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A comparative analysis of methods for scoring human sleep data, in particular sleep spindles, from encephalographic recordings is reported. The authors develop methods for crowdsourcing the identification of sleep spindles and compare the detection performance of experts, non-experts and automated algorithms. Sleep spindles are discrete, intermittent patterns of brain activity observed in human electroencephalographic data. Increasingly, these oscillations are of biological and clinical interest because of their role in development, learning and neurological disorders. We used an Internet interface to crowdsource spindle identification by human experts and non-experts, and we compared their performance with that of automated detection algorithms in data from middle- to older-aged subjects from the general population. We also refined methods for forming group consensus and evaluating the performance of event detectors in physiological data such as electroencephalographic recordings from polysomnography. Compared to the expert group consensus gold standard, the highest performance was by individual experts and the non-expert group consensus, followed by automated spindle detectors. This analysis showed that crowdsourcing the scoring of sleep data is an efficient method to collect large data sets, even for difficult tasks such as spindle identification. Further refinements to spindle detection algorithms are needed for middle- to older-aged subjects.

Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle.

Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.

Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.

Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1 , FOXP1 , GABRA2 , GLR1A , RHOT1 , and TBC1D4 . We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1 -deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca 2+ , and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1 -deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1 methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets. Type 2 diabetes (T2D) is characterized by hyperglycemia caused by insufficient insulin release from pancreatic islets, often in combination with insulin resistance. Here the authors present an epigenetic case-control study in human pancreatic islets revealing changes that contribute to type 2 diabetes development, e.g., epigenetic downregulation of RHOT1.

There are growing demands to ensure animal health and, from a broader perspective, animal welfare, especially for farmed animals. In addition to the newly developed welfare assessment protocols, which provide a harmonised method to measure animal health during farm visits, the question has been raised whether data from existing data collections can be used for an assessment without a prior farm visit. Here, we explore the possibilities of developing animal health scores for fattening pig herds using a) official meat inspection results, b) data on antibiotic usage and c) data from the QS (QS Qualität und Sicherheit GmbH) Salmonella monitoring programme in Germany. The objective is to aggregate and combine these register-like data into animal health scores that allow the comparison and benchmark of participating pig farms according to their health status. As the data combined in the scores have different units of measure and are collected in different abattoirs with possibly varying recording practices, we chose a relative scoring approach using z-transformations of different entrance variables. The final results are aggregated scores in which indicators are combined and weighted based on expert opinion according to their biological significance for animal health. Six scores have been developed to describe different focus areas, such as \"Respiratory Health\", \"External Injuries/ Alterations\", \"Animal Management\", \"Antibiotic Usage\", \"Salmonella Status\" and \"Mortality\". These \"focus\" area scores are finally combined into an \"Overall Score\". To test the scoring method, existing routine data from 1,747 pig farm units in Germany are used; these farm units are members of the QS Qualität und Sicherheit GmbH (QS) quality system. In addition, the scores are directly validated for 38 farm units. For these farm units, the farmers and their veterinarians provided their perceptions concerning the actual health status and existing health problems. This process allowed a comparison of the scoring results with actual health information using kappa coefficients as a measure of similarity. The score testing of the focus area scores using real information resulted in normalised data. The results of the validation showed satisfactory agreement between the calculated scores for the project farm units and the actual health information provided by the related farmers and veterinarians. In conclusion, the developed scoring method could become a viable benchmark and risk assessment instrument for animal health on a larger scale under the conditions of the German system.

Citizen science projects globally have increasingly been implemented in collecting and analysing environmental data. At the same time, these initiatives are often project-based and, therefore, of short duration. This presents a challenge as data from such activities may not be used in research and political decision-making. This research aims to explore the barriers and solutions for establishing a sustainable long-term citizen-based plastic monitoring strategy in fresh waters based on a case study in Accra, Ghana. This case study is particularly relevant due to the significant issue of plastic pollution in the region, limited official monitoring data to effectively address the problem, and the potential role of citizen science in addressing this data gap in the long term. Data on barriers and solutions were collected based on eight expert interviews, a survey amongst 17 stakeholders, and subsequent roundtable discussions with 24 experts and stakeholders from academia, the private sector, the public sector, and civil society. From this, we identified 30 types of barriers and 21 types of solutions to implement citizen science in the long term. These barriers and solutions relate to five fields of action (social, economic, environmental, technical, and management and governance) and four stakeholder groups (public sector, private sector, civil society, and academia) to implement solution pathways for long-term citizen science projects. Based on our findings, we make suggestions as to how citizen science can be implemented more sustainably in the future in different fields of action and from various institutional perspectives. With this, we hope to advance the potential use of citizen science and citizen science data in research and policy design related to plastics in fresh waters.

Novel crop improvement methodologies, including the exploitation of natural genetic variation, are urgently required to feed our rapidly growing human population in the context of global climate change. Here we describe a ‘Fast Identification of Nucleotide variants by DigITal PCR’ (FIND-IT) method for the rapid identification of pre-targeted genetic variants or rare alleles in large genomic populations. Libraries of 500,000 individuals can be screened and desired variants isolated within two weeks. FIND-IT is widely applicable for mining valuable diversity in any genomic population, including elite breeding and wild germplasm collections. The method provides single nucleotide resolution that has been validated by identifying and isolating knockout lines, non-synonymous codon changes and variants of miRNA and transcription factor binding sites in the agronomically important crop barley. In contrast to existing methods, FIND-IT does not require transformation, cloning or enzymatic steps, and is exempt from GMO regulations. Thus, FIND-IT can be applied immediately to elite crop cultivars and can be tailored to minimize or eliminate time-consuming backcrossing requirements. Competing Interest Statement S.K., T.W., H.C.T, M.R., M.C., A.S., O.O. and B.S. are listed as inventors in a patent application WO2018/001884, and S.K., T.W., M.R., J.O and B.S. are listed as inventors in patent application PCT/EP2020/078321, both relating to the methodology and filed by the Carlsberg A/S. Furthermore, S.K., S.B, O.O., H.T., T.W. and J.H. are listed as inventors in a patent application WO2019129736A1, and C.D., P.R.P., S.K., O.O., T.W., M.C., H.T. and M.R. are listed as inventors in a patent application WO2019129739A1, both relating to traits and filed by the Carlsberg A/S. All authors are previous or current Carlsberg A/S employees. B.L.M. is a Distinguished Professor at the Carlsberg Research Laboratory and serves as a consultant for the laboratory. G.B.F. is a Senior Scientific Consultant and Distinguished Professor of Raw Materials at the Carlsberg Research Laboratory. The methodology presented in the manuscript is applied commercially by Traitomic, a business unit at Carlsberg A/S.