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1.
  • 2017
  • swepub:Mat__t
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  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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4.
  • Namkoong, H, et al. (author)
  • DOCK2 is involved in the host genetics and biology of severe COVID-19
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
  • Journal article (peer-reviewed)abstract
    • Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. 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.
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5.
  • Wang, QBS, et al. (author)
  • The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
  • 2022
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Abdellaoui, G., et al. (author)
  • First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
  • 2018
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
  • Journal article (peer-reviewed)abstract
    • EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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20.
  • Armesto, N., et al. (author)
  • Heavy-ion collisions at the LHC-Last call for predictions
  • 2008
  • In: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:5, s. 054001-
  • Research review (peer-reviewed)abstract
    • This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007.
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21.
  • Sugita, S., et al. (author)
  • The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
  • 2019
  • In: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
  • Journal article (peer-reviewed)abstract
    • Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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  • Abe, K., et al. (author)
  • J-PARC Neutrino Beamline Upgrade Technical Design Report
  • 2019
  • Reports (peer-reviewed)abstract
    • In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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  • Sakatani, N., et al. (author)
  • Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
  • 2021
  • In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
  • Journal article (peer-reviewed)abstract
    • Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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  • Imanishi, T., et al. (author)
  • Integrative annotation of 21,037 human genes validated by full-length cDNA clones
  • 2004
  • In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
  • Journal article (peer-reviewed)abstract
    • The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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  • Block, Keith I., et al. (author)
  • Designing a broad-spectrum integrative approach for cancer prevention and treatment
  • 2015
  • In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
  • Research review (peer-reviewed)abstract
    • Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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  • Fujii, J., et al. (author)
  • Identifying the Electronic Character and Role of the Mn States in the Valence Band of (Ga,Mn)As
  • 2013
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:9, s. 097201-
  • Journal article (peer-reviewed)abstract
    • We report high-resolution hard x-ray photoemission spectroscopy results on (Ga,Mn)As films as a function of Mn doping. Supported by theoretical calculations we identify, for both low (1%) and high (13%) Mn doping values, the electronic character of the states near the top of the valence band. Magnetization and temperature-dependent core-level photoemission spectra reveal how the delocalized character of the Mn states enables the bulk ferromagnetic properties of (Ga,Mn)As.
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38.
  • Inagaki-Kawata, Y, et al. (author)
  • Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
  • 2020
  • In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
  • Journal article (peer-reviewed)abstract
    • The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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  • Kang, JS, et al. (author)
  • Risk prediction for malignant intraductal papillary mucinous neoplasm of the pancreas: logistic regression versus machine learning
  • 2020
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 20140-
  • Journal article (peer-reviewed)abstract
    • Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.
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  • Sato, K., et al. (author)
  • First-principles material design and perspective on semiconductor spintronics materials
  • 2009
  • In: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 404:23-24, s. 5237-5243
  • Journal article (peer-reviewed)abstract
    • We investigate the electronic structure and magnetic properties of III–V compound semiconductor based dilute magnetic semiconductors (DMS) from first-principles. The electronic structure of DMS is calculated by using the Korringa–Kohn–Rostoker coherent potential approximation (KKR-CPA) method in connection with the local density approximation (LDA). Describing the magnetic properties by a classical Heisenberg model, effective exchange interactions are calculated by applying magnetic force theorem for two impurities embedded in the CPA medium. With the calculated exchange interactions, TC is estimated by using the mean field approximation, the random phase approximation and the Monte Carlo simulation. In the above compounds, the magnetic interactions are well described from double exchange picture. Due to the short-range interactions, high-TC is difficult to achieve in the presently investigated materials. Based on the present results, two strategies towards high-TC are proposed to realize useful DMS materials. One uses spinodal decomposition to realize high blocking temperature in super-paramagnetic blocking phenomena and the other uses co-doping method to realize high concentration doping of magnetic impurities for high-TC.
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  • Ardo, Shane, et al. (author)
  • Pathways to electrochemical solar-hydrogen technologies
  • 2018
  • In: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
  • Research review (peer-reviewed)abstract
    • Solar-powered electrochemical production of hydrogen through water electrolysis is an active and important research endeavor. However, technologies and roadmaps for implementation of this process do not exist. In this perspective paper, we describe potential pathways for solar-hydrogen technologies into the marketplace in the form of photoelectrochemical or photovoltaic-driven electrolysis devices and systems. We detail technical approaches for device and system architectures, economic drivers, societal perceptions, political impacts, technological challenges, and research opportunities. Implementation scenarios are broken down into short-term and long-term markets, and a specific technology roadmap is defined. In the short term, the only plausible economical option will be photovoltaic-driven electrolysis systems for niche applications. In the long term, electrochemical solar-hydrogen technologies could be deployed more broadly in energy markets but will require advances in the technology, significant cost reductions, and/ or policy changes. Ultimately, a transition to a society that significantly relies on solar-hydrogen technologies will benefit from continued creativity and influence from the scientific community.
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  • Fujita, S., et al. (author)
  • Spatial and temporal variability of snow accumulation rate on the East Antarctic ice divide between Dome Fuji and EPICA DML
  • 2011
  • In: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 5:4, s. 1057-1081
  • Journal article (peer-reviewed)abstract
    • To better understand the spatio-temporal variability of the glaciological environment in Dronning Maud Land (DML), East Antarctica, a 2800-km-long Japanese-Swedish traverse was carried out. The route includes ice divides between two ice-coring sites at Dome Fuji and EPICA DML. We determined the surface mass balance (SMB) averaged over various time scales in the late Holocene based on studies of snow pits and firn cores, in addition to radar data. We find that the large-scale distribution of the SMB depends on the surface elevation and continentality, and that the SMB differs between the windward and leeward sides of ice divides for strong-wind events. We suggest that the SMB is highly influenced by interactions between the large-scale surface topography of ice divides and the wind field of strong-wind events that are often associated with high-precipitation events. Local variations in the SMB are governed by the local surface topography, which is influenced by the bedrock topography. In the eastern part of DML, the accumulation rate in the second half of the 20th century is found to be higher by similar to 15% than averages over longer periods of 722 a or 7.9 ka before AD 2008. A similar increasing trend has been reported for many inland plateau sites in Antarctica with the exception of several sites on the leeward side of the ice divides.
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  • Hirano, T., et al. (author)
  • K2-155: A Bright Metal-poor M Dwarf with Three Transiting Super-Earths
  • 2018
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 155:3
  • Journal article (peer-reviewed)abstract
    • We report on the discovery of three transiting super-Earths around K2-155 (EPIC 210897587), a relatively bright early M dwarf (V = 12.81 mag) observed during Campaign 13 of the NASA K2 mission. To characterize the system and validate the planet candidates, we conducted speckle imaging and high-dispersion optical spectroscopy, including radial velocity measurements. Based on the K2 light curve and the spectroscopic characterization of the host star, the planet sizes and orbital periods are 1.55 -0.17 +0.20 R ⊕ and 6.34365 ±0.00028 days for the inner planet; 1.95 -0.22 +0.27 R ⊕ and 13.85402 ±0.00088 days for the middle planet; and 1.64 -0.17 +0.18 R ⊕ and 40.6835 ±0.0031 days for the outer planet. The outer planet (K2-155d) is near the habitable zone, with an insolation 1.67 ±0.38 times that of the Earth. The planet's radius falls within the range between that of smaller rocky planets and larger gas-rich planets. To assess the habitability of this planet, we present a series of three-dimensional global climate simulations, assuming that K2-155d is tidally locked and has an Earth-like composition and atmosphere. We find that the planet can maintain a moderate surface temperature if the insolation proves to be smaller than ∼1.5 times that of the Earth. Doppler mass measurements, transit spectroscopy, and other follow-up observations should be rewarding, as K2-155 is one of the optically brightest M dwarfs known to harbor transiting planets.
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  • Mizumaki, H, et al. (author)
  • A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia
  • 2021
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:6, s. 1581-1590
  • Journal article (peer-reviewed)abstract
    • Leukocytes that lack HLA allelic expression are frequently detected in patients with acquired aplastic anemia (AA) who respond to immunosuppressive therapy (IST), although the exact mechanisms underlying the HLA loss and HLA allele repertoire likely to acquire loss-of-function mutations are unknown. We identified a common nonsense mutation at position 19 (c.19C>T, p.R7X) in exon 1 (Exon1mut) of different HLA-A and -B alleles in HLA-lacking granulocytes from AA patients. A droplet digital PCR (ddPCR) assay capable of detecting as few as 0.07% Exon1mut HLA alleles in total DNA revealed the mutation was present in 29% (101/353) of AA patients, with a median allele frequency of 0.42% (range, 0.071% to 21.3%). Exon1mut occurred in only 12 different HLA-A (n=4) and HLA-B (n=8) alleles, including B*40:02 (n=31) and A*02:06 (n=15), which correspond to 4 HLA supertypes (A02, A03, B07, and B44). The percentages of patients who possessed at least one of these 12 HLA alleles were significantly higher in the 353 AA patients (92%, P
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48.
  • Salojarvi, Jarkko, et al. (author)
  • Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch
  • 2017
  • In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 49:6, s. 904-912
  • Journal article (peer-reviewed)abstract
    • Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.
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  • Udalski, A., et al. (author)
  • OGLE-2017-BLG-1434Lb : Eighth q < 1 x 10(-4) Mass-Ratio Microlens Planet Confirms Turnover in Planet Mass-Ratio Function
  • 2018
  • In: Acta Astronomica. - 0001-5237. ; 68:1, s. 1-42
  • Journal article (peer-reviewed)abstract
    • We report the discovery of a cold Super-Earth planet (m(p) = 4.4 +/- 0.5 M-circle plus) orbiting a low-mass (M = 0.23 +/- 0.03 M-circle dot) M dwarf at projected separation a(perpendicular to) l = 1.18 +/- 0.10 a.u., i.e., about 1.9 times the distance the snow line. The system is quite nearby for a microlensing planet, D-L = 0.86 +/- 0.09 kpc. Indeed, it was the large lens-source relative parallax pi(rel) = 1.0 mas (combined with the low mass M) that gave rise to the large, and thus well-measured, microlens parallax pi(E) proportional to (pi(rel)/M)(1)(/2) that enabled these precise measurements. OGLE-2017-BLG-1434Lb is the eighth microlensing planet with planet-host mass ratio q < 1 x 10(-4). We apply a new planet-detection sensitivity method, which is a variant of V/V-max, to seven of these eight planets to derive the mass-ratio function in this regime. We find dN/ d lnq proportional to q(P) , with p =1.05(-0.68)(+0.78), which confirms the turnover in the mass function found by Suzuki et al. relative to the power law of opposite sign n = -0.93 +/- 0.13 at higher mass ratios q greater than or similar to 2 x 10(-4). We combine our result with that of Suzuki et al. to obtain p = 0.73(-0.34)(+0.42.)
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