Högskolan i Skövde

Co-occurrence of abiotic stresses, especially drought and salinity, is a natural phenomenon in field conditions and is worse for crop production than any single stress. Nowadays, rigorous methods of meta-analysis and systems biology have made it possible to perform cross-study comparisons of single stress experiments, which can uncover main overlapping mechanisms underlying tolerance to combined stress. In this study, a meta-analysis of RNA-Seq data was conducted to obtain the overlapping gene network of drought and salinity stresses in barley (Hordeum vulgare L.), which identified Rubisco activase A (RcaA) as a hub gene in the dual-stress response. Thereafter, a greenhouse experiment was carried out using two barley genotypes with different abiotic stress tolerance and evaluated several physiochemical properties as well as the expression profile and protein activity of RcaA. Finally, machine learning analysis was applied to uncover relationships among combined stress tolerance and evaluated properties. We identified 441 genes which were differentially expressed under both drought and salinity stress. Results revealed that the photosynthesis pathway and, in particular, the RcaA gene are major components of the dual-stress responsive transcriptome. Comparative physiochemical and molecular evaluations further confirmed that enhanced photosynthesis capability, mainly through regulation of RcaA expression and activity as well as accumulation of proline content, have a significant association with combined drought and salinity stress tolerance in barley. Overall, our results clarify the importance of RcaA in combined stress tolerance and may provide new insights for future investigations. 

Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels were covalently cross-linked by strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, a de novo designed helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density and kinetics, and hydrogel functionality. An array of complementary peptides with different functionalities was developed and used as a toolbox for supramolecular tuning of cell-hydrogel interactions and for controlling enzyme-mediated biomineralization processes. The modular peptide system enabled dynamic modifications of the properties of 3D printed structures, demonstrating a novel route for design of more sophisticated bioinks for four-dimensional bioprinting. © 2020 The Author(s). Published by IOP Publishing Ltd.

Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.

Background: There exist few, if any, practical guidelines for predictive and falsifiable multi-omic data integration that systematically integrate existing knowledge. Disease modules are popular concepts for interpreting genome-wide studies in medicine but have so far not been systematically evaluated and may lead to corroborating multi-omic modules. Result: We assessed eight module identification methods in 57 previously published expression and methylation studies of 19 diseases using GWAS enrichment analysis. Next, we applied the same strategy for multi-omic integration of 20 datasets of multiple sclerosis (MS), and further validated the resulting module using both GWAS and risk-factor-associated genes from several independent cohorts. Our benchmark of modules showed that in immune-associated diseases modules inferred from clique-based methods were the most enriched for GWAS genes. The multi-omic case study using MS data revealed the robust identification of a module of 220 genes. Strikingly, most genes of the module were differentially methylated upon the action of one or several environmental risk factors in MS (n = 217, P = 10− 47) and were also independently validated for association with five different risk factors of MS, which further stressed the high genetic and epigenetic relevance of the module for MS. Conclusions: We believe our analysis provides a workflow for selecting modules and our benchmark study may help further improvement of disease module methods. Moreover, we also stress that our methodology is generally applicable for combining and assessing the performance of multi-omic approaches for complex diseases. 

Skogsstyrelsen redovisar i sin utvärdering av miljömålet Levande skogar 2019 att centrala hinder för uppfyllelse av miljömålet är minskande och fragmenterade livsmiljöer och minskande och/eller små populationer av ett antal hotade arter knutna till skogsekosystemet. En väg framåt för att vända denna trend är att framtidens skogsbruk bland annat bör utvecklas utifrån ett landskapsperspektiv och där hyggesfria skogsbruksmetoder ökar i omfattning.

Länsstyrelserna i Sverige har genom sitt arbete med regionala handlingsplaner för grön infrastruktur identifierat så kallade värdekärnor – områden av stor betydelse för skogsarternas överlevnad. I denna studie har Västra Götalands läns värdekärnor analyserats med avseende på deras förmåga att stödja biologisk mångfald i ett landskapsperspektiv. Arbetet har gjorts i samverkan med Länsstyrelsen för Västra götalands län.

Metoden som använts är Biotope Biodiversity Capacity Indicator (BBCI). Metoden har utvecklats inom forskningsprojektet “Landscape biodiversity capacity: a tool for measuring, monitoring and managing” finansierat av Naturvårdsverkets miljöforskningsanslag (2019-2022).

Resultaten visar vilka geografiskt avgränsade värdekärnor som idag har hög ekologisk funktionalitet och som utgör biologiska överlevnads- och spridningshotspots för arter knutna till barrskogar. Vidare visar resultaten att endast sju kommuner har BBCI-värden över 1, det vill säga, ett hållbart skogslandskap som kan hålla fokusarten i ett 100-årsperspektiv.

För att nå de svenska miljömålen Levande skogar och Ett rikt växt- och djurliv samt skapa bättre förutsättningar för skogens biologiska mångfald att fortleva behöver nuvarande skogsmetoder med trakthyggesbruk anpassas till brukningsformer som tar större hänsyn till skogens ekosystem. Resultaten från denna studie kan ge prioriteringsunderlag för inom vilka produktionsskogar en så kallad återvildning genom förändrad brukningsmetod skulle kunna resultera i betydelsefull ökad ekologisk funktionalitet på landskapsnivå för de västgötska barrskogarna.     

Posttraumatic symptoms, including nightmares, are more prevalent in World War II survivors than in the general population, but how war experiences have affected subsequent dream content in specific survivor populations remains less explored. In the present study, we used self -reports collected in 1973 from Polish Auschwitz survivors (N = 150; 45 women) to investigate the prevalence of posttraumatic symptoms, classified according to the DSM-5 diagnostic criteria for posttraumatic stress disorder (PTSD). Furthermore, we classified main themes, central emotions, and threatening events in the dreams (N = 632) of the survivors, comparing dreams recalled from before, during, and after the war. Of the respondents, 12.7% described experiencing all diagnostic criteria for PTSD. War-related themes were less common in dreams dreamt before than during the war but were most common after the war. Themes related to family and freedom were most likely to appear in dreams dreamt during than before or after the war. The most often occurring emotion was fear, and dreams from after the war were likely to contain more negative and less positive emotions than dreams dreamt during the war. The likelihoods of reporting threatening events and threats involving aggression were higher in dreams dreamt during than before the war and in dreams dreamt after than during the war. In conclusion, PTSD symptoms were common in Polish Auschwitz survivors 30 years after World War II, and the themes, emotions, and threatening events in their dreams seem to reflect lifelong posttraumatic dreaming. We interpret the results as lending support for the threat simulation theory of dreaming.

We welcome you to the 16’th SweCog conference! After the 2020 meeting had to be cancelled, due to the unusual circumstances of facing a worldwide pandemic, we look forward to finally meet again, although the pandemic makes us meet virtually and not in person. 

Fittingly, an emerging theme of this year’s meeting is virtual reality. A technology which creates new ways of interacting with each other and with the world. It is not only a subject of active research, but increasingly also a medium for new creative experiments or applications, as evidenced by one of our keynote speakers this year. VR has become now a more widely available tool in different areas of research, and probably has made its full and final impact not yet. 

SweCog 2021 also features a nod to the word usability day. As technology becomes increasingly present in our daily lives, not the least emphasized through the pandemic, we believe that cognitive science has an important role as a field of research informing the design of usable digital artifacts. As the University of Skövde stands as one example of the close relation between cognitive science and user experience design, we take the opportunity to celebrate the topic of Cognitoon and UX. 

This meeting has been organized jointly by the Interaction lab and the Cognitive Neuroscience lab of the University of Skövde. We are glad to see this interaction happening between the two labs and the two fields. We hope this is not perceived as an “invasion” of the brain scientists documenting the failure of cognitive science as a field (see Nunez et al., 2019), but rather a collaborative move of finding synergies in our research. In this spirit, we hope our meetings continue to bring people together from different parts of Sweden, from different departments, and maybe also from more different disciplines, to discuss our latest research. And despite our enthusiasm for virtual reality, we sincerely hope the next meeting will allow us to meet again in person. 

Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p ≤ 1 × 10−3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3–4) and low (CTCAE 0–1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.

While lake systems in temperate regions have been extensively studied, tropical and subtropical systems have received less attention. Here, we describe the water chemistry and biota of ten inland blue holes on Andros Island, The Bahamas, representative of the morphological, abiotic, and biotic variation among Androsian inland blue holes. The majority of the studied blue holes were vertically stratified with oxic freshwater overlying anoxic saline groundwater of marine origin. Water chemistry (e.g. total phosphorus and nitrogen) in shallow waters was similar among blue holes, while turbidity and water color varied. Presence of hydrogen sulfide and reduced iron in and below the halocline indicate reducing conditions in all stratified blue holes. The biota above the halocline was also similar among blue holes with a few taxa dominating the phytoplankton community, and the zooplankton community consisting of copepods and rotifers. The Bahamas mosquitofish (Gambusia hubbsi) was present in all investigated blue holes, often accompanied by other small planktivorous fish, while the piscivorous bigmouth sleeper (Gobiomorus donnitor) was only present in some of the blue holes. Our field study reinforces that inland blue holes are highly interesting for biogeochemical research, and provide naturally replicated systems for evolutionary studies.

Objective: Vaccines are an effective means to reduce the spread of diseases, but they are sometimes met with hesitancy that needs to be understood. Method: In this study, we analyzed data from a large, cross-country survey conducted between June and August 2021 in 43 countries (N = 15,740) to investigate the roles of trust in government and science in shaping vaccine attitudes and willingness to be vaccinated. Results: Despite significant variability between countries, we found that both forms of institutional trust were associated with a higher willingness to receive a COVID-19 vaccine. Furthermore, we found that conspiratorial thinking and anti-expert sentiments predicted reduced trust in government and science, respectively, and that trust mediated the relationship between these two constructs and ultimate vaccine attitudes. Although most countries displayed similar relationships between conspiratorial thinking and anti-expert sentiments, trust in government and science, and vaccine attitudes, we identified three countries (Brazil, Honduras, and Russia) that demonstrated significantly altered associations between the examined variables in terms of significant random slopes. Conclusions: Cross-country differences suggest that local governments’ support for COVID-19 prevention policies can influence populations’ vaccine attitudes. These findings provide insight for policymakers to develop interventions aiming to increase trust in the institutions involved in the vaccination process.

This study replicated and extended a previous finding that the discussion of dreams increases the level of empathy toward the dreamer from those with whom the dream is discussed. The study addressed mediating variables for the empathy effect. Participants who already knew each other were recruited in dyads and were assigned dream-sharer and discusser roles. Each dyad used the Ullman dream appreciation technique to explore the relationship of the sharer’s dreams to recent experiences in the sharer’s life, with a maximum of 4 dream discussions per dyad (mean length of dreams = 140.15 words, mean discussion length = 23.72 min). The empathy of each member of a dyad toward the other was assessed using a 12-item state empathy questionnaire. A total of 44 participants (females = 26, males = 18, Mage = 26.70) provided empathy scores at baseline and after each dream discussion. For below median baseline empathy scorers, empathy of discussers toward their dream-sharer increased significantly as a result of the dream discussions, with medium effect size, η² = .39. Dream-sharers had a nonsignificant increase in empathy toward their discusser. Change in empathy was not linear across successive discussions, and was not related to length of dream reports, nor length of discussions. These findings of postsleep, social effects of dreaming, with possibly a group bonding function, go beyond theories of dreaming that have a within-sleep emotional or memory processing function for the individual. 

BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA. The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used.

RESULTS: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer.

CONCLUSIONS: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/ .

At the current rates of species extinction on a global level, Red List assessments need to speed up to inform conservation management in a timely manner. This study analyzed the progress made over the last 10 years in red listing aquatic invertebrates in Northern Europe. A survey of 43 freshwater molluscs and 1492 marine crustaceans was carried out for their Red List status in twelve countries during a twenty year interval (2003−2022). Our survey demonstrated that many countries have no national Red List or outdated Red Lists for the freshwater molluscs and only four countries have assessed their existing crustacean species. Alarmingly, we find 13 % fewer occurrence records for the crustaceans and 48 % fewer records for the freshwater molluscs in GBIF in the last 10 years (2013−2022) than in the 10 years previously (2003−2012). A barcode gap analysis reveals more barcodes for the 16S gene (77 %) than for the COI gene (63 %) for the freshwater molluscs and even fewer barcodes for the marine crustaceans (17 % for 16S and 40 % for the COI gene). With the current methods, regular comprehensive red listing of aquatic invertebrates is unrealistic. Here we present a set of scripts that allow automated occurrence and barcode gap analyses on unrepresented species groups. Finally, we discuss ways to increase the number of occurrence records and speed up red listing under existing European frameworks through whole community screening of ecosystems using molecular and other emerging tools.

Objective: After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration. Methods and Results: We used a pig model that progressed into chronic HF over 3 months following MI induction. Integrated gene and metabolite signatures revealed region-specific perturbations in amino acid- and lipid metabolism, insulin signaling and, oxidative stress response. Remote LV, in particular, showed impaired glutamine and arginine metabolism, altered synthesis of lipids, glucose metabolism disorder, and increased insulin resistance. LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation in the remote zone and were found differentially expressed also in the myocardium of patients with ischemic and/or dilated cardiomyopathy. In addition, a simultaneous significant decrease in arginine levels and altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area. Conclusions: This study unravels an array of dysregulated genes and metabolites putatively involved in maladaptive metabolic and vascular remodeling in the non-infarcted myocardium and may contribute to the development of more precise therapies to mitigate progression of chronic HF post-MI.

During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals’ experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy.

Video recording is a common method to study animal behaviour. In honey bee studies, short video-recordings are often used to learn more about a behaviour, but rarely used for their quantification. Standard methods for observing bee behaviour involve behavioural assays or direct observation of a limited subset of marked bees within an observation hive. This means that behaviour at the hive entrance may be overlooked. Here we describe a 4-camera set up for the study of behaviour at hive entrances. With minimal disturbance, we were able to record and quantify all previously described behaviours (9 in total - including self-grooming in drones) on and around the hive entrance. We briefly discuss the general feasibility of video footage and the relative frequency of each observed behaviour. Our conclusion is that video footage is a useful and perhaps overlooked method for unbiased quantification and comparisons of bee behaviour at the hive entrance. With this paper we are publishing some example short video-recordings as online supplementary material for educational purposes.

Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D₃ can be monitored.

Most ecosystem functions and related services involve species interactions across trophic levels, for example, pollination and biological pest control. Despite this, our understanding of ecosystem function in multitrophic communities is poor, and research has been limited to either manipulation in small communities or statistical descriptions in larger ones. Recent advances in food web ecology may allow us to overcome the trade-off between mechanistic insight and ecological realism. Molecular tools now simplify the detection of feeding interactions, and trait-based approaches allow the application of dynamic food web models to real ecosystems. We performed the first test of an allometric food web model's ability to replicate temporally nonaggregated abundance data from the field and to provide mechanistic insight into the function of predation. We aimed to reproduce and explore the drivers of the population dynamics of the aphid herbivore Rhopalosiphum padi observed in ten Swedish barley fields. We used a dynamic food web model, taking observed interactions and abundances of predators and alternative prey as input data, allowing us to examine the role of predation in aphid population control. The inverse problem methods were used for simultaneous model fit optimization and model parameterization. The model captured >70% of the variation in aphid abundance in five of ten fields, supporting the model-embodied hypothesis that body size can be an important determinant of predation in the arthropod community. We further demonstrate how in-depth model analysis can disentangle the likely drivers of function, such as the community's abundance and trait composition. Analysing the variability in model performance revealed knowledge gaps, such as the source of episodic aphid mortality, and general method development needs that, if addressed, would further increase model success and enable stronger inference about ecosystem function. The results demonstrate that confronting dynamic food web models with abundance data from the field is a viable approach to evaluate ecological theory and to aid our understanding of function in real ecosystems. However, to realize the full potential of food web models, in ecosystem function research and beyond, trait-based parameterization must be refined and extended to include more traits than body size. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society

This study characterizes different MTP1 (metal tolerance protein)/ZAT (zinc transporter) homologs involved in zinc (Zn) homeostasis in plants. BLAST analysis of AtMTP1 protein against 15 plant species showed 21 MTP1 homologs. These MTP1 protein homologs generally contain ~400 residues, six transmembrane helices and cation transmembrane transporter activity (GO:0008324), which can be utilized in predicting Zn uptake and tolerance mechanisms. These MTP1 genes having 1 exon are located on chromosomes 2, 7, and 14. Motifs contain conserved sequences of 41–50 residues belonging to the cation efflux family, which may help target binding sites and transcription factors. Further, AtMTP1 shows close similarities with Glycine max and Medicago trunculata. Interactome analysis suggests the association of AtMTP1 with cadmium/zinc-transporting ATPase and ZIP metal ion transporter. The AtMTP1 network is predominantly connected to cadmium/zinc-transporting ATPase (heavy metal ATPase 2, HMA2; heavy metal ATPase 3, HMA3; heavy metal ATPase 4, HMA4), cation efflux protein (MTP11), and metal tolerance protein C3 (AT4G58060). The Genevestigator predicts the high expression potential of AtMTP1 in the apical root during senescence, seedling, and bolting stages in an association with 11 co-expressed genes, mainly linked to estradiol toxicity and heat stress. Besides, AtMTP1 protein homologs possess conserved N-glyco motifs and physicochemical properties. The similarity and interactions of AtMTP1 gene with other genes suggest that Zn homeostasis in plants is associated with the regulation of different genes. These findings may advance our understanding to further develop plants capable of maintaining Zn homeostasis under adverse conditions. © 2021 Elsevier Inc.

MOTIVATION: Complex diseases are due to the dense interactions of many disease-associated factors that dysregulate genes that in turn form so-called disease modules, which have shown to be a powerful concept for understanding pathological mechanisms. There exist many disease module inference methods that rely on somewhat different assumptions, but there is still no gold standard or best performing method. Hence, there is a need for combining these methods to generate robust disease modules.

RESULTS: We developed MODule IdentiFIER (MODifieR), an ensemble R package of nine disease module inference methods from transcriptomics networks. MODifieR uses standardized input and output allowing the possibility to combine individual modules generated from these methods into more robust disease-specific modules, contributing to a better understanding of complex diseases.

AVAILABILITY: MODifieR is available under the GNU GPL license and can be freely downloaded from https://gitlab.com/Gustafsson-lab/MODifieR and as a Docker image from https://hub.docker.com/r/ddeweerd/modifier.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MotivationNetwork-based disease modules have proven to be a powerful concept for extracting knowledge about disease mechanisms, predicting for example disease risk factors and side effects of treatments. Plenty of tools exist for the purpose of module inference, but less effort has been put on simultaneously utilizing knowledge about regulatory mechanisms for predicting disease module hub regulators.

ResultsWe developed MODalyseR, a novel software for identifying disease module regulators and reducing modules to the most disease-associated genes. This pipeline integrates and extends previously published software packages MODifieR and ComHub and hereby provides a user-friendly network medicine framework combining the concepts of disease modules and hub regulators for precise disease gene identification from transcriptomics data. To demonstrate the usability of the tool, we designed a case study for multiple sclerosis that revealed IKZF1 as a promising hub regulator, which was supported by independent ChIP-seq data.

Availability and implementationMODalyseR is available as a Docker image at https://hub.docker.com/r/ddeweerd/modalyser with user guide and installation instructions found at https://gustafsson-lab.gitlab.io/MODalyseR/.

Supplementary informationSupplementary data are available at Bioinformatics Advances online.

The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of the brain-penetrating properties of novel drug molecules. Currently used in vitro models of the BBB include immortalized brain endothelial cell lines and primary brain endothelial cells of human and animal origin. Unfortunately, many cell lines and primary cells do not recreate physiological restriction of transport in vitro. Human-induced pluripotent stem cell (iPSC)-derived brain endothelial cells have proven a promising alternative source of brain endothelial-like cells that replicate tight cell layers with low paracellular permeability. Given the possibility to generate large amounts of human iPSC-derived brain endothelial cells they are a feasible alternative when modelling the BBB in vitro. iPSC-derived brain endothelial cells form tight cell layers in vitro and their barrier properties can be enhanced through coculture with other cell types of the BBB. Currently, many different models of the BBB using iPSC-derived cells are under evaluation to study BBB formation, maintenance, disruption, drug transport and diseases affecting the BBB. This review summarizes important functions of the BBB and current efforts to create iPSC-derived BBB models in both static and dynamic conditions. In addition, it highlights key model requirements and remaining challenges for human iPSC-derived BBB models in vitro.

Evidence from multisensory body illusions suggests that body representations may be malleable, for instance, by embodyingexternal objects. However, adjusting body representations to current task demands also implies that external objects becomedisembodied from the body representation if they are no longer required. In the current web-based study, we induced theembodiment of a two-dimensional (2D) virtual hand that could be controlled by active movements of a computer mouse or ona touchpad. Following initial embodiment, we probed for disembodiment by comparing two conditions: Participants eithercontinued moving the virtual hand or they stopped moving and kept the hand still. Based on theoretical accounts that conceptualizebody representations as a set of multisensory bindings, we expected gradual disembodiment of the virtual hand if the bodyrepresentations are no longer updated through correlated visuomotor signals. In contrast to our prediction, the virtual hand wasinstantly disembodied as soon as participants stopped moving it. This result was replicated in two follow-up experiments. Theobserved instantaneous disembodiment might suggest that humans are sensitive to the rapid changes that characterize action andbody in virtual environments, and hence adjust corresponding body representations particularly swiftly.

Enligt högskoleförordningens examensmål ska studenter efter avslutad utbildning inte bara uppvisa kunskap och förståelse för sitt områdes vetenskapliga grund utan även en rad färdigheter, förmågor, värderingsförmåga och förhållningssätt som inbegriper ett internationellt och interkulturellt perspektiv. Dessa perspektiv kan fås genom internationellt studentutbyte och mobilitet men också genom internationalisering på hemmaplan är tillgängligt för alla studenter. Internationaliseringen bryter språk- och kulturella barriärer, öppnar studenternas internationella perspektiv och bidrar därmed till att öka kvaliteten i utbildningarna och gör studenterna bättre förberedda för ett alltmer mångkulturellt samhälle och en global arbetsmarknad. Personas är fiktiva beskrivningar av typiska användare, förankrade i empiriska data med fokus på användarnas mål, behov, erfarenheter och beteenden. Inom området User Experience Design utgör personas ett viktigt stöd i den användarcentrerade designprocessen. Personas används ofta för att ge liv åt potentiella användare och därmed göra det lättare att ta användarens perspektiv, men har också använts för arbete med utveckling av studenters empatiska förmågor [1] [2]. I detta projekt användes personas för att beskriva studenters mål, behov, erfarenheter och beteenden, i relation till de internationella, interkulturella och globala färdigheter våra studenter behöver i sitt framtida yrkesliv. Syftet är att synliggöra de behov studenterna ska försöka möta och i sin tur söka avspegla detta i utbildningarna. I projektgruppen ingick programansvariga samt personer med erfarenhet av User Experience Design. Efter en kort presentation av projektet och dess resultat genomförs ett digitalt rundabordssamtal.

Syftet med rundabordssamtalet är dels att diskutera allmängiltigheten i de projektresultat som presenterats, dels om personas kan användas för andra ändamål som exempelvis vid utveckling av högre utbildning. Projektledaren fungerar som moderator för samtalet och inleder med en kort Mentimeter-övning där deltagarna får reflektera kring det genomförda projektet och dess relevans för internationalisering i utbildningen. Beroende på antalet deltagare så kan rundabordssamtalet sedan delas in i mindre digitala grupper ledda av övriga projektdeltagare och med en gemensam återsamling med gemensam sammanfattning och avslut. Förväntat utfall från rundabordssamtalet är att sprida arbetssättet med personas men också att vi ska få med oss viktiga synpunkter för det fortsatta arbetet.

[1] Haag, M., & Marsden, N. (2019). Exploring Personas as a Method to Foster Empathy in Student IT Design Teams. International Journal of Technology and Design Education, 29(3), 565–582.

[2] van Rooij, S. W. (2012). Research-Based Personas: Teaching Empathy in Professional Education. Journal of Effective Teaching, 12(3), 77–86.

Studenter ska enligt examensmålen i Högskolelagen (1992:1434) 1 kap. 8 § och Högskoleförordningen (1993:100), bilaga 2 under sin utbildning förvärva kunskaper och förståelse inom sitt ämnesområde samt utveckla sin värderingsförmåga och sitt förhållningssätt. Utöver detta ska de också tränas i färdigheter och förmågor, både sådana som är direkt relaterade till sitt ämnesområde men också färdigheter i informationskompetens, vetenskapligt skrivande och presentationsteknik. Under utbildningarna tränas detta i olika former av rapportskrivning med slutlig examination i examensarbetet. En vanlig uppfattning bland många lärare är att ämnesfokuset i utbildningens upplägg och innehåll gör att studenterna inte alltid hinner med en mer omfattande och fördjupad träning i de generella färdigheterna innan själva examensarbetet, vilket får konsekvenser för genomförandet av och kvaliteten på examensarbetet. Debattartiklar har skrivits om att studenter ofta är dåliga på att skriva (Enefalk et al, 2013; Garberding, 2019), vilket har uppmärksammats i media och lett till vidare diskussioner om en nationell ”skrivkris” eller ett ”skrivglapp”. Färdigheter inom informationskompetens (söka, samla, värdera och hantera information) har också blivit viktigare i dagens informationssamhälle tillsammans med vikten av att hitta relevanta och aktuella vetenskapliga källor.

För att stötta studenterna och minska lärarnas arbetsbelastning har institutionen för biovetenskap genom åren utvecklat stödmaterial i form av en rapportskrivningsmanual, inspelade föreläsningar samt quizzer i Canvas med syftet att utveckla studenternas färdigheter i vetenskapligt skrivande. För att ytterligare utveckla dessa färdigheter har institutionen tillsammans med högskolebiblioteket utformat en kurs om 7,5 hp, Litteratursammanfattning i biovetenskap G2F, som nu ingår i slutet av andra året på samtliga kandidatprogram i biovetenskap. På kursen får studenterna en mer omfattande och fördjupad träning i informationskompetens och vetenskapligt skrivande samtidigt som de fördjupar sig teoretiskt inom sitt valda ämnesområde. I kursen examineras informations-sökning, värdering av information, peer-review, vetenskapligt skrivande samt referenshantering. Kursen gavs första gången våren 2020 (programkurs) samt efterföljande sommar och hösttermin (fristående och distans, halv- respektive kvartsfart).

I detta bidrag presenterar vi kursens upplägg, genomförande och resultat baserat på dessa kurstillfällen. Vår erfarenhet så här långt är att studenterna efter genomgången kurs utvecklat sin litteratursökningsteknik, kunskaper i att värdera material och akademiskt skrivande samt behärskar referenshantering i större utsträckning, vilket bådar gott för kommande examensarbeten. Vad vi skulle vilja trycka på ytterligare vid kommande kurstillfällen är att studenterna i större utsträckning jämför och diskuterar likheter och skillnader i de olika källorna, dvs ”compare and contrast”. Studenterna var också mycket nöjda med kursens upplägg och genomförande, särskilt möjligheten att under en längre tid få fördjupa sig inom ett eget valt biovetenskapligt område.

Kursupplägget och det material som utvecklats kan, efter viss anpassning, tillämpas på de flesta ämnesområden. Materialet finns tillgängligt på högskolan i Canvas Commons.

Referenser

Enefalk, H., Andersson, L.M., Aronsson, A., Englund, V., Novaky, G., Svensson, M., Thisner, F., Ågren, H. & Ågren, M. (2 januari 2013) Våra studenter kan inte svenska. Upsala Nya Tidning. https://unt.se/debatt/vara-studenter-kan-inte-svenska-2027570.aspx

Garberding, P. (25 oktober, 2019) Ökade skrivsvårigheter stressar lärare och studenter. Universitetsläraren. https://universitetslararen.se/2019/10/25/okade-skrivsvarigheter-stressar-larare-och-studenter/

SFS 1992:1434. Högskolelag. Utbildningsdepartementet. Hämtad 11 februari, 2021, från https://www.riksdagen.se/sv/dokument-lagar/dokument/svensk-forfattningssamling/hogskolelag-19921434_sfs-1992-1434

SFS 1993:100. Högskoleförordning. Utbildningsdepartementet. Hämtad 11 februari, 2021, från https://www.riksdagen.se/sv/dokument-lagar/dokument/svensk-forfattningssamling/hogskoleforordning-1993100_sfs-1993-100

Resurser i Canvas Commons

Dokument: Information Literacy Tutorial, Evaluation of Sources and Source Criticism, Literature Search Protocol

Quizzer: Basic Reference Management Quiz, Plagiarism Quiz

Bakgrund

Enligt högskoleförordningens examensordning ska studenter efter avslutad utbildning inte bara uppvisa kunskap och förståelse för sitt områdes vetenskapliga grund utan även en rad generiska färdigheter, förmågor, värderingsförmåga och förhållningssätt. Detta tränas och examineras vanligen i studentuppsatser av olika slag och under olika delar av utbildningen. För att uppnå fördjupade kunskaper i informationskompetens krävs ett strukturerat arbetssätt med progression, att kunskaperna relateras till ämnet och kopplas samman genom konstruktiv länkning av utbildningarnas lärandemål, examinationer och betygskriterier. Kopplingen mellan informationskompetens och ämneskunskaper har exempelvis studerats inom det samhällsvetenskapliga området (Anving et al., 2012). Det finns också exempel på integrerad undervisning i informationskompetens i ämnet ekonomi (Olsson & Näverå, 2019). Här presenterar vi hur lärare i de biovetenskapliga grundutbildningarna och bibliotekets och Studieverkstans personal samverkat med syfte att utveckla undervisningen och höja kvaliteten i utbildningarna genom att integrera informationskompetens och vetenskapligt skrivande i en biovetenskaplig kurs.

Genomförande

Som utgångspunkt för arbetet finns den progressionstrappa i informationskompetens som används vid högskolebiblioteket i Skövde. Denna har anpassats för två biovetenskapliga grundutbildningar och integrerats i olika utbildningsmoment. I detta arbete beskriver vi progressionstrappan och dess koppling till en nytillkommen kurs i utbildningarna, Litteratursammanfattning i biovetenskap, som är på G2F-nivå och omfattar 7,5 högskolepoäng. På kursen får studenterna fördjupa sig i en biovetenskaplig frågeställning, söka, granska och värdera information samt skriva en sammanfattning i formatet av en vetenskaplig review. För att stödja studenterna i deras lärande finns det under kursens gång utbildningsmoment i att söka och värdera information, vetenskapligt skrivande och referentgranskning. Detta stöds av kursmaterial i form av manualer, övningar och protokoll som tagits fram för kursen. I presentationen presenteras läraktiviteterna med tillhörande material och examinationer samt de erfarenheter som gjorts baserat på två undervisningstillfällen under 2020 och 2021 då kursen erbjudits såväl som programkurs samt som fristående kurs.

Resultat

Ett jämlikt samarbete mellan lärare och bibliotekspersonal har varit en förutsättning för att åstadkomma en integrering av informationskompetens i kursen. Vikten av en ömsesidig förståelse för varandras områden är nödvändigt för integrering av informationskompetens i utbildningarna har tidigare beskrivits av Dawes (2019). Kursvärderingar har visat att kursens format fungerat väl och uppskattats av studenterna som fått fördjupa sig i ett område och tillämpat sina kunskaper inom informationskompetens. Studentuppsatserna visade en hög kvalitet med såväl bredd som vetenskapligt djup. Sammanfattningsvis har samarbetet lett till önskat resultat och arbetssättet kan framöver tillämpas på fler utbildningar och inom andra discipliner.

Referenser

Anving, T., Badersten, B., Grandsjö, L., Gustavsson, J., Hedlund, M., Jönsson, K., & Zettergren, A-S. (2012). Informationskompetens – generella färdigheter för fördjupat lärande. I M. Irhammar, G. Amnér, & H. Adell (Red.), Proceedings, Lunds universitets utvecklingskonferens 11, 107-116. Lund University.

Dawes, L. (2019). Faculty perceptions of teaching information literacy to first-year students: A phenomenographic study. Journal of Librarianship & Information Science, 51(2), 545–560. https://doi.org/10.1177/0961000617726129

Olsson, A-K, Näverå, E. (2019). The way to the wave: To integrate media and information literacy in the “scientific wave” throughout a bachelor program in business administration. INTED2019 Proceedings, 3536-3546. https://doi.org/10.21125/inted.2019

Aquatic organisms are constantly at risk of being exposed to potentially harmful chemical compounds of natural or anthropogenic origin. Biological life can for instance respond to chemical stressors by changes in gene expression, and thus, certain gene transcripts can potentially function as biomarkers, i.e. early warnings, of toxicity and chemical stress. A major challenge for biomarker application is the extrapolation of transcriptional data to potential effects at the organism level or above. Importantly, successful biomarker use also requires basal understanding of how to distinguish actual responses from background noise. The aim of this thesis is, based on response magnitude and variation, to evaluate the biomarker potential in a set of putative transcriptional biomarkers of general toxicity and chemical stress.

Specifically, I addressed a selection of six transcripts involved in cytoprotection and oxidative stress: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Moreover, I used metal exposures to serve as a proxy for general chemical stress, and due to their ecological relevance and nature as sedentary filter-feeders, I used bivalves as study organisms.

In a series of experiments, I tested transcriptional responses in the freshwater duck mussel, Anodonta anatina, exposed to copper or an industrial wastewater effluent, to address response robustness and sensitivity, and potential controlled (e.g. exposure concentration) and random (e.g. gravidness) sources of variation. In addition, I performed a systematic review and meta-analysis on transcriptional responses in metal exposed bivalves to (1) evaluate what responses to expect from arbitrary metal exposures, (2) assess the influence from metal concentration (expressed as toxic unit), exposure time and analyzed tissue, and (3) address potential impacts from publication bias in the scientific literature.

Response magnitudes were generally small in relationship to the observed variation, both for A. anatina and bivalves in general. The expected response to an arbitrary metal exposure would generally be close to zero, based on both experimental observations and on the estimated impact from publication bias. Although many of the transcripts demonstrated concentration-response relationships, large background noise might in practice obscure the small responses even at relatively high exposures. As demonstrated in A. anatina under copper exposure, this can be the case already for single species under high resolution exposures to single pollutants. As demonstrated by the meta-regression, this problem can only be expected to increase further upon extrapolation between different species and exposure scenarios, due to increasing heterogeneity and random variation. Similar patterns can also be expected for time-dependent response variation, although the meta-regression revealed a general trend of slightly increasing response magnitude with increasing exposure times.

In A. anatina, gravidness was identified as a source of random variability that can potentially affect the baseline of most assessed biomarkers, particularly when quantified in gills. Response magnitudes and variability in this species were generally similar for selected transcripts as for two biochemical biomarkers included for comparison (AChE, GST), suggesting that the transcripts might not capture early warnings more efficiently than other molecular endpoints that are more toxicologically relevant. Overall, high concentrations and long exposure durations presumably increase the likelihood of a detectable transcriptional response, but not to an extent that justifies universal application as biomarkers of general toxicity and chemical stress. Consequently, without a strictly defined and validated application, this approach on its own appears unlikely to be successful for future environmental risk assessment and monitoring. Ultimately, efficient use of transcriptional biomarkers might require additional implementation of complementary approaches offered by current molecular techniques.

Using a selection of molecular biomarkers, we evaluated responses in freshwater mussels (Anodonta anatina) exposed to effluent from an industrial wastewater treatment facility. The aims of this work were to (1) assess biomarkers of general toxicity under sublethal exposure to an anthropogenic mixture of chemicals, represented by an arbitrary effluent, and (2) evaluate the potential of A. anatina as a bioindicator of pollution. Adult mussels (n = in total 32; 24 males and 8 females) were exposed (96 h) in the laboratory to a fixed dilution of effluent or to a control treatment of standardized freshwater. Metal concentrations were in general higher in the effluent, by an order of magnitude or more, compared to the control. Toxic unit estimates were used as proxies of chemical stress, and Cu, Ni, and Zn were identified as potential major contributors (Cu> Ni > Zn). Six transcriptional (cat, gst, hsp70, hsp90, mt, sod) and two biochemical (AChE, GST) biomarkers were analyzed in two tissues, gills, and digestive glands. Out of the 16 responses (eight biomarkers x two tissues), 14 effect sizes were small (within +/- 28 % of control) and differences non-significant (p > 0.05). Results did however show that (1) AChE activity increased by 40% in gills of exposed mussels compared to control, (2) hsp90 expression was 100% higher in exposed female gills compared to control, and (3) three marker signals (AChE in both tissues, and hsp70 in gills) differed between sexes, independent of treatment. Results highlight a need for further investigation of molecular biomarker variability and robustness in A. anatina.

Molecular biomarkers, like gene transcripts or enzyme activities, are potentially powerful tools for early warning assessment of pollution. However, a thorough understanding of response and baseline variation is required to distinguish actual effects from pollution. Here, we assess the freshwater mussel Anodonta anatina as a biomarker model species for freshwater ecosystems, by testing responses of six transcriptional (cat, gst, hsp70, hsp90, mt, and sod) and two biochemical (AChE and GST) biomarkers to environmentally relevant Cu water concentrations. Mussels (n = 20), collected from a stream free from point source pollution, were exposed in the laboratory, for 96 h, to Cu treatments (< 0.2 mu g/L, 0.77 +/- 0.87 mu g/L, and 6.3 +/- 5.4 mu g/L). Gills and digestive glands were extracted and analyzed for transcriptional and biochemical responses. Biological and statistical effect sizes from Cu treatments were in general small (mean log(2) fold-change <= 0.80 and Cohen's f <= 0.69, respectively), and no significant treatment effects were observed. In contrast, four out of eight biomarkers (cat, gst, hsp70, and GST) showed a significant sex:tissue interaction, and additionally one (sod) showed significant overall effects from sex. Specifically, three markers in gills (cat, mt, GST) and one in digestive gland (AChE) displayed significant sex differences, independent of treatment. Results suggest that sex or tissue effects might obscure low-magnitude biomarker responses and potential early warnings. Thus, variation in biomarker baselines and response patterns needs to be further addressed for the future use of A. anatina as a biomarker model species.

We tested concentration-dependence of selected gene transcripts (cat, gst, hsp70, hsp90, mt and sod) for evaluation as biomarkers of chemical stress. Contrary to the common approach of factorial designs and few exposure concentrations, we used regression across a high-resolution concentration series. Specifically, freshwater mussels (Anodonta anatina) were acutely (96 h) exposed to Cu (13 nominal concentrations, measuring 0.13–1 600 µg/L), and transcripts were measured by RT-qPCR. In digestive glands, cat, hsp90 and mt decreased with water Cu (p < 0.05), but response magnitudes saturated at < 2-fold decreases. In gills, gst, hsp70, hsp90 and mt increased with water Cu (p < 0.05). While hsp70, hsp90 and mt exceeded 2-fold increases within the exposure range, high Cu concentrations were required (38–160 µg/L). Although gill responses were generally more robust compared to digestive glands, overall small response magnitudes and moderate sensitivity may set limit for potential application as general biomarkers of chemical stress.

Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions, and selected six transcripts associated with general toxicity for evaluation: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units (TUs), we normalized different metal exposures to a common scale, as a proxy of concentration. Using Bayesian hierarchical random effect models, we then tested the effects of metal exposure on lnRR, both for metal exposure in general and in meta-regressions using TU and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general as for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was a lnRR of 0.50, corresponding to a 65 % increase relative a non-exposed control. However, when accounting for publication bias, the estimated ‘true’ response showed no such effect. Furthermore, expected response magnitude increased slightly with exposure time, but there was little support for general monotonic concentration-dependence with regards to TU. Altogether, this work reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0–0. 

To date, most studies on the event-related potential (ERP) correlates of conscious perception have examined a single perceptual modality. We compared electrophysiological correlates of visual and auditory awareness in the same experiment to test whether there are modality-specific and modality-general correlates of conscious perception. We used near threshold stimulation and analyzed event-related potentials in response to aware and unaware trials in visual, auditory and bimodal conditions. The results showed modality-specific negative amplitude correlates of conscious perception between 200 and 300 ms after stimulus onset. A combination of these auditory and visual awareness negativities was observed in the bimodal condition. A later positive amplitude difference, whose early part was modality-specific, possibly reflecting access to global workspace, and later part shared modality-general features, possibly indicating higher level cognitive processing involving the decision making, was also observed.

Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity. 

Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.

The first decade of event-related potential (ERP) research had established that the most consistent correlates of the onset of visual consciousness are the early visual awareness negativity (VAN), a posterior negative component in the N2 time range, and the late positivity (LP), an anterior positive component in the P3 time range. Two earlier extensive reviews ten years ago had concluded that VAN is the earliest and most reliable correlate of visual phenomenal consciousness, whereas LP probably reflects later processes associated with reflective/access consciousness. This article provides an update to those earlier reviews. ERP and MEG studies that have appeared since 2010 and directly compared ERPs between aware and unaware conditions are reviewed, and important new developments in the field are discussed. The result corroborates VAN as the earliest and most consistent signature of visual phenomenal consciousness, and casts further doubt on LP as an ERP correlate of phenomenal consciousness. 

Impairments of visuospatial attention, language, and processing speed (PS) are common early after stroke and have been associated with unfavorable short-term functional outcomes but little is known about this relationship in the long-term. This thesis investigates 1) the potential importance of visuospatial inattention (VSI) and language impairments (LI) as predictors of functional outcomes 7 years after an ischemic stroke (studies I-II) and 2) presence of lateralized inattention 7 years after stroke and potential predictors of this phenomenon (study III). Study IV gives a detailed description of the long-term course of PS across 3 months and 7 years after an ischemic stroke. A cohort of 375 consecutive stroke patients was assessed early after stroke for the occurrence (studies I–II and IV) and severity (studies III-IV) of VSI using the Star Cancellation Test (SCT, studies I-IV) and Letter Cancellation Test (LCT, studies III-IV). Language impairments were investigated (studies I-II) by the language item from the Scandinavian Stroke Scale (SSS). At the 7-year follow-up, functional outcomes were measured by the modified Rankin Scale (mRS), the Frenchay Activities Index (FAI) (studies I-II and IV), and the recovery item of Stroke Impact Scale (SIS) (study IV). Patients with a recurrent stroke during the follow-up period were excluded (all studies). The presence of lateralized inattention at the 7-year follow-up (study III) was assessed with the SCT, the LCT, and the neglect item from the NIH Stroke Scale (NIHSS). The long-term course of PS (study IV) was measured by a mirrored copy of the SCT with a time limit of 30 seconds, follow-up assessments of SCT, LCT, and NIHSS were also included in this study. In study I, 235 stroke survivors were included at the follow-up and VSI and stroke severity (SSS) were identified as the significant independent predictors of unfavorable outcomes in mRS and FAI. The early screening of LI did not provide independent prognostic information beyond the information provided by VSI and stroke severity. In study II, 105 individuals with left hemispheric stroke were included at the 7-year follow-up. It was found that the presence of VSI was rather common observed in about one of five patients. VSI was the most important independent predictor of unfavorable outcomes in mRS and FAI. Individuals with both VSI and LI had increased risk of poor outcome compared to those with signs of one of these symptoms. In study III, 188 stroke survivors were included at the 7-year follow-up and about one of ten had signs of lateralized inattention. Independent baseline predictors for these long-term signs were total omissions in target cancellations and inferior performance on visual processing speed. In study IV, 148 subjects were included at follow-up and impaired PS was observed in about one of three individuals at baseline with significant improvement in scores at 3 months followed by a clear decline at 7 years. It was also found that slow PS was related with inferior functional outcome at the 7-year follow-up, also after adjusting for age. Age was related with scores in PS but did not explain the scores of PS for those with lowest speed. Conclusions: Studies I-II emphasize the importance of identifying early symptoms of VSI not only after right hemispheric stroke but also after left hemispheric stroke and particularly for individuals with severe symptoms of LI. A combination of attention and language deficits at the acute phase seems to be rather common among patients with left hemispheric stroke and indicates an increased risk of unfavorable outcomes. Studies III-IV are the first studies to recognize PS as a significant predictor of long-term lateralized inattention and to describe changes in speed across two follow-ups up to 7 years in a stroke cohort. The results from these two studies emphasize the importance of further long-term studies of PS after stroke.

Background and purpose: Visuospatial inattention (VSI) and languageimpairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. Methods: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1–5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian StrokeScale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. Results: The regression model significantly explained variance in the modified Rankin scale (R2= 0.435, P < 0.001) and identified VSI (P=0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for FrenchayActivities Index was also significant (R2= 0.269, P < 0.001) with VSI(P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. Conclusions: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

Objective: Lateralized inattention is a typical sign of neglect and related to poor functional outcome. Knowledge of the long-term course of this phenomenon is limited. The purpose of this study was to investigate presence and predictors for signs of lateralized inattention 7 years after stroke. Methods: From a cohort of acute ischemic stroke patients, aged 18-69 years (n = 297), a consecutive series of 188 survivors without recurrent stroke at follow-up 7 years later were included. Within the first week after stroke onset, stroke severity was assessed according to the Scandinavian Stroke Scale. Target omissions, asymmetry of omissions, and perceptual speed according to Star- and Letter Cancellation Tests were also assessed. Presence of lateralized inattention at the 7-year follow-up was investigated with the Star- and Letter Cancellation Tests and with the neglect item in the National Institutes of Health Stroke Scale. Results: At the follow-up, 22 (11.7%) participants had lateralized inattention and the multivariable regression showed that independent significant baseline predictors were total omissions in target cancellations (P <.001) and inferior baseline performance on visual processing speed (P =.008). Conclusion: About one of ten individuals exhibited signs of lateralized inattention 7 years after stroke. Baseline performance in perceptual processing speed and target omissions independently predicted presence of late signs of lateralized inattention. This is the first time processing speed is recognized as a significant predictor of lateralized inattention several years after the stroke incidence, indicating that the longitudinal course of processing speed following stroke is a critical subject for future research. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 

Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21-/low. These cells are expanded in peripheral blood with age and during chronic inflammatory conditions such as viral infections, malaria, common variable immunodeficiency, and autoimmune diseases. CD21-/low MBCs have gained significant attention; they produce disease-specific antibodies/autoantibodies and associate with key disease manifestations in some conditions. These cells can be divided into subsets based on classical B-cell and other markers, e.g. CD11c, FcRL4, and Tbet which, over the years, have become hallmarks to identify these cells. This has resulted in different names including age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted, or simply CD21-/low B cells. It is however unclear whether the expanded 'CD21-/low' cells in one condition are equivalent to those in another, whether they express an identical gene signature and whether they have a similar function. Here, we will discuss these issues with the goal to understand whether the CD21-/low B cells are comparable in different conditions.

Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols that preserve BM components are necessary to advance the field. This study aims to characterize laminin isoforms expressed in healthy human aortic valves and establish a small animal decellularized aortic valve scaffold for future studies of the BM in tissue engineering. Laminin isoforms were assessed by immunohistochemistry with antibodies specific for individual alpha, beta, and gamma chains. The results indicated that LN-411, LN-421, LN-511, and LN-521 are expressed in human aortic valves (n = 3), forming a continuous monolayer in the endothelial BM, whereas sparsely found in the interstitium. Similar results were seen in rat aortic valves (n = 3). Retention of laminin and other BM components, concomitantly with effective removal of cells and residual DNA, was achieved through 3 h exposure to 1% sodium dodecyl sulfate and 30 min exposure to 1% Triton X-100, followed by nuclease processing in rat aortic valves (n = 3). Our results provide crucial data on the microenvironment of valvular cells relevant for research in both tissue engineering and heart valve biology. We also describe a decellularized rat aortic valve scaffold useful for mechanistic studies on the role of the BM in heart valve regeneration.

The human frontal cortex is asymmetrically involved in motivational and affective processing. Several studies have shown that the left-frontal hemisphere is related to positive and approach-related affect, whereas the right-frontal hemisphere is related to negative and withdrawal-related affect. The present study aimed to investigate whether evolutionarily threatening stimuli modulate asymmetrical frontal activity. We examined hemispheric differences in frontal late positive potentials (f-LPP asymmetry) and frontal alpha power activation (frontal alpha asymmetry, FAA) in response to images depicting snakes, spiders, butterflies, and birds. Results showed that the late component of f-LPP asymmetry, but not FAA, was modulated by the category of stimuli. Specifically, threatening stimuli (snakes and spiders) evoked a relatively large late f-LPP over the right-frontal hemisphere than non-threatening stimuli (birds and butterflies). Moreover, this relatively great right-frontal activity was positively associated with the subjective ratings of fear. Importantly, the subjective ratings of fear were not associated with early brain activity over the occipital or centro-parietal cortices. These results suggest that late f-LPP asymmetry may reflect higher order affective processes, specifically the subjective appraisal of threatening stimuli and the subjective experience of fear, that are independent of the fast and automatic processing of evolutionarily significant and affectively arousing stimuli. 

The hard problem of consciousness is the problem of explaining how and why physical processes give rise to consciousness (Chalmers 1995). Regardless of many attempts to solve the problem, there is still no commonly agreed solution. It is thus very likely that some radically new ideas are required if we are to make any progress. In this paper we turn to quantum theory to find out whether it has anything to offer in our attempts to understand the place of mind and conscious experience in nature. In particular we will be focusing on the ontological interpretation of quantum theory proposed by Bohm and Hiley (1987, 1993), its further development by Hiley (Hiley and Callaghan 2012; Hiley, Dennis and de Gosson 2021), and its philosophical interpretation by Pylkkänen (2007, 2020). The ontological interpretation makes the radical proposal that quantum reality includes a new type of potential energy which contains active information. This proposal, if correct, constitutes a major change in our notion of matter. We are used to having in physics only mechanical concepts, such as position, momentum and force. Our intuition that it is not possible to understand how and why physical processes can give rise to consciousness is partly the result of our assuming that physical processes (including neurophysiological processes) are always mechanical. If, however, we are willing to change our view of physical reality by allowing non-mechanical, organic and holistic concepts such as active information to play a fundamental role, this, we argue, makes it possible to understand the relationship between physical and mental processes in a new way. It might even be a step toward solving the hard problem.

EEG spectral-power density was analyzed in a group of nine highly hypnotizable subjects via ten frontal, central, parietal, and occipital electrodes under four conditions: 1) wake state, 2) neutral hypnosis, 3) hypnotic suggestion for altering perception of tones, and 4) post-hypnosis. Results indicate no theta-power changes between conditions, challenging previous findings that increased theta power is a marker of hypnosis. A decrease in gamma power under hypnotic suggestion and an almost significant decrease under neutral hypnosis were observed, compared to post-hypnosis. Anteroposterior power distribution remained stable over all conditions. The results are discussed and compared to earlier studies, which report heterogenous findings. 

There is a strong anticipated future for human induced pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far, their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g., Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, low-density lipoproteins (LDL), and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker tumor necrosis factor α (TNFα) was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling non-alcoholic steatohepatitis (NASH). Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

As global biodiversity declines, there is an increasing need to create an educated and engaged society. Having people of all ages participate in measuring biodiversity where they live helps to create awareness. Recently, the use of environmental DNA (eDNA) for biodiversity surveys has gained momentum. Here, we explore whether sampling eDNA and sequencing it can be used as a means of rapidly surveying urban biodiversity for educational purposes. We sampled 2 × 1 L of water from each of 15 locations in the city of Trondheim, Norway, including a variety of freshwater, marine, and brackish habitats. DNA was extracted, amplified in triplicate targeting the barcoding fragment of COI gene, and sequenced. The obtained data were analyzed on the novel mBRAVE platform, an online open‐access software and computing resource. The water samples were collected in 2 days by two people, and the laboratory analysis was completed in 5 days by one person. Overall, we detected the presence of 506 BINs identified as belonging to 435 taxa, representing at least 265 putative species. On average, only 5.4% of the taxa were shared among six replicates per site. Based on the observed diversity, three distinct clusters were detected and related to the geographic distribution of sites. There were some taxa shared between the habitats, with a substantial presence of terrestrial biota. Here we propose a new form of BioBlitz, where with noninvasive sampling effort combined with swift processing and straightforward online analyses, hundreds of species can be detected. Thus, using eDNA analysis of water is useful for rapid biodiversity surveys and valuable for educational purposes. We show that rapid eDNA surveys, combined with openly available services and software, can be used as an educational tool to raise awareness about the importance of biodiversity.

This study reports the discovery and evaluation of nanoparticle aided sensitive assays for glycovariants of MUC16 and MUC1 in a unique collection of paired ovarian cyst fluids and serum samples obtained at or prior to surgery for ovarian carcinoma suspicion. Selected glycovariants and the immunoassays for CA125, CA15-3 and HE4 were compared and validated in 347 cyst fluid and serum samples. Whereas CA125 and CA15-3 performed poorly in cyst fluid to separate carcinoma and controls, four glycovariants including MUC16^MGL , MUC16^STn , MUC1^STn and MUC1^Tn provided highly improved separations. In serum, the two STn glycovariants outperformed conventional CA125, CA15-3 and HE4 assays in all sub-categories analysed with main benefits obtained at high specificities and at postmenopausal and early-stage disease. Serum MUC16^STn performed best at high specificity (90-99%), but sensitivity was also improved by the other glycovariants and CA15-3. The highly improved specificity, excellent analytical sensitivity, and robustness of the nanoparticle assisted glycovariant assays carry great promise for improved identification and early detection of ovarian carcinoma in routine differential diagnostics. This article is protected by copyright. All rights reserved.