290 research outputs found

    Lower magnitude and faster waning of antibody responses to SARS-CoV-2 vaccination in anti-TNF-α-treated IBD patients are linked to lack of activation and expansion of cTfh1 cells and impaired B memory cell formationResearch in context

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    Summary: Background: Patients with inflammatory bowel disease (IBD) and healthy controls received primary SARS-CoV-2-mRNA vaccination and a booster after six months. Anti-TNF-α-treated patients showed significantly lower antibody (Ab) levels and faster waning than α4β7-integrin-antagonist recipients and controls. This prospective cohort study aimed to elucidate the underlying mechanisms on the basis of circulating T-follicular helper cells (cTfh) and B memory cells. Methods: We measured SARS-CoV-2- Wuhan and Omicron specific Abs, B- and T-cell subsets at baseline and kinetics of Spike (S)-specific B memory cells along with distributions of activated cTfh subsets before and after primary and booster vaccination. Findings: Lower and faster waning of Ab levels in anti-TNF-α treated IBD patients was associated with low numbers of total and naïve B cells vs. expanded plasmablasts prior to vaccination. Along with their low Ab levels against Wuhan and Omicron VOCs, reduced S-specific B memory cells were identified after the 2nd dose which declined to non-detectable after 6 months. In contrast, IBD patients with α4β7-integrin-antagonists and controls mounted and retained high Ab levels after the 2nd dose, which was associated with a pronounced increase in S-specific B memory cells that were maintained or expanded up to 6 months. Booster vaccination led to a strong increase of Abs with neutralizing capacity and S-specific B memory cells in these groups, which was not the case in anti-TNF-α treated IBD patients. Of note, Ab levels and S-specific B memory cells in particular post-booster correlated with the activation of cTfh1 cells after primary vaccination. Interpretations: The reduced magnitude, persistence and neutralization capacity of SARS-CoV-2 specific Abs after vaccination in anti-TNF-α-treated IBD patients were associated with impaired formation and maintenance of S-specific B memory cells, likely due to absent cTfh1 activation leading to extra-follicular immune responses and diminished B memory cell diversification. These observations have implications for patient-tailored vaccination schedules/vaccines in anti-TNF-α-treated patients, irrespective of their underlying disease. Funding: The study was funded by third party funding of the Institute of Specific Prophylaxis and Tropical Medicine at the Medical University Vienna. The funders had no role in study design, data collection, data analyses, interpretation, or writing of report

    CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses.

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    Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were followed for 28 days. TT-specific serum antibodies were quantified by ELISA and increased in all horses by day 7 after vaccination. CD154 is an established indicator of antigen-reactive T helper cells in other species, but has not been characterized in horses. CD154 detection in equine PBMC by an anti-human CD154 antibody (clone 5C8) was confirmed by Western blots and then applied for flow cytometry. As a common indicator of equine T cell activation, cytokine induction was studied in parallel. T cells were analyzed by multicolor flow cytometry of PBMC after re-stimulation with TT in vitro. Reactive T helper (Th) cells were characterized by increased frequencies of CD4+CD154+ lymphocytes in in vitro TT-re-stimulated PBMC on day 14 after vaccination of the horses compared to pre-vaccination. The majority of all CD154+ cells after TT re-stimulation were CD4+ Th cells, but CD154 was also induced on CD4- cells albeit in lower frequencies. CD154+CD4+ Th cells were enriched in cytokine-expressing cells compared to CD154-CD4+ Th cells. Similar to the CD4+CD154+ frequencies, CD4+IL-4+, CD4+IFN-γ+ and CD4+TNF-α+ were increased after vaccination, but IL-4+ increased later than IFN-γ+ and CD4+TNF-α+, which already exceeded pre-vaccination frequencies on day 7. CD4+CD154+ frequencies correlated positively with those of CD4+IL-4+ (Th2) on day 14, and negatively with CD4+IFN-γ+ induction on day 7, but did not correlate with CD4+TNF-α+ frequencies or TT-specific antibody concentrations. CD154 appears to be a useful marker of antigen-reactive equine Th cells in combination with cytokine expression. The T cell analyses established here with TT can be applied to other antigens relevant for infections or allergies of horses and in horse models for translational research

    Disentangling the electronic structure of an adsorbed graphene nanoring by scanning tunneling microscopy

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    Scanning tunneling microscopy is a powerful tool for determining the electronic structure of surface adsorbates. Here, carbon monoxide functionalized tips enable more accurate probing of the molecular states of graphene nanorings adsorbed on a gold surface. Graphene nanorings are promising model structures to realize persistent ring currents and Aharonov-Bohm effect at the single molecular level. To investigate such intriguing effects, precise molecular characterization is crucial. Here, we combine low-temperature scanning tunneling imaging and spectroscopy with CO functionalized tips and algorithmic data analysis to investigate the electronic structure of the molecular cycloarene C108 (graphene nanoring) adsorbed on a Au(111) surface. We demonstrate that CO functionalized tips enhance the visibility of molecular resonances, both in differential conductance spectra and in real-space topographic images. Comparing our experimental data with ab-initio density functional theory reveals a remarkably precise agreement of the molecular orbitals and enables us to disentangle close-lying molecular states only separated by 50 meV at an energy of 2 eV below the Fermi level. We propose this combination of techniques as a promising new route for a precise electronic characterization of complex molecules and other physical properties which have electronic resonances in the tip-sample junction

    Course of Fecal Calprotectin after mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Diseases

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    Background: Two years into the pandemic, vaccination remains the most effective option to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preliminary studies suggest vaccination efficacy in patients with inflammatory bowel diseases (IBD), but little is known about its impact on chronic intestinal inflammation. Here we assessed the mucosal inflammatory activity in patients with IBD before and after immunization with the mRNA-1273 (Moderna) vaccine by measurement of fecal calprotectin (fCP). Methods: In 42 patients with IBD, the baseline fCP levels obtained prior to the first vaccine were compared with the highest levels measured during and after two doses of vaccination. Patients’ sera were collected after the second dose to evaluate anti-SARS-CoV-2 antibodies’ titers. Results: We observed a significant fCP elevation in 31% of patients after any dose. Vedolizumab was identified as the only agent associated with an fCP increase (OR 12.4, 95% CI [1.6; 120.2], p = 0.0171). Gastrointestinal adverse events were reported in 9.5% of all subjects and in 75% of cases accompanied by an fCP increase. Anti-SARS-CoV-2 antibodies associated only weakly with the fCP increase after the first dose (p = 0.04). Conclusions: Our findings support possible collinearity in pathways of SARS-CoV-2 antigen expression and the pathogenesis of IBD

    Plant Adaptations to Alpine Environments

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    The alpine biome is the life zone above the climatic treeline in mountains. It is the only biome that has a global distribution, with its elevation varying with latitude. Being naturally treeless by definition, its vegetation is composed of small stature plants belonging to the life form graminoids (grasses, sedges, and rushes), herbs, dwarf shrubs and cushion plants covering c. 3.55 Million km2 or 21.5% of the global mountain area of 16.5 Million km2. Driven by the combination of small, compact plant stature and topography effects (exposure, direction to the sun and shelter) the actual climate experienced by these plants and the animals and microbes associated with them is much warmer (heated by the sun) than one would expect from weather station data. This physical manipulation of an otherwise harsh climate explains much of the physiology observed in alpine plant taxa. Because nights are cool, and—at extratropical latitudes—as the growing season gets increasingly short the productivity of alpine ecosystems is limited by the duration of favorable daytime periods and the slow nutrient cycle. Alpine plants are well adapted to the life conditions they experience, and counter wide spread belief, are not particularly stressed. Because topographic diversity provides escapes from unpleasant habitat conditions over very short distances, the alpine biome and its biodiversity are nor particularly vulnerable to climatic change, but rather represent refugia that deserve protection

    Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

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    © Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

    Grasslands of the palaearctic biogeographic realm : introduction and synthesis

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    Grasslands are spontaneously occurring herbaceous vegetation types that are mostly dominated by grasses or other graminoids and have usually >10% herb-layer cover, while woody species area absent or have a significantly lower abundance than the herbs. In the Palaearctic biogeographic realm, natural and secondary grasslands (76% and 24% of all grasslands, respectively) cover about 10.0 million km2, i.e., 18% of its territory, which constitute 41% of global grasslands—more than any other biogeographic realm. In “The encyclopedia of the world’s biomes,” the Palaearctic grasslands are placed in the section “Grasslands and shrublands,” where we defined 10 regions, which are treated in individual chapters: Western Europe, Northern Europe and Baltic States, Eastern Europe, Mediterranean Region, Middle East and Caucasus, Russia, Kazakhstan and Middle Asia, Mongolia, China, and Japan. These regions cover the huge majority of the realm and about 98% of its grasslands. Each chapter describes the extent, physiogeography, origin, biodiversity and typology of the grasslands in the region, the threats for grassland diversity and extent, as well as grassland management and conservation. Grasslands are important habitats for many groups of taxa. Dry calcareous grasslands and steppes constitute habitat of most of Europe’s butterfly and Orthoptera species, and they host significant number of European endemic plants. In small spatial scales (i.e., below 100 m2) Palaearctic grasslands, especially meso-xeric ones, can hold even higher species diversity of plants than tropical rainforests. However, Palaearctic grasslands are also among the most intensively and negatively human-impacted habitats. Changes in grassland management, like overgrazing or other types of intensification as well as abandonment were assessed as the most important recent and future threats. Other important reasons of decline in grassland diversity are habitat loss and altered site conditions. The negative impact of climate change and invasive species is predicted to be stronger in the future. In the last years, various conservation efforts to monitor, maintain and promote grassland extent and diversity were made. However, to counteract the negative trends, these efforts urgently need to be intensified and their efficiency needs to be improved

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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