertensive patients with decreased CA activity compared with the normotensive population, and 37% showed CA activity significantly higher than that of normotensives. Glucose intolerance, insulin resistance, and hyperinsulinemia

Adriana J. Malheiro

Papers

Database resources of the National Center for Biotechnology Information in 2023.

Mondo: Unifying diseases for the world, by the world

Erythrocyte Total Carbonic Anhydrase Esterase Activity in African American Obese Children: Reduction Starts at a Young Age