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Dicer-1 and Dicer-2 facilitate the assembly of siRISC (RNA-induced silencing complex). But genetic analysis has demonstrated that Dcr-1 but not Dcr-2 is required for gene silencing by miRNAs.

To elucidate events in the molecular arms race between the host and pathogen in evaluating plant immunity, a zigzag model is useful for uncovering aspects common to different host-pathogen interactions. By analogy of the steps in virus-host interactions with the steps in the standard zigzag model outlined in recent papers, we may regard RNA silencing as pattern-triggered immunity (PTI) against viruses, RNA silencing suppressors (RSSs) as effectors to overcome host RNA silencing and resistance gene (R-gene)-mediated defense as effector-triggered immunity (ETI) recognizing RSSs as avirulence proteins. However, because the standard zigzag model does not fully apply to some unique aspects in the interactions between a plant host and virus, we here defined a model especially designed for viruses. Although we simplified the phenomena involved in the virus-host interactions in the model, certain specific interactive steps can be explained by integrating additional host factors into the model. These host factors are thought to play an important role in maintaining the efficacy of the various steps in the main pathway of defense against viruses in this model for virus-plant interactions. For example, we propose candidates that may interact with viral RSSs to induce the resistance response. [ABSTRACT FROM AUTHOR]

The role of small RNAs as key regulators of mRNA turnover and translation has been well established. Recent advances indicate that the small RNAs termed microRNAs play important roles in cell proliferation, apoptosis and differentiation. Moreover, the microRNA mechanism is an efficient means to regulate production of a diverse range of proteins. As new microRNAs and their mRNA targets rapidly emerge, it is becoming apparent that RNA-based regulation of mRNAs may rival ubiquitination as a mechanism to control protein levels. [Copyright &y& Elsevier]

β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) has been pursued as a prime target for the treatment of Alzheimer's disease (AD). In this report, we describe the discovery of BACE1 inhibitors with a 1-amino-3,4-dihydro-2,6-naphthyridine scaffold. Leveraging known inhibitors 2a and 2b , we designed the naphthyridine-based compounds by removing a structurally labile moiety and incorporating pyridine rings, which showed increased biochemical and cellular potency, along with reduced basicity on the amidine moiety. Introduction of a fluorine atom on the pyridine culminated in compound 11 which had improved cellular activity as well as further reduced basicity and demonstrated a robust and sustained cerebrospinal fluid (CSF) Aβ reduction in dog. The crystal structure of compound 11 bound to BACE1 confirmed van der Waals interactions between the fluorine on the pyridine and Tyr71 in the flap. [Display omitted] • A 1-amino-3,4-dihydro-2,6-naphthyridine BACE1 inhibitor offering robust and sustained CSF Aβ reduction was identified. • Incorporation of fluoropyridines reduced basicity with increased biochemical and cellular potency, which led to significant central activity. • X-ray analysis confirmed the key interactions of the fluoropyridine moiety with BACE1. [ABSTRACT FROM AUTHOR]

Abstract: The first asymmetric total syntheses of the (+)- and (−)-cryptocaryones are described. Removal of the acetal unit of the enone acetal 5, which was obtained in our previous study from the cyclohexadiene acetal 3, afforded the enone acetal 8 in a one-pot procedure. The acylation of 8 with cinnamoyl chloride and subsequent hydrolysis of the resulting acetal gave the lactol 11. Its oxidation with NIS and tetra-n-butylammonium iodide (TBAI) finally furnished the natural (+)-cryptocaryone 2. The same procedure from ent-3 afforded the unnatural one 1. [Copyright &y& Elsevier]

Abstract: A novel double intramolecular iodoetherification of σ-symmetric diene acetals from (R,R)-hydrobenzoin occurred in highly diastereoselective manners to give tetrahydrofuran moieties with multiple chiral centers in a one-pot operation. The chemoselective discrimination of the two iodomethyl functions in the products was attained in various reactions. The reaction was applied to the concise asymmetric syntheses of rubrenolide and rubrynolide, in which the unit from the chiral auxiliary worked as a template to achieve the chemoselectivity and as the protecting group of the hydroxyl function. [Copyright &y& Elsevier]

Abstract: Cerium ammonium nitrate (CAN) removed hydroxyethyl units from 2-hydroxyethyl ethers and 2-hydroxyethyl amines to produce alcohols and amines in good yields. Especially, removal of the 2-hydroxyethyl ethers from C 2-symmetric diols, chiral 2,3-butanediol and chiral hydrobenzoin, was very useful for asymmetric syntheses using C 2-symmetric diols. The reactions using dual abilities of CAN, i.e., the ability for removal of the 2-hydroxyethyl unit and the ability for acetal hydrolysis by a single electron transfer, were also achieved successfully. The reaction conditions were very mild and efficient, and many functional groups, which can be affected under normal conditions, were unaffected during the reaction. [Copyright &y& Elsevier]

Objective: To examine the correlation between the pulsatility and resistance indices (PI and RI) of the intraovarian artery on the day of follicle aspiration and the oocyte quality, intrafollicular oxidative stress, and luteinization. Pulsatility index and RI on the day of hCG administration also were measured. Design: Prospective study. Setting: Obstetrics and gynecology department of a university medical school in Japan. Patient(s): Thirty-five patients in an IVF-ET program. Intervention(s): The PI and RI of the intraovarian artery were measured by transvaginal color ultrasonographic pulsed wave Doppler on the day of hCG administration and the day of follicle aspiration. Follicular fluids and the granulosa cells were collected at follicle aspiration. Main Outcome Measure(s): The PI and RI of the intraovarian artery blood flow on the day of hCG administration and of follicle aspiration, as well as the rate of development of mature oocytes, follicular fluid steroid levels, and the incidence of apoptosis in the granulosa cells. Result(s): The PI and RI on the day of follicle aspiration were correlated positively with the rate of mature oocytes retrieved (PI: r = 0.429; RI: r = 0.348), were correlated negatively with the incidence of apoptotic mural (PI: r = -0.383; RI: r = -0.459) and cumulus (PI: r = -0.378; RI: r = -0.469) granulosa cells, and were negatively correlated with the concentration of P in the follicular fluid (PI: r = -0.429; RI: r = -0.359). The PI and RI on the day of hCG administration were negatively correlated only with the total number of retrieved oocytes (PI: r = -0.393; RI: r = -0.374). Conclusion(s): The PI and RI of the intraovarian artery blood flow measured on the day of follicle aspiration may be good indicators of the follicle luteinization and oxidation as well as of oocyte quality. [ABSTRACT FROM AUTHOR]

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks. [Copyright &y& Elsevier]