Sustainable use of citrus waste as organic amendment in orange orchards

The use of citrus waste (peel, CW) as organic fertilizer was investigated on soil microbiota and on soil physico-chemical and hydraulic characteristics. The biotic components on CW and the effect on nutritional status, leaf chlorophyll content, fruit set and production of "Tarocco" orange trees were also identified. The citrus waste was supplied to an experimental orchard at different doses: 45 kg m(-2) (with and without Ca(OH)(2) addition) and 90 kg m(-2). The study was conducted in three consecutive years (2015-2017) on 20-year old orange trees at the experimental farm of the University of Catania (Italy). The main results of the study confirm that the use of CW as a biofertilizer offers a great opportunity for sustainable sweet orange production

Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α.

Junction-mediating and regulatory protein (JMY) is a novel p53 cofactor that regulates p53 activity during stress. JMY interacts with p300/CBP, which are ubiquitous transcriptional co-activators that interact with a variety of sequence-specific transcription factors, including hypoxia-inducible factor-1α (HIF-1α). In addition, JMY is an actin-nucleating protein, which, through its WH2 domains, stimulates cell motility. In this study, we show that JMY is upregulated during hypoxia in a HIF-1α-dependent manner. The JMY gene contains HIF-responsive elements in its promoter region and HIF-1α is recruited to its promoter during hypoxia. HIF-1α drives transcription of JMY, which accounts for its induction under hypoxia. Moreover, the enhanced cell motility and invasion that occurs during hypoxia requires JMY, as depleting JMY under hypoxic conditions causes decreased cell motility. Our results establish the interplay between JMY and HIF-1α as a new mechanism that controls cell motility under hypoxic stress

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

Antibacterial Characterization of Novel Synthetic Thiazole Compounds against Methicillin-Resistant Staphylococcus pseudintermedius

Staphylococcus pseudintermedius is a commensal organism of companion animals that is a significant source of opportunistic infections in dogs. With the emergence of clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown to possess potent antibacterial activity against multidrug-resistant strains of Staphylococcus aureus of human and animal concern. Given the genetic similarity between S. aureus and S. pseudintermedius, this study explores the potential use of thiazole compounds as novel antibacterial agents against methicillin-sensitive S. pseudintermedius (MSSP) and MRSP. A broth microdilution assay confirmed these compounds exhibit potent bactericidal activity (at sub-microgram/mL concentrations) against both MSSA and MRSP clinical isolates while the MTS assay confirmed three compounds (at 10 μg/mL) were not toxic to mammalian cells. A time-kill assay revealed two derivatives rapidly kill MRSP within two hours. However, this rapid bactericidal activity was not due to disruption of the bacterial cell membrane indicating an alternative mechanism of action for these compounds against MRSP. A multistep resistance selection analysis revealed compounds 4 and 5 exhibited a modest (twofold) shift in activity over ten passages. Furthermore, all six compounds (at a subinihibitory concentration) demonstrated the ability to re-sensitize MRSP to oxacillin, indicating these compounds have potential use for extending the therapeutic utility of β-lactam antibiotics against MRSP. Metabolic stability analysis with dog liver microsomes revealed compound 3 exhibited an improved physicochemical profile compared to the lead compound. In addition to this, all six thiazole compounds possessed a long post-antibiotic effect (at least 8 hours) against MRSP. Collectively the present study demonstrates these synthetic thiazole compounds possess potent antibacterial activity against both MSSP and MRSP and warrant further investigation into their use as novel antimicrobial agents

The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen

Introduction: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy.Methods: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment.Results: PHD1, PHD2 and PHD3 were detected in 47/179 (26.7%), 85/163 (52.2%) and 69/177 (39%) of tumours at baseline. PHD2 and PHD3 expression was moderate/strong whereas PHD1 expression was generally weak. There was a significant positive correlation between HIF-1α and PHD1 (P = 0.002) and PHD3 (P < 0.05) but not PHD2 (P = 0.41). There was a significant positive relationship between VEGF and PHD1 (P < 0.008) and PHD3 (P = 0.001) but not PHD2 (P = 0.09). PHD1, PHD2 and PHD3 expression was significantly increased after epirubicin therapy (all P < 0.000) with no significant difference in PHD changes between the treatment arms. There was no significant difference in response in tumours that expressed PHDs and PHD expression was not associated with survival.Conclusions: Although expression of the PHDs was not related to response or survival in patients receiving neoadjuvant epirubicin, our data provide the first evidence that these enzymes are upregulated on therapy in breast cancer and that the biological effects independent of HIF make them therapeutic targets. © 2011 Fox et al.; licensee BioMed Central Ltd

BRCA1 tumours correlate with a HIF-1α phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression

BACKGROUND: There are limited data regarding the hypoxia pathway in familial breast cancers. We therefore performed a study of hypoxic factors in BRCA1, BRCA2 and BRCAX breast cancers. METHODS: Immunoperoxidase staining for HIF-1alpha, PHD1, PHD2, PHD3, VEGF and FIH was carried out in 125 (38 BRCA1, 33 BRCA2 and 54 BRCAX) breast carcinomas. These were correlated with clinicopathological parameters and the intrinsic breast cancer phenotypes. RESULTS: BRCA1 tumours correlated with positivity for HIF-1alpha (P=0.008) and negativity for PHD3 (P=0.037). HIF-1alpha positivity (P=0.001), PHD3 negativity (P=0.037) and nuclear FIH negativity (P=0.011) was associated with basal phenotype. HIF-1alpha expression correlated with high tumour grade (P=0.009), negative oestrogen receptor (ER) status (P=0.001) and the absence of lymph node metastasis (P=0.028). Nuclear FIH expression and PHD3 correlated with positive ER expression (P=0.024 and P=0.035, respectively). BRCA1 cancers with positive HIF-1alpha or cytoplasmic FIH had a significantly shorter relapse-free survival (P=0.007 and P=0.049, respectively). CONCLUSIONS: The aggressive nature of BRCA1 and basal-type tumours may be partly explained by an enhanced hypoxic drive and hypoxia driven ER degradation because of suppressed PHD and aberrantly located FIH expression. This may have important implications, as these tumours may respond to compounds directed against HIF-1alpha or its downstream targets

Sedentary subjects have higher PAI-1 and lipoproteins levels than highly trained athletes

Physical exercise protects against the development of cardiovascular disease, partly by lowering plasmatic total cholesterol, LDL-cholesterol and increased HDL-cholesterol levels. In addition, it is now established that reduction plasmatic adiponectin and increased C-reactive protein (CRP) and plasminogen activator inhibitor-1 (PAI-1) levels play a role in the maintenance of an inflammatory state and in the development of cardiovascular disease. This study aimed to examine plasma lipid profile and inflammatory markers levels in individual with sedentary lifestyle and/or highly trained athletes at rest. Methods: Fourteen male subjects (sedentary lifestyle n = 7 and highly trained athletes n = 7) were recruited. Blood samples were collected after an overnight fast (~12 h). The plasmatic lipid profile (Triglycerides, HDL-cholesterol, LDL-cholesterol, total cholesterol, LDL-oxidized and total cholesterol/HDL-c ratio), glucose, adiponectin, C - reactive protein and PAI-1 levels were determined. Results: Total cholesterol, LDL-cholesterol, TG and PAI-1 levels were lower in highly trained athletes group in relation to sedentary subjects (p < 0.01). In addition, we observed a positive correlation between PAI-1 and total cholesterol (r = 0.78; p < 0.0009), PAI-1 and LDL-c (r = 0.69; p < 0.006) and PAI-1 and TG levels (r = 0.56; p < 0.03). The plasma concentration of adiponectin, CRP, glucose, HDL-cholesterol and total cholesterol/HDL-c ratio levels were not different. These results indicate that lifestyle associated with high intensity and high volume exercise induces changes favourable in the lipid profile and PAI-1 levels and may reduce risk cardiovascular diseases