Journals
2014 EN
Uggenti Carolina · De Stefano M. Egle · Costantino Michele
+6 more
Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine‐induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c‐jun, Notch‐1, and Jagged‐1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re‐distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild‐type mice. Therefore, our data demonstrate that acetylcholine mediates axon‐glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 676–691, 2014
Journals
2014 EN
Rosso Gian Luca · Perotto Massimo · Feola Mauro
+1 more
The effectiveness of workplace drug testing (WDT) in Italy has recently been questioned, while very little is known about the real consumption of alcoholic beverages among workers performing hazardous jobs, such as professional drivers (PDs). The aim of this study is to investigate the modality and frequency of WDT execution and of alcohol consumption in the above category. Anonymous questionnaires were used to collect information. Four hundred and ninety‐seven questionnaires were collected; 50.1% declared that they know well in advance when they will be subjected to screening tests for drugs, while 19.5% claimed they have never been subjected to such a test. The greater the number of employees in a company, the greater the likelihood that the tests are performed with a genuinely surprise effect [odds ratio (OR) 2.41, 5.39 and 9.07, respectively, for businesses with 5–14 employees, 15–50 and more than 50, compared with companies with less than 5 employees, p <0.01]. Twenty‐one point four percent declared they drink alcoholic beverages during working hours or work breaks. This attitude is positively correlated with driver seniority [OR 1.07, 95% confidence interval (CI) 1.03–1.11 p <0.01] and is more common in those who operate on mainly international routes (OR 3.34 CI 1.30–8.59 p <0.01) and only occasionally consume meals in restaurants (OR 4.27, CI 1.19–15.42 p <0.05). Fifteen percent of the participants have an AUDIT C score ≥ 5. In conclusion WDT is largely ineffective, particularly in small businesses. The high percentage of PDs who claim to drink during working hours and who are hazardous drinkers requires a further strengthening of prevention strategies in this area. Copyright © 2013 John Wiley & Sons, Ltd.
Journals
2014 EN
Chang Alex C.Y. · Garside Victoria C. · Fournier Michele
+11 more
Background: Valvuloseptal defects are the most common congenital heart defects. Notch signaling–induced endothelial‐to‐mesenchymal transition (EMT) in the atrioventricular canal (AVC) cushions at murine embryonic day (E)9.5 is a required step during early valve development. Insights to the transcriptional network that is activated in endocardial cells (EC) during EMT and how these pathways direct valve maturation are lacking. Results: We show that at E11.5, AVC‐EC retain the ability to undergo Notch‐dependent EMT when explanted on collagen. EC‐Notch inhibition at E10.5 blocks expression of known mesenchymal genes in E11.5 AVC‐EC. To understand the genetic network and AVC development downstream of Notch signaling beyond E9.5, we constructed Tag‐Seq libraries corresponding to different cell types of the E11.5 AVC and atrium in wild‐type mice and in EC‐Notch inhibited mice. We identified 1,400 potential Notch targets in the AVC‐EC, of which 124 are transcription factors (TF). From the 124 TFs, we constructed a transcriptional hierarchy and identify 10 upstream TFs within the network. Conclusions: We validated 4 of the upstream TFs as Notch targets that are enriched in AVC‐EC. Functionally, we show these 4 TFs regulate EMT in AVC explant assays. These novel signaling pathways downstream of Notch are potentially relevant to valve development. Developmental Dynamics 243:894–905, 2014 . © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Giudetti Guido · Giannaccini Martina · Biasci Daniele
+5 more
Background: The transcription factor Rx1, also known as Rax, controls key properties of retinal precursors including migration behavior, proliferation, and maintenance of multipotency. However, Rx1 effector genes are largely unknown. Results: To identify genes controlled by Rx1 in early retinal precursors, we compared the transcriptome of Xenopus embryos overexpressing Rx1 to that of embryos in which Rx1 was knocked‐down. In particular, we selected 52 genes coherently regulated, i.e., actived in Rx1 gain of function and repressed in Rx1 loss of function experiments, or vice versa. RT‐qPCR and in situ hybridization confirmed the trend of regulation predicted by microarray data for the selected genes. Most of the genes upregulated by Rx1 are coexpressed with this transcription factor, while downregulated genes are either not expressed or expressed at very low levels in the early developing retina. Putative direct Rx1 target genes, activated by GR‐Rx1 in the absence of protein synthesis, include Ephrin B1 and Sh2d3c , an interactor of ephrinB1 receptor, which represent candidate novel effectors for the migration promoting activity of Rx1. Conclusions: This study identifies previously undescribed Rx1 regulated genes mainly involved in transcription regulation, cell migration/adhesion, and cell proliferation that contribute to delineate the molecular mechanisms underlying Rx1 activities. Developmental Dynamics 243:1352–1361, 2014 . © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Jin JiuZhen · Warner Dennis R. · Lu Qingxian
+3 more
Background: Transforming growth factor‐β3 (TGF‐β3) plays a central role in mediating secondary palate fusion along the facial midline. However, the mechanisms by which TGF‐β3 functions during secondary palate fusion are still poorly understood. Results : We found that mouse cytokeratin 6α and 17 mRNAs were expressed exclusively in the palate medial edge epithelium on embryonic day 14.5, and this expression was completely abolished in Tgf‐β3 mutant embryos. In contrast, we found that Jagged2 was initially expressed throughout the palate epithelium, but was specifically down‐regulated in the medial edge epithelium during palatal fusion. Jagged2 down‐regulation was regulated by TGF‐β3, since Jagged2 was persistently expressed in palatal medial edge epithelium in Tgf‐β3 null mutant embryos. Moreover, addition of DAPT, a specific inhibitor of Notch signaling, partially rescued the fusion defects in Tgf‐β3 null mutant palatal shelves. Conclusions : Based on these results, together with the previous study indicating that the loss of Jagged2 function promotes embryonic oral epithelial fusion, we concluded that TGF‐β3 mediates palate fusion in part by down‐regulating Jagged2 expression in palatal medial edge epithelium. In addition, cytokeratin 6α and 17 are two TGF‐β3 downstream target genes in palate medial edge epithelium differentiation. Developmental Dynamics 243:1536–1543, 2014 . © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Kula Abigail A. R. · Castillo Dean M. · Dudash Michele R.
+1 more
Plant–insect interactions often are important for plant reproduction, but the outcome of these interactions may vary with environmental context. Pollinating seed predators have positive and negative effects on host plant reproduction, and the interaction outcome is predicted to vary with density or abundance of the partners. We studied the interaction between Silene stellata , an herbaceous perennial, and Hadena ectypa , its specialized pollinating seed predator. Silene stellata is only facultatively dependent upon H. ectypa for pollination because other nocturnal moth co‐pollinators are equally effective at pollen transfer. We hypothesized that for plants without conspecific neighbors, H. ectypa would have higher visitation rates compared to co‐pollinators, and the plants would experience lower levels of H. ectypa pollen deposition. We predicted similar oviposition throughout the study site but greater H. ectypa predation in the area without conspecific neighbors compared to plants embedded in a naturally high density area. We found that H. ectypa had consistently higher visitation than moth co‐pollinators in all host plant contexts. However, H. ectypa pollinator importance declined in areas with low conspecific density because of reduced pollen deposition, resulting in lower seed set. Conversely, oviposition was similar across the study site independent of host plant density. Greater likelihood of very high fruit predation combined with lower pollination by H. ectypa resulted in reduced S. stellata female reproductive success in areas with low conspecific density. Our results demonstrate local context dependency of the outcomes of pollinating seed predator interactions with conspecific host plant density within a population.
Journals
2014 EN
Komajda Michel · Böhm Michael · Borer Jeffrey S
+5 more
Aims Low systolic blood pressure ( SBP ) is associated with poor outcomes in heart failure and complicates management. In a post hoc analysis, we investigated the efficacy and safety of ivabradine in the SHIFT population divided by tertiles of baseline SBP . Methods and Results The analysis comprised 2110 patients with SBP <115 mmHg , 1968 with 115≤ SBP <130 mmHg , and 2427 with SBP ≥130 mmHg . Patients with low SBP were younger, had lower ejection fraction, and were less likely to be at target beta‐blocker dose than patients in the other SBP groups. Ivabradine was associated with a similar relative risk reduction of the composite outcome in the three SBP groups [ SBP <115 mmHg , hazard ratio ( HR ) = 0.84, 95% confidence interval ( CI ) 0.72–0.98; 115≤ SBP <130 mmHg , HR = 0.86, 95% CI 0.72 to 1.03; SBP ≥130 mmHg , HR = 0.77, 95% CI 0.66 to 0.92; P interaction = 0.68]. Similar results were found for cardiovascular mortality ( P interaction = 0.91), hospitalization because of heart failure ( P interaction = 0.79), all‐cause mortality ( P interaction = 0.90), and heart failure mortality ( P interaction = 0.18). There was no evidence for a difference in safety profile according to SBP group. Conclusion The efficacy and safety of ivabradine is independent of SBP . This may have implications for the management of HF patients with low SBP and elevated heart rate.
Journals
2014 EN
Voors Adriaan A. · van Veldhuisen Dirk J. · Robertson Michele
+6 more
Aims We studied the relationship between heart rate and renal function and the effects of heart rate reduction with ivabradine in heart failure patients with and without renal dysfunction. Methods and results From the 6505 patients who were randomized in SHIFT , baseline creatinine and at least one follow‐up measurement were available in 6160 patients. Median follow‐up was 22.9 months. Worsening renal function ( WRF ) was defined as a creatinine increase of ≥0.3 mg/ dL and ≥25% from the baseline value. WRF developed in 1029 (17%) patients and was directly related to baseline heart rate, with an incremental risk of 5% for every 5 b.p.m. heart rate increment ( P = 0.003). WRF was associated with an increased risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death [hazard ratio ( HR ) 1.38, P < 0.001] and of all‐cause mortality ( HR 1.42, P < 0.001). Ivabradine use was associated with a reduction of the primary composite endpoint in patients both with ( HR 0.82, P = 0.023) and without renal dysfunction ( HR 0.81, P < 0.001) at baseline ( P for interaction = 0.89), and tolerability of ivabradine was comparable in the two groups. No differences were found in changes in renal function over time between ivabradine‐ and placebo‐treated patients. Conclusion In chronic stable systolic heart failure patients, heart rate is directly and independently associated with the risk of WRF , but reduction in heart rate by ivabradine had a neutral effect on renal function during 2 years of follow‐up. The beneficial cardiovascular effects and safety of ivabradine were similar in patients with and without renal dysfunction.
Journals
2014 EN
Gomes Tommaso · Caponio Francesco · Paradiso Vito Michele
+3 more
One sample of lampante olive oil, neutralised and bleached by a laboratory‐scale refining plant, was deodorised at the two most frequently adopted temperatures in olive oil refining (220°C and 230°C). The samples of deodorised oil were subjected to oven test at 60°C for 25 days. Aliquots of the oils were sampled at fixed times for analytical determinations, and the oxidative stability was evaluated by measuring the time needed to reach the peroxide value of 20 meq O 2 /kg. The sample that showed the highest oxidative stability was the oil deodorised at the highest temperature. This oil presented a higher level of TAG oligopolymers (TAGP) and lower amounts of oxidised TAGs (ox‐TAG) respect to the oil deodorised at lower temperature. These findings could be explained by the greater pro‐oxidant effect of ox‐TAG respect to TAGP. Practical applications: The results of this paper can help to choose the right deodorisation temperature for an oil. In fact, increasing the deodorisation temperature – other parameters being equal – leads to an increase in the oxidative stability of the refined oil. Therefore it could be an option when refining oils with potentially low stability. Nevertheless, it should be preferred submitting to refining slightly oxidized oils, with lower deodorisation temperatures, in order to obtain oils with low amounts of both ox‐TAG and TAGP. Effect of different deodorisation temperatures on the oxidative stability of an olive oil.
Journals
2014 EN
Ciriminna Rosaria · Pina Cristina Della · Rossi Michele
+1 more
As a result of the booming biodiesel and oleochemicals manufacturing taking place worldwide since more than a decade, 2 million tonnes of glycerol consistently reach the market every year, even though after a decade of growth the total glycerol supply is expected to slightly decrease in 2014. Today the supply of glycerol is entirely independent of its demand, as there is as much glycerol as the amount of vegetable oils and animal fats are hydrolyzed to make oleochemicals, or transesterified to produce biodiesel. This unique situation has led to consistently low glycerol prices, which initiated both the market penetration of glycerol in countries where it was not used due to traditional high price, as well as new uses of glycerol as raw material for the production of value added chemicals. This article sheds light on the market of this uniquely versatile chemical whose number of applications is unique amid all existing chemicals. About 2 million tonnes of glycerol consistently reach the market every year, even though after a decade of growth the total glycerol supply is expected to slightly decrease in 2014. Today the supply of glycerol is entirely independent of its demand, as there is as much glycerol as the amount of vegetable oils and animal fats are hydrolyzed to make oleochemicals, or transesterified to produce biodiesel. This article sheds light on the market of this uniquely versatile chemical whose number of applications is unique amid all existing chemicals.