Studies on Mycobacterium johnei infection in cattle and mice

Abstract Not Provided

Improving Water Quality Through BMPs For Crop Production Systems Whole Farm Soil and Water Management

The major objective of this demonstration project was to assess the usefulness of Global Positioning Systems/Geographic Information Systems (GPS/GIS), water testing, soil testing and yield monitoring in a whole farm water and soil management plan. An important part of this objective was to make recommendations to increase crop productivity and decrease the potential for surface water degradation through erosion and runoff at the farm. The farm was located on 2400 acres in the Bayou de View watershed in Monroe County, Arkansas. The farm lies approximately five miles southwest of the town of Brinkley straddling Highway 17 just south of its intersection with County Road 302 and with U. S. Highway 70. Slightly over 2200 acres were under cultivation and this was generally in a 1 :2 ratio of rice to soybeans, with approximately half of the soybean fields double-cropped with winter wheat each year

HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution

Author Correction: Development of a sensitive, quantitative assay with broad subtype specificity for detection of total HIV-1 nucleic acids in plasma and PBMC

Correction to: Scientific Reports https://doi.org/10.1038/s41598-021-03016-1, published online 28 January 202

The lipids of the common house cricket,Acheta domesticus L. I. Lipid classes and fatty acid distribution

The lipids of the common house cricket,Acheta domesticus L., have been examined with the following results. The fatty acids associated with the lipid extracts do not change significantly from the third through the eleventh week of the crickets’ postembryonic life. The major fatty acids are linoleic (30–40%), oleic (23–27%), palmitic (24–30%), and stearic acids (7–11%). There are smaller amounts of palmitoleic (3–4%), myristic (∼1%), and linolenic acids (<1%). The fatty acid composition of the cricket lipids reflects but is not identical to the fatty acids of the dietary lipids: linoleic (53%), oleic (24%), palmitic (15%), stearic (3%), myristic (2%), and linolenic acid (2%).The amount of triglycerides present in the crickets increases steadily from the second through the seventh or eighth week of postembryonic life, then drops sharply. Other lipid classes, such as hydrocarbons, simple esters, diglycerides, monoglycerides, sterols, and free fatty acids remain about constant. The composition of the fatty acids associated with the tri‐, di‐, and monoglycerides and the free fatty acid fraction are all about the same. The fatty acids associated with the simple esters are high in stearic acid.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142007/1/lipd0247.pd

P08.36 Radioresistance of glioblastoma stem-like cells is associated with DNA replication stress, which is a promising therapeutic target

Introduction: The inevitability of tumour recurrence in glioblastoma (GBM) patients despite multi-modality treatment consisting of surgery, radiotherapy and chemotherapy, is reflected by a median survival of only 14 months. Tumour recurrence is thought to be driven by a small population of glioblastoma stem-like cells (GSCs) that are resistant to conventional therapies. DNA damage response (DDR) pathways have been shown to be up-regulated in GSCs and implicated in radioresistance and treatment failure. However the precise cause of enhanced DDR signalling in GSCs and the extent to which these signalling networks contribute to therapy resistance remains elusive. The objectives of this study were to investigate the underlying cause of DDR upregulation and treatment resistance in GSCs with a view to identifying novel and promising therapeutic targets. Materials and Methods: A panel of primary patient derived GBM cell lines cultured under conditions to enrich for or deplete the tumour stem cell population (GSC vs bulk respectively) were utilised in order to investigate enhanced GSC DDR under basal conditions and in response to ionising radiation. Confirmatory studies were also performed in cells sorted for the putative GSC marker CD133. The effects of a panel of small molecule DDR inhibitor agents on cell survival in GSC and bulk cells were quantified. Results: GSCs exhibited higher levels of total and activated DDR targets ATR, CHK1, ATM and PARP1 under basal conditions and were radioresistant compared to paired bulk populations. This was not due to increased levels of reactive oxygen species (ROS). Instead, we show that RPA is significantly higher in replicating GSCs and confirm by DNA fibre assays that GSCs and CD133+ cells have increased numbers of stalled replication forks, fewer new origins and slower DNA replication compared to bulk or CD133- populations, demonstrating for the first time that replication stress (RS) is a hallmark of GSCs. We identify increased expression of long neural genes as a likely mechanism for RS and DNA double strand breaks (DSBs) in GSCs and show that their radioresistance is reversed by dual inhibition of key RS and DDR proteins ATR and PARP. Conclusions: This study demonstrates the novel finding that replication stress is a hallmark of GSCs and resonates with recently published studies in neural progenitor cells showing that RS preferentially induces DNA DSB in long neural genes. Taken together, we implicate RS as a driver of enhanced DDR in GSCs and identify novel therapeutics with potential to improve clinical outcomes by overcoming the radioresistance of GB

Polarized organic electroluminescence: Ordering from the top

We demonstrate a method for achieving polarized organic electroluminescence for liquid crystalline conjugated polymers that allows the polymer to be deposited directly onto the anode. The technique utilizes a top-down alignment approach whereby the predeposited polymer was aligned from above using a rubbed polyimide master and a smectic liquid crystal transfer layer. The liquid crystal/polyimide master bilayer was sandwiched with the liquid crystalline polymer that had been deposited onto the electrode. The sandwiched layers were then heated to achieve alignment before the removal of the polyimide master and liquid crystal transfer layer. Using this method, poly[2,7-{9,9-di(2-ethylhexyl)}fluorene] (PF2-6) was aligned to give an anisotropic polymer film. Light emitted from single layer light-emitting diodes containing the aligned PF2-6 had integrated dichroic ratios of up to 9.7. At 100 cd/m(2), the single layer devices had external quantum and power efficiencies of 0.08% and 0.05 lm/W, respectively. Bilayer devices containing an electron transport layer between the PF2-6 and the cathode gave emitted light with good dichroic ratios and with the external quantum and power efficiencies at 100 cd/m(2) being increased to 2.2% and 1.1 lm/W. (C) 2003 American Institute of Physics

Breadth of CD8 T-cell mediated inhibition of replication of diverse HIV-1 transmitted-founder isolates correlates with the breadth of recognition within a comprehensive HIV-1 Gag, Nef, Env and Pol potential T-cell epitope (PTE) peptide set.

Full characterisation of functional HIV-1-specific T-cell responses, including identification of recognised epitopes linked with functional antiviral responses, would aid development of effective vaccines but is hampered by HIV-1 sequence diversity. Typical approaches to identify T-cell epitopes utilising extensive peptide sets require subjects' cell numbers that exceed feasible sample volumes. To address this, CD8 T-cells were polyclonally expanded from PBMC from 13 anti-retroviral naïve subjects living with HIV using CD3/CD4 bi-specific antibody. Assessment of recognition of individual peptides within a set of 1408 HIV-1 Gag, Nef, Pol and Env potential T-cell epitope peptides was achieved by sequential IFNγ ELISpot assays using peptides pooled in 3-D matrices followed by confirmation with single peptides. A Renilla reniformis luciferase viral inhibition assay assessed CD8 T-cell-mediated inhibition of replication of a cross-clade panel of 10 HIV-1 isolates, including 9 transmitted-founder isolates. Polyclonal expansion from one frozen PBMC vial provided sufficient CD8 T-cells for both ELISpot steps in 12 of 13 subjects. A median of 33 peptides in 16 epitope regions were recognised including peptides located in previously characterised HIV-1 epitope-rich regions. There was no significant difference between ELISpot magnitudes for in vitro expanded CD8 T-cells and CD8 T-cells directly isolated from PBMCs. CD8 T-cells from all subjects inhibited a median of 7 HIV-1 isolates (range 4 to 10). The breadth of CD8 T-cell mediated HIV-1 inhibition was significantly positively correlated with CD8 T-cell breadth of peptide recognition. Polyclonal CD8 T-cell expansion allowed identification of HIV-1 isolates inhibited and peptides recognised within a large peptide set spanning the major HIV-1 proteins. This approach overcomes limitations associated with obtaining sufficient cell numbers to fully characterise HIV-1-specific CD8 T-cell responses by different functional readouts within the context of extreme HIV-1 diversity. Such an approach will have useful applications in clinical development for HIV-1 and other diseases