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Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin. We show that increasing expression of Cbx7 inhibits the proliferation of DIPG cells and prolongs its residence time. Our results highlight that the residence time of PcG proteins directly correlates with their functions and the search time of PcG proteins is critical for regulating their genomic occupancy. Together, our data provide mechanisms in which the cancer-causing histone mutation alters the binding and search dynamics of epigenetic complexes.

SUMMARY1. We tested the hypothesis that hypervolaemia causes an increase in intrasplenic filtration of cell-free fluid out of the vasculature. To this end we developed a preparation in the anaesthetized rat whereby the splenic vein could be nonocclusively cannulated.2. Haematocrit and plasma protein concentrations were measured in the splenic afferent and efferent blood supplies.3. In response to volume loading with saline (1 % body weight), there was a sustained increase in the arterial-venous differential of haematocrit, i.e. there was a relative increase in the haematocrit of the blood draining from the spleen. There was no such change in plasma protein concentration. By contrast, this degree of volume loading had no effect on the haematocrit of blood passing through the hindquarters of the animal.4. Following volume expansion, there was no significant difference in the protein concentration of the plasma and the lymph fluid collected from the splenic lymphatic duct.5. Distension of the superior vena caval-right atrial junction by means of a small inflatable balloon, caused a similar increase in the splenic venous haematocrit, and again, no change in plasma protein concentration.6. We interpret these results to mean that, in response to expansion of the intravascular space, there is increased intrasplenic filtration of plasma out of the blood and into the lymphatic system.

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Electromagnetic nondestructive tests are important and widely used within the field of nondestructive evaluation (NDE). The recent advances in sensing technology, hardware and software development dedicated to imaging and image processing, and material sciences have greatly expanded the application fields, sophisticated the systems design and made the potential of electromagnetic NDE imaging seemingly unlimited. This review provides a comprehensive summary of research works on electromagnetic imaging methods for NDE applications, followed by the summary and discussions on future directions.

The spleen is an important site of atrial natriuretic factor (ANF)‐induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood‐perfused (1 ml min−1) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1‐28), infused into the splenic artery of anaesthetized male rats, caused a dose‐dependent (0.3‐59 pmol min−1) increase in microvascular pressure from 11.3 ± 0.7 to 14.9 ± 0.5 mmHg and in post‐capillary resistance from 7.2 ± 0.6 to 10.1 ± 1.1 mmHg ml−1. ANF elicited no change in splenic pre‐capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min−1) caused a sustained increase in intrasplenic fluid efflux from 0.1 ± 0.1 to 0.3 ± 0.1 ml min−1, and in capillary filtration coefficient (Kf) from 1.2 ± 0.5 to 2.4 ± 0.6 ml mmHg−1 min−1 (100 g tissue)−1. Mechanical elevation of splenic intravascular pressure (from 11.3 ± 0.7 to 22.4 ± 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 ± 0.3 to 1.4 ± 0.3 ml min−1). The natriuretic peptide receptor‐C (NPRC)‐specific agonist C‐ANF(4‐23) (12.5 and 125 pmol min−1) did not alter splenic intravascular pressure or pre‐/post‐capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min−1), which blocks ANF‐stimulated cGMP production via natriuretic peptide receptor‐A (NPRA), inhibited the ANF‐induced changes in splenic microvascular pressure and post‐capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post‐capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

Stimulation of the atrial volume receptors increases neural traffic to the ventrolateral medulla, which in turn sends output to, and receives input from, the lateral hypothalamic area. An integrated reflex and hormonal response is thus initiated. We wished to investigate first whether atrial distension results in activation of selected nuclei in the forebrain and, second, whether pregnancy modifies this response. Rats were implanted with indwelling intracardiac balloons positioned at the superior vena caval/right atrial junction. One week later, the balloons were inflated. The animals were then anesthetized, their brains fixed by perfusion, and the tissue prepared for visualization of c-fos activity. Atrial distension caused a significant increase in c-fos expression in the paraventricular nucleus, the medial preoptic area, and the lateral septum. This response was markedly attenuated in the pregnant animals. In conclusion, during pregnancy central pathways that are normally activated in responses to volume expansion, fail to respond to atrial distension. We propose that this allows blood volume to increase in the pregnant animal, without triggering homeostatic mechanisms.