Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Production of tocotrienols in seeds of cotton (Gossypium hirsutum L.) enhances oxidative stability and offers nutraceutical potential

Upland cotton (Gossypium hirsutum L.) is an economically important multi-purpose crop cultivated globally for fibre, seed oil and protein. Cottonseed oil also is naturally rich in vitamin E components (collectively known as tocochromanols), with a- and c-tocopherols comprising nearly all of the vitamin E components. By contrast, cottonseeds have little or no tocotrienols, tocochromanols with a wide range of health benefits. Here, we generated transgenic cotton lines expressing the barley (Hordeum vulgare) homogentisate geranylgeranyl transferase coding sequence under the control of the Brassica napus seed-specific promoter, napin. Transgenic cottonseeds had ~twofold to threefold increases in the accumulation of total vitamin E (tocopherols + tocotrienols), with more than 60% c-tocotrienol. Matrix assisted laser desorption ionization-mass spectrometry imaging showed that c-tocotrienol was localized throughout the transgenic embryos. In contrast, the native tocopherols were distributed unequally in both transgenic and non-transgenic embryos. a- Tocopherol was restricted mostly to cotyledon tissues and c-tocopherol was more enriched in the embryonic axis tissues. Production of tocotrienols in cotton embryos had no negative impact on plant performance or yield of other important seed constituents including fibre, oil and protein. Advanced generations of two transgenic events were field grown, and extracts of transgenic seeds showed increased antioxidant activity relative to extracts from non-transgenic seeds. Furthermore, refined cottonseed oil from the two transgenic events showed 30% improvement in oxidative stability relative to the non-transgenic cottonseed oil. Taken together, these materials may provide new opportunities for cottonseed co-products with enhanced vitamin E profile for improved shelf life and nutrition

Fabrication and heating rate study of microscopic surface electrode ion traps

We report heating rate measurements in a microfabricated gold-on-sapphire surface electrode ion trap with trapping height of approximately 240 micron. Using the Doppler recooling method, we characterize the trap heating rates over an extended region of the trap. The noise spectral density of the trap falls in the range of noise spectra reported in ion traps at room temperature. We find that during the first months of operation the heating rates increase by approximately one order of magnitude. The increase in heating rates is largest in the ion loading region of the trap, providing a strong hint that surface contamination plays a major role for excessive heating rates. We discuss data found in the literature and possible relation of anomalous heating to sources of noise and dissipation in other systems, namely impurity atoms adsorbed on metal surfaces and amorphous dielectrics.Comment: 17 pages, 5 figure

Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia

Rituximab-containing chemotherapy remains a viable frontline treatment option for patients with chronic lymphocytic leukemia (CLL) in the era of novel agents. However, its effectiveness in the second-line setting—in relation to previous rituximab exposure in first-line—has hardly been evaluated in a population-based setting. Therefore, in this comprehensive, population-based study, we assessed the impact of first-line treatment with rituximab-containing chemotherapy on the effectiveness of second-line treatment with rituximab-containing chemot

The effectiveness of ibrutinib in chronic lymphocytic leukaemia: a nationwide, population-based study in the Netherlands

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The simulation of the activity dependent neural network growth

It is currently accepted that cortical maps are dynamic constructions that are altered in response to external input. Experience-dependent structural changes in cortical microcurcuts lead to changes of activity, i.e. to changes in information encoded. Specific patterns of external stimulation can lead to creation of new synaptic connections between neurons. The calcium influxes controlled by neuronal activity regulate the processes of neurotrophic factors released by neurons, growth cones movement and synapse differentiation in developing neural systems. We propose a model for description and investigation of the activity dependent development of neural networks. The dynamics of the network parameters (activity, diffusion of axon guidance chemicals, growth cone position) is described by a closed set of differential equations. The model presented here describes the development of neural networks under the assumption of activity dependent axon guidance molecules. Numerical simulation shows that morpholess neurons compromise the development of cortical connectivity.Comment: 10 pages, 2 figure

EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL

gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies