DNA representation of variegating heterochromatic P-element inserts in diploid and polytene tissues of Drosophila melanogaster

Position-effect variegation (PEV) is the mosaic expression of a euchromatic gene brought into juxtaposition with heterochromatin. Fourteen different transformed Drosophila melanogaster lines with variegating P-element inserts were used to examine the DNA levels of these transgenes. Insert sites include pericentric, telomeric and fourth chromosome regions. Southern blot analyses showed that the heterochromatic hsp26 transgenes are underrepresented 1.3- to 33-fold in polytene tissue relative to the endogenous euchromatic hsp26 gene. In contrast, the heterochromatic hsp26 transgenes are present in approximately the same copy number as the endogenous euchromatic hsp26 gene in diploid tissue. It appears unlikely that DNA loss could account for the lack of gene expression in diploid tissues seen with these examples of PEV

Inpatient Management of Bronchial Asthma for the Hospitalist

Asthma is a common inflammatory disease of the airways that leads to significant hospital utilization and health care cost around the world. Despite published guidelines, the diagnosis and treatment of acute asthma exacerbation varies widely due to inconsistent compliance with guidelines. We will review the evidence, guideline recommendations, clinical presentation, risk factors, and management of acute asthma exacerbations, including standard and advanced treatment options for refractory cases.Michael P. Hunter (1), Suman Vaddi (1), Armin Krvavac (1), Hariharan Regunath (1,2), Vamsi P. Guntur (3); 1. Department of Medicine, Division of Pulmonary, Critical Care, and Environmental Medicine, University of Missouri. 2. Department of Medicine, Division of Infectious Diseases, University of Missouri. 3. Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health.Includes bibliographical reference

Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC)

Exercise intolerance is a major manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus infection (PASC, or “long-COVID”). Exercise intolerance in PASC is associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism and mitochondrial dysfunction. It remains unclear whether the profound disturbances in metabolism that have been identified in plasma from patients suffering from acute coronavirus disease 2019 (COVID-19) are also present in PASC. To bridge this gap, individuals with a history of previous acute COVID-19 infection that did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) and were grouped into those that developed PASC (n = 29) and those that fully recovered (n = 16). Plasma samples from the two groups were analyzed via mass spectrometry-based untargeted metabolomics and compared against plasma metabolic profiles of healthy control individuals (n = 30). Observational demographic and clinical data were retrospectively abstracted from the medical record. Compared to plasma of healthy controls or individuals who recovered from COVID-19, PASC plasma exhibited significantly higher free- and carnitine-conjugated mono-, poly-, and highly unsaturated fatty acids, accompanied by markedly lower levels of mono-, di- and tricarboxylates (pyruvate, lactate, citrate, succinate, and malate), polyamines (spermine) and taurine. Plasma from individuals who fully recovered from COVID-19 exhibited an intermediary metabolic phenotype, with milder disturbances in fatty acid metabolism and higher levels of spermine and taurine. Of note, depletion of tryptophan—a hallmark of disease severity in COVID-19—is not normalized in PASC patients, despite normalization of kynurenine levels—a tryptophan metabolite that predicts mortality in hospitalized COVID-19 patients. In conclusion, PASC plasma metabolites are indicative of altered fatty acid metabolism and dysfunctional mitochondria-dependent lipid catabolism. These metabolic profiles obtained at rest are consistent with previously reported mitochondrial dysfunction during exercise, and may pave the way for therapeutic intervention focused on restoring mitochondrial fat-burning capacity