Genetically modified (GM) late blight-resistant potato and consumer attitudes before and after a field visit

Late blight, caused by Phytophthora infestans, is the most devastating disease in potato production. Here, we show full late blight resistance in a location with a genetically diverse pathogen population with the use of GM potato stacked with three resistance (R) genes over three seasons. In addition, using this field trials, we demonstrate that in-the-field intervention among consumers led to change for more favorable attitude generally toward GM crops

Biomechanics of Circumferential Cervical Fixation Using Posterior Facet Cages: A Cadaveric Study.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a common procedure for the treatment of cervical disease. Circumferential procedures are options for multilevel pathology. Potential complications of multilevel anterior procedures are dysphagia and pseudarthrosis, whereas potential complications of posterior surgery include development of cervical kyphosis and postoperative chronic neck pain. The addition of posterior cervical cages (PCCs) to multilevel ACDF is a minimally invasive option to perform circumferential fusion. This study evaluated the biomechanical performance of 3-level circumferential fusion with PCCs as supplemental fixation to anteriorly placed allografts, with and without anterior plate fixation. METHODS: Nondestructive flexibility tests (1.5 Nm) performed on 6 cervical C2-7 cadaveric specimens intact and after discectomy (C3-6) in 3 instrumented conditions: allograft with anterior plate (G+P), PCC with allograft and plate (PCC+G+P), and PCC with allograft alone (PCC+G). Range of motion (ROM) data were analyzed using 1-way repeated-measures analysis of variance. RESULTS: All instrumented conditions resulted in significantly reduced ROM at the 3 instrumented levels (C3-6) compared to intact spinal segments in flexion, extension, lateral bending, and axial rotation (p \u3c 0.001). No significant difference in ROM was found between G+P and PCC+G+P conditions or between G+P and PCC+G conditions, indicating similar stability between these conditions in all directions of motion. CONCLUSION: All instrumented conditions resulted in considerable reduction in ROM. The added reduction in ROM through the addition of PCCs did not reach statistical significance. Circumferential fusion with anterior allograft, without plate and with PCCs, has comparable stability to ACDF with allograft and plate

"Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence

Latently infected, resting memory CD4+ T cells and macrophages represent a major obstacle to the eradication of HIV-1. For this purpose, "shock and kill" strategies have been proposed (activation of HIV-1 followed by stimuli leading to cell death). Histone deacetylase inhibitors (HDACIs) induce HIV-1 activation from quiescence, yet class/isoform-selective HDACIs are needed to specifically target HIV-1 latency. We tested 32 small molecule HDACIs for their ability to induce HIV-1 activation in the ACH-2 and U1 cell line models. In general, potent activators of HIV-1 replication were found among non-class selective and class I-selective HDACIs. However, class I selectivity did not reduce the toxicity of most of the molecules for uninfected cells, which is a major concern for possible HDACI-based therapies. To overcome this problem, complementary strategies using lower HDACI concentrations have been explored. We added to class I HDACIs the glutathione-synthesis inhibitor buthionine sulfoximine (BSO), in an attempt to create an intracellular environment that would facilitate HIV-1 activation. The basis for this strategy was that HIV-1 replication decreases the intracellular levels of reduced glutathione, creating a pro-oxidant environment which in turn stimulates HIV-1 transcription. We found that BSO increased the ability of class I HDACIs to activate HIV-1. This interaction allowed the use of both types of drugs at concentrations that were non-toxic for uninfected cells, whereas the infected cell cultures succumbed more readily to the drug combination. These effects were associated with BSO-induced recruitment of HDACI-insensitive cells into the responding cell population, as shown in Jurkat cell models for HIV-1 quiescence. The results of the present study may contribute to the future design of class I HDACIs for treating HIV-1. Moreover, the combined effects of class I-selective HDACIs and the glutathione synthesis inhibitor BSO suggest the existence of an Achilles' heel that could be manipulated in order to facilitate the "kill" phase of experimental HIV-1 eradication strategies

HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

Oilseed rape transformed with a pea lectin gene

Plants genetically modified (GM) for insect resistance (IR) have to be tested and compared to their non-GM counterparts with respect to several aspects. This thesis summarizes the effects of three transgenic lines of oilseed rape (Brassica napus) expressing pea (Pisum sativum) seed lectin (PSL) in the pollen on a target pest: the pollen beetle (Meligethes aeneus), and a non-target insect: the honey bee (Apis mellifera). The competitive ability of the transgenic plants was tested to evaluate potential invasive characters. Finally, attitudes towards GM crops among Swedish farmers were surveyed. Pollen beetle adults and larvae were exposed to three PSL expressing plant lines and two control lines without any PSL. Fourteen life history parameters were studied and significant differences between transgenes and controls were found for egg size and larval mortality. This means that the modification does not prevent direct damage to the attacked crop but the effects could, together with the action of natural enemies, lead to a reduced pollen beetle population. The sensitivity of honey bee larvae to PSL containing pollen was tested by feeding them diets with high levels of transgenic or control pollen. The addition of pollen had a positive effect on developmental time and larval weight but no differences were detected between transgenic and non-transgenic pollen. Competitive ability was tested by growing transgenic plants either in monoculture or mixed with control plants, with or without pollen beetles, and with or without pollinators (bumblebees). Plant characters related to plant fitness were measured but transgenic plants did not benefit from the transformation regarding pest damage. However, yield was higher on transgenic plants when grown mixed with control plants than when grown in monoculture, and the opposite was true for control plants. A majority of the surveyed farmers were negative to GM crops and considered consumers' unwillingness to buy GM products as the largest drawback, while higher yield was considered the largest potential benefit from growing such crops

Does pea lectin expressed transgenically in oilseed rape (

The European honey bee (Apis mellifera) is important both for pollination and for honey production. Pollen is the major protein source for bees, which exposes them directly to changes in pollen quality e.g. through genetic engineering. In order to create a worst case scenario regarding pea lectin (PSL) expressed transgenically in oilseed rape anthers and pollen, the maximum amount of dried pollen that could be mixed in an artificial diet without negatively affecting larval performance (1.5% w/w) was fed to bee larvae. Pollen from two transgenic plant lines expressing PSL up to 1.2% of total soluble protein and pollen from one non-transgenic line was added to the same diet and used as a pollen control. When these three pollen diets and the control diet (without added pollen) were compared, no negative effect from the pollen of the transgenic plants could be detected on larval mortality, weight, or development time. An increased weight and a reduced developmental time were recorded for larvae on all diets containing pollen when compared to the diet without pollen

Swedish farmers attitudes, expectations and fears in relation to growing genetically modified crops

This study evaluates a survey about Swedish farmers' attitude towards genetically modified (GM) crops, and their perception concerning potential benefits and drawbacks that cropping of an insect resistant (IR) GM variety would involve. The questions were “tick a box” choices, included in a yearly omnibus survey sent to 1000 Swedish farmers (68% response rate). The results showed that a majority of the farmers were negative, although almost one third claimed to be neutral to GM crops. The farmers recognized several benefits both in terms of agricultural production and for the environment, but they were also highly concerned about the consumers' unwillingness to buy GM products. Farmers perceived an increase in yield, but nearly as many farmers thought that there would be no benefits with growing an IR GM crop. Several differences in hopes and concerns of the farmers surveyed were revealed when they were divided in positive, neutral and negative groups. Farmers negative to GM were more concerned than positive farmers about IR GM crops being dangerous for humans, livestock or other organisms to consume. GM-positive farmers seemed to be most concerned about potential problems with growing a marketable crop and expensive seeds, but saw a reduced health risk to the grower, due to less use of pesticides, as a possible benefit. The results among the GM-neutral farmers were in most cases closely related to the positive farmers' choices, implying that they believe that there are advantages with growing an IR GM crop, but also fear potential drawbacks. This general uncertainty about GM IR crops may prevent them from accepting the new technology

Impact of herbivory and pollination on performance and competitive ability of oilseed rape transformed for pollen beetle resistance

Competitive ability of transgenic oilseed rape transformed with a pea lectin gene was estimated by comparisons of its performance when grown in a mixture with its non-transgenic counterpart and when grown singly, with and without pollen beetles present. The experiments were carried out in cages, once with bumblebees as pollinators and once without. In the absence of herbivory but with the presence of bumblebees, singly grown plant lines without lectin generally performed better than lines with lectin. Pollen beetles affected plant growth and reproduction, but there were no consistent differences between the lectin and non-lectin plant lines indicating that the transgenic trait did not protect plants from pest attack. Herbivory reduced the number of seeds when bumblebees were present. In the absence of bumblebees, however, plants produced more seeds with pollen beetles than without, indicating that some pollination was carried out by the beetles. Efficient pollination affected the competitive abilities of the lines; lectin lines were more competitive with bumblebees present and the reverse was true when bumblebees were absent. In the presence of bumblebees, lectin lines gained from being grown mixed with its non-transgenic counterpart. Because the transgenic plants expressed pea lectin in developing pollen it is possible that pollen quality in those plants was reduced, which may explain why the lectin lines had an advantage over non-lectin lines when exchange of pollen between the two plant types was facilitated by bumblebees