Creating a Discipline-specific Commons for Infectious Disease Epidemiology

Objective: To create a commons for infectious disease (ID) epidemiology in which epidemiologists, public health officers, data producers, and software developers can not only share data and software, but receive assistance in improving their interoperability. Materials and Methods: We represented 586 datasets, 54 software, and 24 data formats in OWL 2 and then used logical queries to infer potentially interoperable combinations of software and datasets, as well as statistics about the FAIRness of the collection. We represented the objects in DATS 2.2 and a software metadata schema of our own design. We used these representations as the basis for the Content, Search, FAIR-o-meter, and Workflow pages that constitute the MIDAS Digital Commons. Results: Interoperability was limited by lack of standardization of input and output formats of software. When formats existed, they were human-readable specifications (22/24; 92%); only 3 formats (13%) had machine-readable specifications. Nevertheless, logical search of a triple store based on named data formats was able to identify scores of potentially interoperable combinations of software and datasets. Discussion: We improved the findability and availability of a sample of software and datasets and developed metrics for assessing interoperability. The barriers to interoperability included poor documentation of software input/output formats and little attention to standardization of most types of data in this field. Conclusion: Centralizing and formalizing the representation of digital objects within a commons promotes FAIRness, enables its measurement over time and the identification of potentially interoperable combinations of data and software.Comment: 12 pages, 6 figure

The L1 cell adhesion molecule constrains dendritic spine density in pyramidal neurons of the mouse cerebral cortex

A novel function for the L1 cell adhesion molecule, which binds the actin adaptor protein Ankyrin was identified in constraining dendritic spine density on pyramidal neurons in the mouse neocortex. In an L1-null mouse mutant increased spine density was observed on apical but not basal dendrites of pyramidal neurons in diverse cortical areas (prefrontal cortex layer 2/3, motor cortex layer 5, visual cortex layer 4. The Ankyrin binding motif (FIGQY) in the L1 cytoplasmic domain was critical for spine regulation, as demonstrated by increased spine density and altered spine morphology in the prefrontal cortex of a mouse knock-in mutant (L1YH) harboring a tyrosine (Y) to histidine (H) mutation in the FIGQY motif, which disrupted L1-Ankyrin association. This mutation is a known variant in the human L1 syndrome of intellectual disability. L1 was localized by immunofluorescence staining to spine heads and dendrites of cortical pyramidal neurons. L1 coimmunoprecipitated with Ankyrin B (220 kDa isoform) from lysates of wild type but not L1YH forebrain. This study provides insight into the molecular mechanism of spine regulation and underscores the potential for this adhesion molecule to regulate cognitive and other L1-related functions that are abnormal in the L1 syndrome

Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults.

Thiamine (vitamin B1) is an essential nutrient that serves as a cofactor for a number of enzymes, mostly with mitochondrial localization. Some thiamine-dependent enzymes are involved in energy metabolism and biosynthesis of nucleic acids whereas others are part of the antioxidant machinery. The brain is highly vulnerable to thiamine deficiency due to its heavy reliance on mitochondrial ATP production. This is more evident during rapid growth (i.e., perinatal periods and children) in which thiamine deficiency is commonly associated with either malnutrition or genetic defects. Thiamine deficiency contributes to a number of conditions spanning from mild neurological and psychiatric symptoms (confusion, reduced memory, and sleep disturbances) to severe encephalopathy, ataxia, congestive heart failure, muscle atrophy, and even death. This review discusses the current knowledge on thiamine deficiency and associated morbidity of neurological and psychiatric disorders, with special emphasis on the pediatric population, as well as the putative beneficial effect of thiamine supplementation in autism spectrum disorder (ASD) and other neurological conditions

Post-Translational Modifications of the Paired Box Transcription Factor 7 (Pax7) in Satellite Cells During the Repair of Injured Skeletal Muscle

Satellite cells are normally a quiescent skeletal muscle stem cell pool that upon activation rapidly proliferate and differentiate to repair damaged muscle fibers. The paired box transcription factor 7 (Pax7) is the canonical biomarker for quiescent, activated, and proliferating satellite cells and is rapidly down-regulated upon differentiation into myofibers. However, the factors that regulate the modulation of Pax7 are largely unknown. Post-translational modifications to Pax7 provide a viable means to activate or deactivate this transcription factor through the signaling cascade of skeletal muscle repair and regeneration. The sirtuin 1 (Sirt1) protein, a histone deacetylase, has been shown to be involved in many cellular processes, including the differentiation of myoblasts. Although Sirt1 is noted for its role in the differentiation of myoblasts, it is not known if it directly interacts with Pax7. The general control of amino acid synthesis protein 5-like 2 (GCN5), an acetyltransferase, is known to work in conjunction with Sirt1 modulating PGC-1&agr; in hepatic gluconeogenesis. With this information, it is logical to test if GCN5 also works with Sirt1 in the satellite cell response to muscle injury. The primary objective of this study is to determine the role of GCN5 and Sirt1 on Pax7-mediated regulation of satellite cell function. We tested the novel hypothesis that GCN5 is a binding partner with Pax7 and acts on Pax7 via acetylation leading to satellite cell activation and proliferation while Sirt1 is another binding partner of Pax7 and acts on Pax7 via deacetylation. The tibialis anterior (TA) muscles of wild-type mice were injected with cardiotoxin (CTX) to induce muscle injury. The TA muscles where harvested 4, 7, 14, or 21 days post-injection to analyze the satellite cell response to regulate muscle repair following the CTX injury. Western Blot data showed that the total protein abundance of Pax7, GCN5, and acetylated protein at 57kD (Pax7 molecular weight) were significantly up-regulated 4, 7, and 14 days post CTX injection, but had returned to basal levels by 21 days post CTX injection. From 4 through 14 days post injection Pax7 abundance was ∼592%, 204%, and 219% greater compared to control muscles. GCN5 abundance was ∼215%, 330%, and 213% greater from 4 through 14 days post injection, and acetylated protein at 57kD was ∼651%, 291%, and 404% greater compared to controls. The abundance of Sirt1 protein was significantly increased at 14 days post CTX injection with ∼ 259% greater abundance compared to control muscles and approached basal levels by 21 days post CTX injection. Although not significant, there was ∼111% greater abundance of Sirt1 protein 7 days post CTX injection relative to control muscles. Immunoprecipitation studies showed that GCN5 was directly associated with Pax7 during all recovery time points, with 21 days post CTX injury not having as strong association compared to the other time points. The membrane was then stripped and probed for acetylated lysine, which mirrored the GCN5 association pattern. Sirt1 was also tested for interaction and showed to be directly interacting with Pax7 during the 7, 14, and 21 days post CTX injury time points. Immunohistochemistry confirmed that Pax7 and GCN5 were co-localized to muscle nuclei in the 4 day regenerating muscles; this confirms that Pax7 and GCN5 interact during activation and proliferation of satellite cells. Immunohistochemistry also confirmed that Pax7 and Sirt1 were co-localized in the 14 day regenerating muscles; this confirms that Pax7 and Sirt1 interact during the differentiation of myoblasts. These novel data support the hypotheses that GCN5 acetylates Pax7 to rapidly activate and proliferate satellite cells in response to skeletal muscle damage while Sirt1 deacetylates Pax7 to differentiate myoblasts

Apollo Location Service

<p>The Apollo Location Service is a web service that accesses a database of information about locations in which the identifiers are not only location specific but time specific.</p