The SARS-CoV-2 antibody-dependent enhancement façade.

Antibody-dependent enhancement (ADE) is an immunological paradox whereby sensitization following a primary viral infection results in the subsequent enhancement of a similar secondary infection. This idiosyncratic immune response has been established in dengue virus infections, driven by four antigenically related serotypes co-circulating in endemic regions. Several coronaviruses exhibit antibody-mediated mechanisms of viral entry, which has led to speculation of an ADE capacity for SARS-CoV-2, though in vivo and epidemiological evidence do not currently support this phenomenon.

Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target.

We examined the effects of ∼30 days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3β content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3β was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3.

JNK signaling during IL-3-mediated differentiation contributes to the c-kit-potentiated allergic inflammatory capacity of mast cells.

Mast cells are leukocytes that mediate various aspects of immunity and drive allergic hypersensitivity pathologies. Mast cells differentiate from hematopoietic progenitor cells in a manner that is largely IL-3 dependent. However, molecular mechanisms, including the signaling pathways that control this process, have yet to be thoroughly investigated.

Childhood household dysfunction is associated with reduced left ventricular mass in young adulthood.

The effect of adverse childhood experiences (ACEs) on left ventricular mass (LVM) and left ventricular function remains largely unknown across the lifespan. This study investigated the influence of ACEs on LVM and left ventricular function and whether inflammation influences this relationship. Two hundred forty-eight healthy young adults participated and a final sample of 217 (age, 22.

Adverse childhood experiences are associated with altered cardiovascular reactivity to head-up tilt in young adults.

Adverse childhood experiences (ACEs) are associated with greater prevalence of cardiovascular disease and altered acute stress reactivity. The current study investigated the effect of ACEs on hemodynamic and autonomic responses to orthostatic stress imposed by 60° head-up tilt (HUT) in young adults. Two-hundred twenty-six healthy young adults (age = 22.

Characterization of sclerostin's response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice.

It is well established that sclerostin antagonizes the anabolic Wnt signalling pathway in bone, however, its physiological role in other tissues remains less clear. This study examined the effect of a high-fat diet (HFD) on sclerostin content and downstream markers of the Wnt signaling pathway (GSK3β and β-catenin) within subcutaneous inguinal white adipose tissue (iWAT), and visceral epididymal WAT (eWAT) depots at rest and in response to acute aerobic exercise. Male C57BL/6 mice ( = 40, 18 weeks of age) underwent 10 weeks of either a low-fat diet (LFD) or HFD.

Acute activation of SERCA with CDN1163 attenuates IgE-mediated mast cell activation through selective impairment of ROS and p38 signaling.

Mast cells are granulocytic immune sentinels present in vascularized tissues that drive chronic inflammatory mechanisms characteristic of allergic pathologies. IgE-mediated mast cell activation leads to a rapid mobilization of Ca from intracellular stores, which is essential for the release of preformed mediators via degranulation and de novo synthesized proinflammatory cytokines and chemokines. Given its potent signaling capacity, the dynamics of Ca localization are highly regulated by various pumps and channels controlling cytosolic Ca concentrations.

Carnosic acid inhibits secretion of allergic inflammatory mediators in IgE-activated mast cells via direct regulation of Syk activation.

Mast cells are essential regulators of inflammation most recognized for their central role in allergic inflammatory disorders. Signaling via the high-affinity immunoglobulin E (IgE) receptor, FcεRI, leads to rapid degranulation of preformed granules and the sustained release of newly synthesized proinflammatory mediators. Our group recently established rosemary extract as a potent regulator of mast cell functions, attenuating MAPK and NF-κB signaling.

Targeting glycogen synthase kinase 3 with CHIR99021 negatively regulates allergen-induced mast cell activation.

Mast cells are granulated immune sentinels responsible for allergic inflammation. Allergen-induced FcεRI-signaling leads to rapid degranulation in the early-phase and sustained production and release of pro-inflammatory mediators in the late phase. Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine kinase and a central molecular convergence point for several pro-inflammatory pathways.

No Mediation Effect of Telomere Length or Mitochondrial DNA Copy Number on the Association Between Adverse Childhood Experiences (ACEs) and Central Arterial Stiffness.

Background Adverse childhood experiences (ACEs) have been linked to increased cardiovascular disease (CVD) risk. Previous reports have suggested that accelerated biological aging-indexed by telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)-may contribute to associations between ACEs and cardiovascular health outcomes. Here, we examine the potential mediating effects of TL and mtDNAcn on the association between ACEs and central arterial stiffness-an intermediate cardiovascular health outcome-as a novel pathway linking ACEs to CVD risk among young adults.

Examining the relationships between adverse childhood experiences (ACEs), cortisol, and inflammation among young adults.

Adverse childhood experiences (ACEs) are associated with dysregulation of inflammation and cortisol. The objectives of this study were to use principal component analysis to explore the inflammatory biomarker data to create inflammation composite variables; to examine the relationship between these composite measures of inflammation with ACEs and cortisol; and to assess whether these relationships were moderated by sex. The analysis included 232 young adults from the Niagara Longitudinal Heart Study (NLHS).

Kynurenine metabolism is altered in mdx mice: a potential muscle to brain connection.

New Findings: What is the central question in this study? Promoting muscle health with regular aerobic exercise can improve mental health through a kynurenine metabolic pathway: do conditions of muscle disease such as muscular dystrophy negatively influence this pathway? What is the main finding and its importance? The DBA/2J mdx model of Duchenne muscular dystrophy exhibits altered kynurenine metabolism with less kynurenic acid and peroxisome proliferator-activated receptor-γ coactivator 1-α and higher levels of tumour necrosis factor α mRNA - results associated with anxiety-like behaviour.

Abstract: Regular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. However, the effect of muscle disease on KYN metabolism has not yet been investigated.

Zika Virus Replication in a Mast Cell Model is Augmented by Dengue Virus Antibody-Dependent Enhancement and Features a Selective Immune Mediator Secretory Profile.

Zika virus and dengue virus are evolutionarily related and structurally similar mosquito-borne . These congruencies can lead to cross-reactive antibody binding, whereby antibodies generated from previous dengue virus immunity can augment Zika virus replication . This phenomenon, termed antibody-dependent enhancement, may participate in the clinical manifestations detected in areas with cocirculations where Zika virus is endemic; however, a causal relationship has yet to be determined.

Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation.

Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.

Postexercise serum from humans influences the biological tug of war of APP processing in human neuronal cells.

Neurodegenerative diseases such as Alzheimer's disease (AD) are becoming more prevalent in our aging society. One specific neuropathological hallmark of this disease is the accumulation of amyloid-β (Aβ) peptides, which aggregate to form extraneuronal plaques. Increased Aβ peptides are often observed well before symptoms of AD develop, highlighting the importance of targeting Aβ-producing pathways early on in disease progression.

Profit versus Quality: The Enigma of Scientific Wellness.

The "best of both worlds" is not often the case when it comes to implementing new health models, particularly in community settings. It is often a struggle between choosing or balancing between two components: depth of research or financial profit. This has become even more apparent with the recent shift to move away from a traditionally reactive model of medicine toward a predictive/preventative one.

Perfectionistic cognitions, Interleukin-6, and C-Reactive protein: A test of the perfectionism diathesis stress model.

Previous research has demonstrated that perfectionism is implicated in poorer health and earlier mortality. However, to our knowledge, research has not yet determined how individual differences in perfectionistic cognitions are related to intermediary health markers such as inflammation. Thus, within the theoretical frameworks of the perfectionism diathesis-stress model (Hewitt and Flett, 1993) and the cognitive theory of perfectionism (Flett et al.

Amplified detection of nucleic acids and proteins using an isothermal proximity CRISPR Cas12a assay.

Herein, we describe an isothermal proximity CRISPR Cas12a assay that harnesses the target-induced indiscrimitive single-stranded DNase activity of Cas12a for the quantitative profiling of gene expression at the mRNA level and detection of proteins with high sensitivity and specificity. The target recognition is achieved through proximity binding rather than recognition by CRISPR RNA (crRNA), which allows for flexible assay design. A binding-induced primer extension reaction is used to generate a predesigned CRISPR-targetable sequence as a barcode for further signal amplification.

Serum MMP-3 and its association with central arterial stiffness among young adults is moderated by smoking and BMI.

Central arterial stiffness is an independent predictor of cardiovascular disease. It is characterized by a marked reduction in the elastin-collagen ratio of the arterial wall extracellular matrix (ECM), and is largely the result of degradation of various ECM components. Matrix metalloproteinase-3 (MMP-3) may contribute to central arterial stiffness via its involvement in ECM homeostasis and remodeling.

Tafazzin Modulates Allergen-Induced Mast Cell Inflammatory Mediator Secretion.

Allergic inflammatory diseases are a steadily growing health concern. Mast cells, a driving force behind allergic pathologies, modulate metabolic pathways to carry out various functions following IgE-FcεRI-mediated activation. Tafazzin (TAZ) is a cardiolipin transacylase that functions to remodel, and thereby mature, cardiolipin, which is important for efficient energy production through oxidative phosphorylation.

Linking the hemodynamic consequences of adverse childhood experiences to an altered HPA axis and acute stress response.

Adverse childhood experiences (ACEs), such as maltreatment and severe household dysfunction, represent a significant threat to public health as ACEs are associated with increased prevalence of several chronic diseases. Biological embedding, believed to be rooted in dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, is the prevailing theory by which chronic diseases become imprinted in individuals following childhood adversity. A shift towards HPA axis hypoactivity occurs in response to ACEs exposure and is proposed to contribute towards altered cortisol secretion, chronic low-grade inflammation, and dysregulated hemodynamic and autonomic function.

Black and Green Tea as Well as Specialty Teas Increase Osteoblast Mineralization with Varying Effectiveness.

Many human studies suggest a benefit of tea consumption on bone health. The study objective was to compare the ability of different tea types to promote mineralization. Saos-2 cells underwent mineralization (5 days) in the presence of tea (white: WT, green: GT, black: BT, green rooibos: GR, or red rooibos: RR; 1 μg/mL of polyphenols) or control.