1,071,326 research outputs found

    Evidence Favoring a Positive Feedback Loop for Physiologic Auto Upregulation of hnRNP-E1 during Prolonged Folate Deficiency in Human Placental Cells

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    Background: Previously, we determined that heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) functions as an intracellular physiologic sensor of folate deficiency. In this model, l-homocysteine, which accumulates intracellularly in proportion to the extent of folate deficiency, covalently binds to and thereby activates homocysteinylated hnRNP-E1 to interact with folate receptor-α mRNA; this high-affinity interaction triggers the translational upregulation of cell surface folate receptors, which enables cells to optimize folate uptake from the external milieu. However, integral to this model is the need for ongoing generation of hnRNP-E1 to replenish homocysteinylated hnRNP-E1 that is degraded.Objective: We searched for an interrelated physiologic mechanism that could also maintain the steady-state concentration of hnRNP-E1 during prolonged folate deficiency.Methods: A novel RNA-protein interaction was functionally characterized by using molecular and biochemical approaches in vitro and in vivo.Results: l-homocysteine triggered a dose-dependent high-affinity interaction between hnRNP-E1 and a 25-nucleotide cis element within the 5'-untranslated region of hnRNP-E1 mRNA; this led to a proportionate increase in these RNA-protein complexes, and translation of hnRNP-E1 both in vitro and within placental cells. Targeted perturbation of this RNA-protein interaction either by specific 25-nucleotide antisense oligonucleotides or mutation within this cis element or by small interfering RNA to hnRNP-E1 mRNA significantly reduced cellular biosynthesis of hnRNP-E1. Conversely, transfection of hnRNP-E1 mutant proteins that mimicked homocysteinylated hnRNP-E1 stimulated both cellular hnRNP-E1 and folate receptor biosynthesis. In addition, ferrous sulfate heptahydrate [iron(II)], which also binds hnRNP-E1, significantly perturbed this l-homocysteine-triggered RNA-protein interaction in a dose-dependent manner. Finally, folate deficiency induced dual upregulation of hnRNP-E1 and folate receptors in cultured human cells and tumor xenografts, and more selectively in various fetal tissues of folate-deficient dams.Conclusions: This novel positive feedback loop amplifies hnRNP-E1 during prolonged folate deficiency and thereby maximizes upregulation of folate receptors in order to restore folate homeostasis toward normalcy in placental cells. It will also functionally impact several other mRNAs of the nutrition-sensitive, folate-responsive posttranscriptional RNA operon that is orchestrated by homocysteinylated hnRNP-E1

    Diagnostic correlation between ultrasonography and CT arthrography in rotator cuff disease

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    ������: ��������� ��� ��������� ��������� ������������ ������ ��������� ��� ��������� ������ ������ (CT arthrography, CTA)��� ��������� ��������� ��������� ��������������� ��������� ��������� ������������ ��� ��������� ��������� ��������� ��������������� ���������. ������ ��� ������: ��������� ��� ������������ ��������� 57��������� CTA��� ���������������, ��� ��� 28������������ ��������� ��������� ��������� ���������������. ��������� ��������� ������������ ������, ��������� ������ ��� ��� ��� ������ ��� ��������� ������ ��� ��������� ��������� ��������� ������ ��������� ������ ������������ ���������������. ������: CTA��� ��� ��� ��������� ������ ������������ 86.2%, ������������ 100%, ������ ��� ��������� ��������� ������������ 58.3%, ��������� 87.8%��� ��������� ���������. ��������� ��������� ��� ��� ��������� ������������ ��������� 84.6%, ��������� 86.7% ������ ��� ��������� ������������ ��������� 84.6%, ��������� 73.3%��� ������ ��������� ������������, ��������� ��������� ������������ ������ CTA������ ������ ������������ ���������. ������: ��� ������ ������ ��������� ��� ������������ ��������� ��������� ��������� ������������, CTA��� ������ ������������ ��������� ��������� ��������� ��������� ���, ������ ��� ��������� ������ ������������ ������������, ��������� ��������� ������������ ������ ��� ������ ������������ ���������. Purpose: The aim of this study wasto evaluate the comparison of CT arthrography and ultrasonography, confirmed by the arthroscopic finding in patients with rotator cuff disease. Materials and Methods: We evaluated fifty seven patients with rotator cuff disease underwent CTA and arthroscopy, and twenty eight patients had taken ultrasonographyadditionally. The diagnostic value and prediction for tear size between CTA and ultrasonography were evaluated, as compared to arthroscopic findings. Results: CTA showed a sensitivity of 86.2% and a specificity of 100% in full thickness tear ofsupraspinatus, a sensitivity of 58.3% and a specificity of 87.8% in partial-thickness tear. CTA demonstrated good diagnostic value for full thickness tear, but there was relatively lower value for partial-thickness tear. Ultrasonography showed a sensitivity of 84.6% and a specificity of 86.7% for diagnosing in full thickness tear, a sensitivity of 84.6% and a specificity of 73.3% in partial-thickness tear. Ultrasonography provided good diagnostic value, but, there is lesser accurate result for prediction of tear size. Conclusion: CTA showedgood diagnostic tool of detection full-thickness tear of rotator cuff disease and predicting of tear size. Comparing with ultrasonography, CTA was inferior for detection of partial-thickness tear, but, provided better estimation for tear size

    Visualising Sha[2] in Abelian Surfaces

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    Given an elliptic curve E1 over a number field and an element s in its 2-Selmer group, we give two different ways to construct infinitely many Abelian surfaces A such that the homogeneous space representing s occurs as a fibre of A over another elliptic curve E2. We show that by comparing the 2-Selmer groups of E1, E2 and A, we can obtain information about Sha(E1/K)[2] and we give examples where we use this to obtain a sharp bound on the Mordell-Weil rank of an elliptic curve. As a tool, we give a precise description of the m-Selmer group of an Abelian surface A that is m-isogenous to a product of elliptic curves E1 x E2. One of the constructions can be applied iteratively to obtain information about Sha(E1/K)[2^n]. We give an example where we use this iterated application to exhibit an element of order 4 in Sha(E1/Q).Comment: 17 page

    Large-scale QRPA calculation of E1-strength and its impact on the neutron capture cross section

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    Large-scale QRPA calculations of the E1-strength are performed as a first attempt to microscopically derive the radiative neutron capture cross sections for the whole nuclear chart. A folding procedure is applied to the QRPA strength distribution to take the damping of the collective motion into account. It is shown that the resulting E1-strength function based on the SLy4 Skyrme force is in close agreement with photoabsorption data as well as the available experimental E1-strength at low energies. The increase of the E1-strength at low energies for neutron-rich nuclei is qualitatively analyzed and shown to affect the corresponding radiative neutron capture cross section significantly. A complete set of E1-strength function is made available for practical applications in a table format for all 7<Z<111 nuclei lying between the proton and the neutron drip lines.Comment: 17 pages, 8 figures, accepted for publication in Nucl. Phys.

    The Effects of Antecedents of Outdoor Sportswear Brand Personality on Brand Personality, Attachment and Commitment

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    This study examines the impacts of antecedents on the outdoor sportswear brand personality dimensions and identifies the effects of brand personality dimensions on brand attachment and brand commitment. An online survey was conducted on women in their 20s to 50s, who have experienced to purchase the outdoor sportswear before and 420 responses were analyzed. The results of this study were as follows: 1) The results of factor analysis and the reliability test on the outdoor sportswear brand personality clearly showed factorial structures that include sincerity, excitement, vitality, and prestige. 2) The antecedents of brand personality including quality, price, advertising, and store environment had different influences on the outdoor sportswear brand personality. 3) The dimensions of outdoor sportswear brand personality had a different influence on the brand attachment and commitment. 4) The brand attachment showed a significantly positive influence on the brand commitment. This study indicates that the brand personality could be a useful tool for enhancing the brand attachment and commitment and marketers should develop and utilize the marketing mix according to the brand personality which they want to convey

    The effect of grazing pressure on rotationally grazed pastures in spring/early summer on subsequent sward characteristics

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    peer-reviewedTwo experiments (E1 and E2) were carried out to examine the effect of grazing pressure (GP) in the early part of the grazing season on subsequent sward composition. Three GP levels, equating to 6.35, 4.24 and 3.53 cows/ha in E1, and 6.06, 5.05 and 4.03 cows/ha in E2, were used. The GP treatments were applied between April and July in E1, and April and June in E2. As GP decreased different swards, termed high (HQ), medium (MQ) and low (LQ) quality, were created. The post-grazing sward heights at the end of the GP periods were 6.6, 10.5 and 14.6 (s.e. 0.78) cm in E1, and 5.9, 8.8 and 11.4 (s.e. 0.39) cm in E2, for HQ, MQ and low LQ, respectively. Organic matter digestibility coefficients for herbage from the HQ, MQ and LQ swards during the subsequent grazing cycles averaged 0.770, 0.729 and 0.702 (s.e. 0.0055) in E1, and 0.761, 0.731 and 0.711 (s.e. 0.0038) in E2, respectively. Average live leaf proportions of the HQ, MQ and LQ swards were 0.583, 0.427 and 0.329 (s.e. 0.0193) in E1, and 0.600, 0.474 and 0.362 (s.e. 0.0155) in E2, respectively. GP had a significant effect on the proportion of grass area categorised as short grass (SG). The proportions of SG area in HQ, MQ and LQ were 0.711, 0.579 and 0.445 (s.e. 0.0106), respectively, in E1, and 0.700, 0.556 and 0.441 (s.e. 0.0133), respectively, in E2. Pre-grazing herbage mass (dry matter above 45 mm) was 2,065, 2,736 and 3,700 (s.e. 144.1) kg/ha for HQ, MQ and LQ, respectively, in E1 and 2,688, 3,735 and 4,722 (s.e. 145.0) kg/ha for HQ, MQ and LQ, respectively, in E2. The results show the importance of early season grazing pressure in creating a leafy high-digestibility sward for the remainder of the grazing season

    A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

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    Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons

    A Route to Surface-bound Metalloporphyrins as Models for Oxygen Reduction Catalysts

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    The attachment nonmetal and magnesium ethynyl terminated porphyrin (TEPP and MgTEPP) to glassy carbon electrode was achieved through voltammetry. These attached porphyrins were studied by cyclic voltammetry (CV) and UV-visible spectroscopy. Surface-bound TEPP displayed reversible oxidation and reduction (E1/2 = 0.52 V and E1/2 = -1.74 V vs. ferrocene), and absorbance peak of 425 nm on indium tin oxide (ITO). While surface-bound MgTEPP possessed two reversible oxidations (E1/2 = 0.61 V and E1/2 = 0.97 V vs. Ag/AgCl) and an irreversible (Epc = -1.65 V vs. Ag/AgCl). MgTEPP had an absorbance maximum at 431 nm on ITO. Both porphyrins had irreversible pre-waves, which could be regenerated. This is the first example of covalently-bound Mg porphyrin to an electrode surface
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