1,724 research outputs found
Reusable rule-based cell cycle model explains compartment-resolved dynamics of 16 observables in RPE-1 cells
The mammalian cell cycle is regulated by a well-studied but complex biochemical reaction system. Computational models provide a particularly systematic and systemic description of the mechanisms governing mammalian cell cycle control. By combining both state-of-the-art multiplexed experimental methods and powerful computational tools, this work aims at improving on these models along four dimensions: model structure, validation data, validation methodology and model reusability.
We developed a comprehensive model structure of the full cell cycle that qualitatively explains the behaviour of human retinal pigment epithelial-1 cells. To estimate the model parameters, time courses of eight cell cycle regulators in two compartments were reconstructed from single cell snapshot measurements. After optimisation with a parallel global optimisation metaheuristic we obtained excellent agreements between simulations and measurements. The PEtab specification of the optimisation problem facilitates reuse of model, data and/or optimisation results.
Future perturbation experiments will improve parameter identifiability and allow for testing model predictive power. Such a predictive model may aid in drug discovery for cell cycle-related disorders
Transport behavior of holes in boron delta-doped diamond structures
Boron delta-doped diamond structures have been synthesized using microwave plasma chemical vapor deposition and fabricated into FET and gated Hall bar devices for assessment of the electrical characteristics. A detailed study of variable temperature Hall, conductivity, and field-effect mobility measurements was completed. This was supported by Schr€dinger-Poisson and relaxation time o calculations based upon application of Fermi’s golden rule. A two carrier-type model was developed with an activation energy of 1 cm2/Vs and the bulk valence band with high mobility. This new understanding of the transport of holes in such boron delta-doped structures has shown that although Hall mobility as high as 900 cm2/Vs was measured at room temperature, this dramatically overstates the actual useful performance of the device
Spectral properties of the X-ray binary pulsar LMC X-4 during different intensity states
We present spectral variations of the binary X-ray pulsar LMC X-4 observed
with the RXTE/PCA during different phases of its 30.5 day long third period.
Only out of eclipse data were used for this study. The 3-25 keV spectrum,
modeled with high energy cut-off power-law and iron line emission is found to
show strong dependence on the intensity state. Correlations between the Fe line
emission flux and different parameters of the continuum are presented here.Comment: 4 pages, 4 figure
How thinking hurts:Rumination, worry, and avoidance processes in adjustment to bereavement
Repetitive negative thought plays an important role in the maintenance of mental health problems following bereavement. To date, bereavement researchers have primarily focused on rumination (i.e., repetitive thought about negative events and/or negative emotions), yet the interest in worry (i.e., repetitive thought about uncertain future events) is increasing. Both cognitive processes potentially lead to poorer adaptation to bereavement by contributing to loss-related avoidance and behavioural avoidance of activities. The current study aims to establish the differential associations of rumination and worry with symptoms of depression and prolonged grief and clarify if avoidance processes mediate the associations of rumination and worry with symptom levels. Four hundred seventy-four recently bereaved adults (82% female) filled out questionnaires assessing rumination, worry, loss-related and behavioural avoidance, and depression and prolonged grief symptoms. Rumination and worry were both uniquely associated with depression and prolonged grief symptoms. Compared with worry, rumination related more strongly to prolonged grief symptoms, whereas correlations of both cognitive styles with depression symptoms did not differ. Loss-related avoidance and behavioural avoidance partially mediated the associations of rumination and worry with prolonged grief symptoms. Behavioural avoidance partially mediated the associations of rumination and worry with depression symptoms. Findings suggest that exposure and behavioural activation may be effective interventions to reduce repetitive thinking and psychopathology after bereavement
High glucose up-regulates ENaC and SGK1 expression in HCD-cells
Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised.
Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry.
Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level.
Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy
PHAT Stellar Cluster Survey I. Year 1 Catalog and Integrated Photometry
The Panchromatic Hubble Andromeda Treasury (PHAT) survey is an on-going
Hubble Space Telescope (HST) multi-cycle program to obtain high spatial
resolution imaging of one-third of the M31 disk at ultraviolet through
near-infrared wavelengths. In this paper, we present the first installment of
the PHAT stellar cluster catalog. When completed, the PHAT cluster catalog will
be among the largest and most comprehensive surveys of resolved star clusters
in any galaxy. The exquisite spatial resolution achieved with HST has allowed
us to identify hundreds of new clusters that were previously inaccessible with
existing ground-based surveys. We identify 601 clusters in the Year 1 sample,
representing more than a factor of four increase over previous catalogs within
the current survey area (390 arcmin^2). This work presents results derived from
the first \sim25% of the survey data; we estimate that the final sample will
include \sim2500 clusters. For the Year 1 objects, we present a catalog with
positions, radii, and six-band integrated photometry. Along with a general
characterization of the cluster luminosities and colors, we discuss the cluster
luminosity function, the cluster size distributions, and highlight a number of
individually interesting clusters found in the Year 1 search.Comment: 26 pages, 22 figures, Accepted by Ap
Development of a GEM-TPC prototype
The use of GEM foils for the amplification stage of a TPC instead of a con-
ventional MWPC allows one to bypass the necessity of gating, as the backdrift
is suppressed thanks to the asymmetric field configuration. This way, a novel
continuously running TPC, which represents one option for the PANDA central
tracker, can be realized. A medium sized prototype with a diameter of 300 mm
and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using
a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector
test under realistic experimental conditions should allow us to verify the
spatial resolution for single tracks and the reconstruction capability for
displaced vertexes. A series of physics measurement implying pion beams is
scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como
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Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging
Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction
Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B
Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes, but their specialised functions in mitosis are incompletely understood. Using degron tags for rapid inducible protein removal, we analyse how acute depletion of these proteins affects mitosis. Loss of cyclin A in G2-phase prevents mitotic entry. Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phosphatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown, which requires a decisive shift in the balance of cyclin-dependent kinase Cdk1 and PP2A:B55 activity. Beyond this point, cyclin B/Cdk1 is essential for phosphorylation of a distinct subset of mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how cyclin A, cyclin B and Greatwall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phosphorylation
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