Marine sediments around volcanic islands contain an archive of volcaniclastic deposits, which can be used to reconstruct the volcanic history of an area. Such records hold many advantages over often ...incomplete terrestrial data sets. This includes the potential for precise and continuous dating of intervening sediment packages, which allow a correlatable and temporally constrained stratigraphic framework to be constructed across multiple marine sediment cores. Here we discuss a marine record of eruptive and mass‐wasting events spanning ∼250 ka offshore of Montserrat, using new data from IODP Expedition 340, as well as previously collected cores. By using a combination of high‐resolution oxygen isotope stratigraphy, AMS radiocarbon dating, biostratigraphy of foraminifera and calcareous nannofossils, and clast componentry, we identify five major events at Soufriere Hills volcano since 250 ka. Lateral correlations of these events across sediment cores collected offshore of the south and south west of Montserrat have improved our understanding of the timing, extent and associations between events in this area. Correlations reveal that powerful and potentially erosive density‐currents traveled at least 33 km offshore and demonstrate that marine deposits, produced by eruption‐fed and mass‐wasting events on volcanic islands, are heterogeneous in their spatial distribution. Thus, multiple drilling/coring sites are needed to reconstruct the full chronostratigraphy of volcanic islands. This multidisciplinary study will be vital to interpreting the chaotic records of submarine landslides at other sites drilled during Expedition 340 and provides a framework that can be applied to the stratigraphic analysis of sediments surrounding other volcanic islands.
Key Points
Biostratigraphy, isotope geochemistry, and clast componentry of IODP Site U1396
Deposits are correlated across sites to the south and south west of Montserrat
Results highlight the spatial heterogeneity of deposits around volcanic islands
Abstract Measurement of heart rate variability (HRV) is a non-invasive technique that can be used to investigate the functioning of the autonomic nervous system, especially the balance between ...sympathetic and vagal activity. It has been proven to be very useful in humans for both research and clinical studies concerned with cardiovascular diseases, diabetic autonomic dysfunction, hypertension and psychiatric and psychological disorders. Over the past decade, HRV has been used increasingly in animal research to analyse changes in sympathovagal balance related to diseases, psychological and environmental stressors or individual characteristics such as temperament and coping strategies. This paper discusses current and past HRV research in farm animals. First, it describes how cardiac activity is regulated and the relationships between HRV, sympathovagal balance and stress and animal welfare. Then it proceeds to outline the types of equipment and methodological approaches that have been adapted and developed to measure inter-beats intervals (IBI) and estimate HRV in farm animals. Finally, it discusses experiments and conclusions derived from the measurement of HRV in pigs, cattle, horses, sheep, goats and poultry. Emphasis has been placed on deriving recommendations for future research investigating HRV, including approaches for measuring and analysing IBI data. Data from earlier research demonstrate that HRV is a promising approach for evaluating stress and emotional states in animals. It has the potential to contribute much to our understanding and assessment of the underlying neurophysiological processes of stress responses and different welfare states in farm animals.
•Consistent neuroanatomical correlates of repetitive negative thinking (RNT) were not found.•RNT was commonly related to grey matter volume in prefrontal and cingulate regions.•RNT was associated ...with altered superior longitudinal fasiculus microstructure.•Longitudinal research with older adults, using structural connectivity is needed.
Repetitive negative thinking (RNT) is a cognitive process characterised by intrusive, repetitive, and difficult-to-disengage-from negative thoughts. Heightened RNT levels are prevalent across clinical disorders and have been associated with ill-health (e.g. cardiovascular disease), even at lower, non-clinical levels. Identifying the neuroanatomical correlates of RNT could help characterise structural alterations that transcend diagnostic boundaries and further understanding of the pathogenesis of clinical disorders. We therefore conducted a systematic review to investigate associations between RNT and brain morphology. Following title/abstract and full-text screening, 24 studies were included. We found evidence that RNT severity is associated with grey and white matter volumes/microstructure, particularly in the dorsolateral prefrontal cortex, anterior cingulate cortex and superior longitudinal fasciculus, regions heavily implicated in cognitive control, and emotional processing and regulation. However, inconsistent associations, potentially due to the heterogeneity of included studies (e.g. methodological differences, type of RNT assessed), preclude specific conclusions being reached regarding any one region's association with RNT. Further, given the defuse nature of thoughts, it may be that RNT is associated with distributed brain regions operating within large-scale networks, rather than with a single structure. High quality longitudinal studies, investigating structural networks, are required to confirm the neuroanatomical basis of RNT and elucidate the direction of relationships.
Mutations in the polycystins cause autosomal dominant polycystic kidney disease (ADPKD). Here we show that transmembrane protein 33 (TMEM33) interacts with the ion channel polycystin-2 (PC2) at the ...endoplasmic reticulum (ER) membrane, enhancing its opening over the whole physiological calcium range in ER liposomes fused to planar bilayers. Consequently, TMEM33 reduces intracellular calcium content in a PC2-dependent manner, impairs lysosomal calcium refilling, causes cathepsins translocation, inhibition of autophagic flux upon ER stress, as well as sensitization to apoptosis. Invalidation of TMEM33 in the mouse exerts a potent protection against renal ER stress. By contrast, TMEM33 does not influence pkd2-dependent renal cystogenesis in the zebrafish. Together, our results identify a key role for TMEM33 in the regulation of intracellular calcium homeostasis of renal proximal convoluted tubule cells and establish a causal link between TMEM33 and acute kidney injury.
We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in unimmunized infected (group 1), immunised and boosted (group 2) and infected immunised and boosted (group ...3) adult individuals. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.
Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated.
Forty allo-HCT recipients were included in a ...study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses.
Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4
T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01).
Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination.
The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in ...healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18-45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01
, AS01
, AS03, AS04, or Alum/Al(OH)
at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4
T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1-3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01
group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01
, AS01
, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01
≥ AS01
> AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway.
In order to evaluate the environmental impacts associated with the presence of low-level of pharmaceuticals in waters, chronic ecotoxicity of carbamazepine (CBZ), oxcarbazepine (OxCBZ) and acridine ...9-carboxylic acid (9-CAA) and their mixture was investigated using two species from different trophic levels. Innovative approaches were developed by monitoring: (i) phytometabolites in the duckweed Lemna minor L. and, (ii) alterations at the population, cellular and molecular levels on the cnidarian Hydra circumcincta Schulze 1914, to assess the effects of 14-day chronic exposure. On H. circumcincta, the approach was conducted at 19.5 °C, the optimal growth temperature, and at 23 °C, to simulate global warming impact.
In L. minor, results showed alterations of the nitrogen balance and the chlorophyll indices for OxCBZ and 9-CAA separately at environmental concentrations and for the mixture of the three studied products. However, phenolic compound index deeply varied depending on pharmaceuticals and time of exposure with no specific trend. In H. circumcincta, effects on morphology, reproduction and lipid peroxidation were observed at low level of CBZ. OxCBZ impacted the total antioxidant capacity of H. circumcincta, whereas exposure to 9-CAA affected all parameters, except the reproduction rate. Finally, 14-day exposure to the mixture of the three products also slowed the reproduction rate and altered the morphology of this cnidarian. Higher damages were detected when experiments were conducted at a temperature 3.5 °C above the optimum for Hydra growth, suggesting the relevance of taking into account possible ecotoxicological consequences of global warming. Our results confirmed the necessity of selecting sensitive organisms at different trophic levels to better assess ecotoxicity of pharmaceuticals and their mixture, especially at environmental levels and facing global changes.
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•Exposure to OxCBZ, 9-CAA and the mixture increased the N/C ratio in Lemna minor.•Hydra sets up defense mechanisms to limit lipid peroxidation caused by OxCBZ.•Hydra budding and reproductive rates were slow down by CBZ, OxCBZ and the mixture.•Temperature rising increased pharmaceutical damages on Hydra circumcinct.
Gene duplication is a driver of the evolution of new functions. The duplication of genes encoding homomeric proteins leads to the formation of homomers and heteromers of paralogs, creating new ...complexes after a single duplication event. The loss of these heteromers may be required for the two paralogs to evolve independent functions. Using yeast as a model, we find that heteromerization is frequent among duplicated homomers and correlates with functional similarity between paralogs. Using
evolution, we show that for homomers and heteromers sharing binding interfaces, mutations in one paralog can have structural pleiotropic effects on both interactions, resulting in highly correlated responses of the complexes to selection. Therefore, heteromerization could be preserved indirectly due to selection for the maintenance of homomers, thus slowing down functional divergence between paralogs. We suggest that paralogs can overcome the obstacle of structural pleiotropy by regulatory evolution at the transcriptional and post-translational levels.
Background
Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in ...lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.
Methods
Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels – Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC).
Results
21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS).
Discussion
Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.
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