Normalisation against circadian and age-related disturbances enables robust detection of gene expression changes in liver of aged mice

The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age- related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome

Zinc Status of Horses and Ponies: Relevance of Health, Horse Type, Sex, Age, and Test Material

Little is known about the animal- and diet-related factors that could interfere with the plasma zinc (Zn) concentrations of equines. Additionally, the adequacy of plasma to reflect changes in the Zn intake is unclear. In the first part of this study, the plasma Zn concentrations of hospitalized horses and ponies (n = 538) were measured and evaluated for the impact of the age, sex, horse type, and internal diseases of the animals. In the second part, the effects of increasing dietary Zn chloride hydroxide and Zn methionine supplementations were assessed on the plasma and mane hair Zn concentrations of healthy horses (n = 2) and ponies (n = 8). Part 1: The age, sex, and horse type did not influence the plasma Zn concentrations. No effect of internal diseases was observed, with the exception of higher plasma Zn concentrations in animals with metabolic disorders compared to the control group (p < 0.05). Part 2: Both Zn supplements dose-dependently increased the Zn concentrations in the mane hair (p = 0.003), but not in the plasma of the horses and ponies. In conclusion, the plasma Zn concentrations were widely unaffected by nutritional and non-nutritional factors in equines, while mane hair samples better reflected the dietary Zn supply

Soundscapes on edge - The real-time machine learning approach for measuring Soundscapes on resource-constrained devices

According to the WHO, noise is a growing problem in urban areas and the second most common environmental cause of health issues in Europe. As a complementary approach to noise maps based on sound pressure levels, soundscape maps can be a useful tool for urban planning, providing more information about how people perceive acoustic environments. This study describes an in-situ soundscape monitoring system based on WASN (Wireless Acoustic Sensor Network) for statistical spatial-temporal prediction of soundscapes in urban areas. Soundscape data on specifically defined spatial scales were observed and evaluated using a microcontroller with a 32-bit nRF52840 Nordic Semiconductors CPU and 1MB of memory in a multifunctional urban area. The use of TinyML enabled machine learning algorithms provided state-of-the-art soundscape classification to a low-cost edge device with extreme resource constraints regarding memory, speed, and lack of GPU support. Sound source types are classified into anthrophony, traffic, biophony, and geophony sounds using ESC-50 for evaluation. Our final MFCC-based CNN achieved an accuracy of 81.6% and even reached higher accuracy in the enclosed studio test. The results show that it is computationally feasible to classify soundscapes on low-power microcontrollers and potentially inform decision-makers based on extended sound analysi

Which conditions should be considered as disorders in the International Classification of Diseases (ICD-11) designation of “other specified disorders due to addictive behaviors”?

© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.Background: Gambling and gaming disorders have been included as “disorders due to addictive behaviors” in the International Classification of Diseases (ICD-11). Other problematic behaviors may be considered as “other specified disorders due to addictive behaviors (6C5Y).” Methods: Narrative review, experts’ opinions. Results: We suggest the following meta-level criteria for considering potential addictive behaviors as fulfilling the category of “other specified disorders due to addictive behaviors”:1. Clinical relevance: Empirical evidence from multiple scientific studies demonstrates that the specific potential addictive behavior is clinically relevant and individuals experience negative consequences and functional impairments in daily life due to the problematic and potentially addictive behavior.2. Theoretical embedding: Current theories and theoretical models belonging to the field of research on addictive behaviors describe and explain most appropriately the candidate phenomenon of a potential addictive behavior.3. Empirical evidence: Data based on self-reports, clinical interviews, surveys, behavioral experiments, and, if available, biological investigations (neural, physiological, genetic) suggest that psychological (and neurobiological) mechanisms involved in other addictive behaviors are also valid for the candidate phenomenon.Varying degrees of support for problematic forms of pornography use, buying and shopping, and use of social networks are available.These conditions may fit the category of “other specified disorders due to addictive behaviors”. Conclusion: It is important not to overpathologize everyday-life behavior while concurrently not trivializing conditions that are of clinical importance and that deserve public health considerations. The proposed meta-level-criteria mayhelp guide both research efforts and clinical practice.Peer reviewe

Reduced Lung Function in a Chronic Asthma Model Is Associated with Prolonged Inflammation, but Independent of Peribronchial Fibrosis

In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes.Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-beta)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response

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