High export via small particles before the onset of the North Atlantic spring bloom

Sinking organic matter in the North Atlantic Ocean transfers 1-3 Gt carbon year?1 from the surface ocean to the interior. The majority of this exported material is thought to be in form of large, rapidly sinking particles that aggregate during or after the spring phytoplankton bloom. However, recent work has suggested that intermittent water column stratification resulting in the termination of deep convection can isolate phytoplankton from the euphotic zone, leading to export of small particles. We present depth profiles of large (>0.1mm equivalent spherical diameter, ESD) and small (300m depth, leading to deep mixing of particles as deep as 600m. Subsequent re-stratification could trap these particles at depth and lead to high particle fluxes at depth without the need for aggregation (‘mixed layer pump'). Overall we suggest that pre-bloom fluxes to the mesopelagic are significant, and the role of small sinking particles requires careful consideration

High export via small particles before the onset of the North Atlantic spring bloom

Sinking organic matter in the North Atlantic Ocean transfers 1-3 Gt carbon year?1 from the surface ocean to the interior. The majority of this exported material is thought to be in form of large, rapidly sinking particles that aggregate during or after the spring phytoplankton bloom. However, recent work has suggested that intermittent water column stratification resulting in the termination of deep convection can isolate phytoplankton from the euphotic zone, leading to export of small particles. We present depth profiles of large (&gt;0.1mm equivalent spherical diameter, ESD) and small (&lt;0.1mm ESD) sinking particle concentrations and fluxes prior to the spring bloom at two contrasting sites in the North Atlantic (61°30N, 11°00W and 62°50N, 02°30W) derived from the Marine Snow Catcher and the Video Plankton Recorder. The downward flux of organic carbon via small particles ranged from 23-186 mg C m?2 d?1, often constituting the bulk of the total particulate organic carbon flux. We propose that these rates were driven by two different mechanisms: In the Norwegian Basin, small sinking particles likely reached the upper mesopelagic by disaggregation of larger, faster sinking particles. In the Iceland Basin, a storm deepened the mixed layer to &gt;300m depth, leading to deep mixing of particles as deep as 600m. Subsequent re-stratification could trap these particles at depth and lead to high particle fluxes at depth without the need for aggregation (‘mixed layer pump'). Overall we suggest that pre-bloom fluxes to the mesopelagic are significant, and the role of small sinking particles requires careful consideration. <br/

Primary ciliary dyskinesia: Recent advances in diagnostics, genetics, and characterization of clinical disease

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment ofPCDis not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

Background: Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective: Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods: The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results: Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions: CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6–9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ − 0.13, 95% CI − 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ − 0.17, 95% CI − 0.33, − 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision

Limit distributions of scale-invariant probabilistic models of correlated random variables with the q-Gaussian as an explicit example

Extremization of the Boltzmann-Gibbs (BG) entropy under appropriate norm and width constraints yields the Gaussian distribution. Also, the basic solutions of the standard Fokker-Planck (FP) equation (related to the Langevin equation with additive noise), as well as the Central Limit Theorem attractors, are Gaussians. The simplest stochastic model with such features is N to infinity independent binary random variables, as first proved by de Moivre and Laplace. What happens for strongly correlated random variables? Such correlations are often present in physical situations as e.g. systems with long range interactions or memory. Frequently q-Gaussians become observed. This is typically so if the Langevin equation includes multiplicative noise, or the FP equation to be nonlinear. Scale-invariance, i.e. exchangeable binary stochastic processes, allow a systematical analysis of the relation between correlations and non-Gaussian distributions. In particular, a generalized stochastic model yielding q-Gaussians for all q (including q>1) was missing. This is achieved here by using the Laplace-de Finetti representation theorem, which embodies strict scale-invariance of interchangeable random variables. We demonstrate that strict scale invariance together with q-Gaussianity mandates the associated extensive entropy to be BG.Comment: 6 pages, 1 fig, to appear in EPJ

Atrial natriuretic peptide and leptin interactions in healthy men

Introduction: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo. Methods: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial. Results: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release. Discussion: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559)

Atrial natriuretic peptide and leptin interactions in healthy men

INTRODUCTION: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo. METHODS: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial. RESULTS: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release. DISCUSSION: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559

The influence of T cell development on pathogen specificity and autoreactivity

T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the major histocompatibility (MHC) gene products, which are displayed on the surface of antigen presenting cells. T cells can also interact with peptide-MHC complexes, where the peptide is derived from host (self) proteins. A diverse repertoire of relatively self-tolerant T cell receptors is selected in the thymus. We study a model, computationally and analytically, to describe how thymic selection shapes the repertoire of T cell receptors, such that T cell receptor recognition of pathogenic peptides is both specific and degenerate. We also discuss the escape probability of autoimmune T cells from the thymus.Comment: 12 pages, 7 figure