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University of Miyazaki

UniversityMiyazaki, Japan

Research output, citation impact, and the most-cited recent papers from University of Miyazaki (Japan). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
23.5K
Citations
1.1M
h-index
284
i10-index
22.5K
Also known as
Miyazaki DaigakuUniversity of Miyazaki宮崎大学

Top-cited papers from University of Miyazaki

Satellite-Based Energy Balance for Mapping Evapotranspiration with Internalized Calibration (METRIC)—Model
Richard G. Allen, Masahiro Tasumi, Ricardo Trezza
2007· Journal of Irrigation and Drainage Engineering1.9Kdoi:10.1061/(asce)0733-9437(2007)133:4(380)

Mapping evapotranspiration at high resolution with internalized calibration (METRIC) is a satellite-based image-processing model for calculating evapotranspiration (ET) as a residual of the surface energy balance. METRIC uses as its foundation the pioneering SEBAL energy balance process developed in The Netherlands by Bastiaanssen, where the near-surface temperature gradients are an indexed function of radiometric surface temperature, thereby eliminating the need for absolutely accurate surface temperature and the need for air-temperature measurements. The surface energy balance is internally calibrated using ground-based reference ET to reduce computational biases inherent to remote sensing-based energy balance and to provide congruency with traditional methods for ET. Slope and aspect functions and temperature lapsing are used in applications in mountainous terrain. METRIC algorithms are designed for relatively routine application by trained engineers and other technical professionals who possess a familiarity with energy balance and basic radiation physics. The primary inputs for the model are short-wave and long-wave (thermal) images from a satellite (e.g., Landsat and MODIS), a digital elevation model and ground-based weather data measured within or near the area of interest. ET “maps” (i.e., images) via METRIC provide the means to quantify ET on a field-by-field basis in terms of both the rate and spatial distribution. METRIC has some significant advantages over many traditional applications of satellite-based energy balance in that its calibration is made using reference ET, rather than the evaporative fraction. The use of reference ET for the extrapolation of instantaneous ET from periods of 24h and longer compensates for regional advection effects by not tying the evaporative fraction to net radiation, since ET can exceed daily net radiation in many arid or semi-arid locations. METRIC has some significant advantages over conventional methods of estimating ET from crop coefficient curves in that neither the crop development stages, nor the specific crop type need to be known with METRIC. In addition, energy balance can detect reduced ET caused by water shortage.

Autophagy Is Activated for Cell Survival after Endoplasmic ReticulumStress
Maiko Ogata, Shin‐ichiro Hino, Atsushi Saito, Keisuke Morikawa +4 more
2006· Molecular and Cellular Biology1.8Kdoi:10.1128/mcb.01453-06

Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress.

Ghrelin, a Novel Growth Hormone-Releasing Acylated Peptide, Is Synthesized in a Distinct Endocrine Cell Type in the Gastrointestinal Tracts of Rats and Humans<sup>1</sup>
Yukari Date, Masayasu Kojima, Hiroshi Hosoda, Akira Sawaguchi +4 more
2000· Endocrinology1.8Kdoi:10.1210/endo.141.11.7757

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Petra Mlčochová, Steven A. Kemp, Mahesh Shanker Dhar, Guido Papa +4 more
2021· Nature1.4Kdoi:10.1038/s41586-021-03944-y

. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Complete Genome Sequence of Enterohemorrhagic Eschelichia coli O157:H7 and Genomic Comparison with a Laboratory Strain K-12
Tetsuya Hayashi
2001· DNA Research1.3Kdoi:10.1093/dnares/8.1.11

Escherichia coli O157:H7 is a major food-borne infectious pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Here we report the complete chromosome sequence of an O157:H7 strain isolated from the Sakai outbreak, and the results of genomic comparison with a benign laboratory strain, K-12 MG1655. The chromosome is 5.5 Mb in size, 859 Kb larger than that of K-12. We identified a 4.1-Mb sequence highly conserved between the two strains, which may represent the fundamental backbone of the E. coli chromosome. The remaining 1.4-Mb sequence comprises of O157:H7-specific sequences, most of which are horizontally transferred foreign DNAs. The predominant roles of bacteriophages in the emergence of O157:H7 is evident by the presence of 24 prophages and prophage-like elements that occupy more than half of the O157:H7-specific sequences. The O157:H7 chromosome encodes 1632 proteins and 20 tRNAs that are not present in K-12. Among these, at least 131 proteins are assumed to have virulence-related functions. Genome-wide codon usage analysis suggested that the O157:H7-specific tRNAs are involved in the efficient expression of the strain-specific genes. A complete set of the genes specific to O157:H7 presented here sheds new insight into the pathogenicity and the physiology of O157:H7, and will open a way to fully understand the molecular mechanisms underlying the O157:H7 infection.

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
Bo Meng, Adam Abdullahi, Isabella A.T.M. Ferreira, Niluka Goonawardane +4 more
2022· Nature1.2Kdoi:10.1038/s41586-022-04474-x

Abstract The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2 , and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways 3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.

Efficient de novo assembly of highly heterozygous genomes from whole-genome shotgun short reads
Rei Kajitani, Kouta Toshimoto, Hideki Noguchi, Atsushi Toyoda +4 more
2014· Genome Research1.1Kdoi:10.1101/gr.170720.113

Although many de novo genome assembly projects have recently been conducted using high-throughput sequencers, assembling highly heterozygous diploid genomes is a substantial challenge due to the increased complexity of the de Bruijn graph structure predominantly used. To address the increasing demand for sequencing of nonmodel and/or wild-type samples, in most cases inbred lines or fosmid-based hierarchical sequencing methods are used to overcome such problems. However, these methods are costly and time consuming, forfeiting the advantages of massive parallel sequencing. Here, we describe a novel de novo assembler, Platanus, that can effectively manage high-throughput data from heterozygous samples. Platanus assembles DNA fragments (reads) into contigs by constructing de Bruijn graphs with automatically optimized k-mer sizes followed by the scaffolding of contigs based on paired-end information. The complicated graph structures that result from the heterozygosity are simplified during not only the contig assembly step but also the scaffolding step. We evaluated the assembly results on eukaryotic samples with various levels of heterozygosity. Compared with other assemblers, Platanus yields assembly results that have a larger scaffold NG50 length without any accompanying loss of accuracy in both simulated and real data. In addition, Platanus recorded the largest scaffold NG50 values for two of the three low-heterozygosity species used in the de novo assembly contest, Assemblathon 2. Platanus therefore provides a novel and efficient approach for the assembly of gigabase-sized highly heterozygous genomes and is an attractive alternative to the existing assemblers designed for genomes of lower heterozygosity.

The X-Ray Observatory Suzaku
Kazuhisa Mitsuda, Mark W. Bautz, Hajime Inoue, Richard L. Kelley +4 more
2007· Publications of the Astronomical Society of Japan1.0Kdoi:10.1093/pasj/59.sp1.s1

High-sensitivity wide-band X-ray spectroscopy is the key feature of the Suzaku X-ray observatory, launched on 2005 July 10. This paper summarizes the spacecraft, in-orbit performance, operations, and data processing that are related to observations. The scientific instruments, the high-throughput X-ray telescopes, X-ray CCD cameras, non-imaging hard X-ray detector are also described.

Ghrelin
Timo D. Müller, Rubén Nogueiras, Mark L. Andermann, Zane B. Andrews +4 more
2015· Molecular Metabolism999doi:10.1016/j.molmet.2015.03.005

BACKGROUND: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. SCOPE OF REVIEW: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery. MAJOR CONCLUSIONS: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

CH<sub>3</sub>NH<sub>3</sub>Sn<sub><i>x</i></sub>Pb<sub>(1–<i>x</i>)</sub>I<sub>3</sub> Perovskite Solar Cells Covering up to 1060 nm
Yuhei Ogomi, Atsushi Morita, Syota Tsukamoto, Takahiro Saitho +4 more
2014· The Journal of Physical Chemistry Letters966doi:10.1021/jz5002117

We report photovoltaic performances of all-solid state Sn/Pb halide-based perovskite solar cells. The cell has the following composition: F-doped SnO2 layered glass/compact titania layer/porous titania layer/CH3NH3SnxPb(1-x)I3/regioregular poly(3-hexylthiophene-2,5-diyl). Sn halide perovskite itself did not show photovoltaic properties. Photovoltaic properties were observed when PbI2 was added in SnI2. The best performance was obtained by using CH3NH3Sn0.5Pb0.5I3 perovskite. 4.18% efficiency with open circuit voltage 0.42 V, fill factor 0.50, and short circuit current 20.04 mA/cm(2) are reported. The edge of the incident photon to current efficiency curve reached 1060 nm, which was 260 nm red-shifted compared with that of CH3NH3PbI3 perovskite solar cells.

Highly Luminescent Phase-Stable CsPbI<sub>3</sub> Perovskite Quantum Dots Achieving Near 100% Absolute Photoluminescence Quantum Yield
Feng Liu, Yaohong Zhang, Chao Ding, Syuusuke Kobayashi +4 more
2017· ACS Nano946doi:10.1021/acsnano.7b05442

Perovskite quantum dots (QDs) as a new type of colloidal nanocrystals have gained significant attention for both fundamental research and commercial applications owing to their appealing optoelectronic properties and excellent chemical processability. For their wide range of potential applications, synthesizing colloidal QDs with high crystal quality is of crucial importance. However, like most common QD systems such as CdSe and PbS, those reported perovskite QDs still suffer from a certain density of trapping defects, giving rise to detrimental nonradiative recombination centers and thus quenching luminescence. In this paper, we show that a high room-temperature photoluminescence quantum yield of up to 100% can be obtained in CsPbI3 perovskite QDs, signifying the achievement of almost complete elimination of the trapping defects. This is realized with our improved synthetic protocol that involves introducing organolead compound trioctylphosphine–PbI2 (TOP–PbI2) as the reactive precursor, which also leads to a significantly improved stability for the resulting CsPbI3 QD solutions. Ultrafast kinetic analysis with time-resolved transient absorption spectroscopy evidence the negligible electron or hole-trapping pathways in our QDs, which explains such a high quantum efficiency. We expect the successful synthesis of the “ideal” perovskite QDs will exert profound influence on their applications to both QD-based light-harvesting and -emitting devices.

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy
Marcos Daniel Actis, G. Agnetta, F. Aharonian, A. G. Akhperjanian +4 more
2011· Experimental Astronomy918doi:10.1007/s10686-011-9247-0

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Rapid and Easy<i>In Silico</i>Serotyping of Escherichia coli Isolates by Use of Whole-Genome Sequencing Data
Katrine Joensen, Anna Maria Malberg Tetzschner, Atsushi Iguchi, Frank M. Aarestrup +1 more
2015· Journal of Clinical Microbiology906doi:10.1128/jcm.00008-15

Accurate and rapid typing of pathogens is essential for effective surveillance and outbreak detection. Conventional serotyping of Escherichia coli is a delicate, laborious, time-consuming, and expensive procedure. With whole-genome sequencing (WGS) becoming cheaper, it has vast potential in routine typing and surveillance. The aim of this study was to establish a valid and publicly available tool for WGS-based in silico serotyping of E. coli applicable for routine typing and surveillance. A FASTA database of specific O-antigen processing system genes for O typing and flagellin genes for H typing was created as a component of the publicly available Web tools hosted by the Center for Genomic Epidemiology (CGE) (www.genomicepidemiology.org). All E. coli isolates available with WGS data and conventional serotype information were subjected to WGS-based serotyping employing this specific SerotypeFinder CGE tool. SerotypeFinder was evaluated on 682 E. coli genomes, 108 of which were sequenced for this study, where both the whole genome and the serotype were available. In total, 601 and 509 isolates were included for O and H typing, respectively. The O-antigen genes wzx, wzy, wzm, and wzt and the flagellin genes fliC, flkA, fllA, flmA, and flnA were detected in 569 and 508 genome sequences, respectively. SerotypeFinder for WGS-based O and H typing predicted 560 of 569 O types and 504 of 508 H types, consistent with conventional serotyping. In combination with other available WGS typing tools, E. coli serotyping can be performed solely from WGS data, providing faster and cheaper typing than current routine procedures and making WGS typing a superior alternative to conventional typing strategies.

Comparative Metagenomics Revealed Commonly Enriched Gene Sets in Human Gut Microbiomes
Ken Kurokawa, Takehiko Itoh, Tomomi Kuwahara, Kenshiro Oshima +4 more
2007· DNA Research855doi:10.1093/dnares/dsm018

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes.

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis
Michael Walsh, Peter A. Merkel, Chen Au Peh, Wladimir Szpirt +4 more
2020· New England Journal of Medicine850doi:10.1056/nejmoa1803537

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant
Rigel Suzuki, Daichi Yamasoba, Izumi Kimura, Lei Wang +4 more
2022· Nature748doi:10.1038/s41586-022-04462-1

Abstract The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern 1 . In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion 2,3 , the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.

Selective Activation of the B Natriuretic Peptide Receptor by C-Type Natriuretic Peptide (CNP)
Kerry J. Koller, David Lowe, Gregory L. Bennett, Naoto Minamino +3 more
1991· Science731doi:10.1126/science.1672777

The natriuretic peptides are hormones that can stimulate natriuretic, diuretic, and vasorelaxant activity in vivo, presumably through the activation of two known cell surface receptor guanylyl cyclases (ANPR-A and ANPR-B). Although atrial natriuretic peptide (ANP) and, to a lesser extent, brain natriuretic peptide (BNP) are efficient activators of the ANPR-A guanylyl cyclase, neither hormone can significantly stimulate ANPR-B. A member of this hormone family, C-type natriuretic peptide (CNP), potently and selectively activated the human ANPR-B guanylyl cyclase. CNP does not increase guanosine 3',5'-monophosphate accumulation in cells expressing human ANPR-A. The affinity of CNP for ANPR-B is 50- or 500-fold higher than ANP or BNP, respectively. This ligand-receptor pair may be involved in the regulation of fluid homeostasis by the central nervous system.

Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation
Akatsuki Saito, Takashi Irie, Rigel Suzuki, Tadashi Maemura +4 more
2021· Nature676doi:10.1038/s41586-021-04266-9

Abstract During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society 1 . The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. 2 ). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma
Yoshinari Ichiki, Kazuo Kitamura, Kenji Kangawa, Mari Kawamoto +2 more
1994· FEBS Letters585doi:10.1016/0014-5793(94)80106-1

A specific and sensitive radioimmunoassay for human adrenomedullin has been developed and distribution and characterization of immunoreactive adrenomedullin in human tissue were investigated. The radioimmunoassay specifically recognizes its carboxyterminal region and half maximal inhibition of binding of radioiodinated adrenomedullin(40-52)NH2 was observed at 11 fmol/tube. Immunoreactive adrenomedullin was abundant in adrenal medulla (47.7 +/- 26.1 fmol/mg, mean +/- S.D.) and was ubiquitously found in all tissue examined. The mean plasma concentration of adrenomedullin in three normal individuals was 17.2 +/- 6.4 pg/ml (mean +/- S.D.). By analysis with reverse-phase high-performance liquid chromatography coupled with the radioimmunoassay, most immunoreactive adrenomedullin in the adrenal medulla, atrium and lung was found to be adrenomedullin(1-52)NH2.

Enzyme-Labeling of Antibodies and Their Fragments for Enzyme Immunoassay and Immunohistochemical Staining
Eiji Ishikawa, Masayoshi Imagawa, Seiichi Hashida, Shinji Yoshitake +2 more
1983· Journal of Immunoassay544doi:10.1080/15321818308057011

Abstract The use of an enzyme as a label has a number of advantages over the use of other labels in both immunohistochemistry and immunoassay. Immunofluorescence techniques are not suitable for ultrastructural research on cells, and ferritin-labeled antibodies allow only electronmicroscopic studies. By contrast, enzyme-labeled antibodies permit localization of cellular antigens in relation to tissue structures under light microscope and also demonstration of cellular antigens at an ultrastructural level by electronmicroscopy. Antibody or antibody fragments labeled with enzymes of small molecular weight can more readily permeate cells of tissue sections than ferritin-labeled antibodies. The color of tissue sections prepared by immunoenzymatic techniques is stable for years, while immunofluorescence of tissue sections decreases rapidly when exposed to light. Radioisotope-labeled reagents decay with time; there are health hazards due to radio isotopes; and disposal of radioactive waste is becoming increasingly difficult. By contrast, enzyme-labeled antigens and antibodies are stable for months or even years and there are no problems either of health hazards or of waste disposal with appropriate choice of enzymes and substrates. Under favourable conditions, enzyme immunoassays may be even more sensitive than radioimmunoassays (1). Enzyme-labeled antigens and antibodies have found increasing use during the past decade, reinforced by improvements in enzyme-labeling methods.