STAT3 Impairs STAT5 Activation in the Development of IL-9-Secreting T Cells

Th cell subsets develop in response to multiple activating signals, including the cytokine environment. IL-9-secreting T cells develop in response to the combination of IL-4 and TGF-β, although they clearly require other cytokine signals, leading to the activation of transcription factors including STAT5. In Th17 cells, there is a molecular antagonism of STAT5 with STAT3 signaling, although whether this paradigm exists in other Th subsets is not clear. In this paper, we demonstrate that STAT3 attenuates the ability of STAT5 to promote the development of IL-9-secreting T cells. We demonstrate that production of IL-9 is increased in the absence of STAT3 and cytokines that result in a sustained activation of STAT3, including IL-6, have the greatest potency in repressing IL-9 production in a STAT3-dependent manner. Increased IL-9 production in the absence of STAT3 correlates with increased endogenous IL-2 production and STAT5 activation, and blocking IL-2 responses eliminates the difference in IL-9 production between wild-type and STAT3-deficient T cells. Moreover, transduction of developing Th9 cells with a constitutively active STAT5 eliminates the ability of IL-6 to reduce IL-9 production. Thus, STAT3 functions as a negative regulator of IL-9 production through attenuation of STAT5 activation and function

Scottish theme towns: have new identities enhanced development?

Three small towns in southwest Scotland have recently been branded as distinct theme towns, based on books, artists and food. This is an attempt to make them more attractive to visitors and thereby improve their economy. The objective of this research is to establish whether the new identities possessed by the towns have enhanced their development. It is argued, using data reviewing the past decade, that they have all developed, albeit at different rates, in terms of the economy and culture. Moreover, it is maintained that social capital has been enhanced and is a factor whose importance has been under-appreciated by planners and observers of this type of process. The relevance of the new identity to the pre-branding identity is also seen as a factor in successful development and ideas of authenticity and heritage are brought to bear on the relationship

The ETS family transcription factors Etv5 and PU.1 function in parallel to promote Th9 cell development

The IL-9-secreting Th9 subset of CD4 T helper cells develop in response to an environment containing IL-4 and TGFβ, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report we demonstrate that the ETS transcription factor ETV5 promotes IL-9 production in Th9 cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T cells results in distinct affects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation

The Paranormal is (Still) Normal: The Sociological Implications of a Survey of Paranormal Experiences in Great Britain

Historically, there has been limited sociological interest in the paranormal and no systematic study of reported paranormal experiences. There are also few medium-to-large-scale survey results with nationally representative populations focusing on paranormal experiences. This paper provides details of an exploratory survey conducted in 2009 with a nationally representative sample of 4,096 adults aged 16 years and over across Great Britain. Our findings show that 37% of British adults report at least one paranormal experience and that women, those who are middle-aged or individuals resident in the South West are more likely to report such experiences. These results establish incidence levels of reported paranormal experiences in contemporary Britain. We argue also that they merit a more sustained sociological consideration of the paranormal. In this respect we renew and update the robust justification and call for serious research positioning the paranormal as a social phenomenon, originally proposed well over thirty years ago by Greeley (1975)

Supernova Simulations and Strategies For the Dark Energy Survey

We present an analysis of supernova light curves simulated for the upcoming Dark Energy Survey (DES) supernova search. The simulations employ a code suite that generates and fits realistic light curves in order to obtain distance modulus/redshift pairs that are passed to a cosmology fitter. We investigated several different survey strategies including field selection, supernova selection biases, and photometric redshift measurements. Using the results of this study, we chose a 30 square degree search area in the griz filter set. We forecast 1) that this survey will provide a homogeneous sample of up to 4000 Type Ia supernovae in the redshift range 0.05<z<1.2, and 2) that the increased red efficiency of the DES camera will significantly improve high-redshift color measurements. The redshift of each supernova with an identified host galaxy will be obtained from spectroscopic observations of the host. A supernova spectrum will be obtained for a subset of the sample, which will be utilized for control studies. In addition, we have investigated the use of combined photometric redshifts taking into account data from both the host and supernova. We have investigated and estimated the likely contamination from core-collapse supernovae based on photometric identification, and have found that a Type Ia supernova sample purity of up to 98% is obtainable given specific assumptions. Furthermore, we present systematic uncertainties due to sample purity, photometric calibration, dust extinction priors, filter-centroid shifts, and inter-calibration. We conclude by estimating the uncertainty on the cosmological parameters that will be measured from the DES supernova data.Comment: 46 pages, 30 figures, resubmitted to ApJ as Revision 2 (final author revision), which has subtle editorial differences compared to the published paper (ApJ, 753, 152). Note that this posting includes PDF only due to a bug in either the latex macros or the arXiv submission system. The source files are available in the DES document database: http://des-docdb.fnal.gov/cgi-bin/ShowDocument?docid=624

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Between-Population Outbreeding Affects Plant Defence

Between-population crosses may replenish genetic variation of populations, but may also result in outbreeding depression. Apart from direct effects on plant fitness, these outbreeding effects can also alter plant-herbivore interactions by influencing plant tolerance and resistance to herbivory. We investigated effects of experimental within- and between-population outbreeding on herbivore resistance, tolerance and plant fitness using plants from 13 to 19 Lychnis flos-cuculi populations. We found no evidence for outbreeding depression in resistance reflected by the amount of leaf area consumed. However, herbivore performance was greater when fed on plants from between-population compared to within-population crosses. This can reflect outbreeding depression in resistance and/or outbreeding effects on plant quality for the herbivores. The effects of type of cross on the relationship between herbivore damage and plant fitness varied among populations. This demonstrates how between-population outbreeding effects on tolerance range from outbreeding depression to outbreeding benefits among plant populations. Finally, herbivore damage strengthened the observed outbreeding effects on plant fitness in several populations. These results raise novel considerations on the impact of outbreeding on the joint evolution of resistance and tolerance, and on the evolution of multiple defence strategies