Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder presented with social and communication deficits, restricted, repetitive behaviours and interest. Several recurrently mutated genetic risk-factors have been implicated in ASD manifestation. Chromodomain helicase remodeller (CHD8) is one such gene that is a master regulator mediating the expression of genes controlling neuron functions. We collected 8,124 exonic SNPs in CHD8 from 4 databases representing the general and ASD populations; subjected them to multi-layered analyses on >20 computational tools. We observed that nsSNPs were common in the general population. Distinct hotspots for truncating and nsSNPs were identified within exons encoding the N and C terminals, respectively. Evolutionarily conserved regions involving CHD8 core domains: Helicase-C-terminal, Helicase-ATP-binding and SNF2_N domains, recorded the lowest density but severely pathogenic SNPs. Conversely, evolutionarily variable regions- CHD7-binding and BRK domains- hosted the highest SNPs, but were benign. Post-Translational-Modifications (PTMS) occurred on residues outside domains (P<0.01) i.e., non-conserved regions of CHD8 including the N and C terminals that were determined to be Intrinsically-Disordered-Protein-Regions (IDPRs) with 9 Molecular-Recognition-Features sites. Contrastingly, ASD population recorded significantly higher incidences of truncating SNPs than general population (P<0.0001). ASD-SNPs frequently occurring within core domains were severely damaging and accounted for >30% of all ASD variations. The CHD7-DNA-binding motif, with most PTMs, recorded the highest recurring truncating ASD-SNPs. The CHD8 PPIs effortlessly recapitulated the phenotypes presented by children with CHD8 mutations. 11/13 (84.6%) interacting molecules were IDPs. We identified 9 CHD8 nsSNPs that produced the strongest long-range disturbances, altering the modelled protein’s global conformational dynamics.
Molecular dynamics (MD) simulations are a popular method of studying protein structure and function, but are unable to reliably sample all relevant conformational space in reasonable computational timescales. A range of enhanced sampling methods are available that can improve conformational sampling, but these do not offer a complete solution. We present here a proof-of-principle method of combining MD simulation with machine learning to explore protein conformational space. An autoencoder is used to map snapshots from MD simulations onto the conformational landscape defined by a 2D-RMSD matrix, and we show that we can predict, with useful accuracy, conformations that are not present in the training data. This method offers a new approach to the prediction of new low energy/physically realistic structures of conformationally dynamic proteins and allows an alternative approach to enhanced sampling of MD simulations.
Background: Several studies have explored the predictive value of impulse oscillometry (IOS) for asthma exacerbations in childhood, but its specific parameters are still unclear. Therefore, we designed this meta-analysis to determine the related indicators of acute asthma attacks. Methods: A comprehensive literature search was performed in July 2020 based on Pubmed, Embase, and Web of science database. Weighted mean differences (WMD) were calculated using Fixed-or random-effects models. Results: A total of 615 patients from 6 trials were included in this analysis. IOS may be a useful tool to predict asthma exacerbations. And the results showed that R5 (WMD = − 1.21, 95%CI: −1.55 to −0.87, P＜0.001), Fres (WMD = − 1.34, 95%CI: −2.03 to −0.65,P=0.018) and AX (WMD = − 7.35, 95%CI: −9.94 to −4.76,P＜0.001) had significant correlation with asthma exacerbations. In addition, X5 may also predict the acute attack of asthma (WMD =0.81, 95%CI: 0.56 to 1.01, P＜0.001). Conclusion: R5, AX, Fres, and X5 may be able to identify the risk of an acute attack of asthma. Besides, our research further demonstrated that peripheral airway injury may play an important role in the acute attack of asthma.
Sphagnum mosses account for most accumulated dead organic matter in peatlands. Therefore, understanding their responses to increasing atmospheric CO2 is needed for estimating peatland C balances under climate change. A key process is photorespiration: a major determinant of net photosynthetic C assimilation that depends on the CO2 to O2 ratio. We used climate chambers to investigate photorespiratory responses of Sphagnum fuscum hummocks to recent increases in atmospheric CO2 (from 280 to 400 ppm) under different water table, temperature, and light intensity levels. We tested the photorespiratory variability using a novel method based on deuterium isotopomers (D6S/D6R ratio) of photosynthetic glucose. The effect of elevated CO2 on photorespiration was highly dependent on water table. At low water table (-20 cm), elevated CO2 suppressed photorespiration relative to C assimilation, thus substantially increasing the net primary production potential. In contrast, a high water table (~0 cm) favored photorespiration and abolished this CO2 effect. The response was further tested for Sphagnum majus lawns at typical water table levels (~0 and -7 cm), revealing no effect of CO2 under those conditions. Our results indicate that only hummocks, which typically experience low water table levels, benefit from the 20th century’s increase in atmospheric CO2.
Understanding the evolutionary processes that have molded the genetic structure to adapt to environmental changes is an important component of successful and sustainable long-term management for the fisheries resources. In this study, we analyzed mitochondrial control region (D-loop) sequence data to reveal population genetic variation, phylogeography and demographic history of T. ilisha collected from six locations of the Indian Ocean regions (Bay of Bengal, Arabian Sea and Persian Gulf). High haplotype diversity was found for all of the populations of T. ilisha. The Analysis of Molecular Variance (AMOVA) and conventional population FST comparisons detected both high population-level genetic variation and high degrees of divergence between groups within the Bay of Bengal (Irrawaddy river, MP; the coast of Cox’s Bazar, XP; the delta of Meghna, MP and Hooghly river, IP) and Arabian Sea (the delta of Indus river, PP and the coast of Kuwait, KP). Four cryptic genetic barriers were found for the studied populations of T. ilisha, and the highest degree of population divergence was found between the Eastern Indian Ocean (Arabian Sea and Persian Gulf) and Western Indian Ocean (the Bay of Bengal region) regions based on the Voronoï tessellation of BARRIER analysis. The gene flow analysis detected almost no migration between Eastern and Western part of the Indian Ocean regions. Besides, one-way migration was found from IP to MP population in the Bay of Bengal and from PP of Arabian Sea to KP population of Persian Gulf. Mismatch distribution showed that T. ilisha underwent long-time stable population size. Distinct cryptic genetic barriers, limited gene flows and complex evolutionary process resulted a significant population genetic and phylogeographic structure, and intricate demographic histories of T. ilisha populations. Further, the study provided additional insights for conserving and managing of this fishery resource in its broad geographical distribution coverage.
Background: There is need for a fast, efficient, and safe way to induce tolerance in patients with allergic rhinitis. Methods: Patients with birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis Total Symptom Score, Medication Score and Rhinoconjunctivitis Quality of Life Questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analyzed by flow cytometry and Luminex. Results: The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment. Nine patients had severe adverse events which were judged to be unrelated to the therapy. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased independently of treatment. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased three years after treatment. Conclusion: Intralymphatic immunotherapy against grass and birch pollen allergy was effective, safe and associated with bystander immune modulatory responses.
Background: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food induced anaphylaxis cases in a tertiary paediatric allergy centre. Results: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs 38%; p=0.001), asthma comorbidity (47% vs 35%; p<0.001), relevant co-factors (29% vs 22%; p=0.004) and biphasic reactions (10% vs 4%; p=0.001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs 56% and grade IV 1.1% vs 0.9%; p=0.001). Self-administration of intramuscular adrenaline was low (17% vs 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs 26%; p=0.003). Hospitalisation was higher for peanut anaphylaxis (67% vs 54%; p=0.004). Conclusions: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g. presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.
To the Editor: Asthma is a complex and heterogeneous chronic airway inflammatory disease with the involvement of environmental factors through epigenetic mechanisms.1 Accordingly, repeated injury, repair and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium, which are associated with the pathophysiology of asthma.2Epigenetics is defined by heritable changes in gene expression without changes in the DNA sequence.3 Regulation of gene expression is mediated by different mechanisms such as DNA methylation, histone modifications and RNA-associated silencing by small non-coding RNAs. CpG sites are dinucleotides consisting of guanine and cytosine concentrated in clusters referred to CpG islands found at important regulatory sites, such as promoter and enhancer regions.4 Their de novo methylation occurs in response to various cellular stressors and signals by DNA methyltransferases (DNMT3a and 3b), which add a methyl group to position 5 of cytosine residues at the CpG site. During DNA replication both of the separated strands of DNA carry one methylated cytosine to be used as a template for duplication. Daughter DNA duplex strands will thus be hemi-methylated, which is recognized by a different DNA methyltransferase isoform (DNMT1).5 Because DNA methylation is a reversible process, the DNMTs are considered as a therapeutic target. Several DNMT inhibitors have been identified recently, among the non-nucleoside inhibitors, 4-aminoquoline-based inhibitors, such as SGI-1027 showed potent inhibitory activity. SGI-1027 occupies the binding site of DNMTs resulting in the prevention of access of target DNA to the substrate binding pocket.6We have demonstrated in previous studies from our laboratory that human primary bronchial epithelial cells (HBEC) isolated from patients with asthma showed lower barrier integrity compared to controls.7 To investigate the level of global methylation in HBEC, we investigated control and asthma samples for the long interspersed nuclear element-1 (LINE-1) methylation levels (Figure 1A). HBEC from asthma patients showed a tendency for higher global methylation levels, together with higher expression of 5-methylcytosine (5-mc) in immunofluorescence staining (Figure 1B). Next, we performed methylation profiling (Illumina Infinium EPIC array) to investigate genes methylated in ALI cultures of HBEC. Interestingly, in a highly methylated group of top 100 genes, we found many genes associated with cell growth, ion transport, and cytoskeletal remodeling (Figure S1). We kept our attention on the methylated epigenetic and tight junction (TJ) genes and further focused on TJs, especially zonula occludens and claudins which showed higher methylation in contrast to occludin, which was not methylated (Figure S2). As higher methylation levels were observed in HBEC of asthmatic origin, we inhibited the DNA methyltransferase enzyme with a specific inhibitor, SGI-1027, to demonstrate the role of CpG methylation on epithelial barrier integrity. ALI cultures were treated with the DNA methyltransferase inhibitor for 72 hours. Significantly decreased expression of 5-mc was observed after 48 hours of DNA-methyltransferase inhibition, demonstrating that the methylation of 5-methylcytosine (5-mc) in bronchial epithelium was reversed (Figure 2A). This prompted us to investigate the changes triggered by the inhibitor in epithelial cells. Further experiments showed increased transepithelial electric resistance (TER) in bronchial epithelial cells, in ALI from asthmatic donors after 48 hours of DNMT inhibition (Figure 2B). The link between barrier integrity and TER results were confirmed by the significantly decreased paracellular passage of FITC-labelled 4kD dextran after inhibition of DNMTs (Figure 2C). The reconstitution of TER in asthmatic ALI was associated with decreased protein DNMT1 expression and increased ZO-1 and claudin-18 proteins (Figure 2D). We also observed increased claudin-4, but not occludin expression upon DNMT inhibition (Figure S3). Increased expression of ZO-1 with an intact and honeycomb-like structure in the immunofluorescence staining of bronchial epithelial cells confirmed the effect on protein expression of bronchial epithelial barrier in asthma donors (Figure S4).Defective epithelial barrier has been established in asthma in addition to several chronic inflammatory diseases.8 Direct targeting of the epithelial barrier leakiness for the treatments represents an important target, however so far there is no treatment possibility targeting epigenetic mechanisms. The present study demonstrates an increased global methylation level in HBEC from asthmatic individuals. CpG methylation of specific genes is essential for the defect of epithelial barrier integrity, which is reversed upon DNMT inhibition. The inversion of CpG methylation, restores leakiness in the epithelium in asthma by increasing TER, decreasing paracellular flux and improves the structure of bronchial epithelial cells by increasing the expression of TJ proteins. The better understanding of the importance of epigenetic memory in chronic tissue inflammatory diseases together with the availability of treatment modalities targeting epigenetic mechanisms and transition of these molecules into the clinical studies may lead to curative treatment of allergic and autoimmune inflammatory diseases.9Paulina Wawrzyniak1, PhD,Krzysztof Krawczyk1,3, MSc,Swati Acharya5, PhD,Ge Tan1,7, PhD,Marcin Wawrzyniak1, PhD,Emmanuel Karouzakis4, PhD,Anita Dreher, Sci. Tech.,Bogdan Jakiela2, MD, PhD,Can Altunbulakli1, PhD,Marek Sanak2, MD, PhD,Liam O‘Mahony1,6, PD, PhD,Kari Nadeau5, MD, PhD,Cezmi A. Akdis1, MD1Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland, Christine Kühne-Center for Allergy Research and Education (CK-CARE)2Department of Medicine, Jagiellonian University Medical College, Krakow, Poland3Faculty of Biology and Environmental Protection, Department of Cellular Immunology, Lodz, Poland4Department of Rheumatology, University Hospital of Zurich5Departament of Medicine, Stanford University, United States6 Department of Medicine and School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.7 Functional Genomics Center Zurich, ETH Zurich/University of ZurichCorresponding author:Paulina WawrzyniakSwiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, SwitzerlandObere Strasse 22,7270 Davos, SwitzerlandTel: +41 81 410 08 48Fax: +41 81 410 08 firstname.lastname@example.orgConflict of interest:The authors declare that they have no conflicts of interest.Founding sources:Supported by Swiss National Science Foundation grants 310030_156823, and 320030_176190.Word count: 765Keywords: asthma, tight junction, CpG methylation, DNA methyltransferases,
Neuromuscular respiratory medicine has traditionally focused on mechanically assisted lung ventilation and mucus clearance. These therapies have prolonged survival for patients with Duchenne muscular dystrophy (DMD). However, the field is rapidly evolving in a new direction: it is being revolutionized by molecular and genetic therapies. A good correlation between a patient’s dystrophin mutation and his cardiopulmonary phenotype would allow accurate prediction of patient prognosis and would facilitate the design of studies that assess new DMD therapies. Instead, patient prognosis and the design of valid therapeutic studies are complicated by cardiopulmonary phenotypic discordance and variability, by which a notable proportion of DMD patients have unexpectedly good or poor cardiopulmonary function. The likely cause of phenotypic variability and discordance is genetic modifiers. Once the modifiers that affect cardiopulmonary function are better understood, it should be possible to create a personalized genetic profile that accurately predicts the prognosis of each individual DMD patient. This would allow investigators to assess the effect of new therapies in the context of each patient’s particular cardiopulmonary natural history. Amplification of beneficial cardiopulmonary genetic modifiers and blocking of detrimental modifiers is a promising strategy for creating new DMD therapies. When patients with chronic respiratory failure are treated with assisted ventilation, cardiac function determines their survival. Therefore, prioritizing new cardiac therapies is most likely to prolong patient survival. By focusing on these topics we aim to move neuromuscular respiratory medicine beyond assisted ventilation and coughing and into the age of translational medicine.
To the Editor: The spread of the coronavirus disease-2019 (COVID-19) remains a worsening global health crisis. Although many studies have reported risk factors for severe COVID-19, asthma characterization in COVID-19 is still controversial, with different early reports from China and recent reports from the Europe and United States.1 Prolonged viral shedding is not only a risk factor for poor outcome of COVID-19, but also clues to host immune response against the virus. However, there is limited data on this except for results from relative small group studies.2 In this study, 2 200 adult patients hospitalized for COVID-19 in Daegu were evaluated for prevalence of asthma and clinical outcomes with COVID-19 according to asthma. In addition, the risk factors for delayed viral clearance were evaluated.The prevalence of asthma in patients with COVID-19 was 3.2% which was not different from its prevalence in the Korea National Health and Nutrition Examination Survey (KNHANES) (Figure 1A and Table S1). By age group, the prevalence of asthma showed a similar U-shaped pattern as the general prevalence pattern in Korea. However, the prevalence of asthma in the 19–29-year age group (2.1%) was lower than that of KNHANES (Figure 1B).Table S2 compares the characteristics between the asthma group and the non-asthma group. Older age, overweight, and comorbidity of chronic obstructive pulmonary disease, and initial symptoms of dyspnea and nausea/vomiting were more common in the asthma group. Compared with the non-asthma group, the asthma group had a greater risk of death (13.6%vs. 6.4%, P = 0.02) and a greater need for high-flow oxygen therapy (18.2% vs . 10.5%, P = 0.048) (Figure 1C and Table S3). The higher mortality rate in asthma patients compared with non-asthmatic patients was particularly noticeable in female and overweight patients. Older patients (> 65 years) with asthma tended to have a higher mortality rate than those without asthma (Figure 1D). After adjusting for potential confounders, asthma had no significant association with clinical outcomes of COVID-19 (Figure 1E and Table S4). Meanwhile, older age, male gender, and comorbid diseases including overweight, diabetes, chronic kidney disease, cancer, autoimmune disease, dementia, and other psychological disorder were significant risk factors for mortality (Tables S5 and S6).Asthma is considered to have a lower risk of death than other well-known risk factors.3, 4 However, asthma is a heterogeneous disease and is often associated with atopic and eosinophilic asthma in younger patients. Meanwhile, obese asthma and elderly asthma are known to have common neutrophilic phenotypes.5, 6 The recent results of higher expression of COVID-19 receptors in respiratory specimens with neutrophilic asthma phenotype compared with the eosinophilic asthma phenotype.7 Considering prevalence and clinical outcome results, it is possible that neutrophilic asthma is a risk factor for infection and poor prognosis of COVID-19 rather than eosinophilic asthma.When delayed viral clearance was divided into two groups based on 30 days, 906 patients were included in the non-delayed viral clearance group and 415 patients in the delayed viral clearance group. After adjusting for potential confounders, delayed viral clearance was not significantly associated with asthma (Figure 1E and Table S4). However, older age >65 years (Odds ratio (OR) 2.002, 95% Confidence interval (CI) 1.292–3.101; P = 0.002), comorbid diseases including dementia (OR 3.123, 95% CI 1.833–5.321; P<0.001), and other psychological disorder (OR 2.084, 95% CI 1.178–3.687; P = 0.012), initial symptom of skin rash (OR 15.943, 95% CI 1.613–157.535; P = 0.018), and initial laboratory abnormalities including hemoglobin <10 g/dL (OR 2.156, 95% CI 1.161–4.003; P = 0.015) and C-reactive protein (CRP) ≥1.0 mg/dL (OR 1.588, 95% CI 1.061–2.377; P = 0.025) were significant risk factors for delayed viral clearance. On the other hand, male sex (OR 0.752, 95% CI 0.567–0.997; P = 0.047), hypertension (OR 0.704, 95% CI 0.519–0.953; P = 0.023), and initial symptom of headache (OR 0.673, 95% CI 0.485–0.932; P = 0.017) were significant protective factors for delayed viral clearance (Figure 2A and Table S7). In particular, when limited to the mild COVID-19 group classified as no activity limitations in the outcome parameters, older age, dementia, initial symptoms of skin rash and headache, and initial hemoglobin <10 g/dL showed significant differences (Figure 2B, Table S8).Several factors related to the nervous system were identified as important risk factors for delayed viral clearance. Previous studies have shown that the coronavirus can initially invade the peripheral nerves and enter the central nervous system through a synapse path.8 It is hypothesized that the ability of the immune system to find and remove viruses that have penetrated the nervous system is important for virus clearance. Male sex, hypertension and elevated CRP did not show a significant difference when analyzed only mild patients, and these may be indicators associated with severity rather than a direct effect on viral clearance.Anti-inflammatory drugs such as hydroxychloroquine and systemic steroid were shown to be risk factors for mortality and delayed viral clearance (Table S6 and S8). These medications were used more often when the hospitalization period was extended or when showing poor prognosis factors. Notwithstanding these, our results suggest that anti-inflammatory drugs need to be used with proper consideration of appropriate indications.On May 9, 2020, there were 6,859 patients with PCR-confirmed COVID-19 in Daegu. This data excluded asymptomatic or minimal symptomatic patients who did not require hospitalization. However, our study covered almost all hospitalized patients diagnosed with COVID-19 in Daegu from February to May ,therefore, selection bias is minimized.9 In Korea, most hospitals decided to terminate the quarantine by repeating PCR every week. In addition, the Korea Centers for Disease Control & Prevention (KCDC) thoroughly managed the criteria for quarantine termination and PCR results. Through this, in our study, we were able to perform a large-scale study to confirm the risk factors for delayed viral clearance.In summary, despite the positivity of differences depending on phenotypes, the prevalence of asthma was not significantly different in patients with COVID-19, and asthma did not affect the outcomes of COVID-19. Age, dementia, and initial presentations of headache, skin rash, and anemia were independently associated with viral clearance.
Autoimmune neutropenia of infancy (AIN) is a relatively frequent cause of neutropenia in children. The disease is caused by antibodies recognizing membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb receptor). In this study, we investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR and HLA-DQ alleles with AIN and the association of these genotypes with the presence of anti-HNA-1a autoantibodies. Eighty AIN cases with a median age of 13.5 months were included in this study. Controls were healthy unrelated Danish blood donors. Anti-HNA-1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow-GIFT). Molecular determination of HNA genotypes was determined using real-time polymerase chain reaction (q-PCR). High-resolution HLA-DR and HLA-DQB1 were determined by next-generation sequencing. Antibodies against HNA-1a were detected in 51% (n=41) of AIN patients, and anti-HNA-1b was detected in 3% (n=2) of cases. FCGR3B*01+,*02-,*03- was more common (odds ratio, 6.70; p < 0.0001), and FCGR3B*01-,*02+,*03- was less common (odds ratio, 0.30; p < 0.0001) among AIN cases. HNA-1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02-,*03-genotype (odds ratio, 3.86; p < 0.007). The HLA-DR*14 and HLA-DQB1*05:03 alleles were significantly more common (odds ratio, 7.44; p < 0.0001 and odds ratio, 2.50; p < 0.0001, respectively) in AIN patients. In conclusion the HLA haplotype HLA-DR*14- DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti-HNA-1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01-,*02+,*03- genotype.
The bi-axial 7075-T6 Al alloy samples were designed and manufactured by Friction Stir Welding (FSW). The residual stress profiles were measured. Crack propagation behavior were simulated with five different biaxial loading ratios. ABAQUS software was used to calculate the stress intensity factors (SIFs) and to study the effects of residual stress on crack behaviors. It is found that residual stress can affect the effect of biaxial loading ratio on crack growing. Mode I and mode II SIFs are susceptible to residual stress when λ= 0.5~2. Cracks at the retreating side are much more affected by the residual stress. At given biaxial loading ratio, the distribution characteristics of SIF components have similarity on the advancing side and the retreating side.
To our knowledge, this is the first description of a cytomegalovirus end-organ infection complicating severe COVID-19 disease in an immunocompetent host. Suspicion threshold for opportunistic coinfections should be lowered in severe COVID-19. Serum CMV polymerase chain reaction and colonoscopy should be discussed in presence of persistent digestive disturbances.
Rabies is zoonotic diseases and can cause progressive encephalitis and death. Ante-mortem diagnosis is challenging, and treatment is supportive. We report a young patient presented with classic furious rabies; the diagnosis was confirmed by real-time polymerase chain reaction assays on saliva samples.
DNA metabarcoding is a promising method to increase cost and time efficiency of marine monitoring, providing that the impact of methodological choices on the reliability and reproducibility of results are well understood. Here, we investigated the impact of primer choice, DNA source (bulk DNA or eDNA from the ethanol preservative) and morphological traits (body size and body skeleton) on species detection in four distinct macrobenthos communities from the North Sea. We generated a reference database with COI sequences for macrobenthos from the North sea and applied DNA metabarcoding using five COI primer sets. At most 22% of the ASVs were assigned taxonomy at the phylum level, despite the availability of a nearly complete reference database. However, the unassigned ASVs represented only a small fraction of the total reads (13%). The Leray primer set outperformed the four other primer sets in the number of non-chimeric reads and species detected, and in the recovery of beta diversity patterns. Community composition differed significantly between bulk DNA and eDNA samples, but both sample types were able to differentiate the four communities. Importantly, the probability of detecting a species in the eDNA from the ethanol preservative was significantly lower than for bulk DNA for macrobenthos species with small to medium body size and for species with chitine or CaCO3 in their skeleton. Detection in the bulk DNA samples was not affected by the traits investigated, indicating that monitoring of macrobenthos species will be most robust when using bulk DNA as template for metabarcoding.
The response of crop photosystem activity to a certain level of [CO2] elevation have been widely concerned. However, long-term effects of elevated [CO2] over multi-generations of crops received little attention. Using open-top chambers, we set up two treatments of elevated [CO2] from 2016 to 2019 in rice (Oryza sativa) growing seasons. One treatment was stepwise increase (SI) of +40 µmol mol-1 per season, the other was constant increase (CI) of +200 µmol mol-1. Rice seeds harvested in each [CO2] environment was planted successively. Seeds from ambient [CO2] were also planted in SI and CI OTCs in next year to study the short-term effect. We measured the diurnal change in PSII functionality of leaf in 2019. Results showed that both SI and CI promoted PSII function. SI was more beneficial to improve efficiency of electron trapping and transporting in PSII and performance index of leaf. The maximal photochemical efficiency of PSII decreased linearly with increasing photosynthetic photon flux density throughout the day. Predawn efficiency decreased dramatically with the development of growth stages. Together, we found PSII efficiency benefit from multi-year [CO2] elevation, which could help to better understand the response of electron transport to elevated [CO2].
When describing plant-animal networks, sampling can be performed using plant- or animal-centred approaches. Importantly, while the method affects the characterisation of network structure, how it may affect estimates of interaction dissimilarity across networks is still unknown. Here, we investigated how sampling affects the characterization of pollination networks and their dissimilarities across habitats in a heterogeneous tropical landscape. We also asked whether plant traits influence the difference in interaction specialization according to sampling. Plant-centred networks reported higher interaction and species dissimilarity in space, mainly due to interaction rewiring, while animal-centred networks showed higher specialization and modularity. Floral type and pollination systems affected how specialization was influenced by the sampling method. Combining animal- and plant-centred approaches returned intermediate values for dissimilarity and network metrics, indicating that complementary methods should be used for a better characterization of interaction networks, especially those including groups with distinct mobilities, such as plant and pollinators.
Natural Killer (NK) cell functions are regulated by diverse inhibitory and activating receptors including Killer cell Immunoglobulin-like receptors (KIR) which interact with HLA class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV-HCV co-infected individuals with either SC (n=68) or chronic infection (CI, n=163) compared to uninfected blood donors (Ctrl, n=100). Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV-HCV co-infected individuals (OR=4.30[1.57-12.25], p=0.005). KIR2D+ NK cell repertoire and potential of degranulation of KIR2DL1/S1+ NK cells were similar in SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1+ and KIR2DL2+ NK cells were detected in CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1+ NK cells compared to controls. On the T cell side, higher frequencies of DNAM-1+ and CD57+ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2+ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1+ NK cells in viral context and maintain KIR2DL2/L3/S2+ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV-HIV co-infected European patients.