Life Cycle Strategies of the Centric Diatoms in a Shallow Embayment Revealed by the Plankton Emergence Trap/Chamber (PET Chamber) Experiments

In situ emergence of the centric diatoms from the surface sediment, along with the occurrence of the vegetative cells in the water column, were monitored monthly in a shallow embayment, Ago Bay, of central Japan, where light penetrated to the seafloor. The in situ emergence flux (cells m-2 day-1) was measured by experiments using a ‘plankton emergence trap/chamber (PET chamber)’. During the study period from July 2006 to May 2008, germinating and rejuvenating cells of centric diatoms were successfully collected by the PET chamber. Furthermore, vegetative cells forming long-chain colonies, including the species which have not been known to form resting stage cells, were also found, indicating that these cells already inhabited the surface sediment prior to the start of the PET chamber experiments. The vegetative cells could be cells that grew after germination/rejuvenation and/or cells deposited from the upper layer in the water column. When comparing emergence flux in the PET chamber and the integrated abundance of the vegetative cells in the water column for the diatoms frequently observed, significant positive relationships were found for some diatom taxa. However, even for these taxa that showed a clear relationship, the magnitude of the vegetative population in the water column did not necessarily correlate with that of the emergence flux. These observations indicate that the magnitude of the vegetative population was not regulated directly by the emergence flux. The magnitude of the vegetative population could be dependent on the vegetative growth itself. This implies that the presence of vegetative cells in the water column is important at the time when environmental conditions become suitable for vegetative growth. In this context, the presence of various types of cells, such as germinating, rejuvenating, and vegetative cells, in the sediment is essential as seeds waiting for recruitment into the water column. Consequently, the seafloor in Ago Bay may act as a ‘refuge and nursery’ for centric diatoms. Based on the above, we demonstrated various patterns of life cycle strategies of the diatoms in a shallow coastal water/embayment

SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex

11β-Hydroxysteroid Dehydrogenase-1 Is a Novel Regulator of Skin Homeostasis and a Candidate Target for Promoting Tissue Repair

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the interconversion of cortisone and cortisol within the endoplasmic reticulum. 11β-HSD1 is expressed widely, most notably in the liver, adipose tissue, and central nervous system. It has been studied intensely over the last 10 years because its activity is reported to be increased in visceral adipose tissue of obese people. Epidermal keratinocytes and dermal fibroblasts also express 11β-HSD1. However, the function of the enzymatic activity 11β-HSD1 in skin is not known. We found that 11β-HSD1 was expressed in human and murine epidermis, and this expression increased as keratinocytes differentiate. The expression of 11β-HSD1 by normal human epidermal keratinocytes (NHEKs) was increased by starvation or calcium-induced differentiation in vitro. A selective inhibitor of 11β-HSD1 promoted proliferation of NHEKs and normal human dermal fibroblasts, but did not alter the differentiation of NHEKs. Topical application of selective 11β-HSD1 inhibitor to the dorsal skin of hairless mice caused proliferation of keratinocytes. Taken together, these data suggest that 11β-HSD1 is involved in tissue remodeling of the skin. This hypothesis was further supported by the observation that topical application of the selective 11β-HSD1 inhibitor enhanced cutaneous wound healing in C57BL/6 mice and ob/ob mice. Collectively, we conclude that 11β-HSD1 is negatively regulating the proliferation of keratinocytes and fibroblasts, and cutaneous wound healing. Hence, 11β-HSD1 might maintain skin homeostasis by regulating the proliferation of keratinocytes and dermal fibroblasts. Thus 11β-HSD1 is a novel candidate target for the design of skin disease treatments

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

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

Short-term changes in population structure and vertical distribution of mesopelagic copepods during the spring phytoplankton bloom in the Oyashio region

To evaluate the responses to the spring phytoplankton bloom, short-term changes in population structure and vertical distribution of mesopelagic copepods (Gaetanus simplex, Gaidius variabilis, Pleuromamma scutullata, Paraeuchaeta elongata, P. birostrata, Heterorhabdus tanneri and Heterostylites major) were studied in the Oyashio region. Samples were collected with a 60 mu m mesh VMPS from 9 strata between 0 and 1000 m both day and night on five occasions during March-April 2007. All the species except Heterorhabdidae species performed reproduction during the spring phytoplankton bloom, while no recruitment to copepodid stages was detected because the newly born individuals were eggs or nauplii. The shallower-living species, G. simplex, P. scutullata and P. elongata had nocturnal ascent did l vertical migration (DVM). While suspension feeding copepods cease DVM after 11 April (P. scutullata) or 23 April (G. simplex), carnivorous P. elongata continued DVM over the study period. Since the gut contents of G. simplex showed a nocturnal increment even in the period of no DVM (23 and 29 April), they might be feeding at depth without DVM. Thus, the cessation of DVM in mesopelagic suspension feeding copepods would be induced by the increase of sinking particles (e.g. food for suspension feeders) during the spring phytoplankton bloom. (C) 2012 Elsevier Ltd. All rights reserved

Different Nutrient Availabilities of Surface and Bottom Water under Nutrient-depleted Conditions during Bloom Formation of the Toxic Dinoflagellate Alexandrium tamarense in Osaka Bay, Japan

Alexandriium tamarense is a toxic dinoflagellate known to produce neurotoxins cause paralytic shellfish poisoning to human and marine animals. To understand the growth dynamics of A.tamarense, the seasonal changes in A,tamarense vegetative cells and environmental factors were evaluated using monthly field observations at two fixed stations in Osaka Bay, Japan, from January to May 2008. Additionally, a bioassay with axenic A.tamarense clonal cultures was performed to determine the growth potentials and growth-limiting nutrients of seawater samples collected during the field observations. The density of A.tamarense increased from February to April, and depletions of dissolved phosphate and silicate were observed in the surface layer during this period. The bioassay showed that phosphorous limitation occurred at the surface water of one station during March and April, while nitrogen limitation occurred in the bottom water. Moreover, at the other station, the growth potentials of the bottom water were higher than those of the surface water during February and April. Thus, the differences of nutrient availabilities between surface and bottom water during spring in Osaka Bay potentially allow A.tamarense to grow with nutrients uptake from bottom water by vertical migration