Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent

Kim H.S., Hayashi M., Shibata Y., et al. Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent. Biological and Pharmaceutical Bulletin 22, 532 (1999); https://doi.org/10.1248/bpb.22.532.Cycloprodigiosin hydrochloride (cPrG·HCl) is a stable fluorescent red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. It was found that the compound was incorporated into Plasmodium falciparum cells upon incubation and exhibited a potent antimalarial activity with the concentration required for 50% of the activity being 11 nM, which is stronger than that of chloroquine, a well-known antimalarial agent. The compound did not affect growth rate of mammalian cells. Antimalarial activity of cPrG·HCl was also observed in vivo. These results indicate that cPrG·HCl is a potent antimalarial drug

Antibody titers against SARS-CoV-2 decline, but do not disappear for several months

Background: To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients. Methods: Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay. Findings: The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort. Interpretation: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection

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

A Comparative Study of the Articulatory Development of a Normal Infant and Infants with Cleft Palate.

We described the developmental processes of articulation of meaningless and meaningful speech sounds in 1 normal female infant, in 1 male and 1 female infant with cleft soft palate, and in 1 male and 1 female infant with cleft lip and palate. We described nasals, plosives, fricatives, and affricates. 1. From the beginning of her repetitive babbling period, i. e. from 5 months, the normal female infant articulated meaningless speech sounds actively. At first, she articulated bilabial nasals [m], and plosives [p], [b]. Next, she began to use her tongue to articulate nasals, plosives, and affricates. At first, the articulatory movement of her tongue was not differentiated. She moved her tongue as a whole. The middle part of her tongue touched at hard palate and alveolar, and produced palatal nasals [ɲ], plosives [c], [ƒ], and alveolopalatal affricates [tɕ], [dz]. Then, after 1 year she differentiated her tongue movement at the back part, and articulated velar nasals [ŋ], plosives [k], [ɡ]. At last, after 1 year and 6 months, she differentiated her tongue movement at the front part, and articulated dental or alveolar nasals [n], plosives [t], [d]. 2. The infants with cleft soft palate and the infants with cleft lip and palate began to develop their articulation of meaningless speech sounds after palatoplasty. The processes of their articulation development were almost the same as that of the normal infant, described above. But most of them could not articulate dentals or alveolars by 2 years and 5-7 months. We did not find any difference between the infants with cleft soft palate and the infants with cleft lip and palate. The female infant with cleft lip and palate was the exception. She seemed to have incompetence in velopharyngeal function. 3. The normal infant began to use meaningful words from about 1 year. The number of her meaningful speech sounds increased from 1 year and 6 months. The infants with cleft soft palate and the infants with cleft lip and palate, except the female infant, showed almost the same developmental processes as that of the normal infant. But the number of their meaningful speech sounds, at 2 years and 5-7 months, were smaller than that by the normal infant. 4. The normal infant began to develop her phonemicization process from 1 year and 6 months. The developmental process of her tongue articulatory movement of meaningful speech sounds was the same as that of meaningless speech sounds. Almost 1 year after the age of articulation of meaningless bilabials, palatals, alveolo-palatals, she articulated meaningful bilabials, palatals, and alveolo-palatals. Almost 6 months after the age of articulation of meaningless velars, dentals or alveolars, she articulated meaningful velars, dentals or alveolars. 5. The infants with cleft soft palate and the infants with cleft lip and palate, except the female infant, began to develop their phonemicization processes, just after or several months after palatoplasty, i. e. from about 1 year and 6 months, almost at the same age as the normal infant did. And their developmental plocesses of meaningful speech sounds were almost the same as that in the normal infant. We did not find any difference between the developmental process of meaningful speech sounds in the infants with cleft soft palate and that in the infants with cleft lip and palate, except the female infant. At the same age or several months before the age of articulation of meaningful speech sounds, they articulated these speech as meaningless. The time intervals beween their ages of articulation of meaningless speech sounds and their ages of articulation of meaningful speech sounds were shorter than that of the normal infant. At about 2 years and 6 months, they articulated fewer kinds of speech sounds than the normal infant

Co-infection with SARS-CoV-2 and influenza A virus

Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses