Host immune function can contribute to numerous ecological/evolutionary processes. Ecoimmunological studies, however, typically use one/few phenotypic immune assays and thus do not consider the ...complexity of the immune system. Therefore, "omics" resources that allow quantifying immune activity across multiple pathways are needed for ecoimmunological models. We applied short-read based RNAseq (Illumina NextSeq 500, PE-81) to characterise transcriptome profiles of Lymnaea stagnalis (Gastropoda), a multipurpose model snail species. We used a genetically diverse snail stock and exposed individuals to immune elicitors (injury, bacterial/trematode pathogens) and changes in environmental conditions that can alter immune activity (temperature, food availability).
Immune defence factors identified in the de novo assembly covered elements broadly described in other gastropods. For instance, pathogen-recognition receptors (PRR) and lectins activate Toll-like receptor (TLR) pathway and cytokines that regulate cellular and humoral defences. Surprisingly, only modest diversity of antimicrobial peptides and fibrinogen related proteins were detected when compared with other taxa. Additionally, multiple defence factors that may contribute to the phenotypic immune assays used to quantify antibacterial activity and phenoloxidase (PO)/melanisation-type reaction in this species were found. Experimental treatments revealed factors from non-self recognition (lectins) and signalling (TLR pathway, cytokines) to effectors (e.g., antibacterial proteins, PO enzymes) whose transcription depended on immune stimuli and environmental conditions, as well as components of snail physiology/metabolism that may drive these effects. Interestingly, the transcription of many factors (e.g., PRR, lectins, cytokines, PO enzymes, antibacterial proteins) showed high among-individual variation.
Our results indicate several uniform aspects of gastropod immunity, but also apparent differences between L. stagnalis and some previously examined taxa. Interestingly, in addition to immune defence factors that responded to immune elicitors and changes in environmental conditions, many factors showed high among-individual variation across experimental snails. We propose that such factors are highly important to be included in future ecoimmunological studies because they may be the key determinants of differences in parasite resistance among individuals both within and between natural snail populations.
Caveolin plays an essential role in the formation of characteristic surface pits, caveolae, which cover the surface of many animal cells. The fundamental principles of caveola formation are only ...slowly emerging. Here we show that caveolin expression in a prokaryotic host lacking any intracellular membrane system drives the formation of cytoplasmic vesicles containing polymeric caveolin. Vesicle formation is induced by expression of wild-type caveolins, but not caveolin mutants defective in caveola formation in mammalian systems. In addition, cryoelectron tomography shows that the induced membrane domains are equivalent in size and caveolin density to native caveolae and reveals a possible polyhedral arrangement of caveolin oligomers. The caveolin-induced vesicles or heterologous caveolae (h-caveolae) form by budding in from the cytoplasmic membrane, generating a membrane domain with distinct lipid composition. Periplasmic solutes are encapsulated in the budding h-caveola, and purified h-caveolae can be tailored to be targeted to specific cells of interest.
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► A prokaryotic model system for caveolar biogenesis ► Caveolin is sufficient to induce membrane deformation and cincture of vesicle ► Visualization of polyhedral cage provides molecular model for caveola formation ► Engineered heterologous caveolae provide a genetically encoded nanoparticles
Expression of caveolin in bacteria yields caveolae that bud constitutively. The system affords an unprecedented look at the caveolin coat and indicates that budding in animal cells is specifically regulated.
Owing to the low-gravity conditions in space, space-borne laboratories enable experiments with extended free-fall times. Because Bose-Einstein condensates have an extremely low expansion energy, ...space-borne atom interferometers based on Bose-Einstein condensation have the potential to have much greater sensitivity to inertial forces than do similar ground-based interferometers. On 23 January 2017, as part of the sounding-rocket mission MAIUS-1, we created Bose-Einstein condensates in space and conducted 110 experiments central to matter-wave interferometry, including laser cooling and trapping of atoms in the presence of the large accelerations experienced during launch. Here we report on experiments conducted during the six minutes of in-space flight in which we studied the phase transition from a thermal ensemble to a Bose-Einstein condensate and the collective dynamics of the resulting condensate. Our results provide insights into conducting cold-atom experiments in space, such as precision interferometry, and pave the way to miniaturizing cold-atom and photon-based quantum information concepts for satellite-based implementation. In addition, space-borne Bose-Einstein condensation opens up the possibility of quantum gas experiments in low-gravity conditions
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Acceptance and Commitment Therapy for Moral Injury (ACT-MI; 10-11), is an application of Acceptance and Commitment Therapy principles designed to help individuals live their values, even in the ...presence of moral pain. ACT-MI differs from other emerging treatments for moral injury in that ACT-MI is not based on a traditional syndromal approach to conceptualizing moral injury, which treats moral injury as a collection of signs and symptoms to be reduced. Rather than assuming moral injury causes suffering through a constellation of symptoms that a person
, in ACT-MI, moral injury is defined by what a person
in response to moral pain. Consistent with this framework, we present a unique approach to moral injury case conceptualization that emphasizes function over form, providing clients the opportunity to break free from the patterns of behavior that cause moral injury-related suffering to persist. Rooted in approaches to conceptualizing that have demonstrated utility in extant interventions (e.g., ACT), ACT-MI clinicians conduct ongoing functional analyses to inform case conceptualization and intervention. Functional analysis is used to disrupt the processes maintaining moral injury, as the client and therapist work to identify and intervene on the behaviors reinforcing avoidance and control of painful internal experiences causing moral injury. In the current article, we guide the reader through a framework for applying functional analysis to the conceptualization of moral injury where the reinforcers driving moral injury are explored. We also provide examples of questions that can be used to help uncover the functions of moral injury consistent behavior. Case examples based on our experiences treating moral injury are presented to demonstrate how various types of morally injurious events can evoke different features of moral pain which in turn motivate different repertoires of avoidance and control. These inflexible patterns of avoidance and control create suffering by engaging in behavior designed to escape moral pain, such as social isolation, spiritual disconnection, reduced self-care, suicidal ideation, and substance use. We discuss how to target this suffering using functional analysis to guide treatment decisions, matching interventional processes within ACT-MI to the specific functions that moral injury-related behavior is serving for an individual. We suggest that the use of functional analytic case formulation procedures described herein can assist clients in disrupting behavioral patterns maintaining moral injury and thereby free them to pursue lives of greater meaning and purpose.
This paper examines the effects of Acceptance and Commitment Therapy for depression (ACT-D), and the specific effects of experiential acceptance and mindfulness, in reducing suicidal ideation (SI) ...and depression among Veterans.
Patients included 981 Veterans, 76% male, mean age 50.5 years. Depression severity and SI were assessed using the BDI-II. Experiential acceptance and mindfulness were measured with the Acceptance and Action Questionnaire-II (AAQ-II) and the Five Facet Mindfulness Questionnaire, respectively.
Of the 981 patients, 647 (66.0%) completed 10 or more sessions or finished early due to symptom relief. For Veterans with SI at baseline, mean BDI-II score decreased from 33.5 to 22.9. For Veterans with no SI at baseline, mean BDI-II score decreased from 26.3 to 15.9. Mixed models with repeated measurement indicated a significant reduction in depression severity from baseline to final assessment (b = −10.52, p < .001). After adjusting for experiential acceptance and mindfulness, patients with SI at baseline demonstrated significantly greater improvement in depression severity during ACT-D treatment, relative to patients with no SI at baseline (b = −2.81, p = .001). Furthermore, increases in experiential acceptance and mindfulness scores across time were associated with a reduction in depression severity across time (b = −0.44, p < .001 and b = −0.09, p < .001, respectfully), and the attenuating effect of mindfulness on depression severity increased across time (b = −0.05, p = .042). Increases in experiential acceptance scores across time were associated with lower odds of SI across time (odds ratio = 0.97, 95% CI 0.95, 0.99, p = .016) and the attenuating effect of experiential acceptance on SI increased across time (odds ratio = 0.96, 95% CI 0.92, 0.99, p = .023). Overall the number of patients with no SI increased from 44.5% at baseline to 65% at follow-up.
Veterans receiving ACT-D demonstrated decreased depression severity and decreased odds of SI during treatment. Increases in experiential acceptance and mindfulness scores were associated with reduction in depression severity across time and increases in experiential acceptance scores were associated with reductions in SI across time.
•Acceptance and Commitment Therapy impacts suicidal ideation in Veterans.•Veterans with suicidal ideation showed significant decreases in depression.•Increase in mindfulness is associated with a reduction in depression severity.•Increase in experiential acceptance is associated with lower odds of suicidal ideation.
•Infant sleep habits and neurophysiology are associated with their gut microbiome.•This sleep-brain-gut link is important for infant development.•Sleep and gut microbiota are promising targets for ...early interventions.
Sleep disorders have been linked to alterations of gut microbiota composition in adult humans and animal models, but it is unclear how this link develops. With longitudinal assessments in 162 healthy infants, we present a so far unrecognized sleep-brain-gut interrelationship. First, we report a link between sleep habits and gut microbiota: daytime sleep is associated with bacterial diversity, and nighttime sleep fragmentation and variability are linked with bacterial maturity and enterotype. Second, we demonstrate a sleep-brain-gut link: bacterial diversity and enterotype are associated with sleep neurophysiology. Third, we show that the sleep-brain-gut link is relevant in development: sleep habits and bacterial markers predict behavioral-developmental outcomes. Our results demonstrate the dynamic interplay between sleep, gut microbiota, and the maturation of brain and behavior during infancy, which aligns with the newly emerging concept of a sleep-brain-gut axis. Importantly, sleep and gut microbiota represent promising health targets since both can be modified non-invasively. As many adult diseases root in early childhood, leveraging protective factors of adequate sleep and age-appropriate gut microbiota in infancy could constitute a health promoting factor across the entire human lifespan.
Studies suggest adverse health effects following exposure to bioaerosols in the environment and in particular at workplaces. However, there is still a lack of health-related exposure limits based on ...toxicological or epidemiological studies from environmental health or from the working environment. The aim of this study was to derive health-based exposure limits for bioaerosols that can protect the general population as group “at risk” via environmental exposure using analysis of peer-reviewed studies related to occupational medicine, indoor air and environmental health. The derivation of exposure limits should be conducted by the members of a bioaerosol expert panel according to established toxicological criteria. A systematic review was performed in Medline (PubMed) including studies containing both data on exposure measurements and observed health outcomes. In addition, literature recommended by the experts was considered. A comprehensive search strategy was generated and resulted in a total of n=1569 studies in combination with the literature recommendations. Subsequently, abstracts were screened using defined exclusion criteria yielding a final number of n=44 studies. A standardized extraction sheet was used to combine data on health effects and exposure to different bioaerosols. After full-text screening and extraction according to the defined exclusion criteria n=20 studies were selected all related to occupational exposures comprising the working areas wood processing, farming, waste processing and others. These studies were analyzed in collaboration with the bioaerosol expert network in terms of suitability for derivation of health-related exposure limits. The bioaerosol expert network concluded that none of the analyzed studies provided suitable dose–response relationships for derivation of exposure limits. The main reasons were: (1) lack of studies with valid dose–response data; (2) diversity of employed measuring methods for microorganisms and bioaerosol-emitting facilities; (3) heterogeneity of health effects; (4) insufficient exposure assessment. However, several indicator parameters and exposure concentrations could be identified for different bioaerosol-emitting facilities. Nevertheless, health-related exposure limits are urgently needed especially in approval procedures of facilities like composting plants or livestock farms emitting bioaerosols in the neighbourhood of residents. In the regulatory toxicology framework, it is common to use animal experimental studies for derivation of general exposure limits if appropriate environmental epidemiological studies on harmful substances are lacking. This might be another possibility to obtain health-related exposure limits for specific bioaerosol parameters. Furthermore, we recommend to use suitable measurable outcome parameters related to bioaerosols; to measure bioaerosols according to a protocol representative for exposure pattern and duration at the particular work place; to develop standardized detection methods for indicator parameters; to combine different detection methods to compensate for the limitations of each method; to apply new analysis methods to identify the real risk potential.
The adhesion receptor ADGRA3 (GPR125) is a known spermatogonial stem cell marker, but its impact on male reproduction and fertility has not been examined. Using a mouse model lacking Adgra3 ...(Adgra3−/−), we show that 55% of the male mice are infertile from puberty despite having normal spermatogenesis and epididymal sperm count. Instead, male mice lacking Adgra3 exhibited decreased estrogen receptor alpha expression and transient dilation of the epididymis. Combined with an increased estradiol production, this indicates a post‐pubertal hormonal imbalance and fluid retention. Dye injection revealed a blockage between the ejaculatory duct and the urethra, which is rare in mice suffering from infertility, thereby mimicking the etiologies of obstructive azoospermia found in human male infertility. To summarize, male reproductive tract development is dependent on ADGRA3 function that in concert with estrogen signaling may influence fluid handling during sperm maturation and storage.
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative ...disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism. We demonstrated its functionality and revealed species-specific characteristics of the humanized receptor, compared to the murine ortholog, regarding its receptivity to activation and modulation by 2′,3′-O-(benzoyl-4-benzoyl)-adenosine 5′-triphosphate (BzATP) and trifluoperazine (TFP). This humanized
P2rx7
allele is accessible to spatially and temporally controlled Cre recombinase-mediated inactivation. In contrast to previously generated knockout (KO) mice, none of the described
P2rx7
splice variants evade this null allele. By selective disruption and assessment of human
P2RX7
expression in different brain regions and cell types, we were able to demonstrate that the P2X7R is specifically expressed in glutamatergic pyramidal neurons of the hippocampus. Also, P2X7R is expressed in major non-neuronal lineages throughout the brain, i.e., astrocytes, oligodendrocytes, and microglia. In conclusion, this humanized mouse model provides the means for detailed assessment of human P2X7R function in vivo including evaluation of agonists or antagonists. In addition, this conditional allele will enable future loss-of-function studies in conjunction with mouse models for CNS disorders.
Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that ...regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. In this study, we show that epithelial Gpr35 plays a critical role in goblet cell function. In mice, cell-type-specific deletion of Gpr35 in epithelial cells but not in macrophages results in goblet cell depletion and dysbiosis, rendering these animals more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows that the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota.
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