Although airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized, the condition of ventilation for its occurrence is still being debated. We analyzed a coronavirus disease 2019 (COVID-19) outbreak involving three families in a restaurant in Guangzhou, China, assessed the possibility of airborne transmission, and characterized the associated environmental conditions. We collected epidemiological data, obtained a full video recording and seating records from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the index case. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer gas concentration decay method. This outbreak involved ten infected persons in three families (A, B, C). All ten persons ate lunch at three neighboring tables at the same restaurant on January 24, 2020. None of the restaurant staff or the 68 patrons at the other 15 tables became infected. During this occasion, the measured ventilation rate was 0.9 L/s per person. No close contact or fomite contact was identified, aside from back-to-back sitting in some cases. Analysis of the airflow dynamics indicates that the infection distribution is consistent with a spread pattern representative of long-range transmission of exhaled virus-laden aerosols. Airborne transmission of the SARS-CoV-2 virus is possible in crowded space with a ventilation rate of 1 L/s per person.

Ca 2+ /calmodulin-dependent kinase II (CaMKII) has been implicated in cardiac hypertrophy and heart failure. We generated mice in which the predominant cardiac isoform, CaMKIIδ, was genetically deleted (KO mice), and found that these mice showed no gross baseline changes in ventricular structure or function. In WT and KO mice, transverse aortic constriction (TAC) induced comparable increases in relative heart weight, cell size, HDAC5 phosphorylation, and hypertrophic gene expression. Strikingly, while KO mice showed preserved hypertrophy after 6-week TAC, CaMKIIδ deficiency significantly ameliorated phenotypic changes associated with the transition to heart failure, such as chamber dilation, ventricular dysfunction, lung edema, cardiac fibrosis, and apoptosis. The ratio of IP 3 R2 to ryanodine receptor 2 (RyR2) and the fraction of RyR2 phosphorylated at the CaMKII site increased significantly during development of heart failure in WT mice, but not KO mice, and this was associated with enhanced Ca 2+ spark frequency only in WT mice. We suggest that CaMKIIδ contributes to cardiac decompensation by enhancing RyR2-mediated sarcoplasmic reticulum Ca 2+ leak and that attenuating CaMKIIδ activation can limit the progression to heart failure.

words)Main text (3456 words) AbstractBackground: The role of aerosols in the transmission of SARS-CoV-2 remains debated. We analysed an outbreak involving three non-associated families in Restaurant X in Guangzhou, China, and assessed the possibility of aerosol transmission of SARS-CoV-2 and characterize the associated environmental conditions. : medRxiv preprint 2 Methods: We collected epidemiological data, obtained a video record and a patron seatingarrangement from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the suspected index patient. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer decay method.Results: Three families (A, B, C), 10 members of which were subsequently found to have been infected with SARS-CoV-2 at this time, or previously, ate lunch at Restaurant X on Chinese New Year's Eve (January 24, 2020) at three neighboring tables. Subsequently, three members of family B and two members of family C became infected with SARS-CoV-2, whereas none of the waiters or 68 patrons at the remaining 15 tables became infected. During this occasion, the ventilation rate was 0.75-1.04 L/s per person. No close contact or fomite contact was observed, aside from back-to-back sitting by some patrons. Our results show that the infection distribution is consistent with a spread pattern representative of exhaled virus-laden aerosols.Conclusions: Aerosol transmission of SARS-CoV-2 due to poor ventilation may explain the community spread of COVID-19.

The ␦ B and ␦ C splice variants of Ca 2؉ /calmodulin-dependent protein kinase II (CaMKII), which differ by the presence of a nuclear localization sequence, are both expressed in cardiomyocytes. We used transgenic (TG) mice and CaMKII expression in cardiomyocytes to test the hypothesis that the CaMKII␦ C isoform regulates cytosolic Ca 2؉ handling and the ␦ B isoform, which localizes to the nucleus, regulates gene transcription. Phosphorylation of CaMKII sites on the ryanodine receptor (RyR) and on phospholamban (PLB) were increased in CaMKII␦ C TG. This was associated with markedly enhanced sarcoplasmic reticulum (SR) Ca 2؉ spark frequency and decreased SR Ca 2؉ content in cardiomyocytes. None of these parameters were altered in TG mice expressing the nuclear-targeted CaMKII␦ B . In contrast, cardiac expression of either CaMKII␦ B or ␦ C induced transactivation of myocyte enhancer factor 2 (MEF2) gene expression and up-regulated hypertrophic marker genes. Studies using rat ventricular cardiomyocytes confirmed that CaMKII␦ B and ␦ C both regulate MEF2-luciferase gene expression, increase histone deacetylase 4 (HDAC4) association with 14-3-3, and induce HDAC4 translocation from nucleus to cytoplasm, indicating that either isoform can stimulate HDAC4 phosphorylation. Finally, HDAC4 kinase activity was shown to be increased in cardiac homogenates from either CaMKII␦ B or ␦ C TG mice. Thus CaMKII␦ isoforms have similar effects on hypertrophic gene expression but disparate effects on Ca 2؉ handling, suggesting distinct roles for CaMKII␦ isoform activation in the pathogenesis of cardiac hypertrophy versus heart failure.is the predominant isoform of CaMKII in the heart. Splice variants differing in the presence of a nuclear localization sequence (NLS) show distinct subcellular targeting to either cytoplasmic or nuclear compartments (1-3). The CaMKII␦ B isoform contains an 11 amino acid NLS that is absent from ␦ C . Thus CaMKII heteromers comprised predominantly of ␦ B subunits localize to the nucleus while those with predominantly ␦ C localize to the cytoplasm (1-3). We recently demonstrated that both ␦ B and ␦ C CaMKII are activated in response to pressure overload induced by thoracic aortic banding but that expression of these isoforms is differentially regulated (4). The possibility that there are discrete roles for these two isoforms in regulating Ca 2ϩ homeostasis and gene transcription has not yet been explored.CaMKII has long been implicated as a regulator of Ca 2ϩ homeostasis and excitation-contraction (E-C) coupling in ventricular myocytes. This enzyme has been shown to phosphorylate proteins involved in sarcoplasmic reticulum (SR) Ca 2ϩ handling including the cardiac ryanodine receptors (RyR2) and phospholamban (PLB) (4 -10). Phosphorylation of the RyR2 appears to alter its channel open probability (9 -11) while phosphorylation of PLB by CaMKII can regulate SR Ca 2ϩ uptake (10, 12). Altered intracellular Ca 2ϩ handling plays an important role in the pathogenesis of heart failure with changes in Ca 2ϩ cycling pr...

Rationale Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated as a maladaptive mediator of cardiac ischemic injury. We hypothesized that the inflammatory response associated with in vivo ischemia/reperfusion (I/R) is initiated through CaMKII signaling. Objective To assess the contribution of CaMKIIδ to the development of inflammation, infarct and ventricular dysfunction following in vivo I/R and define early cardiomyocyte-autonomous events regulated by CaMKIIδ using cardiac-specific knockout (KO) mice. Methods and Results Wild-type (WT) and CaMKIIδ KO mice were subjected to in vivo I/R by occlusion of the left anterior descending (LAD) artery for 1-hr followed by reperfusion for various times. CaMKIIδ deletion protected the heart against I/R damage as evidenced by decreased infarct size, attenuated apoptosis and improved functional recovery. CaMKIIδ deletion also attenuated I/R induced inflammation and upregulation of NF-κB target genes. Further studies demonstrated that I/R rapidly increases CaMKII activity, leading to NF-κB activation within minutes of reperfusion. Experiments using cyclosporine A and cardiac-specific CaMKIIδ knockout mice indicate that NF-κB activation is initiated independent of necrosis and within cardiomyocytes. Expression of activated CaMKII in cardiomyocytes lead to I kappa B kinase (IKK) phosphorylation and concomitant increases in nuclear p65. Experiments using an IKK inhibitor support the conclusion that this is a proximal site of CaMKII-mediated NF-κB activation. Conclusions This is the first study demonstrating that CaMKIIδ mediates NF-κB activation in cardiomyocytes following in vivo I/R and suggests that CaMKIIδ serves to trigger, as well as to sustain subsequent changes in inflammatory gene expression that contribute to myocardial I/R damage.

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Rising oceanic and atmospheric oxygen levels through time have been crucial to enhanced habitability of surface Earth environments. Few redox proxies can track secular variations in dissolved oxygen concentrations around threshold levels for metazoan survival in the upper ocean. We present an extensive compilation of iodine-to-calcium ratios (I/Ca) in marine carbonates. Our record supports a major rise in the partial pressure of oxygen in the atmosphere at ~400 million years (Ma) ago and reveals a step change in the oxygenation of the upper ocean to relatively sustainable near-modern conditions at ~200 Ma ago. An Earth system model demonstrates that a shift in organic matter remineralization to greater depths, which may have been due to increasing size and biomineralization of eukaryotic plankton, likely drove the I/Ca signals at ~200 Ma ago.

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