Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth-promoting bacteria and ...fungi in the rhizosphere prime the whole plant body for enhanced defense against a broad range of pathogens and insect herbivores. A wide variety of root-associated mutualists, including Pseudomonas, Bacillus, Trichoderma, and mycorrhiza species sensitize the plant immune system for enhanced defense without directly activating costly defenses. This review focuses on molecular processes at the interface between plant roots and ISR-eliciting mutualists, and on the progress in our understanding of ISR signaling and systemic defense priming. The central role of the root-specific transcription factor MYB72 in the onset of ISR and the role of phytohormones and defense regulatory proteins in the expression of ISR in aboveground plant parts are highlighted. Finally, the ecological function of ISR-inducing microbes in the root microbiome is discussed.
Background: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin‐5 is essential for eosinophil growth, differentiation and migration. A monoclonal ...antibody to human interleukin‐5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD.
Methods: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo‐controlled parallel group design. The primary endpoint of ‘success’ to treatment was defined as the percentage of patients with at least ‘marked improvement’ after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation‐regulated chemokine (TARC) values served as secondary endpoints. Fluticason propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded.
Results: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab‐treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab‐treated group compared with placebo (P < 0.05).
Conclusion: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.
Summary
Background The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e‐health portal for patients with atopic dermatitis (AD), consisting of ...e‐consultation, a patient‐tailored website, monitoring and self‐management training.
Objectives To determine the cost‐effectiveness of individualized e‐health compared with usual face‐to‐face care for children and adults with AD.
Methods A randomized controlled cost‐effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year.
Results In total, 199 patients were included. There were no significant differences in disease‐specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was €24 95% confidence interval (CI) −360 to 383, whereas this difference was −€618 (95% CI −2502 to 1143) for indirect costs. Overall, individual e‐health was expected to save €594 (95% CI −2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e‐health reducing costs was estimated to be ≥ 73%.
Conclusions E‐health during follow‐up of patients with AD is, after initial diagnosis and treatment during face‐to‐face contact, just as effective as usual face‐to‐face care with regard to quality of life and severity of disease. However, when costs are considered, e‐health is likely to result in substantial cost savings. Therefore, e‐health is a valuable service for patients with AD.
Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform ...decision‐making on systemic anti‐inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti‐inflammatory treatment in men and women of reproductive age. Twenty‐one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two‐round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first‐choice long‐term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short‐course prednisolone for flare management. No consensus was reached on second‐choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication‐specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3‐month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared‐care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.
Differential cross sections for Compton scattering from the proton have been measured at scattering angles of 55°, 90°, and 125° in the laboratory frame using quasimonoenergetic linearly (circularly) ...polarized photon beams with a weighted mean energy value of 83.4 MeV (81.3 MeV). These measurements were performed at the High Intensity Gamma-Ray Source facility at the Triangle Universities Nuclear Laboratory. The results are compared to previous measurements and are interpreted in the chiral effective field theory framework to extract the electromagnetic dipole polarizabilities of the proton, which gives α_{E1}^{p}=13.8±1.2_{stat}±0.1_{BSR}±0.3_{theo},β_{M1}^{p}=0.2∓1.2_{stat}±0.1_{BSR}∓0.3_{theo} in units of 10^{-4} fm^{3}.
The incidence of hypertension and cardiovascular disease (CVD) correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are ...abundant in human skin, we hypothesized that exposure to UVA may mobilize NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers, irradiation of the skin with two standard erythemal doses of UVA lowered blood pressure (BP), with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO synthase (NOS) activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2 diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent manner, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability, which may account for the latitudinal and seasonal variations of BP and CVD.
We quantified the relative influence of maternal fidelity to feeding grounds and natal fidelity to breeding grounds on the population structure of humpback whales Megaptera novaeangliae based on an ...ocean-wide survey of mitochondrial (mt) DNA diversity in the North Pacific. For 2193 biopsy samples collected from whales in 10 feeding regions and 8 breeding regions during the winter and summer of 2004 to 2006, we first used microsatellite genotyping (average, 9.5 loci) to identify replicate samples. From sequences of the mtDNA control region (500 bp) we identified 28 unique haplotypes from 30 variable sites. Haplotype frequencies differed markedly among feeding regions (overall F
ST = 0.121, ΦST = 0.178, p < 0.0001), supporting previous evidence of strong maternal fidelity. Haplotype frequencies also differed markedly among breeding regions (overall F
ST = 0.093, ΦST = 0.106, p < 0.0001), providing evidence of strong natal fidelity. Although sex-biased dispersal was not evident, differentiation of microsatellite allele frequencies was weak compared to differentiation of mtDNA haplotypes, suggesting male-biased gene flow. Feeding and breeding regions showed significant differences in haplotype frequencies, even for regions known to be strongly connected by patterns of individual migration. Thus, the influence of migratory fidelity seems to operate somewhat independently on feeding and breeding grounds over an evolutionary time scale. This results in a complex population structure and the potential to define multiple units to conserve in either seasonal habitat.
Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren’s disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research ...has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.
Direct ionization from low energy protons is shown to cause upsets in a 65-nm bulk CMOS SRAM, consistent with results reported for other deep submicron technologies. The experimental data are used to ...calibrate a Monte Carlo rate prediction model, which is used to evaluate the importance of this upset mechanism in typical space environments. For the ISS orbit and a geosynchronous (worst day) orbit, direct ionization from protons is a major contributor to the total error rate, but for a geosynchronous (solar min) orbit, the proton flux is too low to cause a significant number of events. The implications of these results for hardness assurance are discussed.
This study investigated effects of maternal overnutrition on gonadal development and pituitary-gonadal gene expression in cattle fetuses at mid- and late-gestation. Twenty-seven multiparous dry cows ...were fed either high (ad libitum, H) or moderate (M) intake of the same diet. Twelve cows from H (n=6) and M (n=6) intake carrying females fetuses were euthanized at 199 and 268d of gestation (DG; n=3 for H or M on each DG). Fifteen cows from H (n=6) and M intake (n=9) carrying male fetuses were euthanized at 139, 199, and 241 DG (n=2 for H and n=3 for M on each DG). Fetal gonads and pituitary gland were sampled for gene expression and histological analyses. Sex-specific responses to maternal intake were observed. Primordial and total follicle numbers were lower in fetal ovaries from H than in M intake cows. These results were the reverse for preantral and antral follicles. Volumetric proportion and diameter of seminiferous cord were lower in fetal testis of H than M intake cows. The expression level of FSHB was greater in pituitary gland of the female fetus from H compared with M intake cows, irrespective of DG, whereas LHB gene expression did not differ. In males, FSHB and LHB gene expression levels were similar between maternal intake groups. Fetal ovarian expression of P450 aromatase, StAR, BMPR2, TGFBR1, GDF9, FSHR, Bax, and CASP3 genes were higher in H than in M intake cows, irrespective of DG. Fetal testicular expression of StAR, HSD17B3, IGF1, IGF2, and IGF1R genes was higher in M than in H intake cows. The differences in gene expression for steroidogenesis, folliculogenesis, and apoptosis may explain the distinct pattern of follicular growth between offspring of M and H intake cows. By contrast, the lower volumetric proportion, diameter, and length of seminiferous cord may relate to decreased gene expression in fetal testis from H intake cows. In conclusion, maternal H intake seems to affect fetal ovarian follicular growth and number of follicles, which may affect the size of ovarian reserve in their offspring. In male fetus, maternal H intake seems to disturb testicular development and may have implications on sperm production. The underlying mechanism of differential gene expression and the effect on offspring reproductive potential should be the focus of further research, especially considering larger sample size, reducing the chance for type I errors.
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