Root hair polar growth is endogenously controlled by auxin and sustained by oscillating levels of reactive oxygen species (ROS). These cells extend several hundred-fold their original size toward signals important for plant survival. Although their final cell size is of fundamental importance, the molecular mechanisms that control it remain largely unknown. Here we show that ROS production is controlled by the transcription factor RSL4, which in turn is transcriptionally regulated by auxin through several auxin response factors (ARFs). In this manner, auxin controls ROS-mediated polar growth by activating RSL4, which then up-regulates the expression of genes encoding NADPH oxidases (also known as RESPIRATORY BURST OXIDASE HOMOLOG proteins) and class III peroxidases, which catalyze ROS production. Chemical or genetic interference with ROS balance or peroxidase activity affects root hair final cell size. Overall, our findings establish a molecular link between auxin and ROS-mediated polar root hair growth.
BackgroundThere has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria.MethodsWe selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011.ResultsMajor architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information.ConclusionsFNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs.
Expansins are non-hydrolytic cell wall-loosening proteins that are involved in the cell wall modifications that underlie many plant developmental processes. Root hair growth requires the accumulation of cell wall materials and dynamic cell wall modification at the tip region. Although several lines of indirect evidence support the idea that expansin-mediated wall modification occurs during root hair growth, the involvement of these proteins remains to be demonstrated in vivo. In this study, we used RNA interference (RNAi) to examine the biological function of Arabidopsis thaliana EXPANSIN A7 (AtEXPA7), which is expressed specifically in the root hair cell. The root hairspecific AtEXPA7 promoter was used to drive RNAi expression, which targeted two independent regions in the AtEXPA7 transcript. Quantitative reverse transcriptase-PCR analyses were used to examine AtEXPA7 transcript levels. In four independent RNAi transformant lines, RNAi expression reduced AtEXPA7 transcript levels by 25-58% compared to controls. Accordingly, the root hairs of RNAi transformant lines were 25-48% shorter than control plants and exhibited a broader range of lengths than the controls. Our results provide in vivo evidence that expansins are required for root hair tip growth.
ROOT HAIR SPECIFIC (RHS) genes, which contain the root hair-specific cis-element (RHE) in their regulatory regions, function in root hair morphogenesis. Here, we demonstrate that an Arabidopsis thaliana basic helix-loop-helix transcription factor, ROOT HAIR DEFECTVE SIX-LIKE4 (RSL4), directly binds to the RHE in vitro and in vivo, upregulates RHS genes, and stimulates root hair formation in Arabidopsis. Orthologs of RSL4 from a eudicot (poplar [Populus trichocarpa]), a monocot (rice [Oryza sativa]), and a lycophyte (Selaginella moellendorffii) each restored root hair growth in the Arabidopsis rsl4 mutant. In addition, the rice and S. moellendorffii RSL4 orthologs bound to the RHE in in vitro and in vivo assays. The RSL4 orthologous genes contain RHEs in their promoter regions, and RSL4 was able to bind to its own RHEs in vivo and amplify its own expression. This process likely provides a positive feedback loop for sustainable root hair growth. When RSL4 and its orthologs were expressed in cells in nonroot-hair positions, they induced ectopic root hair growth, indicating that these genes are sufficient to specify root hair formation. Our results suggest that RSL4 mediates root hair formation by regulating RHS genes and that this mechanism is conserved throughout the tracheophyte (vascular plant) lineage.
BackgroundThere is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.MethodsWe reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.ResultsAccording to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001).ConclusionsThe results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.
Background Uncoupling protein 1 (UCP1) plays an important role in increasing energy expenditure; thus, it is being considered as a new target for preventing obesity and metabolic complications. In this study, we investigated the effect of quercetin, a naturally occurring flavonoid, on UCP1 expression in white/brown adipose tissues (WAT/BAT). Methods Mice were fed a high-fat diet (HFD) supplemented with or without dietary quercetin for 9 weeks, and 3T3-L1 adipocytes were treated with quercetin. Expression of UCP1 and other thermogenic genes/proteins was measured by real-time polymerase chain reaction and/or Western blotting. Results Dietary quercetin supplementation increased the level of UCP1 in both WAT and/or BAT of HFD-fed obese mice, which was accompanied by upregulated mRNA levels of thermogenesis-related genes. Quercetin supplementation enhanced the plasma norepinephrine level and tended to upregulate β-adrenergic receptor mRNA level in the WAT of HFD-fed obese mice, accompanied by AMP-activated protein kinase (AMPK) activation. Moreover, quercetin enhanced UCP1 expression in 3T3-L1 adipocytes, and this was blunted by treatment with a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist. Conclusion These findings suggest that quercetin upregulates UCP1, implying increased WAT browning and BAT activity, via activation of the AMPK/PPARγ pathway through sympathetic stimulation. Quercetin may be useful for preventing obesity and metabolic complications.
Interleukin-10 (IL-10), an immunosuppressive cytokine, is produced by monocyte/macrophage lineage cells, T cells, and B cells in the immune system. Here, we show that thrombin induces IL-10 expression in cultured rat microglia. Thrombin treatment increases IL-10 mRNA expression after 3 h and IL-10 release into the culture medium 12 h after thrombin treatment. Neutralizing antibodies against IL-10 significantly enhanced TNF-alpha release from thrombin-treated microglia. IL-10 release was suppressed by an inhibitor of p38 MAPK, SB203580 but not by an inhibitor of ERK pathway, PD98059, whereas both SB203580 and PD98059 inhibited TNF-alpha release. These results suggest that thrombin induces IL-10 and TNF-alpha expression through different signaling mechanisms, and that IL-10 inhibits TNF-alpha release as a negative feedback regulation.
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