Effects of temperature on life histories of three endangered Japanese diving beetle species

To elucidate population-increasing factors in the diving beetle Cybister tripunctatus lateralis (Fabricius) (Coleoptera: Dytiscidae) in Japan in recent years, life histories and oviposition patterns were compared among three endangered diving beetle species, Cybister brevis Aube (qualified by the Japanese Red Data List as ‘near threatened’), Cybister chinensis Motschulsky (vulnerable), and C. tripunctatus lateralis (vulnerable). Oviposition in C. brevis, C. chinensis, and C. tripunctatus lateralis was observed from late April to mid-June, from late April to early July, and from late May to mid-August, respectively, under semi-outdoor conditions. There were no interspecies differences in total hatchling production during the reproductive season. In rearing experiments at various temperatures (20, 23, 25, 28, and 30 °C), the mortality of C. tripunctatus lateralis larvae was higher at 20 °C, and gradually lower with increasing temperature up to 30 °C. Adult body size of females in C. tripunctatus lateralis is larger than that of males but there were no significant differences among temperatures (25-30 °C). Cybister brevis had a higher emergence rate at 23?28 °C than at 20 and 30 °C. In C. brevis, the body size of adults reared at 25 or 28 °C was significantly larger than at other temperatures. Cybister chinensis did not differ in emergence rate and adult body size among the five temperature conditions. The developmental zero (i.e., the lower developmental threshold) from the first instar to adult emergence was 11.1 °C for C. brevis, 8.7 °C for C. chinensis,and 16.8 °C for C. tripunctatus lateralis. We speculate how the influence of global warming may have a positive impact on the growth and survival of C. tripunctatus lateralis

Proton beam therapy with concurrent chemotherapy is feasible in children with newly diagnosed rhabdomyosarcoma

BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS. MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients’ clinical information was collected by retrospective medical record review. RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent. CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity

Optic Perineuritis Associated with Nivolumab Treatment for Non-Small Cell Lung Cancer

We report the case of a 54-year-old man who was treated with nivolumab for recurrent squamous cell lung cancer. After 7 cycles of nivolumab treatment, the patient presented to our hospital with right eye vision loss. Gadolinium-enhanced magnetic resonance imaging of the brain showed enhancement around the optic nerve sheath. This finding and his symptoms led to the diagnosis of optic perineuritis (OPN). Steroid pulse therapy was administered twice although there was no remarkable improvement in his visual field defect. The relationship between OPN and nivolumab is unclear. However, immune-related adverse events caused by immune checkpoint inhibitors should be considered

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

Studies on the lymphocyte function bronchial asthma Part 1. Examination of lymphocyte responsiveness with inhalation antigens of bronchial asthma

Various antigens such as mite and fungi have been known to provoke bronchoconstriction in patients with bronchial asthma. The allergic mechanisms of asthmatic attack induced by these antigens were analyzed to clarify the role of cellular immunity in the pathogenesis of bronchial asthma. Mite and Candida antigens were applied to lymphocyte blastogenesis in asthmatic patients. Both lymphocytes in bronchoalveolar lavage fluid (BALF) and in peripheral blood of asthmatic patients responded significantly to mite and Candida antiten. Furthermore, BALF lymphocytes of patients with non-atopic and intractable asthma showed higher responses against Candida antigen than those of patients with atopic and non-intractable asthma, while peripheral blood lymphocytes showed a higher response against mite antigen in patients with atopic and non-intractable asthma. These findings indicate that lymphocytes in lugns sensitized with Candida antigen might play an important role in the pathogenesis of non-atopic and intractable asthma

Studies on the lymphocyte function of bronchial asthma Part 2. Examination of Concanavalin A induced suppressor cell function in patients with bronchial asthma

Cellular immunity in bronchial asthma has become essential for the regulation of various allergic reactions in the asthmatic attack. The function of peripheral blood lymphocytes of asthmatic patients was examined by the concanavalin A (Con A) induced suppressor cell assay. The suppressor activity of lymphocytes in mitogen-induced blastogenesis was shown to be decreased in patints with atopic and intractable asthma in comparison with the normal control. The suppressor activity in mite antigen induced lymphocyte blastogenesis was also decreased in patients with atopic asthma. Furthermore, the decrease of ConA induced suppressor activity correlated with the increase of serum IgE level in patients with atopic asthma. These findings indicate that the decreased suppressor cell activity is part of the mechanism of attack and may play an important role in the pathogensis of bronchial asthma