Human iPS cell–derived alveolar epithelium repopulates lung extracellular matrix

The use of induced pluripotent stem cells (iPSCs) has been postulated to be the most effective strategy for developing patient-specific respiratory epithelial cells, which may be valuable for lung-related cell therapy and lung tissue engineering. We generated a relatively homogeneous population of alveolar epithelial type II (AETII) and type I (AETI) cells from human iPSCs that had phenotypic properties similar to those of mature human AETII and AETI cells. We used these cells to explore whether lung tissue can be regenerated in vitro. Consistent with an AETII phenotype, we found that up to 97% of cells were positive for surfactant protein C, 95% for mucin-1, 93% for surfactant protein B, and 89% for the epithelial marker CD54. Additionally, exposing induced AETII to a Wnt/β-catenin inhibitor (IWR-1) changed the iPSC-AETII–like phenotype to a predominantly AETI-like phenotype. We found that of induced AET1 cells, more than 90% were positive for type I markers, T1α, and caveolin-1. Acellular lung matrices were prepared from whole rat or human adult lungs treated with decellularization reagents, followed by seeding these matrices with alveolar cells derived from human iPSCs. Under appropriate culture conditions, these progenitor cells adhered to and proliferated within the 3D lung tissue scaffold and displayed markers of differentiated pulmonary epithelium

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Size and Composition Distribution of Atmospheric Particles in Southern California

Continuous measurements of single particle size and chemical composition in the atmosphere are made using aerosol time-of-flight mass spectrometers (ATOFMS) operated alongside more conventional reference air sampling instruments at a network of three urban air monitoring sites in southern California. Electrical aerosol analyzers and optical particle counters are employed to acquire continuous particle size distribution data, and inertial impactor and bulk filter samples with 4-h resolution are taken for determination of particle size and chemical composition. Filter and impactor samples also are taken upwind of the air basin at Santa Catalina Island in order to characterize background air quality. The airborne particle size and composition distribution as measured by the cascade impactors at inland sites differ from that over the ocean principally due to depletion of sea salt particles accompanied by the addition of fine carbon-containing particles and secondary aerosol nitrate. Data from the ATOFMS systems create a continuous time series of sodium-, ammonium-, nitrate-, and carbon-containing particle counts that provide a high-resolution view of differences in particle composition as a function of location in the air basin. Results show that the characteristic peak in the Los Angeles area aerosol mass distribution in the 0.2−0.3-μm size range observed during the 1987 SCAQS experiments has been reduced, consistent with reductions in diesel soot and elemental carbon emissions since that time

Size and Composition Distribution of Atmospheric Particles in Southern California

Continuous measurements of single particle size and chemical composition in the atmosphere are made using aerosol time-of-flight mass spectrometers (ATOFMS) operated alongside more conventional reference air sampling instruments at a network of three urban air monitoring sites in southern California. Electrical aerosol analyzers and optical particle counters are employed to acquire continuous particle size distribution data, and inertial impactor and bulk filter samples with 4-h resolution are taken for determination of particle size and chemical composition. Filter and impactor samples also are taken upwind of the air basin at Santa Catalina Island in order to characterize background air quality. The airborne particle size and composition distribution as measured by the cascade impactors at inland sites differ from that over the ocean principally due to depletion of sea salt particles accompanied by the addition of fine carbon-containing particles and secondary aerosol nitrate. Data from the ATOFMS systems create a continuous time series of sodium-, ammonium-, nitrate-, and carbon-containing particle counts that provide a high-resolution view of differences in particle composition as a function of location in the air basin. Results show that the characteristic peak in the Los Angeles area aerosol mass distribution in the 0.2−0.3-μm size range observed during the 1987 SCAQS experiments has been reduced, consistent with reductions in diesel soot and elemental carbon emissions since that time

Experience of Pleasure and Emotional Expression in Individuals with Schizotypal Personality Features

Difficulties in feeling pleasure and expressing emotions are one of the key features of schizophrenia spectrum conditions, and are significant contributors to constricted interpersonal interactions. The current study examined the experience of pleasure and emotional expression in college students who demonstrated high and low levels of schizotypal personality disorder (SPD) traits on self-report questionnaires. One hundred and seventeen subjects with SPD traits and 116 comparison controls were recruited to participate. Cluster analyses conducted in the SPD group identified negative SPD and positive SPD subgroups. The negative SPD group exhibited deficient emotional expression and anticipatory pleasure, but showed intact consummatory pleasure. The positive SPD group reported significantly greater levels of anticipatory, consummatory and total pleasure compared to the control group. Both SPD groups reported significantly more problems in everyday memory and greater levels of depressive and anxiety-related symptoms

Quantitative In Vivo Magnetic Resonance Spectroscopy Using Synthetic Signal Injection

Accurate conversion of magnetic resonance spectra to quantitative units of concentration generally requires compensation for differences in coil loading conditions, the gains of the various receiver amplifiers, and rescaling that occurs during post-processing manipulations. This can be efficiently achieved by injecting a precalibrated, artificial reference signal, or pseudo-signal into the data. We have previously demonstrated, using in vitro measurements, that robust pseudo-signal injection can be accomplished using a second coil, called the injector coil, properly designed and oriented so that it couples inductively with the receive coil used to acquire the data. In this work, we acquired nonlocalized phosphorous magnetic resonance spectroscopy measurements from resting human tibialis anterior muscles and used pseudo-signal injection to calculate the Pi, PCr, and ATP concentrations. We compared these results to parallel estimates of concentrations obtained using the more established phantom replacement method. Our results demonstrate that pseudo-signal injection using inductive coupling provides a robust calibration factor that is immune to coil loading conditions and suitable for use in human measurements. Having benefits in terms of ease of use and quantitative accuracy, this method is feasible for clinical use. The protocol we describe could be readily translated for use in patients with mitochondrial disease, where sensitive assessment of metabolite content could improve diagnosis and treatment

The limits to exercise performance and the future of fatigue research

It is immensely difficult to provide a detailed historical account of the development of fatigue as a concept in the exercise sciences. However, the study of fatigue stretches back centuries to scientists such as Galvani who provided the ideas and tools to undertake experiments related to the electrical impulses needed to animate skeletal muscles [1]. The definitive work of Mosso in the 18th Century stands as a landmark in the study of fatigue [2]. In his book La fatica (fatigue) [2] he concluded that there were two phenomena which categorized fatigue; “The first is the diminution of the muscular force. The second is fatigue as a sensation. That is to say, we have a physical fact which can be measured and compared, and a psychic fact which eludes measurement” [p.154]. Notably, early textbooks such as Physiology of muscular exercise by Bainbridge in 1931 [3] pointed out that the limit of exercise “has often been ascribed to the capacity of the heart alone, but the facts as a whole indicate that the sum of the changes taking place throughout the body brings about the final cessation of effort” [p.176]. It is an interesting fact that research into fatigue is highly complex and consensus about the aetiology of this human condition still evades us. Not surprisingly, even after centuries of research in this area, fatigue is still very much a part of medical and social discourse. There may be several reasons for this, not least of which could be the loss or change in the meaning of the term fatigue. The Oxford Dictionary [4] defines fatigue as “extreme tiredness after exertion; reduction in efficiency of a muscle, organ etc. after prolonged activity”. Compare this definition to that of exhaustion which is often used interchangeably by exercise physiologists and which is defined as “a total loss of strength; to consume or use up the whole of” [4]; clearly, these are substantially different meanings. In addition to these general meanings, there is wide variation in definitions of fatigue in the exercise sciences which include statements such as “the failure to maintain the required or expected force” [5], or “a loss of maximal force generating capacity” [6] or “a reversible state of force depression, including a lower rate of rise of force and a slower relaxation” [7]. There are many more statements or definitions like these which attempt to capture the specific observation that there has been a decline in the ability to produce skeletal muscle tension of a given magnitude in order to quantify the amount of fatigue that has developed

Bioaerosol Mass Spectrometry for Rapid Detection of Individual Airborne Mycobacterium tuberculosis H37Ra Particles

Single-particle laser desorption/ionization time-of-flight mass spectrometry, in the form of bioaerosol mass spectrometry (BAMS), was evaluated as a rapid detector for individual airborne, micron-sized, Mycobacterium tuberculosis H37Ra particles, comprised of a single cell or a small number of clumped cells. The BAMS mass spectral signatures for aerosolized M. tuberculosis H37Ra particles were found to be distinct from M. smegmatis, Bacillus atrophaeus, and B. cereus particles, using a distinct biomarker. This is the first time a potentially unique biomarker was measured in M. tuberculosis H37Ra on a single-cell level. In addition, M. tuberculosis H37Ra and M. smegmatis were aerosolized into a bioaerosol chamber and were sampled and analyzed using BAMS, an aerodynamic particle sizer, a viable Anderson six-stage sampler, and filter cassette samplers that permitted direct counts of cells. In a background-free environment, BAMS was able to sample and detect M. tuberculosis H37Ra at airborne concentrations of >1 M. tuberculosis H37Ra-containing particles/liter of air in 20 min as determined by direct counts of filter cassette-sampled particles, and concentrations of >40 M. tuberculosis H37Ra CFU/liter of air in 1 min as determined by using viable Andersen six-stage samplers. This is a first step toward the development of a rapid, stand-alone airborne M. tuberculosis particle detector for the direct detection of M. tuberculosis bioaerosols generated by an infectious patient. Additional instrumental development is currently under way to make BAMS useful in realistic environmental and respiratory particle backgrounds expected in tuberculosis diagnostic scenarios