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Determining how defects in connexin43 cause skeletal disease.

ABSTRACT: Gap junction channels mediate direct cell-cell communication via the exchange of second messengers, ions, and metabolites from one cell to another. Mutations in several human connexin (cx) genes, the subunits of gap junction channels, disturb the development and function of multiple tissues/organs. In particular, appropriate function of Cx43 is required for skeletal development in all vertebrate model organisms. Importantly, it remains largely unclear how disruption of gap junctional intercellular communication causes developmental defects. Two groups have taken distinct approaches toward defining the tangible molecular changes occurring downstream of Cx43-based gap junctional communication. Here, these strategies for determining how Cx43 modulates downstream events relevant to skeletal morphogenesis were reviewed.

SUBMITTER: Ton QV

PROVIDER: S-EPMC4540067 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Determining how defects in connexin43 cause skeletal disease.

Ton Quynh V QV Iovine M Kathryn MK

Genesis (New York, N.Y. : 2000) 20121016 2

Gap junction channels mediate direct cell-cell communication via the exchange of second messengers, ions, and metabolites from one cell to another. Mutations in several human connexin (cx) genes, the subunits of gap junction channels, disturb the development and function of multiple tissues/organs. In particular, appropriate function of Cx43 is required for skeletal development in all vertebrate model organisms. Importantly, it remains largely unclear how disruption of gap junctional intercellul ...[more]

PMID: 23019186

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Project description:Controversy exists whether the cause of death due to severe acute respiratory syndrome coronavirus 2 is directly related to the infection or to underlying conditions. The purpose of this study is to assess the relationship of severe acute respiratory syndrome coronavirus 2 infection with the cause of death in hospitalized patients.DesignRetrospective observational study; deidentified discharge summaries of deceased patients were reviewed by two intensivists and classified as coronavirus disease 2019-related (caused by severe acute respiratory syndrome coronavirus 2) or coronavirus disease 2019-unrelated (not caused by severe acute respiratory syndrome coronavirus 2 or indeterminate) deaths. For classification disagreement, a separate group of three intensivists reviewed the discharge summaries and arbitrated to determine the cause of death.SettingSingle-center study performed at the University of Texas Medical Branch.PatientsAll adult patients (> 18 yr) admitted from March 10, 2020, to October 22, 2020, with positive severe acute respiratory syndrome coronavirus 2 test results who expired during their hospitalization were identified.InterventionsNone.Measurements and main resultsPatient demographics, comorbidities, prescribed medications, and ventilatory support data were collected. Comparison between groups was performed using t test and chi-square test. During the study period, 1,052 patients were admitted within 14 days of severe acute respiratory syndrome coronavirus 2-positive test results, of whom 100 expired during the hospitalization. Deceased patients were predominantly male and older than 65 years. Obesity (body mass index ≥ 30 kg/m2) was present in 41%, and common comorbidities included hypertension (47%), diabetes (30%), and heart failure (20%). Death was classified as directly caused by severe acute respiratory syndrome coronavirus 2 in 85% and not caused by severe acute respiratory syndrome coronavirus 2 in 5%. An indeterminate cause of death in 10% was due to insufficient information or an atypical presentation. The observed interrater agreement on the cause of death classification was 81%.ConclusionsIn this single-center study, the majority of deaths in severe acute respiratory syndrome coronavirus 2-positive hospitalized patients were related to a typical or atypical presentation of coronavirus disease 2019 disease.

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Determining how defects in connexin43 cause skeletal disease.

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Determining how defects in connexin43 cause skeletal disease.

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