HIF1α is required for NK cell metabolic adaptation during virus infection

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response

Alga-made anti-Hepatitis B antibody binds to human Fcγ receptors.

Microalgae are unicellular eukaryotic organisms which represent an emerging alternative to other cell biofactories commonly used to produce monoclonal antibodies. Microalgae display several biotechnological advantages such as their rapid growth rate and their phototrophic lifestyle allowing low production costs as protein expression is solar-fueled. Recently, a fully assembled recombinant IgG antibody directed against Hepatitis B surface antigen is produced and secreted in the culture medium of the diatom Phaeodactylum tricornutum. A biochemical characterization of this recombinant antibody demonstrated that the Asn-297 is N-glycosylated by oligomannosides. In the immune system, antibodies interact with effector molecules and cells through their Fc part and the recognition of Fcγ receptors (FcγR) which are important for inducing phagocytosis of opsonized microbes. Interactions between IgG and FcγR are influenced by the N-glycan structures present on the Asn-297. In this study, the authors characterized the binding capacity of the anti-hepatitis B recombinant IgG produced in P. tricornutum to two human Fcγ receptors (FcγRI and IIIa) using a cellular binding assay and surface plasmon resonance (SPR). This allowed us to demonstrate that the alga-made antibody is able to bind FcγRI with a reduced affinity and engages FcyRIIIa with 3-times higher affinity compared to a control human IgG1

Infrared study of the multiband low-energy excitations of the topological antiferromagnet MnBi2Te4

With infrared spectroscopy, we studied the bulk electronic properties of the topological antiferromagnet MnBi2Te4 with TN≃25K. With the support of band-structure calculations, we assign the intra- and interband excitations and determine the band gap of Eg≈0.17 eV. We also obtain evidence for two types of conduction bands with light and very heavy carriers. The multiband free-carrier response gives rise to an unusually strong increase of the combined plasma frequency, ωpl, below 300 K. The band reconstruction below TN yields an additional increase of ωpl and a splitting of the transition between the two conduction bands by about 54 meV. Our study thus reveals a complex and strongly temperature-dependent multiband low-energy response that has important implications for the study of the surface states and device applications.The work in Fribourg was supported by the Schweizerische Nationalfonds (SNF) through Grant No. 200020-172611. V.K. acknowledges support by the Deutsche Forschungsgemeinschaft (DFG) through Grant No. KA1694/12-1. N.M. acknowledges the support of the Science Development Foundation under the President of the Republic of Azerbaijan (Grant No. E˙IF-BGM-4-RFTF1/2017-21/04/1-M-02). The work at Beijing was supported by the Natural Science Foundation of China (NSFC Grant No. 11734003), the National Key R&D Program of China (Grants No. 2016YFA0300600 and No. 2020YFA0308800), and the Beijing Natural Science Foundation (Grant No. Z190006). Z.W. acknowledges the support from Beijing Institute of Technology Research Fund Program for Young Scholars. B.S. acknowledges the support of the Fundamental Research Funds for the Central Universities, Grant No. 19lgpy260. E.V.C. acknowledges Saint Petersburg State University (Grant No. ID 73028629). Y.M.D. acknowledges the support of the Natural Science Foundation of China (Grant No. 11874206). M.M.O. acknowledges the support by Spanish Ministerio de Ciencia e Innovación (Grant No. PID2019-103910GB-I00).Peer reviewe

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Residual Stress State of X65 Pipeline Girth Welds Before and After Local and Furnace Post Weld Heat Treatment

This research investigated the effects of global (in other words, furnace-based) and local post weld heat treatment (PWHT) on residual stress (RS) relaxation in API 5L X65 pipe girth welds. Two pipe spools were fabricated using identical pipeline production procedures for manufacturing multi-pass narrow gap welds. Non-destructive neutron diffraction strain scanning was carried out on girth welded pipe spools and stress-free comb samples and also thin slices for the determination of lattice spacing. All residual stress measurements were carried out at the KOWARI strain scanning instrument at the Australian Nuclear Science and Technology Organization (ANSTO)."/jats:p" "jats:p"Residual stresses of two pipe spools (in the as-welded condition) were measured through the thickness in the weld material and adjacent parent metal starting from the weld toe. Three line-scans were completed 3mm below outer surface, at mid thickness and 3mm above the inner surface. PWHT was adopted for stress relaxation; one pipe was conventionally heat treated entirely in an enclosed furnace and the other was locally heated by a flexible ceramic heating pad. Residual stresses were measured after PWHT at exactly the same locations as those used for the as-welded condition. Residual stress states of the two pipe spools in as-welded condition and after PWHT were compared and the results were presented in full stress maps. Additionally, through thickness residual stress profiles and the results of one line scan (3mm below outer surface) were compared with the respective residual stress profiles advised in British Standard BS 7910 “Guide to methods for assessing the acceptability of flaws in metallic structures” and the UK nuclear industry’s R6 procedure. The residual stress states of the two pipe spools measured in the as-welded condition were similar. With the given parameters, local PWHT has effectively reduced residual stresses in the pipe spool to such a level that it prompted the thought that local PWHT can be considered a substitute for global PWHT