Comprehensive analysis of the regulatory roles of auxin in early transdifferentiation into xylem cells

Auxin is essential for the formation of the vascular system. We previously reported that a polar auxin transport inhibitor, 1-N-naphthylphthalamic acid (NPA) decreased intracellular auxin levels and prevented tracheary element (TE) differentiation from isolated Zinnia mesophyll cells, but that additional auxin, 1-naphthaleneacetic acid (NAA) overcame this inhibition. To understand the role of auxin in gene regulation during TE differentiation, we performed microarray analysis of genes expressed in NPA-treated cells and NPA-NAA-treated cells. The systematic gene expression analysis revealed that NAA promoted the expression of genes related to auxin signaling and transcription factors that are known to be key regulators of differentiation of procambial and xylem precursor cells. NAA also promoted the expression of genes related to biosynthesis and metabolism of other plant hormones, such as cytokinin, gibberellin and brassinosteroid. Interestingly, detailed analysis showed that NAA rapidly induces the expression of auxin carrier gene homologues. It suggested a positive feedback loop for auxin-regulating vascular differentiation. Based on these results, we discuss the auxin function in early processes of transdifferentiation into TE

Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a submucosal tumor: a case report

<p>Abstract</p> <p>Background</p> <p>Dome-type carcinoma (DC) is a distinct variant of colorectal adenocarcinoma and less than 10 cases have been described in the literature. Most of the previously reported cases were early lesions and no endoscopic observations have been described so far. We herein report a case of a DC invading the subserosal layer, including endoscopic findings.</p> <p>Case presentation</p> <p>A highly elevated lesion in the transverse colon was diagnosed by colonoscopy in a 77-year-old man. The tumor appeared to be similar to a submucosal tumor (SMT), however, a demarcated area of reddish and irregular mucosa was observed at the top of the tumor. There were no erosions or ulcers. Laparoscopic-assisted right hemicolectomy was performed and pathological examination revealed a well-circumscribed tumor invading the subserosal layer. The tumor was a well-differentiated adenocarcinoma associated with a dense lymphocytic infiltration and showed expansive growth. The overlying mucosal layer showed high-grade dysplasia.</p> <p>Conclusion</p> <p>The present lesion was diagnosed as a DC of the colon invading the subserosal layer. Because the association of mucosal dysplasia is common in DCs, the detection of dysplastic epithelium would be important to discriminate DCs from SMTs.</p

Ventricular pacing inhibition by oversensing due to diaphragmatic myopotential during deep inspiration

AbstractAn 80-year-old man, who had dilated cardiomyopathy with right ventricular (RV) dilatation, underwent implantable cardioverter defibrillator (ICD) implantation for advanced atrioventricular block and primary prevention of sudden cardiac death. Tined and screw-in leads were placed on the right atrial appendage and RV apex, respectively. Ventricular pacing inhibition was detected after surgery due to oversensing by diaphragmatic myopotential occurring only during deep inspiration. We performed re-surgery and switched the screw-in lead for a tined lead. The diaphragmatic myopotential decreased, thereby improving oversensing by diaphragmatic myopotential and ventricular pacing inhibition. It might be beneficial to use a tined lead when placing the ventricular lead at the RV apex for implantation of a pacemaker or ICD if oversensing of diaphragmatic myopotential is observed using a screw-in lead.<Learning objective: Oversensing due to diaphragmatic myopotential is rarely observed. However if it occurs, it becomes a critical problem, which causes pacemaker inhibition or inappropriate ICD shock. However, the method of preventing this problem is unknown. In this case, we demonstrated that a tined-lead may be useful for the prevention of oversensing by diaphragmatic myopotential.

Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men

<p>Abstract</p> <p>Background</p> <p>Combined effects between mitochondrial DNA 5178 (Mt5178) C/A polymorphism and alcohol consumption on the risk of hypertension or hyperuricemia have been reported. The objective of this study was to investigate whether Mt5178 C/A polymorphism modulates the effects of alcohol consumption on the risk of dyslipidemia.</p> <p>Methods</p> <p>A total of 394 male subjects were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effect of Mt5178 polymorphism and alcohol consumption on the risk of dyslipidemia was conducted.</p> <p>Results</p> <p>For men with Mt5178C, alcohol consumption was significantly and negatively associated with the risk of hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol ≥ 140 mg/dl) (<it>P </it>for trend = 0.015). After adjustment for age, body mass index (BMI), habitual smoking, coffee consumption and use of antihypertensive medicine, the odds ratio (OR) for hyper-LDL cholesterolemia was significantly lower in daily drinkers with Mt5178C than non-drinkers with Mt5178C (OR = 0.360, 95% confidence intervals: 0.153-0.847). A significant and negative association between alcohol consumption and serum LDL cholesterol levels was also observed in Mt5178C genotypic men (<it>P </it>for trend < 0.01). On the other hand, the association between Mt5178A genotype and risk of hyper-LDL cholesterolemia does not appear to depend on alcohol consumption.</p> <p>Conclusions</p> <p>For Mt5178C genotypic men, alcohol consumption may reduce the risk of hyper-LDL cholesterolemia.</p

Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis

Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome remodeling and deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active lymphoid differentiation genes. Loss in Ikaros DNA binding activity caused a local increase in Mi-2β chromatin remodeling and histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributed to transcriptionally poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks

Cholesterol accumulation promotes photoreceptor senescence and retinal degeneration

PURPOSE: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors. METHODS: Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina. RESULTS: Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch\u27s membrane thickening. CONCLUSIONS: Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation

TREM2 Expression in Schizophrenia

TREM2 and TYROBP are causal genes for Nasu–Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer’s disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia. Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia. Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P < 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients. Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders

Attenuation of Millimeter Emission from Circumstellar Disks Induced by the Rapid Dust Accretion

From millimeter observations of classical T Tauri stars, it is suggested that dust grains in circumstellar disks have grown to millimeter size or larger. However, gas drag on such large grains induces rapid accretion of the dust. We examine the evolution of dust disks composed of millimeter sized grains, and show that rapid accretion of the dust disk causes attenuation of millimeter continuum emission. If a dust disk is composed mainly of grains of 1 cm to 1 m, its millimeter emission goes off within 10^6 yr. Hence, grains in this size range cannot be a main population of the dust. Considering our results together with grain growth suggested by the millimeter continuum observations, we expect that the millimeter continuum emission of disks comes mainly from grains in a narrow size range of [1 mm -1 cm]. This suggests either that growth of millimeter sized grains to centimeter size takes more than 10^6 yr, or that millimeter sized grains are continuously replenished. In the former case, planet formation is probably difficult, especially in the outer disks. In the latter case, reservoirs of millimeter grains are possibly large (> 10 m) bodies, which can reside in the disk more than 10^6 yr. Constraints on the grain growth time-scale are discussed for the above two cases.Comment: Accepted by ApJ, 17 pages, 15 figure