cis9, trans11-Conjugated Linoleic Acid Differentiates Mouse 3T3-L1 Preadipocytes into Mature Small Adipocytes through Induction of Peroxisome Proliferator-activated Receptor γ

Dietary conjugated linoleic acid (CLA) has been reported to exhibit a number of therapeutic effects in animal models and patients, such as anti-hypertensive, anti-hyperlipidemic, anti-arteriosclerotic, anti-carcinogenic, and anti-diabetic effects. However, the underlying mechanism is not well-characterized. In the present study, the effects of cis(c)9, trans(t)11-CLA on the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes were examined. Treatment with c9, t11-CLA in the presence of insulin, dexamethasone, and 3-isobutyl-1-methyl-xanthine (differentiation cocktail) significantly stimulated the accumulation of triacylglycerol. The microscopic observation of cells stained by Oil Red O demonstrated that c9, t11-CLA increases the amount and proportion of small mature adipocytes secreting adiponectin, a benign adipocytokine, when compared to the differentiation cocktail alone. Furthermore, c9, t11-CLA increased bioactive peroxisome proliferator-activated receptor γ (PPARγ) levels in a nuclear extract of 3T3-L1 cells, suggesting the enhancing effect of this fatty acid on the nuclear transmission of PPARγ, a master regulator of adipocyte differentiation, in 3T3-L1 cells. These results suggest that the therapeutic effects of c9, t11-CLA on lifestyle-related diseases are partially due to the enhanced formation of small adipocytes from preadipocytes via PPARγ stimulation

Two distinct regions in Staphylococcus aureus GatCAB guarantee accurate tRNA recognition

In many prokaryotes the biosynthesis of the amide aminoacyl-tRNAs, Gln-tRNAGln and Asn-tRNAAsn, proceeds by an indirect route in which mischarged Glu-tRNAGln or Asp-tRNAAsn is amidated to the correct aminoacyl-tRNA catalyzed by a tRNA-dependent amidotransferase (AdT). Two types of AdTs exist: bacteria, archaea and organelles possess heterotrimeric GatCAB, while heterodimeric GatDE occurs exclusively in archaea. Bacterial GatCAB and GatDE recognize the first base pair of the acceptor stem and the D-loop of their tRNA substrates, while archaeal GatCAB recognizes the tertiary core of the tRNA, but not the first base pair. Here, we present the crystal structure of the full-length Staphylococcus aureus GatCAB. Its GatB tail domain possesses a conserved Lys rich motif that is situated close to the variable loop in a GatCAB:tRNAGln docking model. This motif is also conserved in the tail domain of archaeal GatCAB, suggesting this basic region may recognize the tRNA variable loop to discriminate Asp-tRNAAsn from Asp-tRNAAsp in archaea. Furthermore, we identified a 310 turn in GatB that permits the bacterial GatCAB to distinguish a U1–A72 base pair from a G1–C72 pair; the absence of this element in archaeal GatCAB enables the latter enzyme to recognize aminoacyl-tRNAs with G1–C72 base pairs

Airway obstruction caused by achalasia: A case report

We report a rare case of airway obstruction caused by megaesophagus associated with achalasia. A 78-year-old man was admitted with post meal dyspnea, decreased consciousness, expiratory and inspiratory wheezing, and respiratory distress. Arterial blood gas analysis showed findings of marked acute respiratory acidosis (pH 7.18, PaCO2 75 mmHg, PaO2 225 mm Hg, HCO3− 22 mmol/L). An emergency laryngoscopy was performed because of a suspected airway obstruction, but no abnormalities were observed from the airway to the glottis. Noninvasive positive pressure ventilation (NPPV) was immediately introduced, and the respiratory rate and breathing pattern was normalized. A chest X-ray showed an enlarged upper mediastinal outline and an ill-defined border of the trachea. A computed tomography (CT) scan showed an enlarged esophagus with a maximum diameter of 9.90 cm, compressing the trachea to the back of the sternal notch. Following removal of the esophageal contents using a nasogastric tube, NPPV was discontinued with no respiratory episodes. After he was stabilized, he was transferred to another hospital for endoscopic myotomy. In a review of the literature, we identified 66 cases of airway obstruction due to achalasia, mainly in older women. None of the patients received NPPV. As a differential diagnosis for acute airway obstruction, achalasia-related airway obstruction should be considered, particularly in older women. Furthermore, since this condition is suspected to involve tracheomalacia, NPPV may be a useful respiratory support therapy

The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.

乳がん細胞の転移を促進する新たなメカニズムの解明 --SALL4 - integrin α6β1系による移動能力の亢進--. 京都大学プレスリリース. 2016-11-08.During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration

Data from: Transcriptional regulation of fruit ripening by tomato FRUITFULL homologs and associated MADS-box proteins

The tomato (Solanum lycopersicum) MADS box FRUITFULL homologs FUL1 and FUL2 act as key ripening regulators and interact with the master regulator MADS box protein RIPENING INHIBITOR (RIN). Here, we report the large-scale identification of direct targets of FUL1 and FUL2 by transcriptome analysis of FUL1/FUL2 suppressed fruits and chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) targeting tomato gene promoters. The ChIP-chip and transcriptome analysis identified FUL1/FUL2 target genes that contain at least one genomic region bound by FUL1 or FUL2 (regions that occur mainly in their promoters) and exhibit FUL1/FUL2-dependent expression during ripening. These analyses identified 860 direct FUL1 targets and 878 direct FUL2 targets; this set of genes includes both direct targets of RIN and nontargets of RIN. Functional classification of the FUL1/FUL2 targets revealed that these FUL homologs function in many biological processes via the regulation of ripening-related gene expression, both in cooperation with and independent of RIN. Our in vitro assay showed that the FUL homologs, RIN, and tomato AGAMOUS-LIKE1 form DNA binding complexes, suggesting that tetramer complexes of these MADS box proteins are mainly responsible for the regulation of ripening

Spatial and Temporal House Price Diffusion in the Netherlands: A Bayesian Network Approach

Following the 2007-08 Global Financial Crisis, there have been a growing research interest on the spatial interrelationships between house prices in many countries. This paper examines the spatio-temporal relationship between house prices in the twelve provinces of the Netherlands using a recently proposed econometric modelling technique called Bayesian graphical vector autoregression (BG-VAR). This network approach enables a data driven identification of the most dominant provinces where house price shocks may largely diffuse through the housing market and it is suitable for analysing the complex spatial interactions between house prices. Using temporal house price volatilities for owner-occupied dwellings, the results show evidence of house price diffusion pattern in distinct sub-periods from different provincial housing sub- markets in the Netherlands. We observed particularly prior to the crisis, diffusion of temporal house price volatilities from Noord-Holland