Multiple Endocrine Neoplasia Type 1 Producing Growth Hormone- Releasing Factor in an Endocrine Pancreatic Tumor

We report a very rare case of multiple endocrine neoplasia type 1 (MEN 1) where a pituitary tumor presenting with acromegaly was associated with a growth hormone-releasing factor (GRF) producing pancreatic tumor. Twenty-seven months after surgery for pituitary adenoma, a 27-year-old male visited our hospital complaining of epigastralgia and back pain. Radiological examination revealed a 7-cm tumor in the pancreatic tail. Endocrinological studies revealed an abnormal increase in the level of growth hormone (GH). After resection of the pancreatic tumor, the GH level was normalized. Immunohistochemical studies confirmed the existence of GRF in the tumor. A diagnosis of GRF-producing pancreatic tumor was established. Nine months after surgery for the pancreatic tumor, the GH level remained normal and the pituitary gland had decreased in size. We speculate that secondary hyperpituitarism was caused by GRF produced by the endocrine pancreatic tumor in this case

Christopher Simpson The Division-Viol, or The Art of PLAYING Ex tempore upon a GROUND. EDITIO SECVNDA Part III "The Method of ordering Division to a Ground" (2)

本訳稿はChristopher Simpson (1605頃－1669) 著 The Division-Viol, or, The Art of PLAYING Ex tempore upon a GROUND. DIVIDED INTO THREE PARTS. EDITIO SECVNDA, London, 1665 のPart III "The Method of ordering Division to a Ground" より§7～§12(pp.42-56)の全訳である

Christopher Simpson The Division-Viol, or, The Art of PLAYING Extempore upon a GROUND. EDITIO SECVNDA Dedication & Recommendation

本訳稿はChristopher Simpson (1605頃－1669) 著 The Division-Viol, or, The Art of PLAYING Ex tempore upon a GROUND. DIVIDED INTO THREE PARTS. EDITIO SECVNDA, London, 1665 の著者による献辞および楽譜出版権所有者による推薦文の全訳である

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

Seven Epithemia taxa (Bacillariophyta) from Lake Akan (Japan) and their salinity tolerances

The ecologies (salinity tolerance) of many diatoms are largely unknown, despite their potential to contribute to more detailed paleoenvironmental reconstructions. This study therefore aimed to investigate the relationship between diatom species and salinity. We cultured seven cosmopolitan benthic diatom species obtained from Lake Akan, a freshwater inland lake in Japan: Epithemia adnata, E. frickei, E. gibba, E. operculata, E. sorex, E. sp. and E. turgida. Each species was cultured at eleven salinities between 0‰ and 50‰. Epithemia adnata, E. frickei and E. sorex had the highest growth rate at a salinity of 3‰, with no further increase observed above 25‰. However, E. gibba had the highest growth rate at a salinity of 5‰, with no increase at salinities ≥ 30‰. These results suggest that E. adnata, E. frickei, E. gibba, and E. sorex grow in freshwater to brackish-water environments. Epithemia operculata and E. sp. proliferated at all salinities, indicating that they can adapt to hypersaline environments. However, E. turgida did not survive in salinities >10‰, making it the species with the narrowest salinity tolerance range. These results provide new knowledge that improves the understanding of the ecology of these species in modern environments and offer insights into paleoenvironmental reconstructions through diatom analysis

Mutation of High-Affinity Methionine Permease Contributes to Selenomethionyl Protein Production in Saccharomyces cerevisiae▿ †

The production of selenomethionine (SeMet) derivatives of recombinant proteins allows phase determination by single-wavelength or multiwavelength anomalous dispersion phasing in X-ray crystallography, and this popular approach has permitted the crystal structures of numerous proteins to be determined. Although yeast is an ideal host for the production of large amounts of eukaryotic proteins that require posttranslational modification, the toxic effects of SeMet often interfere with the preparation of protein derivatives containing this compound. We previously isolated a mutant strain (SMR-94) of the methylotrophic yeast Pichia pastoris that is resistant to both SeMet and selenate and demonstrated its applicability for the production of proteins suitable for X-ray crystallographic analysis. However, the molecular basis for resistance to SeMet by the SMR-94 strain remains unclear. Here, we report the characterization of SeMet-resistant mutants of Saccharomyces cerevisiae and the identification of a mutant allele of the MUP1 gene encoding high-affinity methionine permease, which confers SeMet resistance. Although the total methionine uptake by the mup1 mutant (the SRY5-7 strain) decreased to 47% of the wild-type level, it was able to incorporate SeMet into the overexpressed epidermal growth factor peptide with 73% occupancy, indicating the importance of the moderate uptake of SeMet by amino acid permeases other than Mup1p for the alleviation of SeMet toxicity. In addition, under standard culture conditions, the mup1 mutant showed higher productivity of the SeMet derivative relative to other SeMet-resistant mutants. Based on these results, we conclude that the mup1 mutant would be useful for the preparation of selenomethionyl proteins for X-ray crystallography

Nitzschia taikiensis sp. nov. (Bacillariophyta) – a new brackish diatom from the Toberi River marsh in the eastern Hokkaido, Japan

Nitzschia taikiensis sp. nov. is a brackish diatom species found in the Toberi River marsh, eastern Hokkaido, Japan. This species has characteristics similar to Nitzschia subamphioxoides Hustedt, which was originally described by Hustedt in 1959. In the present study, we conducted a comparative morphological analysis of N. taikiensis and N. subamphioxoides. The obtained results showed that they are different species. Sampling sites of N. taikiensis were located in salt marsh environments with very low salinity (1-5‰), acidic pH (5.2-5.9) and high mud content (95.0-97.5%). Identification of this species was relatively easy based on LM and SEM image analysis of its frustule features, such as the external form and stria density. This species has not been previously reported in Japan, which could be attributed to the reduction or loss of Japanese freshwater and salt marsh environments in the coastal areas, resulting from urban and industrial development