On Rank Problems for Planar Webs and Projective Structures

We present old and recent results on rank problems and linearizability of geodesic planar webs.Comment: 31 pages; LaTeX; corrected the abstract and Introduction; added reference

Intercomparison of five nets used for mesozooplankton sampling

Intercomparison of nets commonly used for mesozooplankton sampling in the Black and Mediterranean seas was attempted within SESAME (Southern European Seas: Assessing and Modelling Ecosystem Changes) project. Five nets were compared: three Juday nets equipped with 150 μm, 180 μm and 200 μm mesh size, Nansen net (100 μm mesh size) and WP2 (200 μm mesh size). Replicated samples were collected at one station in the western Black Sea offshore waters in April 2009. Collected samples were analyzed at species level (except for meroplankton), stages (for copepods) and size length. A decrease of total abundance values was observed with increasing mesh size, due to the significantly higher numbers of animals smaller than 1 mm in the samples obtained by fine mesh size than with coarser nets. Few comparisons were revealed significant for the abundance of animals with 1-2 mm length, while no significance was detected for specimens larger than 2 mm. The above differences resulted in discripancies between nets regarding species and stages composition. Biomass values did not differ significantly between nets, due to the strong contribution to total biomass of the large animals fraction (Calanus euxinus). The smallest and the largest animals revealed high variability between replicates collected by Nansen, Juday- 200 μm and WP2 nets. Correction factors were calculated for the conversion of abundance values between each couple of nets. The detected differences between nets regarding the abundance and biomass, the community taxonomic composition and size structure, as well as the estimated correction factors, provide useful information for the harmonization of data obtained by the above nets in the Black Sea

An objective framework to test the quality of candidate indicators of good environmental status

Large efforts are on-going within the EU to prepare the Marine Strategy Framework Directive's (MSFD) assessment of the environmental status of the European seas. This assessment will only be as good as the indicators chosen to monitor the 11 descriptors of good environmental status (GEnS). An objective and transparent framework to determine whether chosen indicators actually support the aims of this policy is, however, not yet in place. Such frameworks are needed to ensure that the limited resources available to this assessment optimize the likelihood of achieving GEnS within collaborating states. Here, we developed a hypothesis-based protocol to evaluate whether candidate indicators meet quality criteria explicit to the MSFD, which the assessment community aspires to. Eight quality criteria are distilled from existing initiatives, and a testing and scoring protocol for each of them is presented. We exemplify its application in three worked examples, covering indicators for three GEnS descriptors (1, 5, and 6), various habitat components (seaweeds, seagrasses, benthic macrofauna, and plankton), and assessment regions (Danish, Lithuanian, and UK waters). We argue that this framework provides a necessary, transparent and standardized structure to support the comparison of candidate indicators, and the decision-making process leading to indicator selection. Its application could help identify potential limitations in currently available candidate metrics and, in such cases, help focus the development of more adequate indicators. Use of such standardized approaches will facilitate the sharing of knowledge gained across the MSFD parties despite context-specificity across assessment regions, and support the evidence-based management of European seas

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

© 2015 Baishideng Publishing Group Inc. All rights reserved. Aim: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. Methods: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4°C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. Results: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 133.44 vs 206 33.61, P + (0.87 0.22 vs 1.195 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration. Conclusion: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model.Supported by Grants from Fondo de Investigaciones Sanitarias, No. FIS PI12/00519; fellowship from Agència de Gestió d’Ajuts Universitaris i de Recerca, No. 2012FI_B00382; Generalitat de Catalunya, Barcelona, Catalonia, Spain (to Pantazi E)Peer Reviewe

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

© 2015 Baishideng Publishing Group Inc. All rights reserved. Aim: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. Methods: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4°C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. Results: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 133.44 vs 206 33.61, P + (0.87 0.22 vs 1.195 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration. Conclusion: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model.Supported by Grants from Fondo de Investigaciones Sanitarias, No. FIS PI12/00519; fellowship from Agència de Gestió d’Ajuts Universitaris i de Recerca, No. 2012FI_B00382; Generalitat de Catalunya, Barcelona, Catalonia, Spain (to Pantazi E)Peer Reviewe

Detecting ovarian cancer using extracellular vesicles: Progress and possibilities

Ovarian cancer (OC) is the deadliest gynecological malignancy. Most patients are diagnosed when they are already in the later stages of the disease. Earlier detection of OC dramatically improves the overall survival, but this is rarely achieved as there is a lack of clinically implemented biomarkers of early disease. Extracellular vesicles (EVs) are small cell-derived vesicles that have been extensively studied in recent years. They contribute to various aspects of cancer pathology, including tumour growth, angiogenesis and metastasis. EVs are released from all cell types and the macromolecular cargo they carry reflects the content of the cells from which they were derived. Cancer cells release EVs with altered cargo into biofluids, and so they represent an excellent potential source of novel biomarkers for the disease. In this review we describe the latest developments in EVs as potential biomarkers for earlier detection of OC. The field is still relatively young, but a number of studies have shown that EVs and the cargo they carry, including miRNAs and proteins, can be used to detect OC. They could also give insight into the stage of the disease and predict the likely therapeutic outcome. There remain a number of challenges to the use of EVs as biomarkers, but through ongoing research and innovation in this exciting field there is great potential for the development of diagnostic assays in the clinic that could improve patient outcome

Sirtuin 1 in rat orthotopic liver transplantation: An IGL-1 preservation solution approach

© The Author(s) 2015. AIM: To investigate the possible involvement of Sirtuin 1 (SIRT1) in rat orthotopic liver transplantation (OLT), when Institute Georges Lopez 1 (IGL-1) preservation solution is enriched with trimetazidine (TMZ). METHODS: Male Sprague-Dawley rats were used as donors and recipients. Livers were stored in IGL-1 preservation solution for 8h at 4 °C, and then underwent OLT according to Kamada's cuff technique without arterialization. In another group, livers were stored in IGL-1 preservation solution supplemented with TMZ, at 10-6 mol/L, for 8 h at 4 °C and then underwent OLT. Rats were sacrificed 24 h after reperfusion, and liver and plasma samples were collected. Liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity) oxidative stress (malondialdehyde levels), and nicotinamide adenine dinucleotide (NAD+), the co-factor necessary for SIRT1 activity, were determined by biochemical methods. SIRT1 and its substrates (ac-FoxO1, ac-p53), the precursor of NAD+, nicotinamide phosphoribosyltransferase (NAMPT), as well as the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), p-mTOR, p-p70S6K (direct substrate of mTOR), autophagy parameters (beclin-1, LC3B) and MAP kinases (p-p38 and p-ERK) were determined by Western blot. RESULTS: Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preserved in IGL-1 solution alone. In addition, livers preserved in IGL-1 + TMZ presented reduced levels of oxidative stress. This was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity, as indicated by decreased acetylation of p53 and FoxO1. The elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH levels. Up-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of mTOR and its direct substrate (p-p70S6K). As a consequence, autophagy mediators (beclin-1 and LC3B) were overexpressed. Furthermore, MAP kinases were regulated in livers preserved with IGL-1 + TMZ, as they were characterized by enhanced p-ERK and decreased p-p38 protein expression. CONCLUSION: Our study shows that IGL-1 preservation solution enriched with TMZ protects liver grafts from the IRI associated with OLT, through SIRT1 up-regulation.Supported by Fondo de Investigaciones Sanitarias, No. FIS PI12/00519; and Eirini Pantazi is the recipient of a fellowship from AGAUR, No. 2012FI_B00382, Generalitat de Catalunya, Barcelona, Catalonia, Spain.Peer Reviewe

Eco-friendly preparation of electrically conductive chitosan - reduced graphene oxide flexible bionanocomposites for food packaging and biological applications

Electrically conductive materials have been highlighted in the biomedical and food packaging areas. Conventional electrically conductive polymers have limited biodegradability and biocompatibility and should be replaced by suitable biomaterials. Herein, electrically conductive bionanocomposites of chitosan and reduced graphene oxide were produced by a green methodology. The reduced graphene oxide was hydrothermally reduced in the presence of caffeic acid and was dispersed into chitosan. The final bionanocomposites achieved an electrical conductivity of 0.7 S/m in-plane and 2.1 × 10−5 S/m through-plane. The reduced graphene oxide promoted a great enhancement of antioxidant activity and a mechanical reinforcement of chitosan matrix, increasing the tensile strength and decreasing the water solubility. The electrical conductivity, mechanical properties and antioxidant activity of the bionanocomposites can be tuned according to the filler content. These active bionanocomposites, prepared using a green methodology, revealed good electrical and mechanical properties, which make them promising materials for food packaging and biological applications.publishe

SARS-CoV-2/ACE2 Interaction Suppresses IRAK-M Expression and Promotes Pro-Inflammatory Cytokine Production in Macrophages

The major cause of death in SARS-CoV-2 infected patients is due to de-regulation of the innate immune system and development of cytokine storm. SARS-CoV-2 infects multiple cell types in the lung, including macrophages, by engagement of its spike (S) protein on angiotensin converting enzyme 2 (ACE2) receptor. ACE2 receptor initiates signals in macrophages that modulate their activation, including production of cytokines and chemokines. IL-1R-associated kinase (IRAK)-M is a central regulator of inflammatory responses regulating the magnitude of TLR responsiveness. Aim of the work was to investigate whether SARS-CoV-2 S protein-initiated signals modulate pro-inflammatory cytokine production in macrophages. For this purpose, we treated PMA-differentiated THP-1 human macrophages with SARS-CoV-2 S protein and measured the induction of inflammatory mediators including IL6, TNFα, IL8, CXCL5, and MIP1a. The results showed that SARS-CoV-2 S protein induced IL6, MIP1a and TNFα mRNA expression, while it had no effect on IL8 and CXCL5 mRNA levels. We further examined whether SARS-CoV-2 S protein altered the responsiveness of macrophages to TLR signals. Treatment of LPS-activated macrophages with SARS-CoV-2 S protein augmented IL6 and MIP1a mRNA, an effect that was evident at the protein level only for IL6. Similarly, treatment of PAM3csk4 stimulated macrophages with SARS-CoV-2 S protein resulted in increased mRNA of IL6, while TNFα and MIP1a were unaffected. The results were confirmed in primary human peripheral monocytic cells (PBMCs) and isolated CD14+ monocytes. Macrophage responsiveness to TLR ligands is regulated by IRAK-M, an inactive IRAK kinase isoform. Indeed, we found that SARS-CoV-2 S protein suppressed IRAK-M mRNA and protein expression both in THP1 macrophages and primary human PBMCs and CD14+ monocytes. Engagement of SARS-CoV-2 S protein with ACE2 results in internalization of ACE2 and suppression of its activity. Activation of ACE2 has been previously shown to induce anti-inflammatory responses in macrophages. Treatment of macrophages with the ACE2 activator DIZE suppressed the pro-inflammatory action of SARS-CoV-2. Our results demonstrated that SARS-CoV-2/ACE2 interaction rendered macrophages hyper-responsive to TLR signals, suppressed IRAK-M and promoted pro-inflammatory cytokine expression. Thus, activation of ACE2 may be a potential anti-inflammatory therapeutic strategy to eliminate the development of cytokine storm observed in COVID-19 patients