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Özkan, M.

Publications and source records attributed to Özkan, M..

4 recordsLinked to original sources

Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+ activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.

immunology

The IL-10GFP (VeRT-X) mouse strain is not suitable for the detection of IL-10 production by granulocytes during lung inflammation

The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the clear identification of IL-10-producing cells is challenging and, therefore, reporter mouse lines were developed to facilitate their detection. Several such reporter lines utilize GFP, including the IL-10GFP (VeRT-X) reporter strain studied here. In line with previous reports, we found that this IL-10GFP line faithfully reports on the IL-10 production of lymphoid cells. However, we show that the IL-10GFP reporter is not suitable to analyse IL-10 production of myeloid cells during inflammations. During inflammation, the autofluorescence of myeloid cells increased to an extent that entirely masked the IL-10-specific GFP-signal. Our data illustrate a general and important technical caveat using GFP-reporter lines for the analysis of myeloid cells and suggest that previous reports on effector functions of myeloid cells using such GFP-based reporters might require re-evaluation.

immunology

Paradoxical stabilization of relative position in moving frames

To capture where things are and what they are doing, the visual system may extract the position and motion of each object relative to its surrounding frame of referencee.g., 1,2. Here we report a particularly powerful example where a paradoxical stabilization is produced by a moving frame. We first take a frame that moves left and right and we flash its right edge before, and its left edge after, the frames motion. For all frame displacements tested, the two edges are perceived as stabilized, with the left edge on the left and right edge on the right, separated by the frames width as if the frame were not moving. This illusory stabilization holds even when the frame travels farther than its width, reversing the actual spatial order of the two flashes. Despite this stabilization, the motion of the frame is still seen, albeit much reduced, and this hides the paradoxical standstill of relative positions. In a second experiment, two probes are flashed inside the frame at the same physical location before and after the frame moves. Despite being physically superimposed, the probes are perceived widely separated, again as if they were seen in the frames coordinates and the frame were stationary. This illusory separation is set by the distance of the frames travel, independently of its speed. This paradoxical stabilization suggests a link to visual constancy across eye movements where the displacement of the entire visual scene may act as a frame to stabilize the perception of relative locations.

neuroscience

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication

Sheep was among the first domesticated animals, but its demographic history is little understood. Here we present combined analyses of mitochondrial and nuclear polymorphism data from ancient central and west Anatolian sheep dating to the Late Glacial and early Holocene. We observe loss of mitochondrial haplotype diversity around 7500 BCE during the early Neolithic, consistent with a domestication-related bottleneck. Post-7000 BCE, mitochondrial haplogroup diversity increases, compatible with admixture from other domestication centres and/or from wild populations. Analysing archaeogenomic data, we further find that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds, and especially those from central and north Europe. Our results indicate that Asian contribution to south European breeds in the post-Neolithic era, possibly during the Bronze Age, may explain this pattern.

evolutionary biology