Cow milk is under increased scrutiny due to its environmental impact and ethical considerations concerning animal welfare. At the same time, a rising share of consumers is switching to plant-based ...milk substitutes (abbreviated “plant milk”). The objective of this study was (1) to analyze the product image of plant milk and cow milk and (2) to compare the motivational structure behind the consumption of both product categories. For this purpose, a quantitative survey with Austrian consumers was carried out to analyze the product image of plant milk in comparison to cow milk (n = 1001). The product image analysis revealed that the product image of cow milk is still much better than that of plant milk. Amongst others, cow milk is considered to be healthier, more natural, and better for bones. Product image valuation was dependent on the (non-)consumption of plant milk. Plant milk consumers evaluated plant milk significantly better; they considered plant milk to be much better digestible and allergy-free. The qualitative study using means-end-chain analysis, with two sub-samples of interviewees (plant milk consumers, n = 30, and cow milk consumers, n = 30), identified different motives for the consumption of cow milk and plant milk. Motives that were only reported from cow milk consumers are the origin of milk and the support of small-scale dairy production of farmers. Motives of plant milk consumers were much more diverse and included animal welfare and sustainability aspects.
Acute myeloid leukemia (AML) is a phenotypically and prognostically heterogeneous hematopoietic stem cell disease that may be cured in eligible patients with intensive chemotherapy and/or allogeneic ...stem cell transplantation (allo-SCT). Tremendous advances in sequencing technologies have revealed a large amount of molecular information which has markedly improved our understanding of the underlying pathophysiology and enables a better classification and risk estimation. Furthermore, with the approval of the FMS-like tyrosine kinase 3 (FLT3) inhibitor Midostaurin a first targeted therapy has been introduced into the first-line therapy of younger patients with FLT3-mutated AML and several other small molecules targeting molecular alterations such as isocitrate dehydrogenase (IDH) mutations or the anti-apoptotic b-cell lymphoma 2 (BCL-2) protein are currently under investigation. Despite these advances, many patients will have to undergo allo-SCT during the course of disease and depending on disease and risk status up to half of them will finally relapse after transplant. Here we review the current knowledge about the molecular landscape of AML and how this can be employed to prevent, detect and treat relapse of AML after allo-SCT.
About the Authors: Wolfgang Fischer Roles Writing – review & editing * E-mail: fischer@mvp.lmu.de (WF); haas@mvp.lmu.de (RH) Affiliations Medical Microbiology and Hospital Epidemiology, Max von ...Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany, German Center for Infection Research (DZIF), Ludwig-Maximilians-University Munich, Munich, Germany Rainer Haas Roles Writing – original draft, Writing – review & editing * E-mail: fischer@mvp.lmu.de (WF); haas@mvp.lmu.de (RH) Affiliations Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany, German Center for Infection Research (DZIF), Ludwig-Maximilians-University Munich, Munich, Germany ORCID logo http://orcid.org/0000-0002-2761-0947 Citation: Fischer W, Haas R (2020) Different roles of integrin-β1 and integrin-αv for type IV secretion of CagA versus cell elongation phenotype and cell lifting by Helicobacter pylori. Two different ligand–receptor pairs have been described to be involved in this process: interaction of several Cag proteins, including CagL, with different integrin heterodimers, such as α5β1 and αVβ6 integrins 1–3, and interaction of the H. pylori outer membrane protein HopQ with carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) 4, 5. ...we believe that the data shown in the formal comment by Tegtmeyer and Backert are not contradictory to our original data, but just represent earlier or less pronounced stages of the cell reshaping process induced by intracellular phosphorylated CagA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Various gram-negative pathogens express type IV secretion systems (T4SSs) which translocate bacterial virulence factors into host target cells to hijack cellular processes for their own benefit and ...causing disease. The pathology of Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric cancer in humans, strongly depends on a T4SS encoded by the cag pathogenicity island (cagPAI). This T4SS represents a pilus-like structure and a membrane-spanning complex. T4SS assembly is achieved by various protein-protein interactions and several pilus-associated components (CagL, CagI, CagY, and CagA) that allow docking to the host cell integrin member α
β
followed by delivery of its major effector protein, CagA, across the host cell membrane. In addition, recent studies have shown that H. pylori exploits human CEACAM receptors via the adhesin HopQ, encoded outside of the cagPAI, for bacterial adherence and translocation of CagA. Here, we review the composition and assembly of the H. pylori T4SS and its fundamental role in the infection process. We discuss major CagA-dependent and CagA-independent signaling events by the T4SS in vitro and in animal models in vivo, which include the induction of cytoskeletal rearrangements, membrane dynamics, disturbance of cell polarity as well as transcriptional responses involved in inflammation, cell proliferation, and anti-apoptosis. The contribution of these signaling cascades to H. pylori colonization, and pathogenesis is reviewed.
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in ...a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later.
Display omitted
•Lymphocyte numbers in lymph nodes and lymph oscillate over the course of the day•Rhythmic Ccr7 and S1pr1 expression drives rhythmic lymphocyte homing and egress•Adaptive immune responses to immunization and pathogens are time-of-day dependent•Loss of circadian clocks in lymphocytes ablates rhythmic adaptive immune responses
Lymphocyte trafficking through lymph nodes and lymph is an important immune surveillance mechanism of the body. Druzd et al. (2017) demonstrate that this trafficking occurs in a circadian manner and that adaptive immune responses are also time-of-day dependent and are ablated when circadian clock function is lost in T cells.
Graphene quantum dots (GQDs) are a promising next generation nanomaterial with manifold biomedical applications. For real world applications, comprehensive studies on their influence on the ...functionality of primary human cells are mandatory. Here, we report the effects of GQDs on the transcriptome of CD34
hematopoietic stem cells after an incubation time of 36 hours. Of the 20 800 recorded gene expressions, only one, namely the selenoprotein W, 1, is changed by the GQDs in direct comparison to CD34
hematopoietic stem cells cultivated without GQDs. Only a meta analysis reveals that the expression of 1171 genes is weakly affected, taking into account the more prominent changes just by the cell culture. Eight corresponding, weakly affected signaling pathways are identified, which include, but are not limited to, the triggering of apoptosis. These results suggest that GQDs with sizes in the range of a few nanometers hardly influence the CD34
cells on the transcriptome level after 36 h of incubation, thereby demonstrating their high usability for in vivo studies, such as fluorescence labeling or delivery protocols, without strong effects on the functional status of the cells.
The amyloid fibril formation by α -synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson's disease. Epigallocatechin gallate (EGCG) has been reported to be an ...efficient inhibitor of amyloid formation by numerous proteins, among them α -synuclein. Here, we show that this applies only to a small region of the relevant parameter space, in particular to solution conditions where EGCG readily oxidizes, and we find that the oxidation product is a much more potent inhibitor compared to the unmodified EGCG. In addition to its inhibitory effects, EGCG and its oxidation products can under some conditions even accelerate α -synuclein amyloid fibril formation through facilitating its heterogeneous primary nucleation. Furthermore, we show through quantitative seeding experiments that, contrary to previous reports, EGCG is not able to re-model α -synuclein amyloid fibrils into seeding-incompetent structures. Taken together, our results paint a complex picture of EGCG as a compound that can under some conditions inhibit the amyloid fibril formation of α -synuclein, but the inhibitory action is not robust against various physiologically relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterize promising amyloid inhibitors.
The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid ...cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia.
In immunocompromised patients a colonisation with fungi carries the risk to develop serious invasive fungal infection. An early detection is therefore important, but not optimal hitherto. ...Fortunately, molecular genetic methods have increased the sensitivity of fungal detection and limited the time, until results are available. However, their success depends on an efficient extraction of genomic DNA from the fungal cell in the given diagnostic specimen.
To improve the routine DNA preparation method for yeasts and moulds, the impact of bead beating on fungal DNA release was evaluated. PBS, blood and respiratory rinse were spiked with Candida glabrata or Aspergillus fumigatus. DNA was extracted by mechanical bead beating in addition to the different steps of the DNA preparation protocol, which comprised liquid nitrogen treatment, proteinase K digestion and DNA isolation using the EZ1 DNA Tissue Kit and Workstation. In every method variant tested, treatment with liquid nitrogen did not improve the DNA release. Bead beating once followed by proteinase K digestion and EZ1-work-up led to the highest DNA release from fungus, spiked in PBS, and increased the extracted DNA amount of C. glabrata about 100-fold and of A. fumigatus about 10-fold in relation to sole EZ1-work-up. In fungus-spiked respiratory rinse and blood, highest increase in DNA release was measured after triple bead beating with simultaneous proteinase K digestion. Fungal DNA release of C. glabrata increased for >100-fold in respiratory rinse and for >1000-fold in blood and of A. fumigatus for >10-fold in respiratory rinse and about 5- to 10-fold in blood.
The data of this study clearly demonstrate that preparation of fungal DNA from human specimens is optimized by introduction of a bead beating step to the conventional DNA-preparation method without the necessity of a liquid nitrogen step.
Vacuolating cytotoxin A (VacA) is a secreted pore-forming toxin and one of the major virulence factors of Helicobacter pylori (H. pylori), which actively supports the persistence and survival of the ...bacteria in the special ecological niche of the human stomach. H. pylori genomes harbor different allelic forms of the vacA gene, which translate into functionally distinct VacA toxin types. VacA internalizes into various cell types via membrane or specific receptor interactions finally forming acidic endocytic VacA-containing vacuoles (VCVs). In this review, we focus on different characteristics of VacA, its interaction with host cells, the formation and protein content of VCVs and their intracellular transport into human T cells, which finally leads to the immunosuppressive phenotype of VacA. Immunomodulatory activities of VacA on human T cells are discussed with a focus on T-cell proliferation and calcium signaling.
PDF
