2,102 research outputs found
RCAN1.4 regulates VEGFR-2 internalisation, cell polarity and migration in human microvascular endothelial cells
Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the calcineurin pathway in cells. It is expressed as two isoforms in vertebrates: RCAN1.1 is constitutively expressed in most tissues, whereas transcription of RCAN1.4 is induced by several stimuli that activate the calcineurin-NFAT pathway. RCAN1.4 is highly upregulated in response to VEGF in human endothelial cells in contrast to RCAN1.1 and is essential for efficient endothelial cell migration and tubular morphogenesis. Here, we show that RCAN1.4 has a role in the regulation of agonist-stimulated VEGFR-2 internalisation and establishment of endothelial cell polarity. siRNA-mediated gene silencing revealed that RCAN1 plays a vital role in regulating VEGF-mediated cytoskeletal reorganisation and directed cell migration and sprouting angiogenesis. Adenoviral-mediated overexpression of RCAN1.4 resulted in increased endothelial cell migration. Antisense-mediated morpholino silencing of the zebrafish RCAN1.4 orthologue revealed a disrupted vascular development further confirming a role for the RCAN1.4 isoform in regulating vascular endothelial cell physiology. Our data suggest that RCAN1.4 plays a novel role in regulating endothelial cell migration by establishing endothelial cell polarity in response to VEGF
Circadian patterns of Wikipedia editorial activity: A demographic analysis
Wikipedia (WP) as a collaborative, dynamical system of humans is an
appropriate subject of social studies. Each single action of the members of
this society, i.e. editors, is well recorded and accessible. Using the
cumulative data of 34 Wikipedias in different languages, we try to characterize
and find the universalities and differences in temporal activity patterns of
editors. Based on this data, we estimate the geographical distribution of
editors for each WP in the globe. Furthermore we also clarify the differences
among different groups of WPs, which originate in the variance of cultural and
social features of the communities of editors
Cell lineage transport: a mechanism for molecular gradient formation
Gradient formation is a fundamental patterning mechanism during embryo development, commonly related to secreted proteins that move along an existing field of cells. Here, we mathematically address the feasibility of gradients of mRNAs and non-secreted proteins. We show that these gradients can arise in growing tissues whereby cells dilute and transport their molecular content as they divide and grow, a mechanism we termed ‘cell lineage transport.' We provide an experimental test by unveiling a distal-to-proximal gradient of Hoxd13 in the vertebrate developing limb bud driven by cell lineage transport, corroborating our model. Our study indicates that gradients of non-secreted molecules exhibit a power-law profile and can arise for a wide range of biologically relevant parameter values. Dilution and nonlinear growth confer robustness to the spatial gradient under changes in the cell cycle period, but at the expense of sensitivity in the timing of gradient formation. We expect that gradient formation driven by cell lineage transport will provide future insights into understanding the coordination between growth and patterning during embryonic development
Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)
Bovine TB is a major problem for the agricultural industry in several
countries. TB can be contracted and spread by species other than cattle and
this can cause a problem for disease control. In the UK and Ireland, badgers
are a recognised reservoir of infection and there has been substantial
discussion about potential control strategies. We present a coupling of
individual based models of bovine TB in badgers and cattle, which aims to
capture the key details of the natural history of the disease and of both
species at approximately county scale. The model is spatially explicit it
follows a very large number of cattle and badgers on a different grid size for
each species and includes also winter housing. We show that the model can
replicate the reported dynamics of both cattle and badger populations as well
as the increasing prevalence of the disease in cattle. Parameter space used as
input in simulations was swept out using Latin hypercube sampling and
sensitivity analysis to model outputs was conducted using mixed effect models.
By exploring a large and computationally intensive parameter space we show that
of the available control strategies it is the frequency of TB testing and
whether or not winter housing is practised that have the most significant
effects on the number of infected cattle, with the effect of winter housing
becoming stronger as farm size increases. Whether badgers were culled or not
explained about 5%, while the accuracy of the test employed to detect infected
cattle explained less than 3% of the variance in the number of infected cattle
Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report
Estimation and reconstruction of facial creases based on skull crease morphology
This research explores the relationships between the facial creases and the morphology of the underlying skull for supplementary use during forensic facial reconstruction. The correlation between skull morphology and the patterns of facial creases was obtained using the three-dimensional (3D) skull surface scans from the William Bass skeletal collection at the University of Tennessee, USA, which also provided the related ante-mortem face photographs. Superimposition of the facial crease patterns seen in a face photograph with the related skull image enabled the visual analysis of the correlation between the crease and the skull morphology. Qualitative analysis indicated that the infraorbital crease follows the outline of the orbit in 52% of the subjects, while the nasolabial fold (NLF) relates to the canine fossa in 95% of the subjects. The infraorbital crease and NLF were reconstructed in a blind study using ten 3D surface scan skull models and related face photographs from the Helmer collection available in the Centre for Anatomy and Human Identification, the University of Dundee, UK. Correct prediction was obtained in six specimens (60%). One inconclusive result was due to poor photograph quality and three inaccurate results showed an overestimation of the NLF strength although the location of the crease manifestation was correct
Alkaline earth metal ion catalysis of alcoholysis of crown ether aryl acetates. Effect of the base-solvent system
Prenatal Diagnosis of Oculocutaneous Albinism by Electron Microscopy of Fetal Skin
Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis
The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer
Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats
Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses
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