Mitral and Tufted Cells Are Potential Cellular Targets of Nitration in the Olfactory Bulb of Aged Mice

Olfactory sensory function declines with age; though, the underlying molecular changes that occur in the olfactory bulb (OB) are relatively unknown. An important cellular signaling molecule involved in the processing, modulation, and formation of olfactory memories is nitric oxide (NO). However, excess NO can result in the production of peroxynitrite to cause oxidative and nitrosative stress. In this study, we assessed whether changes in the expression of 3-nitrotyrosine (3-NT), a neurochemical marker of peroxynitrite and thus oxidative damage, exists in the OB of young, adult, middle-aged, and aged mice. Our results demonstrate that OB 3-NT levels increase with age in normal C57BL/6 mice. Moreover, in aged mice, 3-NT immunoreactivity was found in some blood vessels and microglia throughout the OB. Notably, large and strongly immunoreactive puncta were found in mitral and tufted cells, and these were identified as lipofuscin granules. Additionally, we found many small-labeled puncta within the glomeruli of the glomerular layer and in the external plexiform layer, and these were localized to mitochondria and discrete segments of mitral and tufted dendritic plasma membranes. These results suggest that mitral and tufted cells are potential cellular targets of nitration, along with microglia and blood vessels, in the OB during aging.     

Knockdown of the Sodium-Dependent Phosphate Co-Transporter 2b (NPT2b) Suppresses Lung Tumorigenesis

The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras ^LA1 mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy.     

Acute Histologic Chorioamnionitis Is a Risk Factor for Adverse Neonatal Outcome in Late Preterm Birth after Preterm Premature Rupture of Membranes

Background

The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.

Methodology/Principal Findings

The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.

Conclusions/Significance

The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.     

Prevalence of and Factors Associated with Albuminuria in the Korean Adult Population: The 2011 Korea National Health and Nutrition Examination Survey

Background

Microalbuminuria is associated with increased risk of renal disease and cardiovascular diseases even in non-diabetic subjects. High incidence rates of microalbuminuria have been found in a number of population-based studies. However, the prevalence and risk factors associated with microalbuminuria in the general population in Korea are unclear.

Objectives

The present study was performed to estimate the prevalence of microalbuminuria and investigate the associated risk factors in the general adult population using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2) data from 2011.

Methods

A total of 5,202 participants (mean age, 45.6 years; men, 2,337; women, 2,865) were included in the analysis. Microalbuminuria was evaluated in participants of KNHANES V-2 based on the urine albumin–creatinine ratio. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation.

Results

The weighted prevalence of microalbuminuria was 5.2% (95% CI, 4.4–6.1) in the general population. The prevalence of albuminuria is increased with age. After adjustment for age and sex, the presence of albuminuria was associated with increased waist circumference, systolic and diastolic blood pressure, aspartate aminotransferase, triglyceride, fasting plasma glucose, and the presence of hypertension and diabetes. In logistic regression analyses, older age, female sex, diabetes, hypertension, and serum aspartate aminotransferase were independently associated with the presence of albuminuria.

Conclusion

The prevalence of microalbuminuria was found to be 5.2%, and conventional risk factors for cardiovascular diseases are closely related to the presence of microalbuminuria in Korea. Microalbuminuria may be a useful marker to identify individuals with increased risk of cardiovascular disease.     

Synthesis and Biological Activity of Sugar-Fluorinated 2′,3′-dideoxy-4′-thioribofuranosyl Nucleosides

Abstract

The efficient DAST fluorination of deoxy-4′-thiopyrimidine nucleosides is reported. The cytidine analogue 3b was marginally effective against HIV.     

Somatic cell transformation into stem cell-like cells induced by different microenvironments

Development of induced pluripotent stem cell (iPSC) technology introduced a novel way to derive pluripotent stem cells, but the genetic manipulation required to generate iPSCs may lead to uncontrolled tumorigenesis of the established cells and thus limit clinical feasibility of the technology. Numerous attempts have been made to date, and alternative reprogramming of somatic cells to reactivate cellular plasticity after differentiation has been suggested. As a result, it had become clear that cell-to-cell interactions and specific acellular environments can be utilized for somatic cell reprogramming. In our previous studies, embryonic stem cell (ESC)-like cells could be derived from transforming ovarian cells and fetal fibroblasts by cell-to-cell interaction or specific cell-mediated microenvironmental factor(s). This cellular event was induced without undertaking genetic manipulation of progenitor cells. Several differences were found between the cellular properties of niche-induced, ESC-like cells and those of genetically manipulated iPSCs and the referenced ESCs. Thus, we provided evidence that terminally differentiated somatic cells either acquire pluripotency-like activity or possess cellular and genetic plasticity under a specific microenvironment and/or cell-to-cell interaction. In this minireview, we discuss derivation of stem cell-like cells under specific microenvironmental conditions in terms of technical perspectives and limitations.     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

Deinococcus swuensis sp. nov., a gamma-radiation-resistant bacterium isolated from soil

Strain DY59^T, a Gram-positive non-motile bacterium, was isolated from soil in South Korea, and was characterized to determine its taxonomic position. Phylogenetic analysis based on the 16S rRNA gene sequence of strain DY59^T revealed that the strain DY59^T belonged to the family Deinococcaceae in the class Deinococci. The highest degree of sequence similarities of strain DY59^T were found with Deinococcus radiopugnans KACC 11999^T (99.0%), Deinococcus marmoris KACC 12218^T (97.9%), Deinococcus saxicola KACC 12240^T (97.0%), Deinococcus aerolatus KACC 12745^T (96.2%), and Deinococcus frigens KACC 12220^T (96.1%). Chemotaxonomic data revealed that the predominant fatty acids were iso-C_15:0 (19.0%), C_16:1 ω7c (17.7%), C_15:1 ω6c (12.6%), iso-C_17:0 (10.3%), and iso-C_17:1 ω9c (10.3%). A complex polar lipid profile consisted of a major unknown phosphoglycolipid. The predominant respiratory quinone is MK-8. The cell wall peptidoglycan contained D-alanine, L-glutamic acid, glycine, and L-ornithine (di-amino acid). The novel strain showed resistance to gamma radiation, with a D₁₀ value (i.e. the dose required to reduce the bacterial population by 10-fold) in excess of 5 kGy. Based on the phylogenetic, chemotaxonomic, and phenotypic data, strain DY59^T (=KCTC 33033^T =JCM 18581^T) should be classified as a type strain of a novel species, for which the name Deinococcus swuensis sp. nov. is proposed.