Innate immune response after BNT162b2 COVID-19 vaccination associates with reactogenicity.

Background: The innate immune response is important for the development of the specific adaptive immunity, however it may also be associated with reactogenicity after vaccination. We explore the association between innate responsiveness, reactogenicity, and antibody response after first COVID-19 vaccination.

Methods: We included 146 healthy Dutch individuals aged 12-59 who received their first BNT162b2 (Comirnaty, Pfizer) COVID-19 vaccination.

A Reference Tissue Implementation of Simultaneous Multifactor Bayesian Analysis (SiMBA) of PET Time Activity Curve Data.

PET analysis is conventionally performed as a two-stage process of quantification followed by analysis. We recently introduced SiMBA (Simultaneous Multifactor Bayesian Analysis), a hierarchical model that performs quantification and analysis for all brain regions of all individuals at once, and in so doing improves both the accuracy of parameter estimation as well as inferential efficiency. However until now, SiMBA has only been implemented for the two-tissue compartment model.

Early immune profiling reveals distinct inflammatory responses between children and adults few days after primary SARS-CoV-2 infection.

Background: To date, it is still not clear why during the COVID-19 pandemic children generally developed no or milder symptoms compared to adults. As innate immune responses are crucial in the early defense against pathogens, we aimed at profiling these responses from both adults and children with a primary SARS-CoV-2 infection.

Methods: In the first months of the pandemic, PBMCs and serum were collected from peripheral blood of adults and children at different time points after testing SARS-CoV-2 PCR positive (PCR+).

Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions.

Hematopoietic stem cells (HSCs) react to various stress conditions. However, it is unclear whether and how HSCs respond to severe anemia. Here, we demonstrate that upon induction of acute anemia, HSCs rapidly proliferate and enhance their erythroid differentiation potential.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Background: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively.

A Novel Transgenic Model to Study Thyroid Axis Activity in Early Life Stage Medaka.

Identifying endocrine disrupting chemicals in order to limit their usage is a priority and required according to the European Regulation. There are no Organization for Economic Co-operation and Development (OECD) test guidelines based on fish available for the detection of Thyroid axis Active Chemicals (TACs). This study aimed to fill this gap by developing an assay at eleuthero-embryonic life stages in a novel medaka () transgenic line.

Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation.

Introduction: A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes.

Functional and molecular profiling of hematopoietic stem cells during regeneration.

Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis.

CD4 T cell-mediated recognition of a conserved cholesterol-dependent cytolysin epitope generates broad antibacterial immunity.

CD4 T cell-mediated immunity against Streptococcus pneumoniae (pneumococcus) can protect against recurrent bacterial colonization and invasive pneumococcal diseases (IPDs). Although such immune responses are common, the pertinent antigens have remained elusive. We identified an immunodominant CD4 T cell epitope derived from pneumolysin (Ply), a member of the bacterial cholesterol-dependent cytolysins (CDCs).

Choosing the source of healthy controls for studies on myeloid malignancies: all bone marrow cells are created equal, but some are more equal than others.

Bone marrow samples from discarded femoral heads are often used as healthy controls in studies investigating the in vitro characteristics of cells from patients with hematologic malignancies. Since patient samples are usually derived from iliac crest aspirates, this carries the risk that the properties of the cells from both sources might be different due to the site and method of harvesting. Comparing BM cells from iliac crest aspirates and femoral heads from age-matched healthy donors, we show that, while mesenchymal stromal cells have indistinguishable properties between both sources, hematopoietic stem and progenitor cells (HSPC) from femoral heads show a considerable proliferative advantage in vitro.

Compartment-specific mutational landscape of clonal hematopoiesis.

Clonal hematopoiesis (CH) is characterized by somatic mutations in blood cells of individuals without hematologic disease. While the mutational landscape of CH in peripheral blood (PB) has been well characterized, detailed analyses addressing its spatial and cellular distribution in the bone marrow (BM) compartment are sparse. We studied CH driver mutations in healthy individuals (n = 261) across different anatomical and cellular compartments.

Diminished Pneumococcal-Specific CD4 T-Cell Response is Associated With Increased Regulatory T Cells at Older Age.

Respiratory infection caused by is a leading cause of morbidity and mortality in older adults. Acquired CD4 T cell mechanism are essential for the protection against colonization and subsequent development of infections by . In this study, we hypothesized that age-related changes within the CD4 T-cell population compromise CD4 T-cell specific responses to , thereby contributing to increased susceptibility at older age.

Gesture is the primary modality for language creation.

How language began is one of the oldest questions in science, but theories remain speculative due to a lack of direct evidence. Here, we report two experiments that generate empirical evidence to inform gesture-first and vocal-first theories of language origin; in each, we tested modern humans' ability to communicate a range of meanings (995 distinct words) using either gesture or non-linguistic vocalization. Experiment 1 is a cross-cultural study, with signal Producers sampled from Australia ( = 30, = 32.

Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis.

The nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated patients respond and of these almost all eventually relapse. New treatment options are urgently needed to improve the clinical management of these patients.

A positron emission tomography study of the serotonin1B receptor effect of electroconvulsive therapy for severe major depressive episodes.

Background: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders, although its molecular mechanism of action is unknown. The serotonin 1B (5-HT) receptor is a potential target for treatment of depression and low 5-HT receptor binding in limbic regions has been reported in previous positron emission tomography (PET) studies of depression.

Methods: The objective of this longitudinal PET study was to examine the effect of ECT for depression on 5-HT receptor binding.

CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease.

Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA).

Sexual Dimorphism in Hepatocyte Xenograft Models.

Humanized liver mouse models are crucial tools in liver research, specifically in the fields of liver cell biology, viral hepatitis and drug metabolism. The livers of these humanized mouse models are repopulated by 3-dimensional islands of fully functional primary human hepatocytes (PHH), which are notoriously difficult to maintain in vitro. As low efficiency and high cost hamper widespread use, optimization is of great importance.

Induction of blood-circulating bile acids supports recovery from myelosuppressive chemotherapy.

Chemotherapeutic agents can reduce bone marrow (BM) activity, causing myelosuppression, a common life-threatening complication of cancer treatment. It is challenging to predict the patients in whom prolonged myelosuppression will occur, resulting in a delay or discontinuation of the treatment protocol. An early indicator of recovery from myelosuppression would thus be highly beneficial in clinical settings.

Vaccines to Protect Older Adults against Pneumococcal Disease.

Determining the optimal vaccination strategy for the protection of the elderly population against pneumococcal disease remains a challenge. Older adults are, second to young infants, most susceptible to become colonized and invaded by Streptococcus pneumoniae, causing serious disease such as bacteremic pneumonia, sepsis, and meningitis. In an era with increasing antimicrobial resistance and the growing susceptible population of aged adults, S.

Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo.

Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained.

Junctional Adhesion Molecule 2 Represents a Subset of Hematopoietic Stem Cells with Enhanced Potential for T Lymphopoiesis.

The distinct lineage potential is a key feature of hematopoietic stem cell (HSC) heterogeneity, but a subset of HSCs specialized for a single lymphoid compartment has not been identified. Here we report that HSCs expressing junctional adhesion molecule 2 (Jam2) at a higher level (Jam2 HSCs) have a greater T cell reconstitution capacity. Jam2 HSCs are metabolically dormant but preferentially differentiate toward lymphocytes, especially T cell lineages.

Response kinetics reveal novel features of ageing in murine T cells.

The impact of ageing on the immune system results in defects in T cell responsiveness. The search for ageing hallmarks has been challenging due to the complex nature of immune responses in which the kinetics of T cell responsiveness have largely been neglected. We aimed to unravel hallmarks of ageing in the kinetics of the murine T cell response.

Single-cell assessment of transcriptome alterations induced by Scriptaid in early differentiated human haematopoietic progenitors during ex vivo expansion.

Priming haematopoietic stem/progenitor cells (HSPCs) in vitro with specific chromatin modifying agents and cytokines under serum-free-conditions significantly enhances engraftable HSC numbers. We extend these studies by culturing human CD133+ HSPCs on nanofibre scaffolds to mimic the niche for 5-days with the HDAC inhibitor Scriptaid and cytokines. Scriptaid increases absolute Lin-CD34+CD38-CD45RA-CD90+CD49f+ HSPC numbers, while concomitantly decreasing the Lin-CD38-CD34+CD45RA-CD90- subset.