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Decrypting the Information Exchange Pathways across the Spliceosome Machinery.

ABSTRACT: Intron splicing of a nascent mRNA transcript by spliceosome (SPL) is a hallmark of gene regulation in eukaryotes. SPL is a majestic molecular machine composed of an entangled network of proteins and RNAs that meticulously promotes intron splicing through the formation of eight intermediate complexes. Cross-communication among the critical distal proteins of the SPL assembly is pivotal for fast and accurate directing of the compositional and conformational readjustments necessary to achieve high splicing fidelity. Here, molecular dynamics (MD) simulations of an 800 000 atom model of SPL C complex from yeast Saccharomyces cerevisiae and community network analysis enabled us to decrypt the complexity of this huge molecular machine, by identifying the key channels of information transfer across long distances separating key protein components. The reported study represents an unprecedented attempt in dissecting cross-communication pathways within one of the most complex machines of eukaryotic cells, supporting the critical role of Clf1 and Cwc2 splicing cofactors and specific domains of the Prp8 protein as signal conveyors for pre-mRNA maturation. Our findings provide fundamental advances into mechanistic aspects of SPL, providing a conceptual basis for controlling the SPL via small-molecule modulators able to tackle splicing-associated diseases by altering/obstructing information-exchange paths.

SUBMITTER: Saltalamacchia A

PROVIDER: S-EPMC7339022 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Decrypting the Information Exchange Pathways across the Spliceosome Machinery.

Saltalamacchia Andrea A Casalino Lorenzo L Borišek Jure J Batista Victor S VS Rivalta Ivan I Magistrato Alessandra A

Journal of the American Chemical Society 20200422 18

Intron splicing of a nascent mRNA transcript by spliceosome (SPL) is a hallmark of gene regulation in eukaryotes. SPL is a majestic molecular machine composed of an entangled network of proteins and RNAs that meticulously promotes intron splicing through the formation of eight intermediate complexes. Cross-communication among the critical distal proteins of the SPL assembly is pivotal for fast and accurate directing of the compositional and conformational readjustments necessary to achieve high ...[more]

PMID: 32275149

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Project description:BackgroundThe COVID-19 pandemic revealed major gaps in public health agencies' (PHAs') data and reporting infrastructure, which limited the ability of public health officials to conduct disease surveillance, particularly among racial or ethnic minorities disproportionally affected by the pandemic. Leveraging existing health information exchange organizations (HIOs) is one possible mechanism to close these technical gaps, as HIOs facilitate health information sharing across organizational boundaries.ObjectiveThe aim of the study is to survey all HIOs that are currently operational in the United States to assess HIO connectivity with PHAs and HIOs' capabilities to support public health data exchange.MethodsDrawing on multiple sources, we identified all potential local, regional, and state HIOs that were operational in the United States as of March 1, 2022. We defined operational as HIOs that facilitated exchange between at least 2 independent entities. We fielded a survey among our census list of 135 HIOs in January-July 2023. The survey confirmed HIO status as well as captured organizational demographics and current and potential support for PHAs. We report descriptive statistics on HIO demographics and connectivity with PHAs. We also include results on services and data available to support PHAs, funding sources to support public health reporting, and barriers to public health reporting. Of the 135 potential HIOs that received the survey, 90 met our definition of an HIO, and 77 completed the survey, yielding an 86% response rate.ResultsWe found that 66 (86%) of HIOs in 45 states were electronically connected to at least 1 PHA, yielding 187 HIO-PHA connections across all HIOs. Among HIOs connected to PHAs, the most common type of public health reporting supported by HIOs was immunization registry (n=39, 64%), electronic laboratory result (n=37, 63%), and syndromic surveillance (n=34, 61%). In total, 58% (n=38) of HIOs connected to PHAs provided data to address COVID-19 information gaps, and an additional 30% (n=20) could do so. The most common types of data provided to PHAs were hospitalization information (n=54, 93%), other demographic data (n=53, 91%), health information (eg, chronic health conditions; n=51, 88%), and hospital laboratory results (n=51, 88%). A total of 64% (n=42) of HIOs provided at least 1 type of data analytic service to PHAs to support COVID-19 pandemic response efforts. Top HIO reported barriers to support PHA activities included limited PHA funding (n=21, 32%) and PHAs' competing priorities (n=15, 23%).ConclusionsOur results show that many HIOs are already connected to PHAs and that they are assuming an emerging role to facilitate public health reporting. HIOs are well-positioned to provide value-added support for public health data exchange and address PHAs' information gaps, as ongoing federal efforts to modernize public health data infrastructure and interoperability continue.

Project description:BackgroundThe integration of medical and dental records is gaining significance over the past 2 decades. However, few studies have evaluated the opinions of practicing dentists on patient medical histories. Questions remain on dentists' information needs; their perception of the reliability of patient-reported medical history; satisfaction with the available information and the methods to gather this information; and their attitudes to other options, such as a health information exchange (HIE) network, to collect patient medical history.ObjectiveThis study aims to determine Indiana dentists' information needs regarding patients' medical information and their opinions about accessing it via an HIE.MethodsWe administered a web-based survey to Indiana Dental Association members to assess their current medical information-retrieval approaches, the information critical for dental care, and their willingness to access or share information via an HIE. We used descriptive statistics to summarize survey results and multivariable regression to examine the associations between survey respondents' characteristics and responses.ResultsOf the 161 respondents (161/2148, 7.5% response rate), 99.5% (n=160) respondents considered patients' medical histories essential to confirm no contraindications, including allergies or the need for antibiotic prophylaxis during dental care and other adverse drug events. The critical information required were medical conditions or diagnosis, current medications, and allergies, which were gathered from patient reports. Furthermore, 88.2% (n=142) of respondents considered patient-reported histories reliable; however, they experienced challenges obtaining information from patients and physicians. Additionally, 70.2% (n=113) of respondents, especially those who currently access an HIE or electronic health record, were willing to use an HIE to access or share their patient's information, and 91.3% (n=147) shared varying interests in such a service. However, usability, data accuracy, data safety, and cost are the driving factors in adopting an HIE.ConclusionsPatients' medical histories are essential for dentists to optimize dental care, especially for those with chronic conditions. In addition, most dentists are interested in using an HIE to access patient medical histories. The findings from this study can provide an alternative option for improving communications between dental and medical professionals and help the health information technology system or tool developers identify critical requirements for more user-friendly designs.

Dataset Information

Decrypting the Information Exchange Pathways across the Spliceosome Machinery.

Publications

Decrypting the Information Exchange Pathways across the Spliceosome Machinery.

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