Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to ...identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of
was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection.
RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.
A survey was conducted in UK regional children's hospitals with paediatric intensive care and paediatric infectious disease (PID) departments to describe the characteristics of paediatric ...antimicrobial stewardship (PAS) programmes. A structured questionnaire was sent to PAS coordinators. ‘Audit and feedback’ was implemented in 13 out of 17 centres. Microbiology-led services were more likely to implement antimicrobial restriction (75% vs 33% in PID-led services), to focus on broad-spectrum antibiotics, and to review patients with positive blood cultures. PID-led services were more likely to identify patients from e-prescribing or drug charts and review all antimicrobials. A PAS network has been established.
We have studied pressure-induced chemical reactions in carbon monoxide using both a diamond anvil cell and a modified large volume press. Our spectroscopic data reveal that carbon monoxide ...disproportionates into molecular CO2 and a solid lactone-type polymer; photochemically above 3.2 GPa, thermochemically above 5 GPa at 300 K, or at 3 GPa and ∼2000 K as achieved by laser heating. The solid product can be recovered at ambient conditions with a high degree of conversion, measured to be up to 95% of the original CO. Its fundamental chemical structure includes β-lactone and conjugated CC, which can be considered a severely modified polymeric carbon suboxide with open ladders and smaller five-membered rings. The polymer is metastable at ambient conditions, spontaneously liberating CO2 gases exothermically. We find that the recovered polymer has a high energy density, 1−8 kJ/g, and is very combustible. We estimate the density of recovered CO polymer to be at least 1.65 g/cm3.
Sodium aluminum hydrides have gained attention due to their high hydrogen weight percent (5.5% ideal) compared to interstitial hydrides, and as a model for hydrides with even higher hydrogen weight ...fraction. The purpose of this paper is to investigate the Ti-compounds that are formed under solution-doping techniques, such as wet doping in solvents such as tetrahydrofuran (THF). Compound formation in Ti-doped sodium aluminum hydrides is investigated using X-ray diffraction (XRD) and magic angle spinning (MAS) nuclear magnetic resonance (NMR). We present lattice parameter measurements of crushed single crystals, which were exposed to Ti during growth. Rietveld refinements indicate no lattice parameter change and thus no solubility for Ti in NaAlH4 by this method of exposure. In addition, X-ray diffraction data indicate that no Ti substitutes in NaH, the final decomposition product for the alanate. Reaction products of completely reacted (33.3 at.%doped) samples that were solvent-mixed or mechanically milled are investigated. Formation of TiAl3 is observed in mechanically milled materials, but not solution mixed samples, where bonding to THF likely stabilizes Ti-based nano-clusters. The Ti in these clusters is activated by mechanical milling.
Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact with the transporter associated with antigen ...processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be a transmembrane glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin superfamily with a probable cytoplasmic endoplasmic reticulum retention signal. Up to four MHC class I-tapasin complexes were found to bind to each TAP molecule. Expression of tapasin in a negative mutant human cell line (220) restored class I-TAP association and normal class I cell surface expression. Tapasin expression also corrected the defective recognition of virus-infected 220 cells by class I-restricted cytotoxic T cells, establishing a critical functional role for tapasin in MHC class I-restricted antigen processing.
Diagnostic criteria for acute FPIES: What are we missing? Vazquez-Ortiz, Marta; Argiz, Laura; Machinena, Adrianna ...
The journal of allergy and clinical immunology in practice (Cambridge, MA),
05/2020, Letnik:
8, Številka:
5
Journal Article
The limited availability of microbiology services in sub-Saharan Africa impedes accurate diagnosis of bacterial pathogens and understanding of trends in prevalence and antibiotic sensitivities. We ...aimed to characterize bacteremia among hospitalized children in The Gambia and to identify factors associated with bacteremia and mortality.
We prospectively studied children presenting with suspected severe infection to 2 urban hospitals in The Gambia, between January 2013 and September 2015. Demographic and anthropometric data, clinical features, management, and blood culture results were documented. Urine screens for antibiotic activity were performed in a subset of participants.
Of 411 children enrolled (median age, 29 months; interquartile range, 11-82), 79.5% (325 of 409) reported prehospital antibiotic use. Antimicrobial activity by urinary screen for antibiotic activity was detected in 70.8% (n = 80 of 113). Sixty-six bacterial pathogens were identified in 65 (15.8%) participants and
predominated. Gram-positive organisms were more commonly identified than Gram-negative (
< .01). Antibiotic resistance against first-line antimicrobials (ampicillin and gentamicin) was common among Gram-negative bacteria (39%; range, 25%-100%). Factors significantly associated with bacteremia included the following: gender, hydration status, musculoskeletal examination findings, admission to the Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine hospital, and meeting sepsis criteria. Those associated with increased mortality were presence of a comorbidity, clinical pallor, tachypnea, and altered consciousness. Tachycardia was associated with reduced mortality.
The bacteremia rate in children with suspected childhood life-threatening infectious diseases in The Gambia is high. The pattern of pathogen prevalence and antimicrobial resistance has changed over time compared with previous studies illustrating the importance of robust bacterial surveillance programs in resource-limited settings.
The physical and chemical properties of 1,4-diphenylbutadiyne (DPB) blended with carbon-supported Pd (DPB–Pd/C) in the form of pellets during hydrogenation were investigated. A thermogravimetric ...analyzer (TGA) was employed to measure the kinetics of the hydrogen uptake by the DPB getter pellets. The kinetics obtained were then used to develop a semi-empirical model, based on gas diffusion into solids, to predict the performance of the getter pellets under various conditions. The accuracy of the prediction model was established by comparing the prediction models with independent experimental data on hydrogen pressure buildup in sealed systems containing DPB getter pellets and subjected to known rates of hydrogen input. The volatility of the hydrogenated DPB products and its effects on the hydrogen uptake kinetics were also analyzed.
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