Why does ga- not appear in the Gothic past participle?

Why does ga- not appear in the Gothic past participle while ge- does in Old English and German? The study on the Cumulative tendency (CT) which Niwa has made for a long time is found to solve this problem. CT is a universal tendency to strengthen a weakened linguistic unit. So I show in 3. how to solve this problem by CT. The Generative Grammar dealing only with structures could not solve this problem but the minimalist approach has made it possible by introducing semantic features. It so happened that a book by Roberts and Roussou (2003) about the minimalist approach to grammaticalization was published. Following their approach I try to solve this problem in 4. The answer to this problem combines the deficiency of inflectional endings, unstableness of the ga-/ge- prefix and a productive prefix system in Old English and German

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17.

Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD

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

Increase in soil pH due to Ca-rich organic matter application causes suppression of the clubroot disease of crucifers

Clubroot disease of cruciferous plants caused by the soil-borne pathogen Plasmodiophora brassicae is difficult to control because the pathogen survives for a long time in soil as resting spores. Disease-suppressive and conducive soils were found during the long-term experiment on the impact of organic matter application to arable fields and have been studied to clarify the biotic and abiotic factors involved in the disease suppression. The fact that a large amount of organic matter, 400 t ha−1 yr−1 farmyard manure (FYM) or 100 t ha−1 yr−1 food factory sludge compost (FSC), had been incorporated for more than 15 yr in the suppressive soils and these soils showed higher pH and Ca concentration than the disease conducive soil led us to hypothesize that an increase in soil pH due to the long-term incorporation of Ca-rich organic matter might be the primary cause of the disease suppression. We have designed a highly reproducible bioassay system to examine this hypothesis. The suppressive and conducive soils were mixed with the resting spores of P. brassicae at a rate of 106 spore g−1 soil, and Brassica campestris was grown in a growth chamber for 8 d. The number of root hair infections was assessed on a microscope. It was found that the incorporation of FYM and FSC at 2.5% (w/w) to the conducive soil suppressed the infection and that the finer particles (5 mm) of FSC inhibited the infection and increased soil pH more effectively. Neutralization of the conducive soil by Ca(OH)2, CaCO3 and KOH suppressed the infection, but the effectiveness of KOH was less than those of Ca(OH)2 and CaCO3. Acidification of the suppressive soils by H2SO4, promoted the infection. The involvement of soil biota in the disease suppression was investigated using the sterilized (γ-ray irradiation) suppressive soils with respect to soil pH. The γ-ray irradiation promoted the infection at pH 5.5, but no infection was observed at pH 7.4 irrespective of the sterilization status. All these observations suggest that soil pH is a major factor in disease suppression by organic matter application and that Ca and soil biota play certain roles in the suppression under the influence of soil pH

A Probe Containing Two Base-discriminating Fluorescent (BDF) Nucleosides for SNP Typing

We have developed a new probe containing two base-discriminating fluorescent (BDF) nucleosides for single nucleotide polymorphism (SNP) typing. It is possible to determine the SNP type using just one probe. We confirmed suitability of the probe from hybridization assay results obtained for the ALDH2 gene