Proteins from Avastin® (bevacizumab) Show Tyrosine Nitrations for which the Consequences Are Completely Unclear

Avastin® (bevacizumab) is a protein drug widely used for cancer treatment although its further use is questionable due to serious side effects reported. As no systematic proteomic study on posttranslational modifications (PTMs) was reported so far, it was the aim of the current study to use a gel-based proteomics method for determination of Avastin®-protein(s)

mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway

Comparative Stability and Sorption Study of Two <i><b>the</b></i>-type Metal–Organic Frameworks with Different Multiplicate Metal–Ligand Interactions in Secondary Building Units

By regulating secondary building units and inducing multiplicate metal–ligand interactions, an unstable anionic framework <b>MOF-Mn₄Cl</b> is structurally modified into a robust neutral framework <b>MOF-Mn₄</b>. Although possessing same network topology, <b>MOF-Mn₄</b> shows a high BET surface area of 1718 m²/g, which is about an 8 times enhancement over <b>MOF-Mn₄Cl</b>

2-DE image of Avastin® is shown providing assignments of identified protein spots.

<p>2-DE image of Avastin® is shown providing assignments of identified protein spots.</p

The modifications verified by HCT and Orbitrap.

<p>The modifications verified by HCT and Orbitrap.</p

Effects of Chahuangjing on Decorporation and Radiation Protection Against Tritiated Water

The purpose of this study was to investigate the effects of Chahuangjing, a novel traditional Chinese medicinal compound, on decorporation and radiation protection against tritiated water (HTO). Sixty male specific-pathogen-free-grade C57BL/6J mice were randomly divided into 12 groups: mice in 4 control groups were intraperitoneally injected with sterile water; mice in 4 HTO groups were intraperitoneally injected with 11.1 × 10 5 Bq/g of HTO; and mice in the other 4 groups were administered with HTO and a Chahuangjing compound (0.2 mL, once daily). After 1, 7, 14, and 21 days, the mice were killed and samples were collected. A liquid scintillation counting method was used for tritium measurement. A fully automated hematology analyzer was used to assess blood samples. The superoxide dismutase (SOD) and malondialdehyde (MDA) content was analyzed using commercial kits. Chahuangjing significantly increased decorporation and shortened the effective half-life of tritium. To a certain extent, Chahuangjing alleviated the HTO-induced reduction in white blood cells and elevated red blood cells after HTO exposure. Moreover, Chahuangjing alleviated the HTO-induced reduction in SOD activity and reduced MDA. Our study demonstrated that Chahuangjing can enhance the elimination of tritium and reduce free radicals to alleviate HTO-induced radiation injury

Identified nitrotyrosine or aminotyrosine modifications in Avastin by HCT and Orbitrap: the software proposes possible modifications on the peptide and subsequently assigns them to “measured m/z”. The theoretical m/z indicates the peptide mass with expected modifications.

a<p>Avastin Heavy chain</p>b<p>Avastin Light chain</p>c<p>Both nitrotyrosine and aminotyrosine modifications are identified at the same Y192 site of Spot 6.</p>d<p>given in Da</p

Self-Assembly of Polyhedral Indium–Organic Nanocages

A synthetic strategy to construct discrete indium–organic polyhedra has been illustrated based on small three-membered windows from a 2,5-pyridinedicarboxylate (PDC) ligand with an angle of 120°. [Et₂NH₂]₆[In₆(PDC)₁₂] (<b>InOF-10</b>) is a high-symmetry octahedron with eight three-membered windows, and [Et₂NH₂]₁₈[In₁₈(BPDC)₆(PDC)₃₀] (<b>InOF-11</b>) is a complex polyhedron derived from 3-edge-removed octahedra with an auxiliary biphenyl-3,3′-dicarboxylate (BPDC) ligand. Moreover, the sorption behavior of the latter is also well investigated

Scheme for the applied differentiation protocol.

<p>In order to initiate human AFS cell differentiation to a Schwann cell phenotype AFS cells were first treated in serum free α-MEM with 1 mM β-mercaptoethanol (Diff. I) for 24 hours. Afterwards cells were incubated in α-MEM supplemented with 10% fetal bovine serum and 35 ng/ml retinoic acid (Diff. II) for 72 hours. Subsequently, cells were cultured in α-MEM containing 10% fetal bovine serum supplemented with 20 ng/mL epidermal growth factor, 20 ng/mL basic fibroblast growth factor, 5 mM forskolin, 5 ng/mL platelet-derived growth factor-AA and 200 ng/mL recombinant human heregulin-beta1 (Diff. III) until day 15 of differentiation. Media was changed every 3 days, indicated by arrows. Pharmacologic (pharm.) treatment, consisting of rapamycin or statin, was applied together with Diff. III media.</p