Registration of N614, A3N615, N616, and N617 Shattercane Genetic Stocks with Cytoplasmic or Nuclear Male Sterility and Juicy or Dry Midribs

Four shattercane [Sorghum bicolor subsp. drummondii (Nees ex Steud.) de Wet ex Davidse] genetic stocks—N614 (Reg. No. GS-652, PI 665684), A3N615 (Reg. No. GS-651, PI 665683), N616 (Reg. No. GS-653, PI 665685), and N617 (Reg. No. GS-654, PI 665686)—with A3 cytoplasmic male sterility or the nuclear male sterility gene ms3 containing either juicy (dd) or dry (DD) culms were developed jointly by the USDA-ARS; the Iowa Agricultural and Home Economics Experiment Station, College of Agriculture and Life Sciences, Iowa State University; and the Agricultural Research Division, Institute of Agriculture and Natural Resources, University of Nebraska. The stocks were released in July 2011. The source material for these genetic stocks was isolated from an archetypical shattercane population found near Lincoln, NE. Release of these genetic stocks makes available shattercane lines with both A3 cytoplasmic male sterility, and ms3 genetic (nuclear) male sterility to facilitate crossing. These genetic stocks also contain juicy (dd) or dry (DD) culms, a visible genetic marker to facilitate screening progeny resulting from crosses. The genetic stocks have immediate application for basic research involving gene flow from cultivated sorghum [Sorghum bicolor (L.) Moench] to shattercane and on the fitness of offspring resulting from such crosses

Promoter keyholes enable specific and persistent multi-gene expression programs in primary T cells without genome modification

Non-invasive epigenome editing is a promising strategy for engineering gene expression programs, yet potency, specificity, and persistence remain challenging. Here we show that effective epigenome editing is gated at single-base precision via 'keyhole' sites in endogenous regulatory DNA. Synthetic repressors targeting promoter keyholes can ablate gene expression in up to 99% of primary cells with single-gene specificity and can seamlessly repress multiple genes in combination. Transient exposure of primary T cells to keyhole repressors confers mitotically heritable silencing that persists to the limit of primary cultures in vitro and for at least 4 weeks in vivo, enabling manufacturing of cell products with enhanced therapeutic efficacy. DNA recognition and effector domains can be encoded as separate proteins that reassemble at keyhole sites and function with the same efficiency as single chain effectors, enabling gated control and rapid screening for novel functional domains that modulate endogenous gene expression patterns. Our results provide a powerful and exponentially flexible system for programming gene expression and therapeutic cell products

Neoliberalism, consultants and the privatisation of public policy formulation: The case of Britain's rail industry

This paper identifies the importance of policy advisers, particularly consultants, in promoting neoliberal prescriptions in public policy formulation in the recent history of British Government. It examines a consultant-dominated attempt to reform British Rail in the 1980s and the fundamental contribution of advisers to the flawed fragmentation and subsequent privatisation of the rail industry. Concepts drawn from Latour's Sociology of Translation are adopted to examine the attempts by Conservative Governments and their private advisory allies to establish networks of support for privatisation. In each of the episodes along the path to privatisation the paper examines attempts to undermine opposition and gain acceptance of the proposed changes with the production of knowledge claims by consultants, that is Latour's process of purification, followed by the consequences for the rail industry. The paper uses critical financial analysis to contrast the knowledge claims made by consultants with the outcomes of rail privatisation, which include extensive, ongoing transfers from taxpayers to private companies. It concludes by highlighting the dangers ensuing from dogmatic and excessive neoliberal public policy formulation

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection

Field damage of sorghum (\u3ci\u3eSorghum bicolor\u3c/i\u3e) with reduced lignin levels by naturally occurring insect pests and pathogens

Sorghum (Sorghum bicolor (L.) Moench) brown midrib (bmr) mutant lines have reduced levels of lignin, which is a potentially useful trait for bioenergy production, but the effects of this trait on insect and plant pathogen interactions are unknown under field conditions. Field-grown bmr6, bmr12, and wild-type (WT) plants were examined for insect and disease damage. In most cases, observed frequency, population, or leaf area damage caused by insects or pathogens on bmr6 or bmr12 plants were not greater than those observed on WT plants in the field or laboratory assays. European corn borers [Ostrinia nubilalis (Hübner)(Lepidoptera: Pyralidae)] often caused lower amounts of leaf damage to bmr6 leaves compared to bmr12 and sometimes WT leaves in the field study. Leaf damage by corn earworms [Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae)] and fall armyworms [Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae)] in laboratory assays was often lower for bmr versus WT leaves. Incidence of disease lesions was significantly higher on bmr6 compared to WT plants for one of three samplings in 2011, but the opposite trend was observed overall in 2012 and no significant differences were noted in 2013. When corn earworms and fall armyworms were fed the excised pith, bmr6 and/or bmr12 pith caused significant morality to one or both insect species in all 3 years. Damage variability between the 3 years may have been due to hotter and drier than normal conditions in 2012. Thus, bmr lines of sorghum suitable for bioenergy production have potential for sustainable production in the field

Field damage of sorghum (\u3ci\u3eSorghum bicolor\u3c/i\u3e) with reduced lignin levels by naturally occurring insect pests and pathogens

Sorghum (Sorghum bicolor (L.) Moench) brown midrib (bmr) mutant lines have reduced levels of lignin, which is a potentially useful trait for bioenergy production, but the effects of this trait on insect and plant pathogen interactions are unknown under field conditions. Field-grown bmr6, bmr12, and wild-type (WT) plants were examined for insect and disease damage. In most cases, observed frequency, population, or leaf area damage caused by insects or pathogens on bmr6 or bmr12 plants were not greater than those observed on WT plants in the field or laboratory assays. European corn borers [Ostrinia nubilalis (Hübner)(Lepidoptera: Pyralidae)] often caused lower amounts of leaf damage to bmr6 leaves compared to bmr12 and sometimes WT leaves in the field study. Leaf damage by corn earworms [Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae)] and fall armyworms [Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae)] in laboratory assays was often lower for bmr versus WT leaves. Incidence of disease lesions was significantly higher on bmr6 compared to WT plants for one of three samplings in 2011, but the opposite trend was observed overall in 2012 and no significant differences were noted in 2013. When corn earworms and fall armyworms were fed the excised pith, bmr6 and/or bmr12 pith caused significant morality to one or both insect species in all 3 years. Damage variability between the 3 years may have been due to hotter and drier than normal conditions in 2012. Thus, bmr lines of sorghum suitable for bioenergy production have potential for sustainable production in the field

Efficacy of Singular and Stacked \u3ci\u3ebrown midrib 6\u3c/i\u3e and \u3ci\u3e12\u3c/i\u3e in the Modification of Lignocellulose and Grain Chemistry

In sorghum, brown midrib (bmr) 6 and 12 impair the last two steps of monolignol synthesis. bmr genes were introduced into grain sorghum to improve the digestibility of lignocellulosic tissues for grazing or bioenergy uses following grain harvest. Near-isogenic grain sorghum hybrids (AWheatland X RTx430) were developed containing bmr6, bmr12, and the bmr6 bmr12 double mutant (stacked), and their impacts were assessed in a two-year field study. The bmr genes did not significantly impact grain or lignocellulosic tissue yield. Lignocellulosic tissue from bmr6, bmr12, and stacked hybrids had reduced lignin content and increased in vitro dry matter digestibility (IVDMD) compared to those of the wild type (WT). The lignin content of the stacked lignocellulosic tissue was further reduced compared to that of bmr6 or bmr12. Surprisingly, bmr12 modestly increased carbohydrates in lignocellulosic tissue, and bmr6 increased fiber and lignin content in grain. These data indicate that bmr6 and bmr12 have broader effects on plant composition than merely lignin content, which has promising implications for both livestock utilization and bioenergy conversion

Efficacy of Singular and Stacked \u3ci\u3ebrown midrib 6\u3c/i\u3e and \u3ci\u3e12\u3c/i\u3e in the Modification of Lignocellulose and Grain Chemistry

In sorghum, brown midrib (bmr) 6 and 12 impair the last two steps of monolignol synthesis. bmr genes were introduced into grain sorghum to improve the digestibility of lignocellulosic tissues for grazing or bioenergy uses following grain harvest. Near-isogenic grain sorghum hybrids (AWheatland X RTx430) were developed containing bmr6, bmr12, and the bmr6 bmr12 double mutant (stacked), and their impacts were assessed in a two-year field study. The bmr genes did not significantly impact grain or lignocellulosic tissue yield. Lignocellulosic tissue from bmr6, bmr12, and stacked hybrids had reduced lignin content and increased in vitro dry matter digestibility (IVDMD) compared to those of the wild type (WT). The lignin content of the stacked lignocellulosic tissue was further reduced compared to that of bmr6 or bmr12. Surprisingly, bmr12 modestly increased carbohydrates in lignocellulosic tissue, and bmr6 increased fiber and lignin content in grain. These data indicate that bmr6 and bmr12 have broader effects on plant composition than merely lignin content, which has promising implications for both livestock utilization and bioenergy conversion