Insulin acts via mitogen-activated protein kinase phosphorylation in rabbit blastocysts

The addition of insulin during in vitro culture has beneficial effects on rabbit preimplantation embryos leading to increased cell proliferation and reduced apoptosis. We have previously described the expression of the insulin receptor (IR) and the insulin-responsive glucose transporters (GLUT) 4 and 8 in rabbit preimplantation embryos. However, the effects of insulin on IR signaling and glucose metabolism have not been investigated in rabbit embryos. In the present study, the effects of 170 nM insulin on IR, GLUT4 and GLUT8 mRNA levels, Akt and Erk phosphorylation, GLUT4 translocation and methyl glucose transport were studied in cultured day 3 to day 6 rabbit embryos. Insulin stimulated phosphorylation of the mitogen-activated protein kinase (MAPK) Erk1/2 and levels of IR and GLUT4 mRNA, but not phosphorylation of the phosphatidylinositol 3-kinase-dependent protein kinase, Akt, GLUT8 mRNA levels, glucose uptake or GLUT4 translocation. Activation of the MAPK signaling pathway in the absence of GLUT4 translocation and of a glucose transport response suggest that in the rabbit preimplantation embryo insulin is acting as a growth factor rather than a component of glucose homeostatic control.     

Switch-Matrix-Based High-Density Microelectrode Array in CMOS Technology

We report on a CMOS-based microelectrode array (MEA) featuring 11,011 metal electrodes and 126 channels, each of which comprises recording and stimulation electronics, for extracellular bidirectional communication with electrogenic cells, such as neurons or cardiomyocytes. The important features include: (i)$~$high spatial resolution at (sub)cellular level with 3150 electrodes per mm$^{2}$ (electrode diameter 7 $mu$ m, electrode pitch 18$ mu$m); (ii) a reconfigurable routing of the recording sites to the 126 channels; and (iii) low noise levels.      

Spin-Flip Raman Scattering on Electrons and Holes in Two-Dimensional (PEA)2PbI4 Perovskites

The class of Ruddlesden–Popper type (PEA)₂PbI₄ perovskites comprises 2D structures whose optical properties are determined by excitons with a large binding energy of about 260 meV. It complements the family of other 2D semiconductor materials by having the band structure typical for lead halide perovskites, that can be considered as inverted compared to conventional III–V and II–VI semiconductors. Accordingly, novel spin phenomena can be expected for them. Spin-flip Raman scattering is used here to measure the Zeeman splitting of electrons and holes in a magnetic field up to 10 T. From the recorded data, the electron and hole Landé factors (g-factors) are evaluated, their signs are determined, and their anisotropies are measured. The electron g-factor value changes from +2.11 out-of-plane to +2.50 in-plane, while the hole g-factor ranges between -0.13 and -0.51. The spin flips of the resident carriers are arranged via their interaction with photogenerated excitons. Also the double spin-flip process, where a resident electron and a resident hole interact with the same exciton, is observed showing a cumulative Raman shift. Dynamic nuclear spin polarization induced by spin-polarized holes is detected in corresponding changes of the hole Zeeman splitting. An Overhauser field of the polarized nuclei acting on the holes as large as 0.6 T can be achieved.     

Diffusional and orientational dynamics of various single terylene diimide conjugates in mesoporous materials

Mesoporous silica materials are ideally suited as host–guest systems in nanoscience with applications ranging from molecular sieves, catalysts, nanosensors to drug-delivery-systems. For all these applications a thorough understanding of the interactions between the mesoporous host system and the guest molecules is vital. Here, we investigate these interactions using single molecule spectroscopy (SMS) to study the dynamics of three different terylene diimide (TDI) dyes acting as molecular probes in hexagonal and lamellar mesoporous silica films. The diffusion behaviour in the hexagonal phase is represented by the trajectories of the single molecules. These trajectories are highly structured and thus provide information about the underlying host structure, such as domain size or the presence of defects inside the host structure. The three structurally different TDI derivatives allowed studying the influence of the molecular structure of the guest on the translational diffusion behaviour in the hexagonal phase and the lamellar phase. In the lamellar phase, the differences between the three guests are quite dramatic. First, two populations of diffusing molecules – one with parallel orientation of the molecules to the lamellae and the other with perpendicular orientation – could be observed for two of the TDI derivatives. These populations differ drastically in their translational diffusion behaviour. Depending on the TDI derivative, the ratio between the two populations is different. Additionally, switching between the two populations was observed. These data provide new insights into host–guest interactions like the influence of the molecular structure of the guest molecules on their diffusional as well as on their orientational behaviour in structurally confined guest systems.     

Combinatorial pharmacologic effects of gemcitabine and its metabolite dFdU

Recent evidence has shown that the gemcitabine metabolite, dFdU, is pharmacologically active. Though less potent, dFdU has a longer half‐life and could potentiate or antagonize the activity of gemcitabine. Hence, studies were undertaken to evaluate the combined effects. Following chemical synthesis, an improved purification procedure for dFdU was developed (80 % yield; >99 % purity). Zebrafish phenotype‐based embryo screens revealed no acute toxicity after gemcitabine or dFdU treatment. Only gemcitabine affected zebrafish development in a dose‐dependent manner. Synergy or antagonism for the combination was not observed. Antitumor effects for dFdU were dose dependent. Antagonism was tumor cell‐line dependent and did not depend on formation of the intracellular active metabolite of gemcitabine, suggesting that the drug–metabolite interaction occurs later. These studies highlight a platform for testing the pharmacologic activity for anticancer agent and metabolite combinations. Such analyses are expected to provide insight into the beneficial or harmful effect(s) of metabolites towards parent drug activity.     

Elastic constants of polycrystalline Ti3AlC2 and Ti3SiC2 measured using coherent inelastic neutron scattering

The magnitude of the single‐crystal elastic constant c₄₄ in the MAX phase Ti₃SiC₂ is under debate. In this paper, estimates for the magnitude of c₄₄ for MAX phases Ti₃AlC₂ and Ti₃SiC₂ are determined from a partially oriented polycrystalline sample via coherent inelastic neutron scattering. The largely quasi‐isotropic nature of these M_n+1AX_n phase elastic constants as previously predicted by density functional theory calculations is confirmed experimentally for Ti₃AlC₂ to be c₄₄=115.3 ± 30.7 GPa. In contrast, Ti₃SiC₂ is confirmed to be shear stiff with c₄₄=402.7 ± 78.3 GPa supporting results obtained by earlier elastic neutron diffraction experiments.     

CSF amine metabolites, clinical symptoms, and body movement in psychiatric patients

The relationships between CSF monoamine metabolites (HVA and 5HIAA), nurses' ratings of clinical symptoms, and telemetered measures of motor movement of ten schizophrenic and ten depressed patients were investigated. There was a significant negative correlation between CSF 5HIAA and both agitation ratings and motor movement in the schizophrenics. CSF HVA correlated positively to anxiety and anger in the depressives. The schizophrenics had a significantly higher CSF HVA than the depressives which appeared unrelated to motor movement. The effects of serotonin turnover and arousal in schizophrenia and the association between CSF metabolite gradients, stress, motor movement, and biogenic amine levels in depression are discussed.