Cancer regression in patients after transfer of genetically engineered lymphocytes

Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.     

Clinical evaluation of intranasal medetomidine–ketamine and medetomidine–S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques

Objective

The aim was to compare efficacy and side effects of induction with medetomidine–ketamine or medetomidine–S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia.

Suitability of sawdust from three tropical timbers for wood-cement composites

Construction material rising cost and global demand for economically-sustainable and environmentally-friendly building resources have necessitated the use of sawdust-cement composite. Wood constituents and cement incompatibility hinder its production and need careful selection of the timber. Sawdust suitability from Triplochiton scleroxylon, Entandrophragma cylindricum and Klainedoxa gabonensis for wood-cement composite was determined by identifying their chemical constituents and their composites’ physico-mechanical properties. T. scleroxylon recorded the minimum total extractive (6.12%), lignin (29.89%) and holocellulose (56.38%) and K. gabonensis the maximum (9.31, 31.59 and 57.5% respectively). Ash content was higher for T. scleroxylon (7.6%) but lower for K. gabonensis (1.53%). T. scleroxylon boards were stronger [Modulus of Elasticity (MOE) = 696.1 N/m²] and more moisture-resistant [Moisture Absorption (MA) = 8.8%] than E. cylindricum (MOE = 625.9 N/m²; MA = 9.5%). K. gabonensis boards crushed after manufacturing due to its incompatibility with cement. T. scleroxylon sawdust is suitable for wood-cement composites due to its more compatible chemical constituents (i.e., lower extractive, lignin, holocellulose contents and more ash) and its boards’ excellent physico-mechanical properties than those for the other timbers. Its sawdust-cement composites could be utilized for cladding and walling. The use of sawdust would increase green building resource base and reduce environmental pollution.     

The impact of seasonal variability in wildlife populations on the predicted spread of foot and mouth disease

Modeling potential disease spread in wildlife populations is important for predicting, responding to and recovering from a foreign animal disease incursion such as foot and mouth disease (FMD). We conducted a series of simulation experiments to determine how seasonal estimates of the spatial distribution of white-tailed deer impact the predicted magnitude and distribution of potential FMD outbreaks. Outbreaks were simulated in a study area comprising two distinct ecoregions in South Texas, USA, using a susceptible-latent-infectious-resistant geographic automata model (Sirca). Seasonal deer distributions were estimated by spatial autoregressive lag models and the normalized difference vegetation index. Significant (P < 0.0001) differences in both the median predicted number of deer infected and number of herds infected were found both between seasons and between ecoregions. Larger outbreaks occurred in winter within the higher deer-density ecoregion, whereas larger outbreaks occurred in summer and fall within the lower deer-density ecoregion. Results of this simulation study suggest that the outcome of an FMD incursion in a population of wildlife would depend on the density of the population infected and when during the year the incursion occurs. It is likely that such effects would be seen for FMD incursions in other regions and countries, and for other diseases, in cases in which a potential wildlife reservoir exists. Study findings indicate that the design of a mitigation strategy needs to take into account population and seasonal characteristics.     

Evolution of a microbial acetyltransferase for modification of glyphosate: a novel tolerance strategy

N-Acetylation is a modification of glyphosate that could potentially be used in transgenic crops, given a suitable acetyltransferase. Weak enzymatic activity (k(cat) = 5 min(-1), K(M) = 1 mM) for N-acetylation of glyphosate was discovered in several strains of Bacillus licheniformis (Weigmann) Chester by screening a microbial collection with a mass spectrometric assay. The parental enzyme conferred no tolerance to glyphosate in any host when expressed as a transgene. Eleven iterations of DNA shuffling resulted in a 7000-fold improvement in catalytic efficiency (k(cat)/K(M)), sufficient for conferring robust tolerance to field rates of glyphosate in transgenic tobacco and maize. In terms of k(cat)/K(M), the native enzyme exhibited weak activity (4-450% of that with glyphosate) with seven of the common amino acids. Evolution of the enzyme towards an improved k(cat)/K(M) for glyphosate resulted in increased activity toward aspartate (40-fold improved k(cat)), but activity with serine and phosphoserine almost completely vanished. No activity was observed among a broad sampling of nucleotides and antibiotics. Improved catalysis with glyphosate coincided with increased thermal stability.     

Variation Among Physical,Compositional, and Wet‐Milling Characteristics of the F1 Generation of Corn Hybrids of Introgressed Exotic and Adapted Inbred Lines

Hybrids with high grain yield and higher starch, protein, or oil content are available to corn growers; however, they result from crossing adapted Corn Belt inbred lines that rarely include exotic germplasm. This study was conducted to determine whether Corn Belt lines introgressed with exotic materials from Argentina, Chile, Uruguay, Cuba, and Florida have appropriate wet‐milling characteristics in their hybrids. Ten lines from the Germplasm Enhancement of Maize (GEM) project with different starch contents were crossed to three adapted inbred lines used as testers. The B73×Mo17 hybrid was used as a control. The F₁ generation of these 30 experimental hybrids was analyzed using both near‐infrared transmittance (NIT) technology and a 100‐g modified wet‐milling procedure, and measuring test and 1,000‐kernel weight. There was great variation among physical, compositional, and wet‐milling characteristics of the experimental hybrids, suggesting that exotic germplasm can be used to improve wet‐milling characteristics of Corn Belt hybrids.