A Policy Impact Analysis of the Mandatory NCAA Sickle Cell Trait Screening Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90062/1/hesr1357.pd

Metallothioneins may not be enough - the role of phytochelatins in invertebrate metal detoxification

'Viewpoint' article

Translational arrest due to cytoplasmic redox stress delays adaptation to growth on methanol and heterologous protein expression in a typical fed-batch culture of Pichia pastoris

Results We have followed a typical fed-batch induction regime for heterologous protein production under the control of the AOX1 promoter using both microarray and metabolomic analysis. The genetic constructs involved 1 and 3 copies of the TRY1 gene, encoding human trypsinogen. In small-scale laboratory cultures, expression of the 3 copy-number construct induced the unfolded protein response (UPR) sufficiently that titres of extracellular trypsinogen were lower in the 3-copy construct than with the 1-copy construct. In the fed-batch-culture, a similar pattern was observed, with higher expression from the 1-copy construct, but in this case there was no significant induction of UPR with the 3-copy strain. Analysis of the microarray and metabolomic information indicates that the 3-copy strain was undergoing cytoplasmic redox stress at the point of induction with methanol. In this Crabtree-negative yeast, this redox stress appeared to delay the adaptation to growth on methanol and supressed heterologous protein production, probably due to a block in translation. Conclusion Although redox imbalance as a result of artificially imposed hypoxia has previously been described, this is the first time that it has been characterised as a result of a transient metabolic imbalance and shown to involve a stress response which can lead to translational arrest. Without detailed analysis of the underlying processes it could easily have been mis-interpreted as secretion stress, transmitted through the UPR

Middle-out reasoning for synthesis and induction

We develop two applications of middle-out reasoning in inductive proofs: Logic program synthesis and the selection of induction schemes. Middle-out reasoning as part of proof planning was first suggested by Bundy et al [Bundy et al 90a]. Middle-out reasoning uses variables to represent unknown terms and formulae. Unification instantiates the variables in the subsequent planning, while proof planning provides the necessary search control. Middle-out reasoning is used for synthesis by planning the verification of an unknown logic program: The program body is represented with a meta-variable. The planning results both in an instantiation of the program body and a plan for the verification of that program. If the plan executes successfully, the synthesized program is partially correct and complete. Middle-out reasoning is also used to select induction schemes. Finding an appropriate induction scheme during synthesis is difficult, because the recursion of the program, which is un..

AEGIS: The Nature of the Host Galaxies of Low-ionization Outflows at z < 0.6

We report on a S/N-limited search for low-ionization gas outflows in the spectra of the 0.11 < z < 0.54 objects in the EGS portion of the DEEP2 survey. Doppler shifts from the host galaxy redshifts are systematically searched for in the Na I 5890,96 doublet (Na D). Although the spectral resolution and S/N limit us to study the interstellar gas kinematics from fitting a single doublet component to each observed Na D profile, the typical outflow often seen in local luminous-infrared galaxies (LIRGs) should be detected at >~ 6 sigma in absorption equivalent width down to the survey limiting S/N (~ 5 per pixel) in the continuum around Na D. The detection rate of LIRG-like outflow clearly shows an increasing trend with star-forming activity and infrared luminosity. However, by virtue of not selecting our sample on star formation, we also find a majority of outflows in galaxies on the red sequence in the rest-frame (U-B, M_B) color-magnitude diagram. Most of these red-sequence outflows are of early-type morphology and show the sign of recent star formation in their UV-optical colors; some show enhanced Balmer H-beta absorption lines indicative of poststarburst as well as high dust extinction. These findings demonstrate that outflows outlive starbursts and suggest that galactic-scale outflows play a role in quenching star formation in the host galaxies on their way to the red sequence. The fate of relic winds, as well as the observational constraints on gaseous feedback models, may be studied in galaxies during their poststarburst phase. We also note the presence of inflow candidates in red, early-type galaxies, some with signs of AGNs/LINERs but little evidence for star formation.Comment: 19 pages & 19 figures (emulateapj); the revision to match the published version in Ap

Unique metabolites protect earthworms against plant polyphenols

All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term ‘drilodefensins’. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide

Mid-IR Luminosities and UV/Optical Star Formation Rates at z<1.4

UV continuum and mid-IR emission constitute two widely used star formation indicators at intermediate and high redshifts. We study 2430 galaxies with z<1.4 in the Extended Groth Strip with MIPS 24 mic observations from FIDEL, spectroscopy from DEEP2, and UV, optical, and near-IR photometry from AEGIS. The data are coupled with stellar population models and Bayesian SED fitting to estimate dust-corrected SFRs. In order to probe the dust heating from stellar populations of various ages, the derived SFRs were averaged over various timescales--from 100 Myr for "current" SFR to 1--3 Gyr for long-timescale SFRs. These SED-based UV/optical SFRs are compared to total infrared luminosities extrapolated from 24 mic observations. We find that for the blue, actively star forming galaxies the correlation between the IR luminosity and the UV/optical SFR shows a decrease in scatter when going from shorter to longer SFR-averaging timescales. We interpret this as the greater role of intermediate age stellar populations in heating the dust than what is typically assumed. This holds over the entire redshift range. Many so-called green valley galaxies are simply dust-obscured actively star-forming galaxies. However, there exist 24 mic-detected galaxies, some with L>10^11 L_sun, yet with little current star formation. For them a reasonable amount of dust absorption of stellar light is sufficient to produce the observed levels of IR. In our sample optical and X-ray AGNs do not contribute on average more than ~50% to the mid-IR luminosity, and we see no evidence for a large population of "IR excess" galaxies (Abridged).Comment: Accepted for publication in ApJ. Content identical to arXiv version 1. No color figure

Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling

Heterologous protein production in the yeast Pichia pastoris can be limited by biological responses to high expression levels; the unfolded protein response (UPR) is a key determinant of the success of protein production in this organism. Here, we used untargeted NMR metabolic profiling (metabolomics) of a number of different recombinant strains, carried out in a miniaturized format suitable for screening-level experiments. We identified a number of metabolites (from both cell extracts and supernatants) which correlated well with UPR-relevant gene transcripts, and so could be potential biomarkers for future high-throughput screening of large numbers of P. pastoris clones.This study was wholly funded by the Bioprocessing Research Industry Club (BRIC), a partnership between BBSRC, EPSRC and a consortium of leading companies (http://www. bbsrc.ac.uk/business/collaborative-research/industry-clubs/bric/background.aspx, Grant reference BBF0049071)