Sputum Inflammatory Mediators Are Increased in Aspergillus fumigatus Culture-Positive Asthmatics.

Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics.

The Case for Adopting the "Species Complex" Nomenclature for the Etiologic Agents of Cryptococcosis.

Cryptococcosis is a potentially lethal disease of humans/animals caused by and . Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that be divided into two species and into five species based on a phylogenetic analysis of 115 isolates.

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course.

Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii.

Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts.

Correction: Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells.

[This corrects the article DOI: 10.1371/journal.pbio.

PLEASANT: Preventing and Lessening Exacerbations of Asthma in School-age children Associated with a New Term - a cluster randomised controlled trial and economic evaluation.

Background: Asthma episodes and deaths are known to be seasonal. A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer vacation. A fall in prescription collection in the month of August has been observed, and was associated with an increase in the number of unscheduled contacts after the return to school in September.

Efficient Nonviral Transfection of Primary Intervertebral Disc Cells by Electroporation for Tissue Engineering Application.

Low back pain (LBP) is an increasing global health problem associated with intervertebral disc (IVD) trauma and degeneration. Current treatment options include surgical interventions with partial unsatisfactory outcomes reported such as failure to relieve LBP, nonunions, nerve injuries, or adjacent segment disease. Cell-based therapy and tissue engineered IVD constructs supplemented with transfected disc cells that incorporate factors enhancing matrix synthesis represent an appealing approach to regenerate the IVD.

Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2.

Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis.

Interactions between π-conjugated chromophores in a giant molecular spoked wheel.

We discuss the intriguing photophysics of a giant molecular spoked wheel of π-conjugated arylene-alkynylene chromophores on the single-molecule level. This "molecular mesoscopic" structure, CH, shows fast switching between the 12 identical chromophores since the fluorescence is unpolarised but only one chromophore emits at a time.

Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury.

Crypt epithelial survival and regeneration after injury require highly coordinated complex interplay between resident stem cells and diverse cell types. The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after radiation-induced injury is unclear. Intestinal epithelial cells (IECs) were isolated and purified and utilized for experimental analysis.

Perovskite-perovskite tandem photovoltaics with optimized band gaps.

We demonstrate four- and two-terminal perovskite-perovskite tandem solar cells with ideally matched band gaps. We develop an infrared-absorbing 1.2-electron volt band-gap perovskite, FACsSnPbI, that can deliver 14.

Dispositional self-control: relationships with aerobic capacity and morning surge in blood pressure.

The psychological, behavioral and psychosocial implications of self-control are well established, but relatively little is known about its implications for physical health. This study examined the association between self-control and two important indicators of cardiovascular risk: morning blood pressure surge (MBPS) and maximum oxygen consumption (VO). Undergraduate students (N = 78) completed a measure of dispositional self-control (Brief Self-Control Scale), participated in a 24-h ambulatory assessment of heart rate (HR) and blood pressure (BP), and completed the YMCA Cycle Ergometer Submaximal Test.

Using Flow Cytometry to Analyze Cryptococcus Infection of Macrophages.

Flow cytometry is a powerful analytical technique, which is increasingly being used to study the interaction between host cells and intracellular pathogens. Flow cytometry is capable of measuring a greater number of infected cells within a sample compared to alternative techniques such as fluorescence microscopy. This means that robust quantification of rare events during infection is possible.

New weapons in the Cryptococcus infection toolkit.

The global burden of fungal infections is unacceptably high. The human fungal pathogen Cryptococcus neoformans causes cryptococcosis and accounts for a significant proportion of this burden. Cryptococci undergo a number of elaborate interactions with their hosts, including survival and proliferation within phagocytes as well as dissemination to the central nervous system and other tissues.

Eradicating infectious disease using weakly transmissible vaccines.

Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution.

The complex biology and contribution of Staphylococcus aureus in atopic dermatitis, current and future therapies.

Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of U.K. children and is a major cause of occupation-related disability.

Design and engineering of a transmissible antiviral defense.

Background: We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus.

The price of complexity in financial networks.

Financial institutions form multilayer networks by engaging in contracts with each other and by holding exposures to common assets. As a result, the default probability of one institution depends on the default probability of all of the other institutions in the network. Here, we show how small errors on the knowledge of the network of contracts can lead to large errors in the probability of systemic defaults.

Micropatterned Endotracheal Tubes Reduce Secretion-Related Lumen Occlusion.

Tracheal intubation disrupts physiological homeostasis of secretion production and clearance, resulting in secretion accumulation within endotracheal tubes (ETTs). Novel in vitro and in vivo models were developed to specifically recapitulate the clinical manifestations of ETT occlusion. The novel Sharklet™ micropatterned ETT was evaluated, using these models, for the ability to reduce the accumulation of both bacterial biofilm and airway mucus compared to a standard care ETT.

Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells.

It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respond, expand, and differentiate into memory-like cells in a ligand-specific manner. MHC I-binding inhibitory receptors, including those belonging to the Ly49 and KIR families, are expressed in a variegated manner, which creates ligand-specific diversity within the NK cell pool.

A comprehensive transcriptional map of primate brain development.

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons.

Top tips for reflection.

I made a commitment, months ago, to go through revalidation ahead of schedule. It seemed a good idea when sitting by the fire, catching up with emails and Twitter on a dark winter's evening.

Regulatory Roles of Dclk1 in Epithelial Mesenchymal Transition and Cancer Stem Cells.

The identification of functionally relevant subpopulations of therapy-resistant cancer cells is a challenge. These cells, intrinsically resistant to conventional therapy, can cause recurrence. Evidence has suggested that therapy-resistant cancer cells are likely epithelial-mesenchymal transition (EMT) cells and/or stem-like cells called cancer stem cells (CSCs).

Impact of a motivated performance task on autonomic and hemodynamic cardiovascular reactivity.

Motivated performance (MP) tasks include mental stressors characterized by a high degree of motivation, individual engagement, and sympathetic overstimulation. It is therefore important to document the independent influence of motivation apart from engagement on markers of cardiovascular autonomic modulation, including vasomotor tone (low-frequency systolic blood pressure, LFSBP), blood pressure homeostasis (baroreflex sensitivity, BRS), and myocardial oxygen consumption (rate pressure product, RPP). Accordingly, an arithmetic task (AT) was used to manipulate motivation to evaluate its impact on cardiovascular reactivity.