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•Sophisticated analytical techniques covered.•Review includes all types of tea.•Authentication of tea.•Focus on flavonoids and derived compounds.
Progress in analytical tools have led ...to a deeper insight into the chemical constitution and reaction pathways during the tea manufacture. However, the challenges have also changed as “new” teas are traded internationally which makes the authentication much more complicated. This micro-review demonstrates that despite all the achievements in the field of validated methods, authenticity, non-targeted methods we still have some gaps. New reactions products have been detected and those might be useful for authenticity purposes. As regards definitions of certain types of tea it makes sense to combine compositional data generated by validated targeted methods with non-targeted work to get a clearer view. Some more work seems to be necessary to get e.g. a deeper insight in the fate of proanthocyanidins during different types of processing and to develop a concept to quantify the thearubigins. There was progress in our knowledge of the thearubigin fraction in the last decade, however, there are still concepts to develop.
Abstract
Classical dendritic cells (cDC) are professional antigen-presenting cells (APC) that regulate immunity and tolerance. Neutrophil-derived cells with properties of DCs (nAPC) are observed in ...human diseases and after culture of neutrophils with cytokines. Here we show that FcγR-mediated endocytosis of antibody-antigen complexes or an anti-FcγRIIIB-antigen conjugate converts neutrophils into nAPCs that, in contrast to those generated with cytokines alone, activate T cells to levels observed with cDCs and elicit CD8
+
T cell-dependent anti-tumor immunity in mice. Single cell transcript analyses and validation studies implicate the transcription factor PU.1 in neutrophil to nAPC conversion. In humans, blood nAPC frequency in lupus patients correlates with disease. Moreover, anti-FcγRIIIB-antigen conjugate treatment induces nAPCs that can activate autologous T cells when using neutrophils from individuals with myeloid neoplasms that harbor neoantigens or those vaccinated against bacterial toxins. Thus, anti-FcγRIIIB-antigen conjugate-induced conversion of neutrophils to immunogenic nAPCs may represent a possible immunotherapy for cancer and infectious diseases.
Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both ...cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.
Significance Synthetic nanoparticles containing either protein or peptide antigen and the immunosuppressant rapamycin are capable of inducing durable and specific resistance to mounting immune responses toward the antigen. This immunological tolerance operates on lymphocytes even after multiple immunogenic challenges with the antigen and adding enhancers of immune responses (adjuvants). As a result, the animals treated with these tolerogenic nanoparticles (tNPs) show reduced allergic hypersensitivity disorders, protection from disease relapse in a model of multiple sclerosis, and prevention of inhibitory antidrug antibody responses in an animal model of hemophilia A. These results show the potential for nanocarriers to modify the immunoreactivity of a given molecule by providing tolerogenic instructions to the immune system, thereby preventing or reversing pathological and neutralizing immune responses.
Gibbons (Family Hylobatidae) are a suitable model for exploring hybridization in pair-living primates as several species form hybrid zones. In Khao Yai National Park, Thailand, white-handed gibbons ...(Hylobates lar) and pileated gibbons (Hylobates pileatus) are distributed parapatrically and hybridize in a narrow zone. Their phenotypic characteristics suggest limited inter-species gene flow, although this has never been assessed. To uncover the history and degree of gene flow between the two species, we studied the genetic structure of gibbons in the hybrid zone by analyzing fecal DNA samples, phenotypic characteristics, vocalizations and individuals' social status. We determined eight autosomal single nucleotide variant (SNV) loci, and mitochondrial DNA (mtDNA) and Y-chromosomal haplotypes of 72 gibbons. We compared these markers with reference types of wild pureblood white-handed gibbons (n = 12) in Kaeng Krachan National Park and pureblood pileated gibbons (n = 4) in Khao Soi Dao Wildlife Sanctuary. Autosomal genotypic analyses confirmed the various levels of mixed ancestry for several adult gibbons with or without atypical phenotypic traits in Khao Yai National Park. In some other adult gibbons, the mixed ancestry was not detected in either autosomal SNVs or their phenotypic traits but the mtDNA. Both male and female adult hybrids formed reproductive units mainly with a phenotypic pureblood partner and many of them produced offspring. Taken together, our results suggest that once hybridization occurs, white-handed-pileated-gibbon hybrids can reproduce with either parental species and that the backcrossing and thus introgression may occur in successive generations, with no drastic changes in phenotypic appearance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
Natural killer cell memory Paust, Silke; von Andrian, Ulrich H
Nature immunology,
06/2011, Letnik:
12, Številka:
6
Journal Article
Recenzirano
Natural killer (NK) cells are bone marrow–derived granular lymphocytes that have a key role in immune defense against viral and bacterial infections and malignancies. NK cells are traditionally ...defined as cells of the innate immune response because they lack RAG recombinase–dependent clonal antigen receptors. However, evidence suggests that specific subsets of mouse NK cells can nevertheless develop long-lived and highly specific memory to a variety of antigens. Here we review published evidence of NK cell–mediated, RAG-independent adaptive immunity. We also compare and contrast candidate mechanisms for mammalian NK cell memory and antigen recognition with other examples of RAG-independent pathways that generate antigen receptor diversity in non-mammalian species and discuss NK cell memory in the context of lymphocyte evolution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Trypanosomatids are single-cell eukaryotic parasites. Unlike higher eukaryotes, they control gene expression post-transcriptionally and not at the level of transcription initiation. This involves all ...known cellular RNA circuits, from mRNA processing to mRNA decay, to translation, in addition to a large panel of RNA-interacting proteins that modulate mRNA abundance. However, other forms of gene regulation, for example by lncRNAs, cannot be excluded. LncRNAs are poorly studied in trypanosomatids, with only a single lncRNA characterized to date. Furthermore, it is not clear whether the complete inventory of trypanosomatid lncRNAs is known, because of the inherent cDNA-recoding and DNA-amplification limitations of short-read RNA sequencing. Here, we overcome these limitations by using long-read direct RNA sequencing (DRS) on nanopore arrays. We analyze the native RNA pool of the two main lifecycle stages of the African trypanosome
with a special emphasis on the inventory of lncRNAs. We identify 207 previously unknown lncRNAs, 32 of which are stage-specifically expressed. We also present insights into the complexity of the
transcriptome, including alternative transcriptional start and stop sites and potential transcript isoforms, to provide a bias-free understanding of the intricate RNA landscape in
.
A marker for the severeness and disease progress of COVID-19 is overexpression of serum amyloid A (SAA) to levels that in other diseases are associated with a risk for SAA amyloidosis. To understand ...whether SAA amyloidosis could also be a long-term risk of SARS-CoV-2 infections, we have used long all-atom molecular dynamic simulations to study the effect of a SARS-CoV-2 protein segment on SAA amyloid formation. Sampling over 40 μs, we find that the presence of the nine-residue segment SK9, located at the C-terminus of the envelope protein, increases the propensity for SAA fibril formation by three mechanisms: it reduces the stability of the lipid-transporting hexamer shifting the equilibrium toward monomers, it increases the frequency of aggregation-prone configurations in the resulting chains, and it raises the stability of SAA fibrils. Our results therefore suggest that SAA amyloidosis and related pathologies may be a long-term risk of SARS-CoV-2 infections.
The Multiple Roles of Exosomes in Metastasis Weidle, Ulrich H; Birzele, Fabian; Kollmorgen, Gwen ...
Cancer genomics & proteomics,
02/2017, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on ...their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes.
Differentiation of naive CD4+ T cells into T helper (Th) cells is a defining event in adaptive immunity. The cytokines and transcription factors that control Th cell differentiation are understood, ...but it is not known how this process is orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3 chemokine receptor was required for optimal generation of interferon-γ (IFN-γ)-secreting Th1 cells in vivo. By using a CXCR3 ligand reporter mouse, we found that stromal cells predominately expressed the chemokine ligand CXCL9 whereas hematopoietic cells expressed CXCL10 in LNs. Dendritic cell (DC)-derived CXCL10 facilitated T cell-DC interactions in LNs during T cell priming while both chemokines guided intranodal positioning of CD4+ T cells to interfollicular and medullary zones. Thus, different chemokines acting on the same receptor can function locally to facilitate DC-T cell interactions and globally to influence intranodal positioning, and both functions contribute to Th1 cell differentiation.
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► CXCR3 is required on CD4+ T cells for optimal Th1 cell differentiation in vivo ► CXCL9 and CXCL10 are both required for optimal Th1 cell IFN-γ production in vivo ► CXCR3 enhances T cell-DC interactions in LNs for optimal Th1 cell differentiation ► CXCR3 positions priming T cells in LNs for optimal Th1 cell differentiation
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