Debt-financed fiscal policy, public capital, and endogenous growth

This study investigates the conflicting effects of a debt-financed fiscal policy on endogenous growth in an overlapping generations model with public capital and debt. Although an accumulation of public capital enhances the production efficiency of private capital, it also impedes private capital accumulation by distorting savings allocations through public debt issuance. With a low deficit ratio, the fiscal policy brings new equilibria to an unstable economy. Meanwhile, a debt-financed fiscal policy with a higher deficit ratio causes a fiscal collapse and secular stagnation

How Does Automation Affect Economic Growth and Income Distribution in a Two-Class Economy?

This study uses a growth model with automation technology to consider two classes---workers and capitalists---and investigates how advances in automation technology affect economic growth and income distribution. In addition to the two production factors labor and traditional capital, we consider automation capital as the third production factor. We also introduce Pasinetti-type saving functions into the model to investigate how the difference between the capitalists' and workers' saving rates affect economic growth and income distribution. When the capitalists' saving rate is higher than a threshold level, per capita output exhibits endogenous growth irrespective of the workers' savings rate. In this case, the income gap between workers and capitalists widens over time. When the capitalists' saving rate is less than the threshold level, two different long-run states occur depending on the workers' saving rate: the capitalists' own automation capital share approaches a constant, and it approaches zero. In both cases, the per capita output growth is zero and the income gap between the two classes becomes constant over time

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Battlefield hypothesis.

<p>(A) When pneumonia occurs, the numbers of both the causative pathogen and human inflammatory cells increase at the inflammation site. Meanwhile, the colonizing pathogen lags behind. The ratio of pathogen to human cells may be a good indicator for the differentiation of the causative pathogen from the colonizing pathogen. (B) The cell number ratio is measurable by quantitative PCR. The Ct (threshold cycle) is the PCR cycle at which a statistically significant fluorescent signal is first observed. Ct_pathogen is the Ct for the pathogen-specific gene, Ct_human is the Ct for the human-specific gene, and both are log-proportional to the number of the cells (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024474#pone-0024474-g002" target="_blank"><b>Figure 2</b></a>). Accordingly, ΔCt_pathogen =  −(Ct_pathogen−Ct_human) is log-proportional to the ratio of pathogen to human cells. (C) Because ΔCt_pathogen indicates the ratio of pathogen to human cells, we may be able to determine the ΔCt_pathogen cutoff, a ΔCt_pathogen value above which a pathogenic role of the pathogen in pneumonia is strongly suggested.</p

Protocol for the prospective observatory study.

<p># The number was determined so that the primary endpoint is evaluated at a resolution of 0.1.</p

Relationship between cell number and Ct.

<p>Log-linear relationships between the copy number of pathogen-specific sequence and Ct_pathogen and between the copy number of the human-specific sequence and Ct_human. (A) <i>S. pneumoniae</i>, <i>H. influenzae</i>, <i>Pseudomonas</i> spp., or <i>M. catarrhalis</i> was suspended in sputum. DNA was then purified from the suspension, and the target sequences specific to each organism were amplified by PCR. A log-linear relationship indicates that the sputum does not contain molecules that inhibit isolation of DNA or exponential amplification by PCR. Experiments were done in triplicate. A bar indicates standard deviation. (B) Human genomic DNA isolated from sputum was serially diluted, and a DNA sequence in the human SFTPC gene (arbitrarily selected from human genes, of which sequence is specific to human by BLAST search of GenBank database; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024474#pone-0024474-t002" target="_blank"><b>Table 2</b></a>) was amplified. A log-linear relationship indicates that the sputum does not contain molecules that inhibit isolation of DNA or exponential amplification by PCR.</p

Patients' characteristics.

<p>Patients' characteristics.</p