The role of OTULIN in skin inflammation and cell death

The skin epithelium provides a physical and immunologically active multilayered barrier that protects the body from environmental factors and mediates cellular immune responses. Especially mechanisms regulating the cell survival and cell death of epidermal keratinocytes play a crucial role in maintaining tissue homeostasis. Inflammatory and cell death signalling is tightly controlled by linear ubiquitination, mediated via the E3 ligase Linear Ubiquitin Assembly Complex (LUBAC) to initiate innate immune responses. LUBAC itself is controlled by OTU deubiquitinase with linear specificity (OTULIN), a deubiquitinating enzyme that specifically degrades linear ubiquitin chains. Mouse model studies suggested that OTULIN deficiency results in loss of LUBAC components and cell death-mediated inflammation. Interestingly, mutations in the gene encoding OTULIN cause the OTULIN-related autoinflammatory syndrome (ORAS), a human genetic disease presented with complex pathological features and systemic inflammation affecting multiple organs, including the skin. The role of OTULIN in regulating skin homeostasis, inflammation and cell death is poorly understood and remains to be elucidated. The aim of this study was to investigate the biological function of OTULIN in the skin and to unravel the underlying cellular processes. The results acquired in this thesis reveal that OTULIN prevents skin inflammation by inhibiting keratinocyte necroptosis. In detail, deleting OTULIN in the mouse epidermis causes skin lesions that develop in different parts of the skin, including the tail. Those lesions resemble papilloma-like structures and are displayed with an inflammatory gene expression profile. Our genetic studies demonstrate that this skin pathology is driven by TNFR1 mediated RIPK1 kinase-dependent cell death. Furthermore, RIPK3 and MLKL deficiency strongly protect mice lacking OTULIN in keratinocytes from skin inflammation, thereby identifying necroptosis as a key driver, whereas FADD-dependent apoptosis plays a minor role in the skin disease development. Additionally, MyD88 deficiency strongly delayed and ameliorated skin pathology, implying that microbiota-dependent stimuli contribute to the pathogenesis in OTULINE-KO mice. Taken together, the data presented in this study uncover a key role for OTULIN in the epidermis in preventing cell death and inflammation to maintain skin homeostasis

How space-number associations may be created in preliterate children : six distinct mechanisms

The directionality of space-number association (SNA) is shaped by cultural experiences. It usually follows the culturally dominant reading direction. Smaller numbers are generally associated with the starting side for reading (left side in Western cultures), while larger numbers are associated with the right endpoint side. However, SNAs consistent with cultural reading directions are present before children can actually read and write. Therefore, these SNAs cannot only be shaped by the direction of children's own reading/writing behavior. We propose six distinct processes - one biological and five cultural/educational - underlying directional SNAs before formal reading acquisition: (i) Brain lateralization, (ii) Monitoring adult reading behavior, (iii) Pretend reading and writing, and rudimentary reading and writing skills, (iv) Dominant attentional directional preferences in a society, not directly related to reading direction, (v) Direct spatial-numerical learning, (vi) Other spatial-directional processes independent of reading direction. In this mini-review, we will differentiate between these processes, elaborate when in development they might emerge, discuss how they may create the SNAs observed in preliterate children and propose how they can be studied in the future

Co-occurrence, stability and manifestation of child and adolescent mental health problems: a latent transition analysis

Background Complex constellations of socio-emotional and behavioural problems (i.e., mental health problems) in childhood and adolescence are common and heighten the risk for subsequent personality, anxiety and mood disorders in adulthood. Aims of this study included the examination of patterns of mental health problems (e.g., externalizing-internalizing co-occurrence) and their transitions to reported mental disorders by using a longitudinal person-centered approach (latent class and latent transition analysis). Methods The sample consisted of 1255 children and adolescents (51.7% female, mean age = 12.3 years, age range 8–26 years) from three time points of the comprehensive mental health and wellbeing BELLA study. Children and their parents completed the German SDQ (Strength and Difficulties Questionnaire, Goodman, 1997) and reported on diagnoses of ADHD, depression, and anxiety. Results Latent class analysis identified a normative class, an emotional problem class, and a multiple problem class. According to latent transition analysis, the majority of the sample (91.6%) did not change latent class membership over time; 14.7% of individuals showed a persistent pattern of mental health problems. Diagnoses of mental disorders were more likely to be reported by individuals in the emotional problem or multiple problem class. Conclusions Results highlight the need for early prevention of mental health problems to avoid accumulation and manifestation in the transition to adolescence and young adulthood

The Transcriptome of Compatible and Incompatible Interactions of Potato (Solanum tuberosum) with Phytophthora infestans Revealed by DeepSAGE Analysis

Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). Understanding the molecular basis of resistance and susceptibility to late blight is therefore highly relevant for developing resistant cultivars, either by marker-assissted selection or by transgenic approaches. Specific P. infestans races having the Avr1 effector gene trigger a hypersensitive resistance response in potato plants carrying the R1 resistance gene (incompatible interaction) and cause disease in plants lacking R1 (compatible interaction). The transcriptomes of the compatible and incompatible interaction were captured by DeepSAGE analysis of 44 biological samples comprising five genotypes, differing only by the presence or absence of the R1 transgene, three infection time points and three biological replicates. 30.859 unique 21 base pair sequence tags were obtained, one third of which did not match any known potato transcript sequence. Two third of the tags were expressed at low frequency (<10 tag counts/million). 20.470 unitags matched to approximately twelve thousand potato transcribed genes. Tag frequencies were compared between compatible and incompatible interactions over the infection time course and between compatible and incompatible genotypes. Transcriptional changes were more numerous in compatible than in incompatible interactions. In contrast to incompatible interactions, transcriptional changes in the compatible interaction were observed predominantly for multigene families encoding defense response genes and genes functional in photosynthesis and CO2 fixation. Numerous transcriptional differences were also observed between near isogenic genotypes prior to infection with P. infestans. Our DeepSAGE transcriptome analysis uncovered novel candidate genes for plant host pathogen interactions, examples of which are discussed with respect to possible function

RNA pathfinder - Global properties of neutral networks

Global properties of the genotype-phenotype map induced by RNA secondary structures can be described by random graph theory. The success of this approach depends on details of the respective secondary structure. A small selection of these dependencies

Neonatal symptomatic thromboembolism in Germany: two year survey

two year surve

How space-number associations may be created in preliterate children: six distinct mechanisms

The directionality of space-number association (SNA) is shaped by cultural experiences. It usually follows the culturally dominant reading direction. Smaller numbers are generally associated with the starting side for reading (left side in Western cultures), while larger numbers are associated with the right endpoint side. However, SNAs consistent with cultural reading directions are present before children can actually read and write. Therefore, these SNAs cannot only be shaped by the direction of children’s own reading/writing behavior. We propose six distinct processes - one biological and five cultural/educational - underlying directional space-number associations before formal reading acquisition: (i) Brain lateralization (ii) Monitoring adult reading behavior, (iii) Pretend reading and writing, and rudimentary reading and writing skills, (iv) Dominant attentional directional preferences in a society, not directly related to reading direction, (v) Direct spatial-numerical learning, (vi) Other spatial-directional processes independent of reading direction. In this mini-review, we will differentiate between these processes, elaborate when in development they might emerge, discuss how they may create the space-number associations observed in preliterate children and propose how they can be studied in the future

3D Point Clouds and Eye Tracking for Investigating the Perception and Acceptance of Power Lines in Different Landscapes

The perception of the visual landscape impact is a significant factor explaining the public’s acceptance of energy infrastructure developments. Yet, there is lack of knowledge how people perceive and accept power lines in certain landscape types and in combination with wind turbines, a required setting to achieve goals of the energy turnaround. The goal of this work was to demonstrate how 3D point cloud visualizations could be used for an eye tracking study to systematically investigate the perception of landscape scenarios with power lines. 3D visualizations of near-natural and urban landscapes were prepared based on data from airborne and terrestrial laser scanning. These scenes were altered with varying amounts of the respective infrastructure, and they provided the stimuli in a laboratory experiment with 49 participants. Eye tracking and questionnaires served for measuring the participants’ responses. The results show that the point cloud-based simulations offered suitable stimuli for the eye tracking study. Particularly for the analysis of guided perceptions, the approach fostered an understanding of disturbing landscape elements. A comparative in situ eye tracking study is recommended to further evaluate the quality of the point cloud simulations, whether they produce similar responses as in the real world.ISSN:2414-408