Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host

Since 2003, H5N1 influenza viruses have caused over 400 known cases of human infection with a mortality rate greater than 60%. Most of these cases resulted from direct contact with virus-contaminated poultry or poultry products. Although only limited human-to-human transmission has been reported to date, it is feared that efficient human-to-human transmission of H5N1 viruses has the potential to cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral transmission among humans is largely unknown. In this study, we used guinea pigs as a mammalian model to study the transmission of six different H5N1 avian influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35) and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated animals to naïve contact animals. Our mutagenesis analysis revealed that the amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at 158–160, was responsible for HA binding to sialylated glycans and was critical for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates

Upper ocean biogeochemistry of the oligotrophic North Pacific Subtropical Gyre : from nutrient sources to carbon export

Subtropical gyres cover 26–29% of the world’s surface ocean and are conventionally regarded as ocean deserts due to their permanent stratification, depleted surface nutrients, and low biological productivity. Despite tremendous advances over the past three decades, particularly through the Hawaii Ocean Time-series and the Bermuda Atlantic Time-series Study, which have revolutionized our understanding of the biogeochemistry in oligotrophic marine ecosystems, the gyres remain understudied. We review current understanding of upper ocean biogeochemistry in the North Pacific Subtropical Gyre, considering other subtropical gyres for comparison. We focus our synthesis on spatial variability, which shows larger than expected dynamic ranges of properties such as nutrient concentrations, rates of N2 fixation, and biological production. This review provides new insights into how nutrient sources drive community structure and export in upper subtropical gyres. We examine the euphotic zone in subtropical gyres as a two-layered vertically structured system: a nutrient-depleted layer above the top of the nutricline in the well-lit upper ocean and a nutrient-replete layer below in the dimly lit waters. These layers vary in nutrient supply and stoichiometries and physical forcing, promoting differences in community structure and food webs, with direct impacts on the magnitude and composition of export production. We evaluate long-term variations in key biogeochemical parameters in both of these euphotic zone layers. Finally, we identify major knowledge gaps and research challenges in these vast and unique systems that offer opportunities for future studies

Research and analysis on the value path of innovation and entrepreneurship education based on SPSS statistical analysis modeling

In this study, the linear regression equation is used to express the quantitative dependence of the variables and variables of the value of innovation and entrepreneurship education, the regression equation is optimized based on the BP neural network, and the regression analysis model of innovation and entrepreneurship education is constructed, and the significance test of the equation is carried out through the ANOVA method. The large sample research method was used to obtain samples of research material for public innovation and entrepreneurial education value cognition, which were then analyzed using SPSS software. The differences in gender, age, education, and specialty on the value cognition of innovation and entrepreneurship education are investigated by ANOVA, and the model constructed in this paper is used to explore the influence of an individual’s social consciousness, innovation, and entrepreneurship environment and education on their value cognition of entrepreneurship education, to summarize the value path of innovation and entrepreneurship education. From the current situation of value cognition and difference analysis, the value cognition level of innovation and entrepreneurship education of the survey respondents scored 3.78, and the significance of attitude willingness and individual value cognition in the single-factor analysis of age was 0.048 and 0.024, which were less than 0.05, and age had a significant effect on the overall cognition level

The impact of co‐administration of ketoconazole and rifampicin on the pharmacokinetics of apremilast in healthy volunteers

AIMS: Two clinical studies were conducted to determine possible drug−drug interactions between apremilast and a strong CYP3A4 inhibitor, ketoconazole, or a potent CYP3A4 inducer, rifampicin. The main objectives of these two studies were to evaluate the impact of multiple doses of ketoconazole on the pharmacokinetics of apremilast and its metabolites, and the effect of multiple oral doses of rifampicin on the pharmacokinetics of apremilast. METHODS: These single centre, open label, sequential treatment studies in healthy subjects included two treatment periods for ketoconazole and three treatment periods for rifampicin. Apremilast was administered as a 20 mg (ketoconazole study) or 30 mg (rifampicin study) single oral dose. RESULTS: Ketoconazole increases overall exposure (AUC(0,∞)) of apremilast by ≈36% (2827 vs. 2072 ng ml(−1) h, 90% CI = 126.2, 147.5) and peak exposure (C(max)) by 5% (247 vs. 236 ng ml(−1)). Multiple doses of rifampicin increase apremilast clearance ≈3.6-fold and decrease apremilast mean AUC(0,∞) by ≈72% (3120 vs. 869 ng ml(−1) h, 90% CI = 25.7, 30.4) and C(max) (from 290 vs. 166 ng ml(−1)) relative to that of apremilast given alone. A 30 min intravenous infusion of rifampicin 600 mg had negligible effects on the overall exposure (AUC(0,∞)) of apremilast (2980 vs. 3120 ng ml(−1) h, 90% CI = 88.0, 104.1). CONCLUSION: Ketoconazole slightly decreased apremilast clearance, resulting in a small increase in AUC which is probably not meaningful clinically. However, the effect of CYP3A4 induction by rifampicin on apremilast clearance is much more pronounced than that of CYP3A4 inhibition by ketoconazole. Strong CYP3A4 inducers may result in a loss of efficacy of apremilast because of decreased drug exposure

Improvement of Erosion-Corrosion Behavior of AISI 420 Stainless Steel by Ion-Assisted Deposition ZrN Coatings

In this paper, a pragmatic technique has been developed to evaluate the erosion-corrosion behavior of three kinds of ZrN coatings (i.e., monolayer, multilayer, and gradient layers) which were deposited on AISI 420 martensitic stainless steel using an ion-assisted deposition technology. Among them, the monolayer coating refers to the coating with no change in composition and structure, the multilayer coating refers to the coating with alternating change of Zr/ZrN, and the gradient coating refers to the ZrN coating by increasing N2 partial pressure gradually. The morphology, composition, and microhardness of these ZrN coatings were examined by means of integrating the scanning electron microscopy (SEM), X-ray diffraction (XRD), and Knoop hardness measurements, while anodic polarization tests and salt fog spray tests in a simulated industrial environment have been performed to evaluate and identify the corrosion mechanisms of these coatings. The surface microhardness and corrosion resistance of the AISI420 martensitic stainless steel is found to be significantly improved by depositing the ion-assisted deposition ZrN coatings. The study indicates that the erosion-corrosion behavior in the slurry is the result of the synergistic effect of small-angle erosion and acid solution corrosion. Three ZrN coatings hinder the slurry erosion-corrosion behavior from two aspects (i.e., erosion resistance of small-angle particles as well as corrosion resistance of the substrate), thereby significantly improving the erosion-corrosion resistance of AISI 420 stainless steel. In addition, the ZrN gradient coatings show a much better erosion-corrosion resistance than that of the monolayer/multilayer ZrN coating because they have excellent crack resistance, bearing capacity, and electrochemical performance

Deep‐Water Formation in the North Pacific During the Late Miocene Global Cooling

International audienceAbstract A multiproxy study including organic carbon and bulk nitrogen isotopes along with major and trace element concentrations in sediments from Integrated Ocean Drilling Program (IODP) Sites U1425 and U1430 in the Japan Sea have been conducted in order to trace deep‐water evolution in the Japan Sea and the North Pacific since the late Miocene. The high total organic carbon (TOC) flux, as well as other published geochemical and sedimentary evidence, indicates the occurrence of anoxic deep‐water in the Japan Sea before ∼7.4 Ma. The low‐nitrogen isotope values probably suggest nearly complete denitrification. In contrast, the sharply enhanced biological production but decreased burial of organic matter during ∼7.4–4 Ma, as shown by high enrichment factor of Ba (Ba EF ) values, together with low TOC flux, highlights enhanced deep‐water oxygenation in the Japan Sea during that time. We suggest that deep‐water formation in the North Pacific ventilated the deep Japan Sea via northern deep seaways before the sea became semi‐closed in the early Pliocene. The synchronously increased equator‐to‐pole temperature gradients driven by late Miocene global cooling may have caused southward shift of mid‐latitude storm tracks, coupled with the weakened East Asian summer monsoon and moisture transport, leading to decreased precipitation in mid‐latitude regions. The potential increases in surface salinity in the North Pacific may have broken the ocean stratification and favored deep‐water formation, and further caused deep‐water ventilation in the Japan Sea