EFFECTS OF THE CANADIAN WHEAT BOARD ON THE U.S. WHEAT INDUSTRY

The practices of the Canadian Wheat Board (CWB) are an important issue in U.S. - Canada trade disputes and WTO negotiations. This study analyzes the CWB?s effect on U.S. producers by reviewing findings from previous research and developing models to analyze CWB wheat exports to the United States and the competitive structure of Canadian wheat exports in the world market. U.S. grain producers could benefit from the removal of the CWB as the United States could become more competitive in export markets. However, elimination of the CWB could also result in an increase in Canadian wheat exports to the United States as Canadian producers near the border could sell directly to the United States to take advantage of market opportunities. The net effect is difficult to quantify. The net benefits may be significant in the short run, but reduced significantly in the long run. Similarly, if Canada reforms its wheat board by eliminating trade-distorting subsidies, the United States may increase its exports and Canadian exports to the United States may increase. The net benefits from reforming the CWB could be greater than those from eliminating it. However, the United States could benefit the most from complete elimination of state trading enterprises (STEs), since they have elements distorting trade flows and the United States competes with several STEs in the world wheat market.Canadian Wheat Board, state trading enterprises, price discrimination, wheat exports, Crop Production/Industries, International Relations/Trade,

Comparative analysis of Drosophila and mammalian complexins as fusion clamps and facilitators of neurotransmitter release

The SNARE-binding protein complexin (Cpx) has been demonstrated to regulate synaptic vesicle fusion. Previous studies are consistent with Cpx functioning either as a synaptic vesicle fusion clamp to prevent premature exocytosis, or as a facilitator to directly stimulate release. Here we examined conserved roles of invertebrate and mammalian Cpx isoforms in the regulation of neurotransmitter release using the Drosophila neuromuscular junction as a model synapse. We find that SNARE binding by Cpx is required for its role as a fusion clamp. All four mammalian Cpx proteins (mCpx), which have been demonstrated to facilitate release, also function as fusion clamps when expressed in Drosophila cpx null mutants, though their clamping abilities vary between isoforms. Moreover, expression of mCpx I, II or III isoforms dramatically enhance evoked release compared to mCpx IV or Drosophila Cpx. Differences in the clamping and facilitating properties of complexin isoforms can be partially attributed to differences in the C-terminal membrane tethering domain. Our findings indicate that the function of complexins as fusion clamps and facilitators of fusion are conserved across evolution, and that these roles are genetically separable within an isoform and across different isoforms.National Institutes of Health (U.S.) (NIH Grant NS064750)National Institutes of Health (U.S.) (NIH Grant NS40296

A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease

Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases characterized by movement disorders, psychiatric disturbances and cognitive decline. Brain tissue from HD and HDL2 patients shows degeneration of the striatum and ubiquitinated inclusions immunoreactive for polyglutamine (polyQ) antibodies. Despite these similarities, the diseases result from different genetic mutations. HD is caused by a CAG repeat expansion in the huntingtin (HTT) gene, while HDL2 results from an expansion at the junctophilin 3 (JPH3) locus. Recent evidence indicates that the HDL2 expansion may give rise to a toxic polyQ protein translated from an antisense mRNA derived from the JPH3 locus. To investigate this hypothesis, we generated and characterized a Drosophila HDL2 model and compared it with a previously established HD model. We find that neuronal expression of HDL2-Q15 is not toxic, while the expression of an expanded HDL2-Q138 protein is lethal. HDL2-Q138 forms large nuclear aggregates, with only smaller puncta observed in the cytoplasm. This is in contrast to what is observed in a Drosophila model of HD, where polyQ aggregates localize exclusively to the cytoplasm. Altering localization of HLD2 with the addition of a nuclear localization or nuclear export sequence demonstrates that nuclear accumulation is required for toxicity in the Drosophila HDL2 model. Directing HDL2-Q138 to the nucleus exacerbates toxicity in multiple tissue types, while confining HDL2-Q138 to the cytoplasm restores viability to control levels. We conclude that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms are likely to drive toxicity in Drosophila models of these disorders.National Institutes of Health (U.S.) (Grants NS40296 and MH104536)JPB Foundatio

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

Neuronal pentraxins mediate synaptic refinement in the developing visual system

Peer reviewedPublisher PD

Efficient near-infrared organic light-emitting diodes with emission from spin doublet excitons

The development of luminescent organic radicals has resulted in materials with excellent optical properties for near-infrared (NIR) emission. Applications of light generation in this range span from bioimaging to surveillance. Whilst the unpaired electron arrangements of radicals enable efficient radiative transitions within the doublet-spin manifold in organic light-emitting diodes (OLEDs), their performance is limited by non-radiative pathways introduced in electroluminescence. Here, we present a host:guest design for OLEDs that exploits energy transfer with demonstration of up to 9.6% external quantum efficiency (EQE) for 800 nm emission. The tris(2,4,6-trichlorophenyl)methyl-triphenylamine (TTM-TPA) radical guest is energy-matched to the triplet state in a charge-transporting anthracene-derivative host. We show from optical spectroscopy and quantum-chemical modelling that reversible host-guest triplet-doublet energy transfer allows efficient harvesting of host triplet excitons

Xylamine, an Irreversible Inhibitor of Norepinephrine Uptake, is Transported by This Same Uptake Mechanism in Cultured Rat Superior Cervical Ganglia1

ABSTRACT ABBREVIATiONS

A multi-parametric flow cytometric assay to analyze DNA–protein interactions

Interactions between DNA and transcription factors (TFs) guide cellular function and development, yet the complexities of gene regulation are still far from being understood. Such understanding is limited by a paucity of techniques with which to probe DNA–protein interactions. We have devised magnetic protein immobilization on enhancer DNA (MagPIE), a simple, rapid, multi-parametric assay using flow cytometric immunofluorescence to reveal interactions among TFs, chromatin structure and DNA. In MagPIE, synthesized DNA is bound to magnetic beads, which are then incubated with nuclear lysate, permitting sequence-specific binding by TFs, histones and methylation by native lysate factors that can be optionally inhibited with small molecules. Lysate protein–DNA binding is monitored by flow cytometric immunofluorescence, which allows for accurate comparative measurement of TF-DNA affinity. Combinatorial fluorescent staining allows simultaneous analysis of sequence-specific TF-DNA interaction and chromatin modification. MagPIE provides a simple and robust method to analyze complex epigenetic interactions in vitro

Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) \u3e /=2 in at least 7 patients in either VUR or control cohort based on optimization of signal-to-noise ratio. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly upregulated and 36 downregulated (q \u3c 0.075, |FC| \u3e 1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were overrepresented among the study cohort