Factors involved in cellular sensitivity to anthrax lethal toxin.

The lethal factor (LF) component of Bacillus anthracis lethal toxin (LeTx) cleaves mitogen activated protein kinase kinases (MAPKKs) in a variety of different cell-types, yet not all cells are susceptible to the toxin. Previous studies revealed that this toxin rapidly kills macrophages from specific genetic backgrounds whereas most other cell types are resistant. The reason for this selective killing is unclear, but suggests other factors may also be involved in LeTx intoxication. In the current study, DNA membrane arrays were used to identify broad changes in macrophage physiology after treatment with LeTx. Expression of genes, regulated by MAPKK activity did not change significantly, yet a series of genes under glycogen synthase kinase-3-beta (GSK-3beta) regulation changed expression following LeTx treatment. Correlating with these transcriptional changes, GSK-3beta was found to be below detectable levels in toxin-treated cells, and, an inhibitor of GSK-3beta, LiCl, sensitized resistant IC-21 macrophages to LeTx. In addition, zebrafish embryos treated with LeTx showed signs of delayed pigmentation and cardiac hypertrophy; both processes are subject to regulation by GSK-3beta. A putative compensatory response to loss of GSK-3beta was indicated by differential expression of three motor proteins following toxin treatment, and kiflc, a motor protein involved in sensitivity to LeTx, increased expression in toxin-sensitive cells yet decreased in resistant cells following toxin treatment. Differential expression of microtubule associating proteins and a decrease in the level of cellular tubulin were detected in LeTx-treated cells, both of which can result from loss of GSK-3beta activity. In addition to examining the cellular impact of LeTx on macrophages, studies were performed in order to identify additional factors that govern LeTx sensitivity among different cell-types. Specifically, comparisons were made regarding the rate of toxin entry among macrophage and non-macrophage lines. These studies revealed differences in the rate of toxin entry among the cell lines tested, which, in turn, could contribute to the differences in susceptibility of these lines. Together, the data presented in this thesis provide new information on LeTx's overall influence on macrophage physiology, and suggest that loss of GSK-3beta as well as changes in kinesin motor proteins and microtubule stability contributes to cytotoxicity

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains.</p> <p>Methods</p> <p>This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the <it>APOE </it>gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (<it>LIPC </it>-514C>T, LIPC -250G>A) were considered.</p> <p>Results</p> <p>At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the <it>APOE </it>E3/E3 genotype, LDL-cholesterol (<it>P </it>= 0.02) increased in the NGI group (n = 7), and TAG (<it>P </it>= 0.03) and TAG:HDL-cholesterol (<it>P </it>= 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread.</p> <p>Conclusions</p> <p>In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the <it>APOE </it>E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.</p

Earth Observations and Integrative Models in Support of Food and Water Security

Global food production depends upon many factors that Earth observing satellites routinely measure about water, energy, weather, and ecosystems. Increasingly sophisticated, publicly-available satellite data products can improve efficiencies in resource management and provide earlier indication of environmental disruption. Satellite remote sensing provides a consistent, long-term record that can be used effectively to detect large-scale features over time, such as a developing drought. Accuracy and capabilities have increased along with the range of Earth observations and derived products that can support food security decisions with actionable information. This paper highlights major capabilities facilitated by satellite observations and physical models that have been developed and validated using remotely-sensed observations. Although we primarily focus on variables relevant to agriculture, we also include a brief description of the growing use of Earth observations in support of aquaculture and fisheries

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^&#x3e;0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

The Primordial Inflation Polarization Explorer (PIPER)

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne cosmic microwave background (CMB) polarimeter designed to search for evidence of inflation by measuring the large-angular scale CMB polarization signal. BICEP2 recently reported a detection of B-mode power corresponding to the tensor-to-scalar ratio r = 0.2 on ~2 degree scales. If the BICEP2 signal is caused by inflationary gravitational waves (IGWs), then there should be a corresponding increase in B-mode power on angular scales larger than 18 degrees. PIPER is currently the only suborbital instrument capable of fully testing and extending the BICEP2 results by measuring the B-mode power spectrum on angular scales $\theta$ = ~0.6 deg to 90 deg, covering both the reionization bump and recombination peak, with sensitivity to measure the tensor-to-scalar ratio down to r = 0.007, and four frequency bands to distinguish foregrounds. PIPER will accomplish this by mapping 85% of the sky in four frequency bands (200, 270, 350, 600 GHz) over a series of 8 conventional balloon flights from the northern and southern hemispheres. The instrument has background-limited sensitivity provided by fully cryogenic (1.5 K) optics focusing the sky signal onto four 32x40-pixel arrays of time-domain multiplexed Transition-Edge Sensor (TES) bolometers held at 140 mK. Polarization sensitivity and systematic control are provided by front-end Variable-delay Polarization Modulators (VPMs), which rapidly modulate only the polarized sky signal at 3 Hz and allow PIPER to instantaneously measure the full Stokes vector (I, Q, U, V) for each pointing. We describe the PIPER instrument and progress towards its first flight.Comment: 11 pages, 7 figures. To be published in Proceedings of SPIE Volume 9153. Presented at SPIE Astronomical Telescopes + Instrumentation 2014, conference 915

The Grizzly, September 27, 1994

Berry\u27s Political Future Uncertain • Violence in Haiti Will Not be Tolerated • Status of Citizenship Questioned • What is Newman Society? • On Being Reared in the U.S. • What Scares Me • Rabinor Opens Lectures on Eating Disorders • UC Volleyball Battles Floor Problems and Injuries • UC X-C Runners are New and Improved • Defense to do it for Eagles • Bears Drop Close One to Western Marylandhttps://digitalcommons.ursinus.edu/grizzlynews/1341/thumbnail.jp

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

Identification and immune assessment of T cell epitopes in five Plasmodium falciparum blood stage antigens to facilitate vaccine candidate selection and optimization

The hurdles to effective blood stage malaria vaccine design include immune evasion tactics used by the parasite such as redundant invasion pathways and antigen variation among circulating parasite strains. While blood stage malaria vaccine development primarily focuses on eliciting optimal humoral responses capable of blocking erythrocyte invasion, clinically-tested Plasmodium falciparum (Pf) vaccines have not elicited sterile protection, in part due to the dramatically high levels of antibody needed. Recent development efforts with non-redundant, conserved blood stage antigens suggest both high antibody titer and rapid antibody binding kinetics are important efficacy factors. Based on the central role of helper CD4 T cells in development of strong, protective immune responses, we systematically analyzed the class II epitope content in five leading Pf blood stage antigens (RH5, CyRPA, RIPR, AMA1 and EBA175) using in silico, in vitro, and ex vivo methodologies. We employed in silico T cell epitope analysis to enable identification of 67 HLA-restricted class II epitope clusters predicted to bind a panel of nine HLA-DRB1 alleles. We assessed a subset of these for HLA-DRB1 allele binding in vitro, to verify the in silico predictions. All clusters assessed (40 clusters represented by 46 peptides) bound at least two HLA-DR alleles in vitro. The overall epitope prediction to in vitro HLA-DRB1 allele binding accuracy was 71%. Utilizing the set of RH5 class II epitope clusters (10 clusters represented by 12 peptides), we assessed stimulation of T cells collected from HLA-matched RH5 vaccinees using an IFN-γ T cell recall assay. All clusters demonstrated positive recall responses, with the highest responses – by percentage of responders and response magnitude – associated with clusters located in the N-terminal region of RH5. Finally, a statistically significant correlation between in silico epitope predictions and ex vivo IFN-γ recall response was found when accounting for HLA-DR matches between the epitope predictions and donor HLA phenotypes. This is the first comprehensive analysis of class II epitope content in RH5, CyRPA, RIPR, AMA1 and EBA175 accompanied by in vitro HLA binding validation for all five proteins and ex vivo T cell response confirmation for RH5

The Grizzly, October 4, 1994

1994 Homecoming Court Spotlighted • Research Opportunities • Family Day \u2794 a Success • Arms Embargo Still Intact • Mining Industry Saved From Taxation • Homecoming Queen Nominees • New Lab Expands Horizons of Freshman Biologists • Recycling Lets Everyone Breathe a Little Easier • Kilmartin Lightens up Lower Lounge • Bright Moments and Sweet Sounds • Executing Justice with Pro-Theatre • Suggestions, Please! • Exploring Secrets & Truths Otherwise Unknown • Jam at the Trench • A Lesson in Life • The Real World: Collegeville • Prejudice Can Eclipse Unique Differences • Swarthmore Hands Bears Second Straight Defeat • UC Volleyball Loses Pair • UC Captain\u27s Council Set to Make Changeshttps://digitalcommons.ursinus.edu/grizzlynews/1342/thumbnail.jp