Chlorophyll-deficient gene and morphological variations in Korean populations of maize (Zea mays)

We studied cultivated and naturalized Korean maize populations to determine the extent to which the chlorophylldeficient mutation and the phenotypic variations of two morphological characters (i.e., red coleoptiles and epicotyls, and the number of the first root hairs) are maintained. The frequency of the chlorophyll-deficient mutant gene (2.73% on average) was highly variable. Frequencies of red coleoptiles and epicotyls also were higher than expected from a mutation-selection balance. The average number of hairy phenotypes within populations was 1.8, ranging from 0.0 to 4.0. Naturalized populations were closely related to with cultivated communities. Most striking, however, was the more significant difference among populations than within populations with regard to both the frequency of chlorophyll-deficient mutant genes and the phenotypic variations of our two morphological characters. On a per-gene basis, the majority of the phenotypic variation (mean of 73.3%) resided among populations.     

DNAX-activating Protein 10 (DAP10) Membrane Adaptor Associates with Receptor for Advanced Glycation End Products (RAGE) and Modulates the RAGE-triggered Signaling Pathway in Human Keratinocytes

The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of many inflammatory, degenerative, and hyperproliferative diseases, including cancer. Previously, we revealed mechanisms of downstream signaling from ligand-activated RAGE, which recruits TIRAP/MyD88. Here, we showed that DNAX-activating protein 10 (DAP10), a transmembrane adaptor protein, also binds to RAGE. By artificial oligomerization of RAGE alone or RAGE-DAP10, we found that RAGE-DAP10 heterodimer formation resulted in a marked enhancement of Akt activation, whereas homomultimeric interaction of RAGE led to activation of caspase 8. Normal human epidermal keratinocytes exposed to S100A8/A9, a ligand for RAGE, at a nanomolar concentration mimicked the pro-survival response of RAGE-DAP10 interaction, although at a micromolar concentration, the cells mimicked the pro-apoptotic response of RAGE-RAGE. In transformed epithelial cell lines, A431 and HaCaT, in which endogenous DAP10 was overexpressed, and S100A8/A9, even at a micromolar concentration, led to cell growth and survival due to RAGE-DAP10 interaction. Functional blocking of DAP10 in the cell lines abrogated the Akt phosphorylation from S100A8/A9-activated RAGE, eventually leading to an increase in apoptosis. Finally, S100A8/A9, RAGE, and DAP10 were overexpressed in the psoriatic epidermis. Our findings indicate that the functional interaction between RAGE and DAP10 coordinately regulates S100A8/A9-mediated survival and/or apoptotic response of keratinocytes.     

Truncation of annexin A1 is a regulatory lever for linking epidermal growth factor signaling with cytosolic phospholipase A2 in normal and malignant squamous epithelial cells

Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A(2) (cPLA(2)), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca(2+)-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA(2), resulting in inhibition of cPLA(2) activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp(12), and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.     

The changes of histopathology and serum anti-sparganum IgG in experimental sparganosis of mice

The present study is intended to observe the chronologic changes of experimental sparganosis by histopathological observation and detection of circulating anti-sparganum IgG antibody using ELISA. Each of 25 mice was infected with five spargana, and they were examined after 1, 2, 4, 10 weeks or 6 months from infection. The followings are summarized results. 1. The plerocercoids were detected in the subcutaneous tissue of the trunk, neck or axilla, but a few often extended into the skeletal muscle. The recovery rates were 72% at the first week, 80% at the second week, 95% at the fourth week, 92% at the tenth week and 100% at the sixth month. The larvae grew slowly in both length and weight until 6 months. 2. Histopathologically, most of the larvae were observed alive in the soft tissue or skeletal muscle. Numerous eosinophils, neutrophils, lymphocytes and plasma cells were infiltrated focally around the worms by the second week, but they surrounded the worms to form a layer of inflammatory reaction after 4 weeks of infection. Also histiocytes and fibroblasts began to appear around the inflammatory cells at 4 weeks. After 10 weeks, the worms encircled by a thin fibrous layer were found. After 6 months, the worms were surrounded by either fibrous tissue or active inflammatory cells. The inflammation looked more severe in the tracks left by the worms, rather than around the worms. 3. The level of anti-sparganum IgG antibody in the serum showed an increase by the fourth week, and a rapid and continuous increase was observed thereafter by the tenth week after infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lysophosphatidic acid-induced c-fos up-regulation involves cyclic AMP response element-binding protein activated by mitogen- and stress-activated protein kinase-1

Lysophosphatidic acid (LPA) is a lipid growth factor that exerts diverse biological effects through its cognate receptor-mediated signaling cascades. Recently, we reported that LPA stimulates cAMP response element-binding protein (CREB) through mitogen- and stress-activated protein kinase-1 (MSK1). Previously, LPA has been shown to stimulate c-fos mRNA expression in Rat-2 fibroblast cells via a serum response element binding protein (SRF). However, involvement of CREB in LPA-stimulated c-fos gene expression is not elucidated yet. To investigate the CREB-mediated c-fos activation by LPA, various c-fos promoter-reporter constructs containing wild-type and mutated SRE and CRE were tested for their inducibility by LPA in transient transfection assays. LPA-stimulated c-fos promoter activation was markedly decreased when SRE and CRE were mutated. A dominant negative CREB significantly down-regulated the LPA-stimulated c-fos promoter activation. Chromatin immunoprecipitation assay revealed that LPA induced an increased binding of phosphorylated CREB and CREB-binding protein (CBP) to the CRE region of the endogenous c-fos promoter. Immunoblot analyses with various pharmacological inhibitors further showed that LPA induces up-regulation of c-fos mRNA level by activation of ERK, p38 MAPK, and MSK1. Taken together, our results suggest that CREB plays an important role in up-regulation of c-fos mRNA level in LPA-stimulated Rat-2 fibroblast cells.     

A Prospective Study of Fatty Liver Index and Incident Hypertension: The KoGES-ARIRANG Study

Background

Although non-alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, its influence on hypertension development is poorly understood. We investigated whether fatty liver disease, as assessed by the fatty liver index, could predict the development of hypertension independently of systemic insulin resistance, inflammatory status and adipokine levels.

Methods

Prospective cohort study of 1,521 adults (484 men and 1037 women) aged 40 to 70 years without baseline hypertension examined. An equation was used to calculate fatty liver index and classify patients as follows: fatty liver index <30, no non-alcoholic fatty liver disease; fatty liver index ≥60, non-alcoholic fatty liver disease; and 30≤ fatty liver index <60, intermediate fatty liver index.

Results

During an average of 2.6 years of follow-up, 153 subjects (10.06%) developed hypertension. Fatty liver index was positively associated with baseline blood pressure, homeostasis model assessment of insulin resistance, urinary albumin/creatinine excretion, and high sensitivity C-reactive protein. After adjustment for confounding factors, including markers of insulin resistance, systemic inflammation and adiponectin levels, the odds ratio [95% confidence interval] for the incident hypertension increased in a graded manner with fatty liver index (<30 vs. 30–59 vs. ≥60 = 1 vs. 1.83 [1.16~2.88] vs. 2.09 [1.08~4.055], respectively).

Conclusions

Non-alcoholic fatty liver disease assessed by fatty liver index was an independent risk factor for hypertension. Our findings suggest that fatty liver index, a simple surrogate indicator of fatty liver disease, might be useful for identifying subjects at high risk for incident hypertension in clinical practice.     

Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination

The inhibitor of apoptosis protein DIAP1 inhibits Dronc-dependent cell death by ubiquitinating Dronc. The pro-death proteins Reaper, Hid and Grim (RHG) promote apoptosis by antagonizing DIAP1 function. Here we report the structural basis of Dronc recognition by DIAP1 as well as a novel mechanism by which the RHG proteins remove DIAP1-mediated downregulation of Dronc. Biochemical and structural analyses revealed that the second BIR (BIR2) domain of DIAP1 recognizes a 12-residue sequence in Dronc. This recognition is essential for DIAP1 binding to Dronc, and for targeting Dronc for ubiquitination. Notably, the Dronc-binding surface on BIR2 coincides with that required for binding to the N termini of the RHG proteins, which competitively eliminate DIAP1-mediated ubiquitination of Dronc. These observations reveal the molecular mechanisms of how DIAP1 recognizes Dronc, and more importantly, how the RHG proteins remove DIAP1-mediated ubiquitination of Dronc.