Mitigating tradeoffs in plant breeding

Tradeoffs among plant traits help maintain relative fitness under unpredictable conditions and maximize reproductive success. However, modifying tradeoffs is a breeding challenge since many genes of minor effect are involved. The intensive crosstalk and fine-tuning between growth and defense responsive phytohormones via transcription factors optimizes growth, reproduction, and stress tolerance. There are regulating genes in grain crops that deploy diverse functions to overcome tradeoffs, e.g., miR-156-IPA1 regulates crosstalk between growth and defense to achieve high disease resistance and yield, while OsALDH2B1 loss of function causes imbalance among defense, growth, and reproduction in rice. GNI-A1 regulates seed number and weight in wheat by suppressing distal florets and altering assimilate distribution of proximal seeds in spikelets. Knocking out ABA-induced transcription repressors (AITRs) enhances abiotic stress adaptation without fitness cost in Arabidopsis. Deploying AITRs homologs in grain crops may facilitate breeding. This knowledge suggests overcoming tradeoffs through breeding may expose new ones

The Remarkably Featureless High Resolution X-ray Spectrum of Mrk 478

An observation of Mrk 478 using the Chandra Low Energy Transmission Grating Spectrometer is presented. The source exhibited 30-40% flux variations on timescales of order 10000 s together with a slow decline in the spectral softness over the full 80 ks observation. The 0.15--3.0 keV spectrum is well fitted by a single power law with photon index of Gamma = 2.91 +/- 0.03. Combined with high energy data from BeppoSAX, the spectrum from 0.15 to 10 keV is well fit as the sum of two power laws with Gamma = 3.03 +/- 0.04, which dominates below 2 keV and 1.4 +/- 0.2, which dominates above 2 keV (quoting 90% confidence uncertainties). No significant emission or absorption features are detected in the high resolution spectrum, supporting our previous findings using the Extreme Ultraviolet Explorer but contradicting the claims of emission lines by Hwang & Bowyer (1997). There is no evidence of a warm absorber, as found in the high resolution spectra of many Sy 1 galaxies including others classified as narrow line Sy 1 galaxies such as Mrk 478. We suggest that the X-ray continuum may result from Comptonization of disk thermal emission in a hot corona through a range of optical depths.Comment: 21 pages, 7 figures; accepted for publication in the Astronomical Journa

Nanotopographical effects on mesenchymal stem cell morphology and phenotype

There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation. Understanding the effects of nanotopography on cell adhesion and morphology and the consequences of cell shape changes in the nucleus, and consequently, gene expression offers new approaches to the elucidation and potential control of stem cell differentiation. In the current study we have used molecular approaches in combination with immunohistology and transcript analysis to understand the role of nanotopography on mesenchymal stem cell morphology and phenotype. Results demonstrate large changes in cell adhesion, nucleus and lamin morphologies in response to the different nanotopographies. Furthermore, these changes relate to alterations in packing of chromosome territories within the interphase nucleus. This, in turn, leads to changes in transcription factor activity and functional (phenotypical) signalling including cell metabolism. Nanotopography provides a useful, non-invasive tool for studying cellular mechanotransduction, gene and protein expression patterns, through effects on cell morphology. The different nanotopographies examined, result in different morphological changes in the cyto- and nucleo-skeleton. We propose that both indirect (biochemical) and direct (mechanical) signalling are important in these early stages of regulating stem cell fate as a consequence of altered metabolic changes and altered phenotype. The current studies provide new insight on cell-surface interactions and enhance our understanding of the modulation of stem cell differentiation with significant potential application in regenerative medicine

Customizable, engineered substrates for rapid screening of cellular cues

Biophysical cues robustly direct cell responses and are thus important tools for in vitro and translational biomedical applications. High throughput platforms exploring substrates with varying physical properties are therefore valuable. However, currently existing platforms are limited in throughput, the biomaterials used, the capability to segregate between different cues and the assessment of dynamic responses. Here we present a multiwell array (3x8) made of a substrate engineered to present topography or rigidity cues welded to a bottomless plate with a 96-well format. Both the patterns on the engineered substrate and the well plate format can be easily customized, permitting systematic and efficient screening of biophysical cues. To demonstrate the broad range of possible biophysical cues examinable, we designed and tested three multiwell arrays to influence cardiomyocyte, chondrocyte and osteoblast function. Using the multiwell array, we were able to measure different cell functionalities using analytical modalities such as live microscopy, qPCR and immunofluorescence. We observed that grooves (5 µm in size) induced less variation in contractile function of cardiomyocytes. Compared to unpatterned plastic, nanopillars with 127 nm height, 100 nm diameter and 300 nm pitch enhanced matrix deposition, chondrogenic gene expression and chondrogenic maintenance. High aspect ratio pillars with an elastic shear modulus of 16 kPa mimicking the matrix found in early stages of bone development improved osteogenic gene expression compared to stiff plastic. We envisage that our bespoke multiwell array will accelerate the discovery of relevant biophysical cues through improved throughput and variety

Real-time monitoring of exhaled volatiles using atmospheric pressure chemical ionization on a compact mass spectrometer

© 2016 Future Science Ltd.Aim: Breath analyses have potential to detect early signs of disease onset. Ambient ionization allows direct combination of breath gases with MS for fast, on-line analysis. Portable MS systems would facilitate field/clinic-based breath analyses. Results & methodology: Volunteers ingested peppermint oil capsules and exhaled volatile compounds were monitored over 10 h using a compact mass spectrometer. A rise and fall in exhaled menthone was observed, peaking at 60-120 min. Real-time analysis showed a gradual rise in exhaled menthone postingestion. Sensitivity was comparable to established methods, with detection in the parts per trillion range. Conclusion: Breath volatiles were readily analyzed on a portable mass spectrometer through a simple inlet modification. Induced changes in exhaled profiles were detectable with high sensitivity and measurable in real-time

Natural drivers of multidecadal Arctic sea ice variability over the last millennium

This is the final version. Available from Nature Research via the DOI in this record.The climate varies due to human activity, natural climate cycles, and natural events external to the climate system. Understanding the different roles played by these drivers of variability is fundamental to predicting near-term climate change and changing extremes, and to attributing observed change to anthropogenic or natural factors. Natural drivers such as large explosive volcanic eruptions or multidecadal cycles in ocean circulation occur infrequently and are therefore poorly represented within the observational record. Here we turn to the first high-latitude annually-resolved and absolutely dated marine record spanning the last millennium, and the Paleoclimate Modelling Intercomparison Project (PMIP) Phase 3 Last Millennium climate model ensemble spanning the same time period, to examine the influence of natural climate drivers on Arctic sea ice. We show that bivalve oxygen isotope data are recording multidecadal Arctic sea ice variability and through the climate model ensemble demonstrate that external natural drivers explain up to third of this variability. Natural external forcing causes changes in sea-ice mediated export of freshwater into areas of active deep convection, affecting the strength of the Atlantic Meridional Overturning Circulation (AMOC) and thereby northward heat transport to the Arctic. This in turn leads to sustained anomalies in sea ice extent. The models capture these positive feedbacks, giving us improved confidence in their ability to simulate future sea ice in in a rapidly evolving Arctic.Natural Environment Research Council (NERC)Natural Environment Research Council (NERC)Natural Environment Research Council (NERC)Leverhulme TrustAustralian Research CouncilEuropean Union’s Horizon 202

Label-free segmentation of co-cultured cells on a nanotopographical gradient

The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents

Patient Activity and Survival Following Implantable Cardioverter-Defibrillator Implantation: The ALTITUDE Activity Study

Background: Physical activity data are collected automatically by implantable cardioverter-defibrillators (ICDs). Though these data potentially provide a quantifiable and easily accessible measure of functional status, its relationship with survival has not been well studied. Methods and Results: Patients enrolled in the Boston Scientific LATITUDE remote monitoring system from 2008 to 2012 with ICDs were eligible. Remote monitoring data were used to calculate mean daily activity at baseline (30 to 60 days after implantation), and longitudinally. Cox regression was used to examine the association between survival and increments of 30 minutes/day in both (1) mean baseline activity and (2) time-varying activity, with both adjusted for demographic and device characteristics. A total of 98 437 patients were followed for a median of 2.2 years (mean age of 67.7±13.1 years; 71.7% male). Mean baseline daily activity was 107.5±66.2 minutes/day. The proportion of patients surviving after 4 years was significantly higher among those in the most versus least active quintile of mean baseline activity (90.5% vs. 50.0%; log-rank P value, <0.001). Lower mean baseline activity (i.e., incremental difference of 30-minutes/day) was independently associated with a higher risk of death (adjusted hazard ratio [AHR], 1.44; 95% confidence interval [CI], 1.427 to 1.462). Time-varying activity was similarly associated with a higher risk of death (AHR, 1.48; 95% CI, 1.451 to 1.508), indicating that a patient having 30 minutes per day less activity in a given month has a 48% increased hazard for death when compared to a similar patient in the same month. Conclusions: Patient activity measured by ICDs strongly correlates with survival following ICD implantation

Metabolic profiling of human saliva before and after induced physiological stress by ultra-high performance liquid chromatography-ion mobility-mass spectrometry

A method has been developed for metabolite profiling of the salivary metabolome based on protein precipitation and ultra-high performance liquid chromatography coupled with ion mobility-mass spectrometry (UHPLC–IM–MS). The developed method requires 0.5 mL of human saliva, which is easily obtainable by passive drool. Standard protocols have been established for the collection, storage and pre-treatment of saliva. The use of UHPLC allows rapid global metabolic profiling for biomarker discovery with a cycle time of 15 min. Mass spectrometry imparts the ability to analyse a diverse number of species reproducibly over a wide dynamic range, which is essential for profiling of biofluids. The combination of UHPLC with IM–MS provides an added dimension enabling complex metabolic samples to be separated on the basis of retention time, ion mobility and mass-to-charge ratio in a single chromatographic run. The developed method has been applied to targeted metabolite identification and untargeted metabolite profiling of saliva samples collected before and after exercise-induced physiological stress. δ-Valerolactam has been identified as a potential biomarker on the basis of retention time, MS/MS spectrum and ion mobility drift time

Synthesis of Core-Shell Polymer Particles in Supercritical Carbon Dioxide via Iterative Monomer Addition

A new, robust methodology for the synthesis of polystyrene-poly(methyl methacrylate) (PS-PMMA) core-shell particles using seeded dispersion polymerisation in supercritical carbon dioxide is reported, where the core-shell ratio can be controlled predictably via manipulation of reagent stoichiometry. The key development is the application of an iterative addition of the MMA shell monomer to the pre-prepared PS core. Analysis of the materials with differing core-shell ratios indicate that all are isolated as single particle populations with distinct and controllable core-shell morphologies