PITX2 is a homeobox transcription factor involved in embryonic left/right signaling and more recently has been associated to cardiac arrhythmias. Genome wide association studies have pinpointed PITX2 as a major player underlying atrial fibrillation (AF). We have previously described that PITX2 expression is impaired in AF patients. Furthermore, distinct studies demonstrate that Pitx2 insufficiency leads to complex gene regulatory network remodeling, i.e. Wnt>microRNAs, leading to ion channel impairment and thus to arrhythmogenic events in mice. Whereas large body of evidences has been provided in recent years on PITX2 downstream signaling pathways, scarce information is available on upstream pathways influencing PITX2 in the context of AF. Multiple risk factors are associated to the onset of AF, such as e.g. hypertension (HTN), hyperthyroidism (HTD) and redox homeostasis impairment. In this study we have analyzed whether HTN, HTD and/or redox homeostasis impact on PITX2 and its downstream signaling pathways. Using rat models for spontaneous HTN (SHR) and experimentally-induced HTD we have observed that both cardiovascular risk factors lead to severe Pitx2 downregulation. Interesting HTD, but not SHR, leads to up-regulation of Wnt signaling as well as deregulation of multiple microRNAs and ion channels as previously described in Pitx2 insufficiency models. In addition, redox signaling is impaired in HTD but not SHR, in line with similar findings in atrial-specific Pitx2 deficient mice. In vitro cell culture analyses using gain- and loss-of-function strategies demonstrate that Pitx2, Zfhx3 and Wnt signaling influence redox homeostasis in cardiomyocytes. Thus, redox homeostasis seems to play a pivotal role in this setting, providing a regulatory feedback loop. Overall these data demonstrate that HTD, but not HTN, can impair Pitx2>>Wnt pathway providing thus a molecular link to AF.

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Injury to olive tree trunks and branches because of biotic and abiotic factors, such as pruning and mechanical harvesting, attracts the olive pyralid moth Euzophera pinguis Haworth (Lepidoptera: Pyralidae). This moth has become increasingly important in the Mediterranean region during recent years. The use of an entomopathogenic fungus for wound dressing for pest control is reported for the first time in this study. Beauveria bassiana (Ascomycota: Hypocreales) strain EABb 08/04-Ep was originally obtained from a diseased E. pinguis larva and has shown effective E. pinguis control in an olive crop in Jaén, Andalusia, Spain, under field conditions during the spring and fall of 2008 and 2009 and the spring of 2011. Experimental artificial 30 by 30-mm square wound cages were large enough to allow the E. pinguis females to oviposit. Approximately 80 and 40-60% of the control wounds contained live larvae in the experiments that occurred during the spring and fall, respectively. The B. hassiana wound dressing gave similar results as the chlorpyrifos wound dressing throughout the experiment, with efficacies reaching 80-85% in the spring and 90-95% in the autumn. The B. bassiana fungus was recovered from 60-90% of the wounds at the completion of the experiments and after 60 d of treatment. These data indicate that strain EABb 08/04-Ep applied to the pruning wounds can be an effective tool for the microbial control of E. pinguis in olive crops. Moreover, B. bassiana may be used within integrated pest management strategies to minimize chemicals, depending on the population density of the pyralid moth.