Leech antihemostatic proteins share the T-knot scaffold, a disulfide-reinforced structural motif

The occurrence of similar topologies among unrelated proteins is an emerging theme in structural biology. Here we report that the T-knot scaffold, a disulfide-reinforced structural motif shared by knottins and EGF-like proteins, is also present in leech antihemostatic proteins. Our finding emphasizes the versatile nature of this small structural motif, representing a compact structural unit suitable for the diverse biological functions performed by knottins, EGF-like proteins and leech antihemostatic proteins.     

Aneurysms of the supra-aortic trunks in Takayasu''s disease. Report of two cases

Two new canine osteosarcoma cell lines were established. One (OOS) was established from a 10-year-old female maltese dog with mandibular osteosarcoma and the other (HOS) from a 7-year-old male mongrel dog with scapular osteosarcoma. Histopathological types of OOS and HOS were mixed and fibroblastic cell type, respectively. Transmission electron microscopic features of HOS revealed prominent rough endoplasmic reticulum, suggesting higher malignancy comparing to OOS. Doubling time of OOS and HOS were 45.0 +/- 0.5 hr and 42.0 +/- 0.1 hr, respectively. Alkaline phosphatase activities of OOS and HOS were quite low. Histological features of tumor tissues produced by transplantation of these cells into nude mice were identical to those of original osteosarcomas.     

Bioclogging of Sand due to Biodegradation of Aircraft Deicing Fluid

The biodegradation of propylene glycol (PG) and PG-based aircraft deicing fluid (ADF) at initial concentrations of 400–100,000?mg/L was investigated in saturated sand columns operated under nitrogen-limited conditions that are expected occur in the environment. PG biodegradation resulted in the accumulation of 0.4–1.4?mg volatile solids/g sand, which decreased the hydraulic conductivity of the sand by 23–99.8%. At loading up to 0.27?mg ADF or PG/g sand/d, greater than 99% PG removal and 88% soluble chemical oxygen demand (COD) removal were achieved. At higher loading, removal efficiency decreased but the removal rate increased to 11.2?mg?PG/g sand/day and up to 10.7?mg COD/g sand/day. As ADF or PG loading increased causing more nitrogen-limited conditions and likely a greater amount of PG fermentation, cell yields decreased and a greater fraction of incomplete mineralization of the ADF and PG were noted as measured by higher residual soluble COD. The results indicate that natural attenuation of PG in groundwater is likely to occur in association with potentially significant bioclogging.     

Molecular‐Level Switching of Polymer/Nanocrystal Non‐Covalent Interactions and Application in Hybrid Solar Cells

Hybrid composites obtained upon blending conjugated polymers and colloidal semiconductor nanocrystals are regarded as attractive photo­active materials for optoelectronic applications. Here it is demonstrated that tailoring nanocrystal surface chemistry permits to control non‐covalent and electronic interactions between organic and inorganic components. The pending moieties of organic ligands at the nanocrystal surface are shown to not merely confer colloidal stability while hindering charge separation and transport, but drastically impact morphology of hybrid composites during formation from blend solutions. The relevance of this approach to photovoltaic applications is demonstrated for composites based on poly(3‐hexylthiophene) and lead sulfide nanocrystals, considered as inadequate until this report, which enable the fabrication of hybrid solar cells displaying a power conversion efficiency that reaches 3%. By investigating (quasi)steady‐state and time‐resolved photo‐induced processes in the nanocomposites and their constituents, it is ascertained that electron transfer occurs at the hybrid interface yielding long‐lived separated charge carriers, whereas interfacial hole transfer appears hindered. Here a reliable alternative aiming to gain control over macroscopic optoelectronic properties of polymer/nanocrystal composites by mediating their non‐covalent interactions via ligands' pending moieties is provided, thus opening new possibilities towards efficient solution‐processed hybrid solar cells.     

Synthesis of Free NH 2‐(Aminomethyl)indoles through Copper‐Catalyzed Reaction of 3‐(ortho‐Trifluoroacetamidophenyl)‐1‐propargylic Alcohols with Amines and Palladium/Copper‐ Cocatalyzed Domino Three‐Component Sonogashira Cross‐Coupling/Cyclization/Substitution Reactions

Free NH 2‐(aminomethyl)indoles have been prepared via copper‐catalyzed cyclization of 3‐(ortho‐trifluoroacetamidophenyl)‐1‐propargylic alcohols in the presence of primary or secondary amines. The synthesis has been developed into a simple and very efficient domino three‐component Sonogashira cross‐coupling/cyclization/substitution process that, omitting the isolation of 3‐(ortho‐trifluoroacetamidophenyl)‐1‐propargylic alcohols, provides access to this class of compounds by treating 2‐iodotrifluoroacetanilides, propargylic alcohols, and primary or secondary amines with a copper/palladium catalyst system.

     

Redundancy of autocrine loops in human osteosarcoma cells

With the aim of identifying innovative therapeutic strategies for osteosarcoma patients who are refractory to conventional chemotherapy, we analyzed the in vitro effects of the blockage of autocrine circuits. Since the insulin-like growth factor-I receptor (IGF-IR)-mediated loop is relevant to the growth of osteosarcoma, we analyzed the activity of the IGF-IR-blocking antibody alphaIR3 in both sensitive and multidrug-resistant osteosarcoma cell lines. Only limited effects, however, were observed, suggesting the simultaneous existence of other autocrine circuits. Indeed, in a representative panel of 12 human osteosarcoma cell lines, in addition to the IGF-IR-mediated circuit, we demonstrated also a loop mediated by epidermal growth factor receptor as well as the presence of nerve growth factor, low-affinity nerve growth factor receptor as well as tyrosine receptor kinase A in the great majority of osteosarcomas. Therapies based on the inhibition of single circuits may have only limited effects in osteosarcoma, whereas the use of suramin, a drug which, besides other activities, non-selectively interferes with the binding of growth factors to their receptors, appears as a promising alternative, in both sensitive and drug-resistant osteosarcoma cells.     

Towards Ideal Magnetofluorescent Nanoparticles for Bimodal Detection of Breast‐Cancer Cells

An increasing number of novel molecular markers based on nanomaterials for tumor diagnostics have been developed in recent years. Many efforts have focused on the achievement of site‐targeted bioconjugated nanoparticles. In contrast, the mechanisms of toxicity, endocytosis, and degradation pathways are still poorly understood, despite their primary importance for clinical translation. In this study, three different model nanoscale magnetofluorescent particle systems (MFNs) are designed and fabricated. These nanoparticles are evaluated in terms of size, morphology, zeta potential, fluorescence efficiency, capability of enhancing T₂ relaxivity of water protons, and stability. Accordingly, two are developed and the mechanism of internalization, the intracellular fate, and the toxicity in MCF‐7 adenocarcinoma cells are studied. Besides the well‐documented size effect, the anionic charge seems to be a crucial factor for particle internalization, as MFN penetration through the cell membrane could be modulated by surface charge. Ultrastructural analysis of transmission electron micrographs combined with evidence from confocal microscopy reveals that MFNs are internalized by clathrin‐mediated endocytosis and macropinocytosis. Moreover, MFNs are found in EEA1‐positive endosomes and in lysosomes, indicating that they follow a physiological pathway of endocytosis. Magnetorelaxometric analysis demonstrates that MFNs enable the detection of 5 × 10⁵ cells mL^?1 after treatment with particle dosages as low as 30 µg mL^?1. Hence, MFNs appear to be a valuable and safe bimodal contrast agent that can be developed for the noninvasive diagnosis of breast cancer.