Universal patterns of stem cell fate in cycling adult tissues

In cycling tissues that exhibit high turnover, tissue maintenance and repair are coordinated by stem cells. But, how frequently stem cells are replaced following differentiation, aging or injury remains unclear. By drawing together the results of recent lineage-tracing studies, we propose that tissue stem cells are routinely lost and replaced in a stochastic manner. We show that stem cell replacement leads to neutral competition between clones, resulting in two characteristic and recurring patterns of clone fate dynamics, which provide a unifying framework for interpreting clone fate data and for measuring rates of stem cell loss and replacement in vivo. Thus, we challenge the concept of the stem cell as an immortal, slow-cycling, asymmetrically dividing cell.A.M.K. is supported by the Engineering and Physical Sciences Research Council fellowship

Basolateral Junction Proteins Regulate Competition for the Follicle Stem Cell Niche in the Drosophila Ovary

Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs) in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl) or discs large (dlg), undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib), do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones

Evaluation of Short-term Psychoanalytic Child Therapy (PaCT) for Young Children with Depressive Disorders: Results from a Pilot Study

Depressive disorders in early childhood are associated with high psychosocial impairment and tend to remain stable over time without adequate treatment. Short-term psychoanalytic therapy is a common form of child psychotherapy, yet there is a lack of empirical evaluation of this approach for young children with depressive disorders. Therefore, this secondary evaluation of a study on the treatment of anxiety disorders used an uncontrolled pre-post design in a clinical setting to investigate whether children with depressive comorbidity would evidence significant diagnostic and symptomatic remission after treatment with manualized short-term Psychoanalytic Child Therapy (PaCT). Nineteen children who had an anxiety disorder and a (subclinical) depressive disorder (assessed with the Preschool Age Psychiatric Assessment using DSM-IV criteria) were treated with PaCT. After treatment, 15 of 19 children (78.94 %) were remitted and 15 of 17 children (88.24 %; 2 were lost to follow-up) were free of depressive disorders at the 6-month follow-up. Further analyses revealed significant effects for pre- to post and pre- to follow-up comparisons regarding internalizing symptoms and overall problems using parent- and (nursery-)teacher-ratings. These results suggest that short-term PaCT shows promise as a treatment for childhood depressive disorders

Mid-infrared frequency comb spanning an octave based on an Er fiber laser and difference-frequency generation

We describe a coherent mid-infrared continuum source with 700 cm-1 usable bandwidth, readily tuned within 600 - 2500 cm-1 (4 - 17 \mum) and thus covering much of the infrared "fingerprint" molecular vibration region. It is based on nonlinear frequency conversion in GaSe using a compact commercial 100-fs-pulsed Er fiber laser system providing two amplified near-infrared beams, one of them broadened by a nonlinear optical fiber. The resulting collimated mid-infrared continuum beam of 1 mW quasi-cw power represents a coherent infrared frequency comb with zero carrier-envelope phase, containing about 500,000 modes that are exact multiples of the pulse repetition rate of 40 MHz. The beam's diffraction-limited performance enables long-distance spectroscopic probing as well as maximal focusability for classical and ultraresolving near-field microscopies. Applications are foreseen also in studies of transient chemical phenomena even at ultrafast pump-probe scale, and in high-resolution gas spectroscopy for e.g. breath analysis.Comment: 8 pages, 2 figures revised version, added reference

High use of SABAs is associated with higher exacerbation rate in Dutch patients with asthma

Funding This study is funded by General Practitioners Research Institute and AstraZeneca Netherlands. The REALISE survey was funded by Mundipharma International Limited (Cambridge, UK). Acknowledgements We would like to thank the core study team, Thys van der Molen, Monica Fletcher, and David Price, the initial researchers of the REALISE study, for their advice on this study. We would like to thank Mundipharma Pharmaceuticals the Netherlands, for providing the data for this study.Peer reviewedPublisher PD

Prebiotic Organic Microstructures

Micro- and sub-micrometer spheres, tubules and fiber-filament soft structures have been synthesized in our experiments conducted with 3 MeV proton irradiations of a mixture of simple inorganic constituents, CO, N2 and H2O. We analysed the irradiation products, with scanning electron microscopy (SEM) and atomic force microscopy (AFM). These laboratory organic structures produced wide variety of proteinous and non-proteinous amino acids after HCl hydrolysis. The enantiomer analysis for D-, L- alanine confirmed that the amino acids were abiotically synthesized during the laboratory experiment. Considering hydrothermal activity, the presence of CO2 and H2, of a ferromagnesian silicate mineral environment, of an Earth magnetic field which was much less intense during Archean times than nowadays and consequently of a proton excitation source which was much more abundant, we propose that our laboratory organic microstructures might be synthesized during Archean times. We show similarities in morphology and in formation with some terrestrial Archean microstructures and we suggest that some of the observed Archean carbon spherical and filamentous microstructures might be composed of abiogenic organic molecules. We further propose a search for such prebiotic organic signatures on Mars. This article has been posted on Nature precedings on 21 July 2010 [1]. Extinct radionuclides as source of excitation have been replaced by cosmic radiations which were much more intense 3.5 Ga ago because of a much less intense Earth magnetic field. The new version of the article has been presented at the ORIGINS conference in Montpellier in july 2011 [2] and has since been published in Origins of Life and Evolution of Biospheres 42 (4) 307-316, 2012. 
DOI: 10.1007/s11084-012-9290-5 

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On the dynamical generation of the Maxwell term and scale invariance

Gauge theories with no Maxwell term are investigated in various setups. The dynamical generation of the Maxwell term is correlated to the scale invariance properties of the system. This is discussed mainly in the cases where the gauge coupling carries dimensions. The term is generated when the theory contains a scale explicitly, when it is asymptotically free and in particular also when the scale invariance is spontaneously broken. The terms are not generated when the scale invariance is maintained. Examples studied include the large $N$ limit of the $CP^{N-1}$ model in $(2+\epsilon)$ dimensions, a 3D gauged $\phi^6$ vector model and its supersymmetric extension. In the latter case the generation of the Maxwell term at a fixed point is explored. The phase structure of the $d=3$ case is investigated in the presence of a Chern-Simons term as well. In the supersymmetric $\phi^6$ model the emergence of the Maxwell term is accompanied by the dynamical generation of the Chern-Simons term and its multiplet and dynamical breaking of the parity symmetry. In some of the phases long range forces emerge which may result in logarithmic confinement. These include a dilaton exchange which plays a role also in the case when the theory has no gauge symmetry. Gauged Lagrangian realizations of the 2D coset models do not lead to emergent Maxwell terms. We discuss a case where the gauge symmetry is anomalous.Comment: 38 pages, 4 figures; v2 slightly improved, typos fixed, references added, published versio

On the nonequilibrium entropy of large and small systems

Thermodynamics makes definite predictions about the thermal behavior of macroscopic systems in and out of equilibrium. Statistical mechanics aims to derive this behavior from the dynamics and statistics of the atoms and molecules making up these systems. A key element in this derivation is the large number of microscopic degrees of freedom of macroscopic systems. Therefore, the extension of thermodynamic concepts, such as entropy, to small (nano) systems raises many questions. Here we shall reexamine various definitions of entropy for nonequilibrium systems, large and small. These include thermodynamic (hydrodynamic), Boltzmann, and Gibbs-Shannon entropies. We shall argue that, despite its common use, the last is not an appropriate physical entropy for such systems, either isolated or in contact with thermal reservoirs: physical entropies should depend on the microstate of the system, not on a subjective probability distribution. To square this point of view with experimental results of Bechhoefer we shall argue that the Gibbs-Shannon entropy of a nano particle in a thermal fluid should be interpreted as the Boltzmann entropy of a dilute gas of Brownian particles in the fluid

An Immersive Virtual Reality Curriculum for Pediatric Hematology Clinicians on Shared Decision-making for Hydroxyurea in Sickle Cell Anemia

Although hydroxyurea (HU) is an effective treatment for sickle cell anemia, uptake remains low. Shared decision-making (SDM) is a recommended strategy for HU initiation to elicit family preferences; however, clinicians lack SDM training. We implemented an immersive virtual reality (VR) curriculum at 8 pediatric institutions to train clinicians on SDM that included counseling virtual patients. Clinicians’ self-reported confidence significantly improved following the VR simulations on all communication skills assessed, including asking open-ended questions, eliciting specific concerns, and confirming understanding (Ps≤0.01 for all). VR may be an effective method for educating clinicians to engage in SDM for HU