Estrogen Receptor β Signaling Induces Autophagy and Downregulates Glut9 Expression

Glut9 is highly expressed in the human kidney proximal convoluted tubular and plays a crucial role in the regulation of plasma urate levels. The gene effects were stronger among women. Our results show that 17-β-estradiol (E2) through ER (estrogen receptor) β downregulates Glut9 protein expression on human renal tubular epithelial cell line (HK2). Intriguingly, E2 does not affect the expression of Glut9 mRNA. ERβ is linked to PTEN, the PTEN gene negatively regulates the PI3K/AKT pathway, and the PI3K/AKT pathway inhibition may lead to autophagy. Further study indicates that ERβ may affect the expression of Glut9 though autophagy.     

Mixed-Backbone Oligonucleotides Containing Phosphorothioate and Methylphosphonate Linkages as Second Generation Antisense Oligonucleotide

Abstract

Antisense oligonucleotides are being studied as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have synthesized phosphorothioate oligonucleotides containing methylphosphonate linkages at the 5′-end, the 3′-end, or in the center, and have evaluated the impact of these linkages on the biophysical properties, biological properties, and some of the safety parameters.     

Study on Disulfur-Backboned Nucleic Acids: Part 3. Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyuridine and Deoxycytidine

A general method is described for synthesizing 3′,5′-dithio-2′-deoxypyrimidine nucleosides 6 and 13 from normal 2′-deoxynucleosides. 2,3′-Anhydronucleosides 2 and 9 are applied as intermediates in the process to reverse the conformation of 3′-position on sugar rings. The intramolecular rings of 2,3′-anhydrothymidine and uridine are opened by thioacetic acid directly to produce 3′-S-acetyl-3′-thio-2′-deoxynucleosides 3 or 5. To cytidine, OH^? ion exchange resin was used to open the ring and 2′-deoxycytidine 10 was abtained in which 3′-OH group is in threo-conformation. The 3′-OH is activated by MsCl, and then substituted by potassium thioacetate to form the S,S′-diacetyl-3′,5′-dithio-2′-deoxycytidine 12. The acetyl groups in 3′,5′ position are removed rapidly by EtSNa in EtSH solution to afford the target molecules 6 and 13. The differences of synthetic routes between uridine and cytidine are also discusssed.     

Delayed Treatment Effects of Xanthine Oxidase Inhibition on Systolic Overload-Induced Left Ventricular Hypertrophy and Dysfunction

The nonpurine selective xanthine oxidase (XO) inhibitor febuxostat attenuates development of left ventricular (LV) hypertrophy and dysfunction in mice when treatment is initiated within 1 hour of transverse aortic constriction (TAC). This study investigated whether a 7-day delay of treatment with the XO inhibitors febuxostat or allopurinol would reverse TAC-induced changes after onset of heart failure (HF). Neither treatment significantly affected TAC-induced LV hypertrophy; only febuxostat caused a modest improvement in LV function (～10% increase in LV ejection fraction). However, the purine analog allopurinol tended to increase mortality compared with vehicle or febuxostat in HF mice.     

The Influences of A Nitrogen Atom Position in Dinucleoside 2-,3-,4-Pyridylphosphonates on Fragmentation Patterns in Electrospray Ionization Multistage Tandem Mass Spectra

2-,3-,4-Pyridylphosphonates and their phosphonothioate congeners were analyzed by electrospray ionization multistage tandem mass spectrometry (ESI-MSⁿ). It was found that the fragmentation pathways of these compounds were not influenced to any detectable extent by the stereochemistry at the phosphorus centers but were sensitive to the position of a nitrogen atom in the pyridine ring of these compounds. Possible mechanisms for fragmentations of the investigated compounds are discussed in detail.

     

Complex Interaction and Adsorption of Glyphosate and Lead in Soil

Glyphosate [N-(phosphonomethyl)-glycine] is a herbicide widely used in large quantities in agricultural applications. It is also known to form complexes with metal ions, although its influence on metal behavior, such as lead (Pb) in soil, is not well understood. In this study, the adsorption and co-adsorption of Pb and glyphosate were determined on two soils [a red (RS) soil, Udic Ferrisol, and a yellow-brown (YB) soil, Udic Luvisol] of distinctly different chemical characteristics at varying pH conditions. Results indicate that the adsorption of lead and glyphosate strongly depends on soil types: the RS soil, characterized by a relatively high iron/aluminum content but a low pH and organic matter content, shows a much lower adsorption capacity for Pb but a higher sorption for glyphosate than the YB soil. The co-existence of Pb and glyphosate in soils resulted in complex interactions among Pb, glyphosate, Pb-glyphosate complexes, and soil minerals. The presence of glyphosate decreased Pb adsorption on the two soils, which was attributed primarily to the formation of soluble Pb-glyphosate complexes having relatively low affinities to soil surfaces. On the other hand, addition of Pb increased the adsorption of glyphosate on both soils, which was attributed to: (1) a decreased solution pH due to the ion exchange between Pb²⁺ and H⁺ on soil surfaces; and (2) increased sorption sites where Pb was adsorbed and acted as a bridge between glyphosate and the soil. The present study illustrates that the complex interactions among glyphosate, Pb, and soil may have important implications for the mobility and bioavailability of Pb in soil and should thus be considered in future environmental risk assessments.     

piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

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Highlights? MIWI is a substrate of APC/C, and piRNA loading is essential for MIWI ubiquitination ? piRNA loading promotes MIWI binding to the APC/C substrate-binding subunit ? MIWI and piRNAs are coordinately eliminated in late spermatids ? Inhibition of MIWI destruction in late spermatids prevents sperm maturation     

Application of Semipermeable Membrane Devices (SPMDs) and Benthic Mussels to Evaluate the Bioavailability of Sediment-associated DDTs

Bioavailability of dichlorodiphenyltrichloroethanes (DDTs) in surface sediments was evaluated with semipermeable membrane devices (SPMDs) and two different sediment-dwelling benthic mussels, Bellamya aeruginosa (B. aeruginosa) and Corbicula fluminea (C. fluminea). After 28d laboratory exposure, the positive correlations of DDT concentrations between both SPMDs and benthic mussels with sediments documented that the bioavailability of DDTs was mainly affected by surrounding sediments, while the observed differences of DDT concentrations and congener proportions between B. aeruginosa and C. fluminea were due to the specific physiological characteristics of organisms and different physico-chemical properties of contaminants. Comparisons between SPMDs and benthic mussels showed higher values of biota-sediment accumulation factors (BSAF, 0.63-3.61 for B. aeruginosa and 2.19-17.08 for C. fluminea) than device accumulation factors (DAF, 1.00-1.74). This indicated that living organisms bioaccumulated much more DDTs from sediments than SPMDs due to the different exposure and uptake routes. Strong positive associations between DDTs in SPMDs and benthic mussels indicated SPMDs could mimic the bioaccumulation of DDTs, especially in C. fluminea. However, given the distinct differences observed for both concentrations and congener proportions of DDTs in SPMDs and B. aeruginosa, future study should be directed to develop reliable models with various sediment-dwelling organisms before SPMDs are routinely used in field study.