Architectures of archaeal GINS complexes, essential DNA replication initiation factors

<p>Abstract</p> <p>Background</p> <p>In the early stage of eukaryotic DNA replication, the template DNA is unwound by the MCM helicase, which is activated by forming a complex with the Cdc45 and GINS proteins. The eukaryotic GINS forms a heterotetramer, comprising four types of subunits. On the other hand, the archaeal GINS appears to be either a tetramer formed by two types of subunits in a 2:2 ratio (α₂β₂) or a homotetramer of a single subunit (α₄). Due to the low sequence similarity between the archaeal and eukaryotic GINS subunits, the atomic structures of the archaeal GINS complexes are attracting interest for comparisons of their subunit architectures and organization.</p> <p>Results</p> <p>We determined the crystal structure of the α₂β₂GINS tetramer from <it>Thermococcus kodakaraensis </it>(<it>Tko</it>GINS), comprising Gins51 and Gins23, and compared it with the reported human GINS structures. The backbone structure of each subunit and the tetrameric assembly are similar to those of human GINS. However, the location of the C-terminal small domain of Gins51 is remarkably different between the archaeal and human GINS structures. In addition, <it>Tko</it>GINS exhibits different subunit contacts from those in human GINS, as a consequence of the different relative locations and orientations between the domains. Based on the GINS crystal structures, we built a homology model of the putative homotetrameric GINS from <it>Thermoplasma acidophilum </it>(<it>Tac</it>GINS). Importantly, we propose that a long insertion loop allows the differential positioning of the C-terminal domains and, as a consequence, exclusively leads to the formation of an asymmetric homotetramer rather than a symmetrical one.</p> <p>Conclusions</p> <p>The DNA metabolizing proteins from archaea are similar to those from eukaryotes, and the archaeal multi-subunit complexes are occasionally simplified versions of the eukaryotic ones. The overall similarity in the architectures between the archaeal and eukaryotic GINS complexes suggests that the GINS function, directed through interactions with other protein components, is basically conserved. On the other hand, the different subunit contacts, including the locations and contributions of the C-terminal domains to the tetramer formation, imply the possibility that the archaeal and eukaryotic GINS complexes contribute to DNA unwinding reactions by significantly different mechanisms in terms of the atomic details.</p

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Development of a mugineic acid family phytosiderophore analog as an iron fertilizer

Iron (Fe) is an essential nutrient, but is poorly bioavailable because of its low solubility in alkaline soils; this leads to reduced agricultural productivity. To overcome this problem, we first showed that the soil application of synthetic 2′-deoxymugineic acid, a natural phytosiderophore from the Poaceae, can recover Fe deficiency in rice grown in calcareous soil. However, the high cost and poor stability of synthetic 2′-deoxymugineic acid preclude its agricultural use. In this work, we develop a more stable and less expensive analog, proline-2′-deoxymugineic acid, and demonstrate its practical synthesis and transport of its Fe-chelated form across the plasma membrane by Fe(III)•2’-deoxymugineic acid transporters. Possibility of its use as an iron fertilizer on alkaline soils is supported by promotion of rice growth in a calcareous soil by soil application of metal free proline-2’-deoxymugineic acid

ガン カガク リョウホウ ニオケル ショウカカン ドクセイ ト ケッセイ Diamine Oxidase DAO カッセイ ニ カンスル ケントウ

There are so many patients with advanced gastric cancer who undergo systemic chemotherapy worldwide. The quality of life（QOL）of patients with gastric cancer who receive chemotherapy is often lowed by various gastrointestinal toxicities during the chemotherapy. Nutrition is also impaired by gastrointestinal toxicities. However, it is difficult to predict their occurrence in advance and further there is no good serum marker for nutrition in the patients treated with chemotherapy. Thus, it is important to objectively evaluate and predict the toxicity of the digestive tract during cancer chemotherapy. Diamine Oxidase（DAO）is an enzyme that is expressed in intestinal epithelial cells. Recently it has been reported that DAO activity may reflect damage or atrophy of the intestinal villi, and therefore it may be a sensitive serum marker for nutritional state. In this study, we measured serum DAO activity of patients with gastric cancer treated with systemic chemotherapy, and investigated the correlation between DAO activity and gastrointestinal toxicities. Six patients with gastric cancer, who were treated by docetaxel+cisplatin+S‐１combination chemotherapy, were enrolled. DAO activity was measured by sensitive colorimetric assay. DAO activities diminished after treatment in４patients with moderate to severe gastrointestinal toxicities. In contrast, they did not change in２patients with no gastrointestinal toxicities. Our results may suggest that DAO activity is a good serum marker for the gastrointestinal toxicities as well as nutrition state in patients who receive systemic chemotherapy. More large scale study is needed to warrant

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron

Biomass-Balance Table for evaluating bioenergy resources

Bioenergy is expected to become one of the key energy resources to cope with global warming and exhaustion of fossil fuel resources. Biomass is renewable and free from net CO2 emissions as long as it is maintained sustainably. There are several studies concerning bioenergy potential, but they are hardly comparable because of the complexity of the assumed parameters, which relate to food, timber and paper supply, forest management, etc. In this study, bioenergy (expressed in Joules) is divided into plantation bioenergy produced on land and bioenergy recovered from biomass residues in the processes of harvest, conversion and consumption for food, timber and paper. We propose a "Biomass Balance Table", which shows systematically the flows of various biomass forms. The scheme of a Biomass-Balance Table is similar to that of an energy-balance table. The steps of the biomass processing (i.e. harvesting, conversion and consumption) are expressed in the column, and biomass forms are expressed in the row. Tables have been constructed for 10 regions in the world in 1990. The world has an existing energy potential from biomass residues of 88 EJ (i.e. 26% of 335 EJ of primary energy supply in 1990) and Japan has 2.02 EJ (10% of 19.52 EJ of primary energy supply in 1990). North America, the former USSR and eastern Europe, and Western Europe have large potentials of wood biomass residues and other Asian countries and the centrally-planned economies of Asia have large potentials food biomass residues.

Scenario analysis of bioenergy resources and CO2 emissions with a global land use and energy model

The purpose of the present study is to evaluate bioenergy supply potentials, land use changes, and CO2 emissions in the world, using a global land use and energy model (GLUE) including land use competitions and overall biomass flows. Through a set of simulations, the following results were obtained: (1) Supply potentials of energy crops produced from surplus arable lands will be strongly affected by food supply and demand parameters in the future, such as animal food demand per capita. (2) The policy option, i.e. the world, large-scale introduction of modern fuelwood by felling and planting in existing forest, will cause drastic reduction of the mature forest area but will cause little reduction of the accumulated CO2 emissions coming from both energy and forest sectors. One reason for this is that the additional CO2 emissions owing to the land use conversion from the mature forest to the growing forest will partly cancel out the CO2 reduction owing to the fuel substitution from fossil fuels to fuelwood. (3) When energy recovery of paper scrap is given priority to material recycling, bioenergy will substitute partly for fossil fuels; however the decrease in recycled paper scrap will cause an increase in roundwood felling demand. Hence, the results will be similar to those of (2).Bioenergy supply potential CO2 emissions Land uses Biomass flow Paper recycling