A Statistically-Robust Model of the Axomyelin Unit under Normal Physiologic Conditions with Application to Disease States.

Despite tremendous progress in characterizing the myriad cellular structures in the nervous system, a full appreciation of the interdependent and intricate interactions between these structures is as yet unfulfilled. Indeed, few more so than the interaction between the myelin internode and its ensheathed axon. More than a half-century after the ultrastructural characterization of this axomyelin unit, we lack a reliable understanding of the physiological properties, the significance and consequence of pathobiological processes, and the means to gauge success or failure of interventions designed to mitigate disease.

Circulating ANGPTL3/8 Concentrations Are Associated With an Atherogenic Lipoprotein Profile and Increased CHD Risk in Swedish Population-Based Studies.

Background: Binding of ANGPTL (angiopoietin-like protein)-3 to ANGPTL8 generates a protein complex (ANGPTL3/8) that strongly inhibits LPL (lipoprotein lipase) activity, as compared with ANGPTL3 alone, suggesting that ANGPTL3/8 concentrations are critical for the regulation of circulation lipoprotein concentrations and subsequent increased coronary heart disease (CHD) risk. To test this hypothesis in humans, we evaluated the associations of circulating free ANGPTL3 and ANGPTL3/8 complex concentrations with lipoprotein concentrations and CHD risk in 2 prospective cohort studies.

Methods: Fasting blood samples were obtained in conjunction with the baseline evaluation of 9479 subjects from 2 population-based Swedish cohorts of middle-aged men and women.

XOR-Derived ROS in Tie2-Lineage Cells Including Endothelial Cells Promotes Aortic Aneurysm Progression in Marfan Syndrome.

Background: Marfan syndrome (MFS) is an inherited disorder caused by mutations in the gene encoding fibrillin-1, a matrix component of extracellular microfibrils. The main cause of morbidity and mortality in MFS is thoracic aortic aneurysm and dissection, but the underlying mechanisms remain undetermined.

Methods: To elucidate the role of endothelial XOR (xanthine oxidoreductase)-derived reactive oxygen species in aortic aneurysm progression, we inhibited in vivo function of XOR either by endothelial cell (EC)-specific disruption of the gene or by systemic administration of an XOR inhibitor febuxostat in MFS mice harboring the missense mutation p.

Modern perspective of the Rice Diet for hypertension and other metabolic diseases.

Background: In the early 1940s, before antihypertensive drugs were available, the Rice Diet Programme (RDP) was developed to treat severe hypertension and, later, diabetes and obesity. Despite significant advancements in dietary management for these conditions since then, debates remain regarding the proper guidelines for sodium and macronutrients intakes. The patient care records of RDP offer a unique source of longitudinal examination of a very low sodium (<10 mmol/day), fat, cholesterol and protein diet on blood pressure (BP), other health markers and survival.

Detection of early relapse in multiple myeloma patients.

Background: Multiple myeloma (MM) represents the second most common hematological malignancy characterized by the infiltration of the bone marrow by plasma cells that produce monoclonal immunoglobulin. While the quality and length of life of MM patients have significantly increased, MM remains a hard-to-treat disease; almost all patients relapse. As MM is highly heterogenous, patients relapse at different times.

Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment.

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.

Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation.

γδ T cells producing either interleukin-17A (γδ cells) or interferon-γ (γδ cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ cell versus γδ cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ cells versus γδ cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively.

Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Generation of a human induced pluripotent stem cell line (BIHi292-A) from PBMCs of a female patient diagnosed with Nasu-Hakola disease (NHD)/polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) carrying a novel heterozygous mutation in the TREM2 gene.

NHD/PLOSL is an orphan disease characterized by progressive presenile dementia associated with recurrent fractures due to polycystic bone lesions. In this study, we generated the human induced pluripotent stem cell (hiPSC) line BIHi292-A from a 30-year-old women diagnosed with NHD/PLOSL, carrying two compound heterozygous frameshift mutations [c.313del (p.

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.

Background And Objectives: Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.

Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.

Serum Immunoglobulin G Levels and Nicastrin Variation in Hidradenitis Suppurativa.

Importance: Variation in nicastrin (NCSTN) is associated with a monogenic subtype of hidradenitis suppurativa. Dysregulation of humoral immunity has been suggested as a potential mechanistic link between NCSTN variation and hidradenitis suppurativa. There is a paucity of biomarkers that can predict disease-associated variation.

Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.

Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.

Imaging Single Particle Profiler to Study Nanoscale Bioparticles Using Conventional Confocal Microscopy.

Single particle profiling (SPP) is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles, and lipoproteins in a single particle and high throughput manner. The initial version requires the single photon counting modules for data acquisition, which limits its adoptability. Here, we present imaging-based SPP (iSPP) that can be performed by imaging a spot over time in the common imaging mode with confocal detectors.

Expression and function of Connexin 43 and Connexin 37 in the murine zona glomerulosa.

The zona glomerulosa (ZG) synthesizes the mineralocorticoid aldosterone. The primary role of aldosterone is the maintenance of volume and electrolyte homeostasis. Aldosterone synthesis is primarily regulated via tightly controlled oscillations in intracellular calcium levels in response to stimulation.

Immunomodulatory Potential of a Bibenzyl-dihydrophenanthrene Derivative Isolated from .

Bibenzyls and dihydrophenanthrenes exhibit promising immunomodulatory effects in various human diseases. In this study, we isolated one new dihydrophenanthrene derivative (), two new bibenzyl-dihydrophenanthrene derivatives () along with 12 known compounds (-) from the methanol extract of . These compounds were identified by using physicochemical analyses and spectroscopic methods.

Comparison of immune responses to SARS-CoV-2 spike following Omicron infection or Omicron BA.4/5 vaccination in kidney transplant recipients.

Background: The emergence of novel SARS-CoV-2 variants challenges immunity, particularly among immunocompromised kidney transplant recipients (KTRs). To address this, vaccines have been adjusted to circulating variants. Despite intensive vaccination efforts, SARS-CoV-2 infections surged among KTRs during the Omicron wave, enabling a direct comparison of variant-specific immunity following-vaccination against Omicron BA.

The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity.

Introduction: Periodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by . We previously demonstrated an increased antibody response to arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA.

Dental and oral health assessments in the German National Cohort (NAKO).

Background: Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Visual and Orthoptic Development After DSAEK for CHED in Children Younger than 8 years: Case Series and Literature Review.

Purpose: Congenital hereditary endothelial dystrophy (CHED) impairs the sensitive phase of visual development. We examined results of Descemet stripping automated endothelial keratoplasty (DSAEK) for CHED regarding the critical period for amblyogenic factors.

Methods: Retrospective analysis of 11 eyes of 6 consecutive patients with CHED younger than 8 years treated with DSAEK and a PubMed-based literature search on management and optimal timing of the intervention.