652 research outputs found

    The Formal Dynamism of Categories: Stops vs. Fricatives, Primitivity vs. Simplicity

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    Minimalist Phonology (MP; Pöchtrager 2006) constructs its theory based on the phonological epistemological principle (Kaye 2001) and exposes the arbitrary nature of standard Government Phonology (sGP) and strict-CV (sCV), particularly with reference to their confusion of melody and structure. For Pöchtrager, these are crucially different, concluding that place of articulation is melodic (expressed with elements), while manner of articulation is structural. In this model, the heads (xN and xO) can license and incorporate the length of the other into their own interpretation, that is xN influences xO projections as well as its own and vice versa. This dynamism is an aspect of the whole framework and this paper in particular will show that stops and fricatives evidence a plasticity of category and that, although fricatives are simpler in structure, stops are the more primitive of the two. This will be achieved phonologically through simply unifying the environment of application of the licensing forces within Pöchtrager's otherwise sound onset structure. In doing so, we automatically make several predictions about language acquisition and typology and show how lenition in Qiang (Sino-Tibetan) can be more elegantly explained

    The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac

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    Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled) thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and beta-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton

    Aminophospholipid Translocase TAT-1 Promotes Phosphatidylserine Exposure during C. elegans Apoptosis

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    SummaryPhospholipids are distributed asymmetrically across the plasma-membrane bilayer of eukaryotic cells: Phosphatidylserine (PS), phosphatidylethanolamine, and phosphoinositides are predominantly restricted to the inner leaflet, whereas phophatidylcholine and sphingolipids are enriched on the outer leaflet [1, 2]. Exposure of PS on the cell surface is a conserved feature of apoptosis and plays an important role in promoting the clearance of apoptotic cells by phagocytosis [3]. However, the molecular mechanism that drives PS exposure remains mysterious. To address this issue, we studied cell-surface changes during apoptosis in the nematode C. elegans. Here, we show that PS exposure can readily be detected on apoptotic C. elegans cells. We generated a transgenic strain expressing a GFP::Annexin V reporter to screen for genes required for this process. Although none of the known engulfment genes was required, RNAi knockdown of the putative aminophospholipid transporter gene tat-1 abrogated PS exposure on apoptotic cells. tat-1(RNAi) also reduced the efficiency of cell-corpse clearance, suggesting that PS exposure acts as an “eat-me” signal in worms. We propose that tat-1 homologs might also play an important role in PS exposure in mammals

    Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

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    <p>Abstract</p> <p>Background</p> <p>Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3β (GSK-3β), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the <it>vastus lateralis</it>, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2.</p> <p>Results</p> <p>Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins.</p> <p>Conclusions</p> <p>This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.</p

    Dissolved and particulate barium distributions along the US GEOTRACES North Atlantic and East Pacific zonal transects (GA03 and GP16): global implications for the marine barium cycle

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    Author Posting. © American Geophysical Union, 2022. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 36(6), (2022): e2022GB007330, https://doi.org/10.1029/2022gb007330.Processes controlling dissolved barium (dBa) were investigated along the GEOTRACES GA03 North Atlantic and GP16 Eastern Tropical Pacific transects, which traversed similar physical and biogeochemical provinces. Dissolved Ba concentrations are lowest in surface waters (∼35–50 nmol kg−1) and increase to 70–80 and 140–150 nmol kg−1 in deep waters of the Atlantic and Pacific transects, respectively. Using water mass mixing models, we estimate conservative mixing that accounts for most of dBa variability in both transects. To examine nonconservative processes, particulate excess Ba (pBaxs) formation and dissolution rates were tracked by normalizing particulate excess 230Th activities. Th-normalized pBaxs fluxes, with barite as the likely phase, have subsurface maxima in the top 1,000 m (∼100–200 μmol m−2 year−1 average) in both basins. Barite precipitation depletes dBa within oxygen minimum zones from concentrations predicted by water mass mixing, whereas inputs from continental margins, particle dissolution in the water column, and benthic diffusive flux raise dBa above predications. Average pBaxs burial efficiencies along GA03 and GP16 are ∼37% and 17%–100%, respectively, and do not seem to be predicated on barite saturation indices in the overlying water column. Using published values, we reevaluate the global freshwater dBa river input as 6.6 ± 3.9 Gmol year−1. Estuarine mixing processes may add another 3–13 Gmol year−1. Dissolved Ba inputs from broad shallow continental margins, previously unaccounted for in global marine summaries, are substantial (∼17 Gmol year−1), exceeding terrestrial freshwater inputs. Revising river and shelf dBa inputs may help bring the marine Ba isotope budget more into balance.The International GEOTRACES Programme is possible in part thanks to the support from the U.S. National Science Foundation (Grant OCE-1840868) to the Scientific Committee on Oceanic Research (SCOR). This research was supported by the National Science Foundation under Grant No. NSF OCE-0927951, NSF OCE-1137851, NSF OCE-1261214, and NSF OCE-1925503 to A. M. Shiller; NSF OCE-1829563 to R. F. Anderson; NSF OCE-0927064 and NSF OCE-1233688 to R. F. Anderson and M. Q. Fleisher; NSF OCE-0927754 to R. Lawrence Edwards; NSF OCE-1233903 to R. Lawrence Edwards and H. Cheng; NSF OCE-0926860 to L. F. Robinson; NSF OCE-0963026 and NSF OCE-1518110 to P. J. Lam; and NSF OCE-1232814 to B. S. Twining

    Factors influencing the practice of new graduate nurses : a focused ethnography of acute care settings

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    Aim: To explore the influence of an acute care setting on competency deployment of new graduate nurses (NGNs) from a competency -based undergraduate programme . Background: In the last 15 years, nursing education has shifted to competency -based education (CBE). Few studies have focused on how NGNs from these reformed programmes use the competencies they have developed. To be paradigmatically coherent with the nature of a competence, studies should also examine how context influences nursing practice and competency deployment. Design: A focused ethnography of three acute care units from one academic hospital in Canada. Methods: Purposive and snowball sampling strategies were used to recruit 19 participants: NGNs (n = 4), nurse preceptors (n = 2), clinical nurse specialists (n = 9) , and nurse managers (n = 4). Data were collected through individual interviews, focus groups , observation and documentation. Data were analysed according to Roper and Shapira’s (2000) ethnographic nursing analysis framework. Results: Organizational and individual factors were identified as influencing NGNs ’ competenc y deployment. Organizational factors are orientation, stability, workload, and the scientific culture of the unit. Personal factors have been linked to groups of professionals: for NGNs, personality and clinical placements during their initial education; for nurses working with NGNs, to be role models, to promote integration and to denounce bullying; and for other health professionals, to recognize nursing expertise. Conclusion: One way to s mooth the transition from academic to clinical settings for NGNs is by offering transition or orientation programmes that will provide them with stability and a reduced workload, allowing them to progressively deploy their competencies. Relevance to clinical practice: Organizational and individual factors influence how new graduate nurses deploy their competencies. Clinical educators and nurse managers can help new nurses by acting on these factors

    Intramolecular additions of various π-nucleophiles to chemoselectively activated amides and application to the synthesis of (±)-tashiromine

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    Abstract: Vilsmeier-Haack type cyclizations proved to be particularly efficient for generating parts of the polycyclic cores of many alkaloids, although only monocyclizations have so far been reported. With the goal of rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit the Vilsmeier-Haack reaction by utilizing iminium ions successively generated and trapped with tethered nucleophiles. To develop such a strategy, we had to set the first cyclization. This constitutes a great challenge in itself because amide activation conditions are usually not compatible with tethered nucleophiles, except for indoles and aromatic rings which have already been reported. This paper describes the comprehensive study of intramolecular addition of silyl enol ethers, allylsilanes, and enamines to chemoselectively activated formamides, aliphatic amides, and lactams. Good to excellent yields were obtained for the 5-exo, 6-exo, and 6-endo modes of cyclization. Moreover, we demonstrated that the species in solution after the cyclization are iminium ions. This is highly encouraging for the development of bis-cyclization strategies. An expeditious total synthesis of (()-tashiromine is also reported

    A new method for the determination of low-level actinium-227 in geological samples

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    Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Radioanalytical and Nuclear Chemistry 296 (2013): 279-283, doi:10.1007/s10967-012-2140-0.We developed a new method for the determination of 227Ac in geological samples. The method uses extraction chromatographic techniques and alpha-spectrometry and is applicable for a range of natural matrices. Here we report on the procedure and results of the analysis of water (fresh and seawater) and rock samples. Water samples were acidified and rock samples underwent total dissolution via acid leaching. A DGA (N,N,N’,N’-tetra-n-octyldiglycolamide) extraction chromatographic column was used for the separation of actinium. The actinium fraction was prepared for alpha spectrometric measurement via cerium fluoride micro-precipitation. Recoveries of actinium in water samples were 80±8 % (number of analyses n=14) and in rock samples 70±12 % (n=30). The minimum detectable activities (MDA) were 0.017-0.5 Bq kg-1 for both matrices. Rock sample 227Ac activities ranged from 0.17 to 8.3 Bq kg-1 and water sample activities ranged from below MDA values to 14 Bq kg-1of 227Ac. From the analysis of several standard rock and water samples with the method we found very good agreement between our results and certified values

    Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

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    BACKGROUND: This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer. METHODS: A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome. RESULTS: Hsp-27 staining was indicative of higher Gleason score (P7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome (P<0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements (chi2 trend=31.4, P<0.001), although this distribution did not have prognostic significance. INTERPRETATION: This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome (P<0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers
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