Wobbling Motion in Atomic Nuclei with Positive-Gamma Shapes

The three moments of inertia associated with the wobbling mode built on the superdeformed states in 163Lu are investigated by means of the cranked shell model plus random phase approximation to the configuration with an aligned quasiparticle. The result indicates that it is crucial to take into account the direct contribution to the moments of inertia from the aligned quasiparticle so as to realize J_x > J_y in positive-gamma shapes. Quenching of the pairing gap cooperates with the alignment effect. The peculiarity of the recently observed 163Lu data is discussed by calculating not only the electromagnetic properties but also the excitation spectra.Comment: 11 pages, 6 figure

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Establishment of a bacterial infection model using the European honeybee, Apis mellifera L.

Injection of human pathogenic bacteria (Pseudomonas aeruginosa, Serratia marcescens, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) into the hemocoel of honeybee (Apis mellifera L.) workers kills the infected bees. The bee-killing effects of the pathogens were affected by temperature, and the LD₅₀ values at 37°C were more than 100-fold lower than those at 15°C. Gene-disrupted S. aureus mutants of virulence genes such as agrA, saeS, arlR, srtA, hla, and hlb had attenuated bee-killing ability. Nurse bees were less susceptible than foragers and drones to S. aureus infection. Injection of antibiotics clinically used for humans had therapeutic effects against S. aureus infections of bees, and the ED₅₀ values of these antibiotics were comparable with those determined in mammalian models. Moreover, the effectiveness of orally administered antibiotics was consistent between honeybees and mammals. These findings suggest that the honeybee could be a useful model for assessing the pathogenesis of human-infecting bacteria and the effectiveness of antibiotics

Establishment of a bacterial infection model in the honeybee.

<p>A, Images of sample injection into the body cavities of bees (left) and oral administration (right). In the left panel, bees anesthetized on ice were injected into the abdomen with 25 µl of each sample using a 1-ml syringe. In the right panel, anesthetized bees were placed in 1.5-ml tubes and fixed with paper tape. Ten microliters of sample containing sucrose was directly administered to bees extending the proboscis. B–C, Survival of in-hive worker bees (n = 20) after infection with Gram-negative (left) and Gram-positive (right) bacteria. Overnight culture of each bacterium was diluted 100-fold with saline. Survival numbers of bees were monitored at 25°C (B) or 37°C (C). The data shown are representative of three experiments with similar results. D, Effect of incubation temperature on survival of in-hive worker bees after <i>S. aureus</i> infection. LD₅₀ values were determined 24 h after injection with a live bacterial suspension of <i>S. aureus</i> (n = 5).</p

Therapeutic effects of antibiotics against bacterial infection in honeybees.

<p>A, Effect of co-injection of vancomycin or gentamycin on survival of in-hive worker bees infected with <i>S. aureus</i> (n = 20). B, Dose-dependency of therapeutic effects of antibiotics on <i>S. aureus</i> infection in in-hive worker bees. Survival numbers were determined 24 h after infection (n = 5).</p

Comparison of susceptibilities to bacterial infection between honeybees in different labor divisions.

<p>LD₅₀ values of <i>S. aureus</i> were determined 24 h after infection in either in-hive workers, out-hive workers, or drones (n = 5–8). Data represent mean ± SDs of three experiments. Statistical analysis was performed by one-way ANOVA, and differences compared with the in-hive workers group were analyzed by Dunnett’s multiple comparison tests (*, p<0.05).</p