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Johansson, P.

Publications and source records attributed to Johansson, P..

13 recordsLinked to original sources

Bayesian modeling of longitudinal metatranscriptomes of broiler meat spoilage microbiomes shows shared predictive signature associated with spoilage at refrigerated temperatures

Microbial spoilage of packaged meat is driven by complex microbial succession and related metabolic activity, yet conventional shelf-life assessment is mainly based on shelf-life studies relying on culturing and sensory analysis. In routine quality assurance, results are obtained retrospectively, and they are only indirectly linked to the metabolic activity related to sensory deterioration. Functional, time informative approaches that capture the active metabolic state of the spoilage microbiome and predict the rate of spoilage are lacking. We developed a censoring-aware Gaussian process (CAGP) framework to model longitudinal pathway expression profiles from broiler meat metatranscriptomes collected over consecutive storage days at 4 or 6{degrees}C. Samples were annotated using odor-based sensory scores defining fresh, early-spoilage, and late-spoilage phases. Because observed zeros in pathway-level data may reflect non-detection rather than true absence, the model treats low values as left-censored observations below a soft detection threshold while estimating smooth temporal trajectories with uncertainty. In leave-one-out prediction within the 4{degrees}C time-series, predicted sampling days differed from the true days by an average of 0.43 days, and predicted spoilage phases agreed with the sensory classification. Trajectories learned at 4{degrees}C also transferred to an independent 6{degrees}C time-series at the spoilage-phase level, suggesting that shared functional spoilage programs are preserved despite temperature-dependent changes in spoilage rate. Cross-entropy ranking further identified pathway modules carrying time- and phase-informative signals across temperatures. Overall, this framework provides a probabilistic approach for linking metatranscriptomic functional dynamics to sensory spoilage progression, supporting shelf-life assessment beyond retrospective microbial enumeration. IMPORTANCEShelf-life evaluation of meat products still relies heavily on microbial counts, targeted detection of spoilage organisms, and sensory panels. However, microbial abundance and species-level composition do not always predict when a product becomes unacceptable, because spoilage depends on the active metabolic state of the microbiome and can vary between strains, production lots, and storage conditions. This study shows that longitudinal metatranscriptomics, combined with censoring-aware Bayesian time-series modeling, can recover functional pathway trajectories aligned with sensory spoilage progression. By identifying pathway-level signatures that transfer across refrigeration temperatures, the approach moves shelf-life assessment from retrospective enumeration toward predictive, function-based monitoring. In this study, a spoilage signature refers to a set of microbial pathway trajectories whose expression patterns are informative of storage time and sensory spoilage phase. These signatures could support future tools for earlier spoilage detection, better shelf-life estimation, and improved control of product quality in meat production.

bioinformatics↗

Longitudinal RNA Seq analyses reveal the prominent role of Vagococcus in broiler meat spoilage microbiome

BackgroundRaw broiler meat products are highly perishable, and microbial activity is the main factor limiting their shelf lives. The spoilage microbiomes of broiler meat products have been studied mainly using traditional culturing methods and 16S rRNA gene amplicon sequencing, neither of which can show the activity of whole microbiome. Previous metatranscriptomic research of broiler spoilage has also remained limited to specific spoilage organisms rather than entire microbiomes. ResultsOur longitudinal study of broiler meat spoilage discovered the successions of active bacterial microbiomes and metabolic pathway activities of spoilers at 4{degrees}C and 6{degrees}C. Samples taken daily were subjected to metatranscriptomic analyses in combination with non-targeted metabolomic, traditional microbiology, and sensory analyses until advanced spoilage took place. Carnobacterium divergens, Carnobacterium maltaromaticum and Vagococcus proximus were the most active species at both temperatures. Carnobacteria are known poultry spoilers whereas Vagococcus proximus, a species recently described, played an unexpected active role in the microbiome. It became dominant in samples stored at 6{degrees}C and its activity increased also at 4{degrees}C after the use-by date. Central carbohydrate metabolism was the most common KEGG orthology pathway module of the microbiome at both temperatures. C. divergens and C. maltaromaticum showed stable metabolic profiles during the spoilage process, whereas V. proximus displayed a shift from high ATP synthesis activity to increased fatty acid and carbohydrate metabolism when spoilage advanced in samples stored at 4{degrees}C. Non-targeted metabolomics showed similar metabolomic trends across both temperatures. At 6{degrees}C, time-dependent changes were generally more pronounced, and the spoilage markers tyramine and spermidine showed greater accumulation. ConclusionsAs expected, the rate of spoilage is higher at 6 than 4{degrees}C, however we did not anticipate a similar overall trajectory of the spoilage processes. Our results link V. proximus as a key active spoiler in broiler meat and demonstrate the efficacy of using RNA-seq together with metabolomics to decode the function of a meat spoilage microbiome. This demonstrates that spoilage microbiomes consist of active species we have been neglecting due to the technological limitations of the standard methods. Future studies targeting to the metabolism and detecting of Vagococcus are warranted.

microbiology↗

Multiphasic myelination and dendritic growth modulate qMRI signals in human visual cortex.

How does myelin develop in human visual cortex? By combining immunohistochemistry with in vivo and postmortem magnetic resonance imaging of longitudinal relaxation rate (R1), which increases with myelin content, we find that myelin and R1 increase across development but follow distinct trajectories. Immunohistochemistry reveals two phases of myelination: an infant phase of limited oligodendrogenesis, with myelin restricted to deep cortical layers, followed by widespread myelination across all layers during childhood. Cortical R1 also increases across development and correlates with myelin by childhood. However, in infancy, R1 increases outpace myelin growth and instead tracks dendritic arborization, indicating that the microstructural drivers of R1 change across development. We hypothesize that deep layer myelination in infancy contributes to early visual function whereas later myelination of superficial layers enables prolonged cortical plasticity and learning of complex visual behaviors.

neuroscience↗

Macrophage ferroptosis inhibits Aspergillus conidial killing in lung transplantation

Immune suppression heightens the risk for fungal infections, but the mechanisms that result in clinical disease are poorly understood. Here we demonstrate that macrophage ferroptosis, an iron-dependent form of regulated cell death, inhibits Aspergillus fumigatus (Af) killing. In a mouse tracheal transplant model of Af infection, we observed an increase in macrophage lipid peroxidation, a decreased expression of negative ferroptosis regulators Gpx4 and Slc7a11, and an increase in positive regulators Ptgs2 and Nox2, relative to syntransplants. Depletion of macrophages in transplant recipients decreased Af invasion. In vitro, iron overload reduced macrophage viability and decreased their capability to kill Af spores, through a decrease in lysosomal acidification and lysosomal loss. Treatment with ferrostatin-1, a ferroptosis inhibitor, and deferasirox (an iron chelator) restored Af killing. Ferroptotic alveolar macrophages isolated from lung transplant patients also showed a decreased ability to kill Af spores and the patients bronchoalveolar lavage was characterized by higher iron levels and markers of ferroptotic stress compared to non-lung transplants. These characteristics were strongly correlated with a clinical history of fungal infections, independent of immune suppressive medications. Our findings indicate that macrophage ferroptosis augments the risk of invasive aspergillosis, representing a novel mechanism for host immune dysfunction. Graphical AbstractSchematic of proposed mechanism underlying ferroptosis induced immune dysregulation and increased Af invasion in lung transplantation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/643092v1_ufig1.gif" ALT="Figure 1"> View larger version (104K): org.highwire.dtl.DTLVardef@1112102org.highwire.dtl.DTLVardef@18e2ec1org.highwire.dtl.DTLVardef@19f9c5forg.highwire.dtl.DTLVardef@1d325e8_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Assessing Forearm Exertion in Manual Tasks with Surface EMG: A Comparative Analysis of Through-Forearm vs. Muscle Specific EMG Placements

BackgroundHand-intensive work is associated with musculoskeletal disorders (MSDs) such as carpal tunnel syndrome, tendinitis, and nerve entrapment. Estimating internal load on tissues like tendons and muscles in the hand and forearm is essential but challenging. Consequently, external force or self-reported exertion are often used as proxies for internal load assessment. Surface electromyography (sEMG) provides a promising method for continuous and objective monitoring of force. Through-forearm sEMG - placing one electrode on the flexors and one on the extensors - has been suggested as a pragmatic approach for capturing physical load under different wrist and forearm postures. However, further validation is needed to determine its accuracy in predicting exertion and force across diverse tasks, as well as to understand what specific aspects of muscle activity it captures. This study aimed to compare through-forearm sEMG with two common muscle-specific placements, i.e., the forearm extensor and flexor, in estimating force and perceived exertion during hand-intensive tasks and to explore the correlations of sEMG signals between these three sEMG placements. MethodsSixteen participants performed four simulated tasks, i.e. gripping, thumb-pressing, screwing, and key-pinching, at five exertion levels following a modified OMNI-Resistance Exercise Scale (OMNI-RES). The sEMG signals from the through-forearm, extensor, and flexor placements were recorded alongside exerted force. Polynomial mixed-effects models were used to estimate self-rated exertion and exerted force from muscle activity. Pearson correlation and linear mixed-effects models were used to explore correlations of sEMG signals between these three sEMG placements. ResultsAll sEMG placements predicted self-rated exertion and exerted force with strong model fit (R2 > 0.95 in most tasks) and high precision (residual SD < 1 for self-rated exertion, and < 5% for force in most tasks). However, moderate inter-subject and inter-task variability was observed. Through-forearm sEMG consistently outperformed both extensor and flexor placements across tasks by a small margin. The sEMG signals obtained from the three sEMG placements were highly correlated, and through-forearm sEMG could be expressed as a linear combination of extensor and flexor signals. DiscussionThe findings suggest that exertion estimation with a single-channel sEMG is feasible, although individual calibrations and additional task-specific information may be necessary for real-world applications. Through-forearm sEMG placement marginally outperformed extensor and flexor placements, which could be due to its integration of muscle activities from both muscle groups. ConclusionThe through-forearm sEMG placement provides slightly better performance estimating exertion than muscle-specific placements in the assessed manual tasks, possibly due to its integration of information from multiple muscles. Further research is needed to explore methods for individual calibration and ways to obtain task-specific information to enhance applicability in broader real-world settings.

bioengineering↗

Survivin in synergy with BAF/SWI complex binds bivalent chromatin regions and activates DNA damage response in CD4+ T cells

This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3). Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on cis-regulatory elements of genes which execute DNA damage control in primary human CD4+ cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFN{gamma}-stimulated CD4+ cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFN{gamma} in CD4+ cells of patients with rheumatoid arthritis identified arthritogenic BRG1hi cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile. Together, this study demonstrates the function of BvCR in DNA damage control of CD4+ cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity. SummaryThis study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFN{gamma}-stimulated CD4+ T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.

immunology↗

APOE4/4 is linked to damaging lipid droplets in Alzheimer's microglia

Several genetic risk factors for Alzheimers Disease (AD) implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and AD pathology remains poorly understood. Through single-nucleus RNA-sequencing of AD brain tissue, we have identified a microglial state defined by the expression of the lipid droplet (LD) associated enzyme ACSL1 with ACSL1-positive microglia most abundant in AD patients with the APOE4/4 genotype. In human iPSC-derived microglia (iMG) fibrillar A{beta} (fA{beta}) induces ACSL1 expression, triglyceride synthesis, and LD accumulation in an APOE-dependent manner. Additionally, conditioned media from LD-containing microglia leads to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for AD with microglial LD accumulation and neurotoxic microglial-derived factors, potentially providing novel therapeutic strategies for AD.

neuroscience↗

Chronic lymphocytic leukemia includes a tumor subset resembling memory B cells that develop early and persist

Intratumor heterogeneity (ITH) refers to the coexistence of distinct cancer cell subpopulations within a single tumor, each with unique molecular and functional properties. Understanding the dynamics and evolution of ITH is crucial for predicting tumor progression and the development of therapy resistance. Here, we conducted a comprehensive investigation of ITH in Chronic Lymphocytic Leukemia (CLL) and identified a subpopulation that carried the CLL B-cell receptor rearrangement but contrasted from the CLL main population by low CD5 and high CD20 expression and highly mutated Ig-genes. This CLL-related memory B-cell population shared somatic driver mutations with the main CLL population but also exhibited exclusive somatic mutations. Phylogenetic analysis suggested a pathogenically early generation of these CLL-related B cells before monoclonal B lymphocytosis or CLL manifestation. Our data indicated that CLL-related B cells have self-replenishing potential, as they diminish upon treatment but recover indistinguishably on relapse. This contrasts with the main CLL population, which mostly represents a selective and novel expansion of the CLL-related B cells. This differentiation capacity into conventional CLL cells, and the expression of leukemic stem cell signatures further supported their tumorigenic capacity. We propose that these CLL-related B cells represent a pool of highly diversified, early-stage CLL precursor cells, which persist in the shape of "malignant memory B cells". Longitudinal analyses of these CLL precursor cells suggested that they form a reservoir of malignant, leukemia-originating cells which contribute during disease progression to CLL outgrowth and clonal evolution.

immunology↗

Longitudinal metatranscriptomic analysis of a meat spoilage microbiome detects abundant continued fermentation and environmental stress responses during shelf life and beyond.

Microbial food spoilage is a complex phenomenon associated with the succession of the specific spoilage organisms (SSO) over the course of time. We performed a longitudinal metatranscriptomic study on a modified atmosphere packaged (MAP) beef product to increase understanding of the longitudinal behavior of a spoilage microbiome during shelf life and onward. Based on the annotation of the mRNA reads, we recognized three stages related to the active microbiome that were descriptive for the sensory quality of the beef: acceptable product (AP), early spoilage (ES) and late spoilage (LS). Both the 16S RNA taxonomic assignments from the total RNA and functional annotations of the active genes showed that these stages were significantly different from each other. However, the functional gene annotations showed more pronounced difference than the taxonomy assignments. Psychrotrophic lactic acid bacteria (LAB) formed the core of the SSO according to the transcribed reads. Leuconostoc species were the most abundant active LAB throughout the study period, whereas the activity of Streptococcaceae (mainly Lactococcus) increased after the product was spoiled. In the beginning of the experiment, the community managed environmental stress by cold-shock responses which were followed by the expression of the genes involved in managing oxidative stress. Glycolysis, pentose phosphate pathway and pyruvate metabolism were active throughout the study at a relatively stable level. However, the proportional activity of the enzymes in these pathways changed over time. For example, acetate kinase activity was characteristic for the AP stage whereas formate C-acetyltransferase transcription was associated with spoilage. ImportanceIt is generally known which organisms are the typical SSO in foods, whereas the actively transcribed genes and pathways during microbial succession are poorly understood. This knowledge is important since better approaches to food quality evaluation and shelf life determination are needed. Thus, we conducted this study to find longitudinal markers that are connected to quality deterioration. These kind of RNA markers could be used to develop novel type of rapid quality analysis tools in the future. New tools are needed since even though SSO can be detected and their concentrations determined using the current microbiological methods, results from these analyses cannot predict how close timewise a spoilage community is from production of clear sensory defects. Main reason for this is that the species composition of a spoilage community does not change dramatically during late shelf life, whereas the ongoing metabolic activities lead to the development of notable sensory deterioration.

microbiology↗

Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics

The human infant B cell system is considered premature or impaired. Here we show that most cord blood B cells are mature and functional as seen in adults, albeit with distinct transcriptional programs providing accelerated responsiveness to T cell-independent and T cell-dependent stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into antibody-secreting cells, thereby presumably limiting memory B cell formation. The neonatal Ig-repertoire is highly variable, but conserved, showing recurrent B cell receptor (BCR) clonotypes frequently shared between neonates. Our study demonstrates that cord blood B cells are not impaired but differ from their adult counterpart in a conserved BCR repertoire and rapid but transient response dynamics. These properties may account for the sensitivity of neonates to infections and limited effectivity of vaccination strategies. Humanized mice suggest that the distinctness of cord blood versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice. Still, our findings reveal overall limited comparability of human cord blood B cells and murine B-1 cells. Significance StatementNeonates and infants suffer from enhanced susceptibility to infections. Our study contrasts with the current concept of a premature or impaired B cell system in neonates, by showing that most cord blood B cells are mature and functional. However, their responses are rapid but provide only short-term protection, which may help to improve infant vaccination strategies. We propose an altered perspective on the early human B cell system, which looks similar to but functions differently from the adult counterpart. Finally, our analysis indicates that cord blood- and adult B cell development occur layered as in mice, but certain mouse models still may offer a limited view on human neonatal B cell immunity.

immunology↗

Monotherapy efficacy of BBB-permeable small molecule activators of PP2A in glioblastoma

Glioblastoma (GB) is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumor suppressors has not been thoroughly studied as yet as a GB therapeutic strategy. Tumor suppressor Protein Phosphatase 2A (PP2A), is inhibited by non-genetic mechanisms in GB, and thus it would be potentially amendable for therapeutic reactivation. Here we demonstrate, that small molecule activators of PP2A (SMAPs), NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood-brain barrier (BBB), and in vivo partition to mouse brain tissue after oral dosing. In vitro, SMAPs exhibit robust cell killing activity against five established GB cell lines, and nine patient-derived primary glioma cell lines. Collectively these cell lines have heterogenous genetic background, kinase inhibitor resistance profile, and stemness properties; and they represent different clinical GB subtypes. Oral dosing of either of the SMAPs significantly reduced growth of infiltrative intracranial GB tumors. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested GB cell lines, also significantly increased survival of mice bearing orthotopic GB xenografts. In summary, this report presents a proof-of-principle data for BBB-permeable tumor suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background.

cancer biology↗

Ecological speciation in European whitefish is driven by a large-gaped predator

Lake-dwelling fish that form species pairs/flocks characterized by body size divergence are important model systems for speciation research. While several sources of divergent selection have been identified in these systems, their importance for driving the speciation process remains elusive. A major problem is that in retrospect, we cannot distinguish selection pressures that initiated divergence from those acting later in the process. To address this issue, we reconstructed the initial stages of speciation in European whitefish (Coregonus lavaretus) using data from 357 populations of varying age (26-10 000 years). We find that whitefish speciation is driven by a large-growing predator, the northern pike (Esox lucius). Pike initiates divergence by causing a largely plastic differentiation into benthic giants and pelagic dwarfs; ecotypes that will subsequently develop partial reproductive isolation and heritable differences in gill raker number. Using an eco-evolutionary model, we demonstrate how pikes habitat specificity and large gape size are critical for imposing a between-habitat trade-off, causing prey to mature in a safer place or at a safer size. Thereby, we propose a novel mechanism for how predators may cause dwarf/giant speciation in lake-dwelling fish species.

evolutionary biology↗

Influence of Vocal Feedback on Emotions Provides Causal Evidence for the Self-Perception Theory

Emotional reactions are usually accompanied by vocalizations whose acoustic features are largely impacted by the physiological state of the body. While many theoretical frameworks emphasize the role played by the perception of bodily changes in the emergence of emotional feelings, few attempts have been made to assess the impact of vocal self-perception in this process. Here, we address this question by asking participants to deliberate out loud about how they would feel in various imaginary situations while we covertly manipulate their voices in order to make them sound emotional. Perceiving these artificial expressive cues in their own voice altered participants inferences about how they would feel. Crucially, this effect of vocal self-perception on felt emotions was abolished when participants detected our manipulation either explicitly or implicitly. Beyond demonstrating that vocal self-perception plays a role in the emergence of emotions, these results provide causal evidence for self-perception theories.

neuroscience↗