Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.The research was supported by the Republic of Korea (Government-wide R&D Fund project for infectious disease research (GFID), HG18C0084)

Crystal structure and proteomics analysis of empty virus-like particles of Cowpea mosaic virus

Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C-terminus of the small (S) subunit. The intact C-terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C-termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed

Climatic yield potential of Japonica???type rice in the Korean Peninsula under RCP scenarios using the ensemble of multi???GCM and multi???RCM chains

Rice production in the Korean Peninsula (KP) in the near future (2021-2050) is analysed in terms of the climatic yield potential (CYP) index for Japonica-type rice. Data obtained from the dynamically downscaled daily temperature and sunshine duration for the Historical period (1981-2010) and near future under two Representative Concentration Pathway (RCP4.5 and RCP8.5) scenarios are utilized. To reduce uncertainties that might be induced by using a Coupled General Circulation Model (CGCM)-a Regional Climate Model (RCM) chain in dynamical downscaling, two CGCM-three RCM chains are used to estimate the CYP index. The results show that the mean rice production decreases, mainly due to the increase of the temperature during the grain-filling period (40 days after the heading date). According to multi model ensemble, the optimum heading date in the near future will be approximately 12 days later and the maximum CYP will be even higher than in the Historical. This implies that the rice production is projected to decrease if the heading date is selected based on the optimum heading date of Historical, but to increase if based on that of near future. The mean rice production during the period of ripening is projected to decrease (to about 95% (RCP4.5) and 93% (RCP8.5) of the Historical) in the western and southern regions of the KP, but to increase (to about 104% (RCP4.5) and 106% (RCP8.5) of the Historical) in the northeastern coastal regions of the KP. However, if the optimum heading date is selected in the near future climate, the peak rice production is projected to increase (to about 105% (RCP4.5) and 104% (RCP8.5) of the Historical) in the western, southern and northeastern coastal regions of the KP, but to decrease (to about 98% (RCP4.5) and 96% (RCP8.5) of the Historical) in the southeastern coastal regions of the KP

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories.Methods: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age.Findings: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran.Interpretation: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings.Copyright (C) 2021 World Health Organization; licensee Elsevier.</p

A single amino acid substitution in the movement protein enables the mechanical transmission of a geminivirus

Begomoviruses of the Geminiviridae are usually transmitted by whiteflies and rarely by mechanical inoculation. We used tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus, to address this issue. Most ToLCNDV isolates are not mechanically transmissible to their natural hosts. The ToLCNDV-OM isolate, originally identified from a diseased oriental melon plant, is mechanically transmissible, while the ToLCNDV-CB isolate, from a diseased cucumber plant, is not. Genetic swapping and pathological tests were performed to identify the molecular determinants involved in mechanical transmission. Various viral infectious clones were constructed and successfully introduced into Nicotiana benthamiana, oriental melon, and cucumber plants by Agrobacterium-mediated inoculation. Mechanical transmissibility was assessed via direct rub inoculation with sap prepared from infected N. benthamiana. The presence or absence of viral DNA in plants was validated by PCR, Southern blotting, and in situ hybridization. The results reveal that mechanical transmissibility is associated with the movement protein (MP) of viral DNA-B in ToLCNDV-OM. However, the nuclear shuttle protein of DNA-B plays no role in mechanical transmission. Analyses of infectious clones carrying a single amino acid substitution reveal that the glutamate at amino acid position 19 of MP in ToLCNDV-OM is critical for mechanical transmissibility. The substitution of glutamate with glycine at this position in the MP of ToLCNDV-OM abolishes mechanical transmissibility. In contrast, the substitution of glycine with glutamate at the 19th amino acid position in the MP of ToLCNDV-CB enables mechanical transmission. This is the first time that a specific geminiviral movement protein has been identified as a determinant of mechanical transmissibility

Effects of the Immunomodulatory Agent Cordyceps militaris on Airway Inflammation in a Mouse Asthma Model

Cordyceps militaris is a well-known fungus with immunomodulatory activity. It is generally used in traditional Chinese medicine to treat hemoptysis, bronchial or lung inflammation, and urogenital disorders. The purpose of our study was to evaluate the effect of cultivated C. militaris on airway inflammation in a mouse asthma model. Methods: BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and were then given intranasal OVA on Day 14 and Days 25-27. Randomized treatment groups of sensitized mice were administered C. militaris, prednisolone, montelukast, or placebo by gavage from Days 15-27. Airway hyperreactivity to aerosolized methacholine was determined. Bronchoalveolar lavage fluid and serum were analyzed to assess airway inflammation. Results: OVA-sensitized mice developed a significant airway inflammatory response that was inhibited by prednisolone and montelukast, whilst C. militaris reduced airway inflammation less effectively. Airway hyperresponsiveness to methacholine was observed in OVA-sensitized mice and was reversed by both prednisolone and montelukast. C. militaris initially reversed airway hyperreactivity, but this effect disappeared at higher methacholine doses. Conclusion: C. militaris can modulate airway inflammation in asthma, but it is less effective than prednisolone or montelukast. These results demonstrate that C. militaris is unable to adequately block the potent mediators of asthmatic airway inflammation