This paper presents new geometrical flow equations for the theoretical modeling of biomolecular surfaces in the context of multiscale implicit solvent models. To account for the local variations near the biomolecular surfaces due to interactions between solvent molecules, and between solvent and solute molecules, we propose potential driven geometric flows, which balance the intrinsic geometric forces that would occur for a surface separating two homogeneous materials with the potential forces induced by the atomic interactions. Stochastic geometric flows are introduced to account for the random fluctuation and dissipation in density and pressure near the solvent-solute interface. Physical properties, such as free energy minimization (area decreasing) and incompressibility (volume preserving), are realized by some of our geometric flow equations. The proposed approach for geometric and potential forces driving the formation and evolution of biological surfaces is illustrated by extensive numerical experiments and compared with established minimal molecular surfaces and molecular surfaces. Local modification of biomolecular surfaces is demonstrated with potential driven geometric flows. High order geometric flows are also considered and tested in the present work for surface generation. Biomolecular surfaces generated by these approaches are typically free of geometric singularities. As the speed of surface generation is crucial to implicit solvent model based molecular dynamics, four numerical algorithms, a semi-implicit scheme, a Crank-Nicolson scheme, and two alternating direction implicit (ADI) schemes, are constructed and tested. Being either stable or conditionally stable but admitting a large critical time step size, these schemes overcome the stability constraint of the earlier forward Euler scheme. Aided with the Thomas algorithm, one of the ADI schemes is found to be very efficient as it balances the speed and accuracy.

M/Cu 2 O (M ¼ Ag, Au) heterogeneous nanocrystals are successfully prepared by depositing noble metal nanoparticles onto the surfaces of Cu 2 O octahedral nanocrystals through a simple photocatalytic process. The samples are characterized by means of X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX). The influence of the light source and solution temperature on the deposition of noble metal (taking Ag as an example) nanoparticles has been studied. The experimental results show that visible light is more favorable for the deposition of Ag nanoparticles onto Cu 2 O nanocrystals, and a solution temperature of more than 30 C can prevent the erosion of Cu 2 O. The photocatalytic properties of the prepared M/Cu 2 O heterogeneous nanocrystals are studied, showing enhanced photocatalytic activities.

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Management of brain tumours in children would benefit from improved non-invasive diagnosis, characterisation and prognostic biomarkers. Metabolite profiles derived from in-vivo MRS have been shown to provide such information. Studies indicate that using optimum a priori information on metabolite contents in the construction of linear combination (LC) models of MR spectra leads to improved metabolite profile estimation. Glycine (Gly) is usually neglected in such models due to strong overlap with myo-inositol (mI) and a low concentration in normal brain. However, biological studies indicate that Gly is abundant in high-grade brain tumours. This study aimed to investigate the quantitation of Gly in paediatric brain tumours using MRS analysed by LCModel, and its potential as a non-invasive biomarker of malignancy. Single-voxel MRS was performed using PRESS (TR 1500 ms, TE 30 ms/135 ms) on a 1.5 T scanner. Forty-seven cases (18 high grade (HG), 17 low grade (LG), 12 ungraded) were retrospectively selected if both short-TE and long-TE MRS (n = 33) or short-TE MRS and high-resolution magic-angle spinning (HRMAS) of matched surgical samples (n = 15) were available. The inclusion of Gly in LCModel analyses led to significantly reduced fit residues for both short-TE and long-TE MRS (p < 0.05). The Gly concentrations estimated from short-TE MRS were significantly correlated with the long-TE values (R = 0.91, p < 0.001). The Gly concentration estimated by LCModel was significantly higher in HG versus LG tumours for both short-TE (p < 1e-6) and long-TE (p = 0.003) MRS. This was consistent with the HRMAS results, which showed a significantly higher normalised Gly concentration in HG tumours (p < 0.05) and a significant correlation with the normalised Gly concentration measured from short-TE in-vivo MRS (p < 0.05). This study suggests that glycine can be reliably detected in paediatric brain tumours using in-vivo MRS on standard clinical scanners and that it is a promising biomarker of tumour aggressiveness.

Many growth factors and cytokines are involved in liver regeneration. Of them, only hepatopoietin (HPO)/ALR (augmenter of liver regeneration) is a specifically hepatotrophic factor originally identified from the cytosol of regenerating or hyperplastic hepatic cells. Previous reports indicate that extracellular HPO triggers the MAPK pathway by binding its specific receptor on the cell surface. However, its function in the cytosol of hepatocytes is unclear. Here we identified that JAB1 (Jun activation domain-binding protein 1), a co-activator of AP-1, which is essential for liver regeneration, specifically interacts with intracellular HPO. JAB1 colocalizes with HPO in nuclei of hepatic cells or COS-7 cells. As an intracrine factor, the intracellular function of HPO is to increase c-Jun phosphorylation independent of c-Jun amino-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) -1 and -2, and leads to potentiation of JAB1-mediated AP-1 activation. Amino acids 1-63 of HPO molecule are sufficient to bind to JAB1, but the full-length HPO is necessary for its intracellular signaling. Taken together, these results elucidate a novel mechanism of intracrine cytokine signaling by specifically modulating the AP-1 pathway through JAB1, in a MAPK-independent fashion.

BackgroundBrain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. 1H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients.Patients and methodsShort echo time (30 ms) single voxel 1H MRS was performed on children attending Birmingham Children’s Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35 months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power.ResultsLipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (p < 0.05). A multivariate model of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p < 5e–5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules.ConclusionsMRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy.

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