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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 


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
limit of the model in dimensions, a 3D gauged
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 case is investigated in the presence of a Chern-Simons
term as well. In the supersymmetric 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
GPs’ strategies in exploring the preschool child’s wellbeing in the paediatric consultation
Background:
Although General Practitioners (GPs) are uniquely placed to identify children with emotional, social, and behavioural problems, they succeed in identifying only a small number of them. The aim of this article is to explore the strategies, methods, and tools employed by GPs in the assessment of the preschool child’s emotional, mental, social, and behavioural health. We look at how GPs address parental care of the child in general and in situations where GPs have a particular awareness of the child.
Method:
Twenty-eight Danish GPs were purposively selected to take part in a qualitative study which combined focus-group discussions, observation of child consultations, and individual interviews with GPs.
Results:
Analysis of the data suggests that GPs have developed a set of methods, and strategies to assess the preschool child and parental care of the child. They look beyond paying narrow attention to the physical health of the child and they have expanded their practice to include the relations and interactions in the consultation room. The physical examination of the child continues to play a central role in doctor-child communication.
Conclusion:
The participating GPs’ strategies helped them to assess the wellbeing of the preschool child but they often find it difficult to share their impressions with parents
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
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