The Carboxyl-Terminal Segment of Apolipoprotein A-V Undergoes a Lipid-Induced Conformational Change

Apolipoprotein (apo) A-V is a 343-residue, multidomain protein that plays an important role in regulation of plasma triglyceride homeostasis. Primary sequence analysis revealed a unique tetraproline sequence (Pro293-Pro296) near the carboxyl terminus of the protein. A peptide corresponding to the 48-residue segment beyond the tetraproline motif was generated from a recombinant apoA-V precursor wherein Pro295 was replaced by Met. Cyanogen bromide cleavage of the precursor protein, followed by negative affinity chromatography, yielded a purified peptide. Nondenaturing polyacrylamide gel electrophoresis verified that apoA-V(296-343) solubilizes phospholipid vesicles, forming a relatively heterogeneous population of reconstituted high-density lipoprotein with Stokes’ diameters\u3e17 nm. At the same time, apoA-V(296-343) failed to bind a spherical lipoprotein substrate in vitro. Far-UV circular dichroism spectroscopy revealed the peptide is unstructured in buffer yet adopts significant R-helical secondary structure in the presence of the lipid mimetic solvent trifluoroethanol (TFE; 50% v/v). Heteronuclear multidemensional NMR spectroscopy experiments were conducted with uniformly 15N- and 15N/13C-labeled peptide in 50% TFE. Peptide backbone assignment and secondary structure prediction using TALOSþ reveal the peptide adopts R-helix secondary structure from residues 309 to 334. In TFE, apoA-V(296-343) adopts an extended amphipathic R-helix, consistent with a role in lipoprotein binding as a component of full-length apoA-V

Evaluating the Grammars of Children who Speak Nonmainstream Dialects of English

In this article, we review three clinical responses to the study and evaluation of grammar in children who speak nonmainstream dialects of English. Then we introduce a fourth, system based response that views nonmainstream dialects of English, such as African American English (AAE) and Southern White English (SWE) as made up of dialect-specific and dialect-universal features. To illustrate the usefulness of a system-based approach and to distinguish our two terms from others in the dialect literature, we present AAE and SWE relative clause data from two previously published studies. Following this, we present new findings from AAE- and SWE-speaking children’s use of past tense and past participles to further demonstrate the value of examining larger units (i.e., systems) of a grammar to identify a child’s language strengths and weaknesses. We conclude by arguing that a system-based approach moves us beyond our field’s preoccupation with the nonmainstream aspects of children’s dialects while also moving us beyond Brown’s 14 morphemes. Although the focus of the article is on assessment, the content is relevant to the treatment of grammar because effective promotion of any child’s grammar (including the grammars of those who speak nonmainstream dialects of English) will occur only when we begin to view the child’s grammar as a system rather than as a sum of its parts

Eimeria collieie n. sp. (Apicomplexa:Eimeriidae) from the western long-necked turtle (Chelodina colliei)

A new species, Eimeria collieie n. sp., is described from the western long-necked turtle (Chelodina colliei). Sporulated oocysts (n = 35) are spherical to subspherical, with colourless single layer oocyst wall, 0.6 ± 0.2 (0.4-0.7) μm thick. Oocyst with elongated ellipsoid sporocysts. Oocyst length, 29.8 ± 0.4 (28.2-31.0) μm; oocyst width, 29.4 ± 0.3 (28.0-30.8) μm; oocyst length/width (L/W) ratio, 1.0 ± 0.03 (1.0-1.05). Micropyle, oocyst residuum and polar granule were absent. Sporocysts with sporocyst residuum and 2 sporozoites. Sporocyst length, 21.6 ± 0.4 (21.2-22.0) μm; sporocyst width, 6.0 ± 0.3 (5.7-6.3) μm; sporocyst L/W ratio, 3.6 ± 0.2 (3.4-3.8). Stieda, parastieda and substieda bodies were absent. Sporozoite length, 14.0 ± 0.2 (13.8-14.2) μm; sporozoite width, 2.6 ± 0.2 (2.4-2.8) μm; sporozoite L/W ratio, 5.46 ± 0.10 (5.4-5.6). Molecular analysis was conducted at three loci: the 18S and 28S ribosomal RNA (rRNA), and the mitochondrial cytochrome oxidase gene (COI). At the 18S rRNA locus, E. collieie n. sp. shared 96.4% and 98.3% genetic similarity to E. ranae (GenBank accession number: EU717219) and E. arnyi (AY613853) respectively. At the 28S rRNA locus, E. collieie n. sp. shared 91.6% genetic similarity to E. papillata (GenBank accession number: GU593706) and phylogenetic analysis at this locus placed E. collieie n. sp. in aseparateclade. At the COI locus, E. collieie n. sp. shared 92.7% genetic similarity to Eimeria setonicis (GenBankaccession number: KF225638) from a quokka (Setonix brachyurus) in Western Australia. Reptile-derived sequences were not available for the 28S rRNA and the COI loci. Based on morphological and molecular data, this isolate is a new species of coccidian parasite that, to date, has only been found in western long-necked turtles

Development of a novel approach to the assessment of eye-hand coordination

Background Current methods to measure eye–hand coordination (EHC) have been widely applied in research and practical fields. However, some aspects of the methods, such as subjectivity, high price, portability, and high appraisal contribute to difficulties in EHC testing. New methods The test was developed on an Apple iPad® and involves tracing up to 13 shapes with a stylus pen. The time taken to complete each trace and the spatial accuracy of the tracing is automatically recorded. The difficulty level for each shape was evaluated theoretically based on the complexity and length of outline. Ten adults aged 31.5 ± 7.8 years and five children aged 9.4 ± 1.1 years with normal vision participated. Results In adults, the time taken to trace and number of errors significantly decreased from the first to the second attempt (p < 0.05) but not thereafter, suggesting a learning effect with repeatability after a practice attempt. Time taken and number of errors in children were both higher in monocular than binocular viewing conditions (p = 0.02 and p < 0.01, respectively) while adults’ performance was similar in both viewing conditions. Comparison with existing methods Existing EHC tests are subjective in clinics and require higher skills and cost in research, and measure gross EHC. This novel test has been developed to address some of the limitations. Conclusions The test is engaging for children and adults and is an objective method with potential for the assessment of fine EHC, suited to clinic-based and research use in ophthalmic or brain trauma settings, and in developmental disorders

A luminous blue kilonova and an off-axis jet from a compact binary merger at z=0.1341

The recent discovery of a faint gamma-ray burst (GRB) coincident with the gravitational wave (GW) event GW 170817 revealed the existence of a population of low-luminosity short duration gamma-ray transients produced by neutron star mergers in the nearby Universe. These events could be routinely detected by existing gamma-ray monitors, yet previous observations failed to identify them without the aid of GW triggers. Here we show that GRB150101B was an analogue of GRB170817A located at a cosmological distance. GRB 150101B was a faint short duration GRB characterized by a bright optical counterpart and a long-lived X-ray afterglow. These properties are unusual for standard short GRBs and are instead consistent with an explosion viewed off-axis: the optical light is produced by a luminous kilonova component, while the observed X-rays trace the GRB afterglow viewed at an angle of ~13 degrees. Our findings suggest that these properties could be common among future electromagnetic counterparts of GW sources.Comment: 28 pages, 8 figures, 2 tables. Accepted for publicatio

Obtaining strong ferromagnetism in diluted Gd-doped ZnO thin films through controlled Gd-defect complexes

We demonstrate the fabrication of reproducible long-range ferromagnetism (FM) in highly crystalline Gdx Zn 1−xO thin films by controlling the defects. Films are grown on lattice-matched substrates by pulsed laser deposition at low oxygen pressures (≤25 mTorr) and low Gd concentrations (x ≤ 0.009). These films feature strong FM (10 μB per Gd atom) at room temperature. While films deposited at higher oxygen pressure do not exhibit FM, FM is recovered by post-annealing these films under vacuum. These findings reveal the contribution of oxygen deficiency defects to the long-range FM. We demonstrate the possible FM mechanisms, which are confirmed by density functional theory study, and show that Gd dopants are essential for establishing FM that is induced by intrinsic defects in these films

Comparison of First-Line Dual Combination Treatments in Hypertension: Real-World Evidence from Multinational Heterogeneous Cohorts.

Background and objectives: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D).Methods: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure.Results: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97-1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87-1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95-1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01-1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01-1.17; p=0.040) than A+D.Conclusions: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice