The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected ...cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.
After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver ...function compared with standard static cold storage (SCS). We present a preliminary single‐center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded. Transplanted NMP grafts were matched 1:3 with transplanted SCS livers. Median NMP was 11.5 h (range 3.3–22.5 h) with one DCD liver perfused for 22.5 h. All transplanted livers functioned, and serum transaminases, bilirubin, international normalized ratio, and lactate levels corrected in NMP recipients similarly to controls. Graft survival at 30 days (primary outcome) was not statistically different between groups on an intent‐to‐treat basis (p = 0.25). Intensive care and hospital stays were significantly more prolonged in the NMP group. This preliminary experience demonstrates feasibility as well as potential technical risks of NMP in a North American setting and highlights a need for larger, randomized studies.
This paper describes a preliminary Canadian single‐center experience with clinical ex vivo normothermic liver perfusion and transplantation. See the video at amjtransplant.com/videos.
Viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. The mechanism initiating antiviral immunity during stealth viral replication is ...unknown, but recent data demonstrate that defective viral genomes generated at peak virus replication are critical for this process in vivo. This article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes generated during natural infections.
Background
This study investigated sensory processing in a sample of Spanish children with autism spectrum disorder (ASD). Specifically, the study aimed to explore (1) the prevalence and distribution ...of atypical sensory processing patterns, (2) the relationship between adaptive and maladaptive behaviour with atypical sensory processing and (3) the possible relationship between sensory subtype and maternal stress.
Methods
The short sensory profile 2 (Dunn 2014) and the vineland adaptive behavior scale (Sparrow et al. 1984) were administered to examine the sensory processing difficulties and maladaptive behaviours of 45 children with ASD aged 3 to 14; their mothers also completed the parenting stress index‐short form (Abidin 1995).
Results
Atypical sensory features were found in 86.7% of the children; avoider and sensor being the two most common patterns. No significant relationship was found between atypical sensory processing and adaptive behaviour. However, the analysis showed a strong relationship between sensory processing and maladaptive behaviour. Both maladaptive behaviour and sensory processing difficulties correlated significantly with maternal stress although maternal stress was predicted only by the sensory variable, and in particular by the avoider pattern.
Conclusions
The findings suggest that sensory features in ASD may be driving the high prevalence of parental stress in carers. They also suggest that the effect on parental stress that has been attributed traditionally to maladaptive behaviours may be driven by sensory difficulties. The implications of these findings are discussed in relation to the development of interventions and the need to explore contextual and cultural variables as possible sources of variability.
One of the options available for coping with current property requirements is to increase microalloying contents. As well as affecting austenite microstructural evolution, this can lead to a larger ...contribution of precipitation and dislocation density hardening to the mechanical strength. However, it also results in more complex interactions between the strengthening mechanisms, making it difficult to optimize operation parameters. In this work, plane strain compression tests were carried out to produce different austenite microstructures with two low carbon steels microalloyed with different Nb levels (0.04% and 0.11%), followed by coiling simulations in the 500 to 700°C temperature range. The mechanical properties of the transformed microstructures were determined via tensile testing and the specimens were characterized using optical microscopy, EBSD and TEM. Similar austenite grain sizes and strain accumulation levels were obtained for both steels, and as a result, it was observed that increasing Nb content had a small effect on the grain size of the transformed microstructures. On the other hand, the coiling temperature significantly affected the mechanical strength. The lowest strength values are obtained for 700°C; these increase significantly at 600°C (≅90 and 140MPa increase in the Yield Strength (YS) for the low and high Nb steels, respectively) and decrease slightly at 500°C. At the conditions investigated, similar dislocation density levels were determined for both steels, which indicates that the larger YS increase observed for the high Nb steel must be mainly due to the effect of precipitates formed during or after phase transformation.
Gravity generated by large masses has been observed using a variety of probes from atomic interferometers to torsional balances. However, gravitational coupling between small masses has never been ...observed so far. Here, we demonstrate sensitive displacement sensing of the Brownian motion of an optically trapped 7 mg pendulum motion whose natural quality factor is increased to 10^{8} through dissipation dilution. The sensitivity for an integration time of one second corresponds to the displacement generated in a millimeter-scale gravitational experiment between the probe and a 100 mg source mass, whose position is modulated at the pendulum mechanical resonant frequency. Development of such a sensitive displacement sensor using a milligram-scale device will pave the way for a new class of experiments where gravitational coupling between small masses in quantum regimes can be achieved.
Highlights • Innate RSV control involves the coordinated action of various cellular processes. • These processes include cell stress, death, and innate immune responses. • RSV utilizes multiple ...mechanisms to evade the host responses. • RSV DVGs are the primary triggers of innate immunity in mice and humans. • New evidence suggests a critical role of DVGs in RSV pathogenesis.
We present the development of a high- Q monolithic silica pendulum weighing 7 milligram. The measured Q value for the pendulum mode at 2.2 Hz was 2.0 × 106. To the best of our knowledge this is the ...lowest dissipative milligram-scale mechanical oscillator to date. By employing this suspension system, the optomechanical displacement sensor for gravity measurements we recently reported in Matsumoto et al. Phys. Rev. Lett. 122, 071101 (2019) can be improved to realize quantum-noise-limited sensing at several hundred hertz. In combination with the optical spring effect, the amount of intrinsic dissipation measured in the pendulum mode is enough to satisfy requirements for measurement-based quantum control of a massive pendulum confined in an optical potential. This paves the way for not only testing dark matter via quantum-limited force sensors, but also Newtonian interaction in quantum regimes, namely, between two milligram-scale oscillators in quantum states, as well as improving the sensitivity of gravitational-wave detectors.
Aims
This study investigates the antimicrobial activity in Staphylococcus aureus isolates (methicillin‐sensitive S. aureus (MSSA) and methicillin‐resistant S. aureus (MRSA)) and antioxidant activity ...of green propolis, Baccharis dracunculifolia DC extracts and Artepillin C™.
Methods and Results
The amount of Artepillin C in different extracts was determined by high performance liquid chromatography analysis. Minimum inhibitory concentration 90 (MIC90) was determined using 40 isolates of S. aureus inoculated in Müeller–Hinton agar culture medium containing the green propolis and B. dracunculifolia DC extracts. PVEE (green propolis ethanolic extract) and BDEH (B. dracunculifolia hexanic extract) showed the greatest antimicrobial activity with MIC90 values of 246·3 and 295·5 μg ml−1 respectively. Green propolis ethanolic and hexanic extracts (PVEE and PVEH respectively) showed the greatest antioxidant activity assessed by DPPH (1,1‐diphenyl‐2‐picryl hydrazyl radical) with IC50 values of 13·09 and 95·86 μg ml−1 respectively.
Conclusions
Green propolis ethanolic displays better antimicrobial and antioxidant activities compared to other extracts. These activities may be related to the presence of Artepillin C in synergism with the other constituents of the extracts.
Significance and Impact of the Study
In this study, the antimicrobial activity of the extracts of green propolis and B. dracunculifolia DC demonstrated in MRSA and MSSA clinical isolates indicated that they can be important tools to treat infections caused by these bacteria.
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