Synthesis and characterization of chromium-isothiocyanate-4-methylpyridine complexes

The synthesis and single crystal X-ray structure of trans-[HNC₆H₇][Cr(NCS)₄(NC₆H₇)₂] (1) and mer-[Cr(NCS)₃(NC₆H₇)₃] (2) are reported. Compound 1 was synthesized by refluxing chromium powder and thiourea in 4-methylpyridine. The isothiocyanate ligand is believed to be generated from the isomerization of thiourea to ammonium thiocyanate during synthesis. Compound 2 was prepared from CrCl₃ and KSCN in 4-methylpyridine. The reaction conditions for both compounds yielded a mixture of [Cr(NCS)_x(NC₆H₇)_6−x]^3−x isomers (x = 0-6), which were analyzed by HPLC. The thermal properties of trans-[HNC₆H₇][Cr(NCS)₄(NC₆H₇)₂] were analyzed by thermogravimetric analysis/differential scanning calorimetry-mass spectroscopy (TGA/DSC-MS), and the compound was found to oxidize to CrO₂ in three major weight loss steps when heated to 1000 °C in dry air.     

Leaf extraction and analysis framework graphical user interface: segmenting and analyzing the structure of leaf veins and areoles

Interest in the structure and function of physical biological networks has spurred the development of a number of theoretical models that predict optimal network structures across a broad array of taxonomic groups, from mammals to plants. In many cases, direct tests of predicted network structure are impossible given the lack of suitable empirical methods to quantify physical network geometry with sufficient scope and resolution. There is a long history of empirical methods to quantify the network structure of plants, from roots, to xylem networks in shoots and within leaves. However, with few exceptions, current methods emphasize the analysis of portions of, rather than entire networks. Here, we introduce the Leaf Extraction and Analysis Framework Graphical User Interface (LEAF GUI), a user-assisted software tool that facilitates improved empirical understanding of leaf network structure. LEAF GUI takes images of leaves where veins have been enhanced relative to the background, and following a series of interactive thresholding and cleaning steps, returns a suite of statistics and information on the structure of leaf venation networks and areoles. Metrics include the dimensions, position, and connectivity of all network veins, and the dimensions, shape, and position of the areoles they surround. Available for free download, the LEAF GUI software promises to facilitate improved understanding of the adaptive and ecological significance of leaf vein network structure.     

A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke

The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 ? and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 ?. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG(GMPPCP) to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.     

Pilot trial of interleukin-2 and zoledronic acid to augment γδ T cells as treatment for patients with refractory renal cell carcinoma

Prior to the advent of VEGF-targeted therapies, renal cell carcinoma (RCC) was among the few solid tumors shown to respond to cytokine-based therapies such as interleukin-2 (IL-2) and interferon alpha. Previous work has shown that aminobisphosphonates, including zoledronic acid (ZA), are capable of activating human Vγ9 Vδ2 T cells in vitro, and these cells can be further expanded with IL-2. Moreover, these Vγ9 Vδ2 T cells have cytolytic activity in vitro to multiple human tumor cell lines. In the current report, we have conducted a pilot trial in patients with metastatic RCC, evaluating different doses of ZA in combination with low-dose IL-2 to determine whether combining these agents can promote in vivo proliferation of Vγ9 Vδ2 T cells and elicit an antitumor response. In 12 patients evaluated, no objective clinical responses were observed by RECIST criteria; however, two patients experienced prolonged stable disease. A modest increase in Vγ9 Vδ2 T-cell frequency could be detected by Day 8 of therapy in four of the nine patients who received at least one cycle of therapy, but not to the magnitude anticipated from preclinical models. Repeated administration of IL-2 and ZA resulted in both a diminished in vivo percentage of Vγ9 Vδ2 T cells as well as impaired expansion in vitro after the first cycle of therapy. These results suggest that repeated administration of IL-2 and ZA, at the doses and schedules used in this trial, may actually inhibit the proliferative capacity of Vγ9 Vδ2 T cell in patients with metastatic RCC.