155 research outputs found

    The semantics and morphology of Mixtec mood and aspect

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    From the introduction: This study presents a relatively detailed description of the grammatical categories of mood and aspect in three Mixtec languages. Our goals include morphology in a broad sense, covering both meaning and form. Our focus is a grammatical category known in Mixtec studies as \u27aspect\u27, which distinguishes three forms of every verb, generally called completive, continuative, and potential. We present a view of the system that differs somewhat from previous work, suggesting that the system is primarily modal, not aspectual in character. Partly, this is just a matter of how terms like \u27mood\u27 and \u27aspect\u27 are defined, but there is a more fundamental difference. We would like to suggest that the system is best analyzed in terms of two binary divisions, one between realis and irrealis mood, and a second within realis mood between perfective and imperfective aspect. We believe this leads to an insightful understanding of the meaning and usage of these categories, and also of their formal expression, inasmuch as it mirrors their semantic structure. In the process, we are also able to give a first description of this system in three previously unstudied Mixtec languages. Our perspective is a comparative one, concentrating on those characteristics that are common to all three languages, and especially those which are found throughout Mixtec

    Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

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    Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis

    The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

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    <p>Abstract</p> <p>Background</p> <p>It has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease.</p> <p>Objective</p> <p>We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.</p> <p>Design</p> <p>In an open label, randomized, parallel-design study with blinded endpoints, subjects with primary hypercholesterolemia (n = 116) were assigned to receive during 12 weeks, a daily dose of 25 g of fiber (corresponding to 6 g of soluble fibers) plus rosuvastatin 40 mg (n = 28), rosuvastatin 40 mg alone (n = 30), sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber (n = 28), or sinvastatin 40 mg plus ezetimibe 10 mg (n = 30) alone.</p> <p>Results</p> <p>The four assigned therapies produced similar changes in total cholesterol, LDL-cholesterol, and triglycerides (p < 0.001 vs. baseline) and did not change HDL-cholesterol. Fiber intake decreased plasma campesterol (p < 0.001 vs. baseline), particularly among those patients receiving ezetimibe (p < 0.05 vs. other groups), and β-sitosterol (p = 0.03 vs. baseline), with a trend for lower levels in the group receiving fiber plus ezetimibe (p = 0.07). Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol (p = 0.003 vs. other groups). Compared to non-fiber supplemented individuals, those treated with fibers had weight loss (p = 0.04), reduced body mass index (p = 0.002) and blood glucose (p = 0.047).</p> <p>Conclusion</p> <p>Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Additional benefits include improvement in blood glucose and anthropometric parameters.</p

    Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

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    The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation
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