The FALCON concept: multi-object spectroscopy combined with MCAO in near-IR

A large fraction of the present-day stellar mass was formed between z=0.5 and z~3 and our understanding of the formation mechanisms at work at these epochs requires both high spatial and high spectral resolution: one shall simultaneously} obtain images of objects with typical sizes as small as 1-2kpc(~0''.1), while achieving 20-50 km/s (R >= 5000) spectral resolution. The obvious instrumental solution to adopt in order to tackle the science goal is therefore a combination of multi-object 3D spectrograph with multi-conjugate adaptive optics in large fields. A partial, but still competitive correction shall be prefered, over a much wider field of view. This can be done by estimating the turbulent volume from sets of natural guide stars, by optimizing the correction to several and discrete small areas of few arcsec2 selected in a large field (Nasmyth field of 25 arcmin) and by correcting up to the 6th, and eventually, up to the 60th Zernike modes. Simulations on real extragalactic fields, show that for most sources (>80%), the recovered resolution could reach 0".15-0".25 in the J and H bands. Detection of point-like objects is improved by factors from 3 to >10, when compared with an instrument without adaptive correction. The proposed instrument concept, FALCON, is equiped with deployable mini-integral field units (IFUs), achieving spectral resolutions between R=5000 and 20000. Its multiplex capability, combined with high spatial and spectral resolution characteristics, is a natural ground based complement to the next generation of space telescopes.Comment: ESO Workshop Proceedings: Scientific Drivers for ESO Future VLT/VLTI Instrumentation, 10 pages and 5 figure

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Characterization of tau positron emission tomography tracer [(18)F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias

INTRODUCTION: Aggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [(18)F]AV-1451 in a range of dementias. METHODS: Phosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias. RESULTS: [(18)F]AV-1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism-17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non-tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups. DISCUSSION: [(18)F]AV-1451 binds to tau in AD, and some other tauopathies. However, evidence for a non-tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic

Brd1 Gene in Maize Encodes a Brassinosteroid C-6 Oxidase

The role of brassinosteroids in plant growth and development has been well-characterized in a number of plant species. However, very little is known about the role of brassinosteroids in maize. Map-based cloning of a severe dwarf mutant in maize revealed a nonsense mutation in an ortholog of a brassinosteroid C-6 oxidase, termed brd1, the gene encoding the enzyme that catalyzes the final steps of brassinosteroid synthesis. Homozygous brd1–m1 maize plants have essentially no internode elongation and exhibit no etiolation response when germinated in the dark. These phenotypes could be rescued by exogenous application of brassinolide, confirming the molecular defect in the maize brd1-m1 mutant. The brd1-m1 mutant plants also display alterations in leaf and floral morphology. The meristem is not altered in size but there is evidence for differences in the cellular structure of several tissues. The isolation of a maize mutant defective in brassinosteroid synthesis will provide opportunities for the analysis of the role of brassinosteroids in this important crop system

Dawn and Dusk Set States of the Circadian Oscillator in Sprouting Barley (Hordeum vulgare) Seedlings

The plant circadian clock is an internal timekeeper that coordinates biological processes with daily changes in the external environment. The transcript levels of clock genes, which oscillate to control circadian outputs, were examined during early seedling development in barley (Hordeum vulgare), a model for temperate cereal crops. Oscillations of clock gene transcript levels do not occur in barley seedlings grown in darkness or constant light but were observed with day-night cycles. A dark-to-light transition influenced transcript levels of some clock genes but triggered only weak oscillations of gene expression, whereas a light-to-dark transition triggered robust oscillations. Single light pulses of 6, 12 or 18 hours induced robust oscillations. The light-to-dark transition was the primary determinant of the timing of subsequent peaks of clock gene expression. After the light-to-dark transition the timing of peak transcript levels of clock gene also varied depending on the length of the preceding light pulse. Thus, a single photoperiod can trigger initiation of photoperiod-dependent circadian rhythms in barley seedlings. Photoperiod-specific rhythms of clock gene expression were observed in two week old barley plants. Changing the timing of dusk altered clock gene expression patterns within a single day, showing that alteration of circadian oscillator behaviour is amongst the most rapid molecular responses to changing photoperiod in barley. A barley EARLY FLOWERING3 mutant, which exhibits rapid photoperiod–insensitive flowering behaviour, does not establish clock rhythms in response to a single photoperiod. The data presented show that dawn and dusk cues are important signals for setting the state of the circadian oscillator during early development of barley and that the circadian oscillator of barley exhibits photoperiod-dependent oscillation states

Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia.

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). We now report the first description of a homozygous patient and compare it to a series of heterozygous cases. The patient developed early-onset frontotemporal dementia without additional features. Neuropathological analysis showed c9FTD/ALS characteristics, with abundant p62-positive inclusions in the frontal and temporal cortices, hippocampus and cerebellum, as well as less abundant TDP-43-positive inclusions. Overall, the clinical and pathological features were severe, but did not fall outside the usual disease spectrum. Quantification of C9orf72 transcript levels in post-mortem brain demonstrated expression of all known C9orf72 transcript variants, but at a reduced level. The pathogenic mechanisms by which the hexanucleotide repeat expansion causes disease are unclear and both gain- and loss-of-function mechanisms may play a role. Our data support a gain-of-function mechanism as pure homozygous loss of function would be expected to lead to a more severe, or completely different clinical phenotype to the one described here, which falls within the usual range. Our findings have implications for genetic counselling, highlighting the need to use genetic tests that distinguish C9orf72 homozygosity

Adjusting Phenotypes by Noise Control

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks

Health promotion in primary care: How should we intervene? A qualitative study involving both physicians and patients

<p>Abstract</p> <p>Background</p> <p>The effects of tobacco, physical exercise, diet, and alcohol consumption on morbidity and mortality underline the importance of health promotion and prevention (HPP) at the primary health care (PHC) level. Likewise, the deficiencies when putting such policies into practice and assessing their effectiveness are also widely recognised. The objectives of this research were: a) to gain an in-depth understanding of general practitioners' (GPs) and patients' perceptions about HPP in PHC, and b) to define the areas that could be improved in future interventions.</p> <p>Methods</p> <p>Qualitative methodology focussed on the field of health services research. Information was generated on the basis of two GP-based and two patient-based discussion groups, all of which had previously participated in two interventions concerning healthy lifestyle promotion (tobacco and physical exercise). Transcripts and field notes were analysed on the basis of a sociological discourse-analysis model. The results were validated by triangulation between researchers.</p> <p>Results</p> <p>GPs and patients' discourses about HPP in PHC were different in priorities and contents. An overall explanatory framework was designed to gain a better understanding of the meaning of GP-patient interactions related to HPP, and to show the main trends that emerged from their discourses. GPs linked their perceptions of HPP to their working conditions and experience in health services. The dimensions in this case involved the orientation of interventions, the goal of actions, and the evaluation of results. For patients, habits were mainly related to ways of life particularly influenced by close contexts. Health conceptions, their role as individuals, and the orientation of their demands were the most important dimensions in patients' sphere.</p> <p>Conclusions</p> <p>HPP activities in PHC need to be understood and assessed in the context of their interaction with the conditioning trends in health services and patients' social micro-contexts. On the basis of the explanatory framework, three development lines are proposed: the incorporation of new methodological approaches according to the complexity of HPP in PHC; the openness of habit change policies beyond the medical services; and the effective commitments in the medium to long term by the health services themselves at the policy management level.</p