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In this work, the combined effects of sodium lactate and modified atmosphere packaging (MAP) in extending the shelf life of a ready-to-cook fresh skewer, made up of raw pork chops and semi-dried vegetable mix (i.e. zucchini, peppers and tomatoes), were investigated. In the first experimental step, a sodium lactate solution was used to dip pork chops at three different concentrations: 20, 40 and 60% w/w. The second part of the work was focused on the use of MAP. In particular, the following MAPs were tested: MA1 (50%O2/30%CO2/20%N2), MA2 (70%O2/30%CO2), MA3 (30%O2/70%CO2) and MA4 (30%O2/30%CO2/40%N2). Finally, the optimal concentration of sodium lactate and the best gas composition were combined. The samples were stored at 4 °C; their microbial and sensory qualities were monitored along the entire observation period. The results indicate that the shelf life of the investigated ready-to-cook meal can be extended by approximately 83%, if compared with the control skewer packaged in air. The best preservation strategy is the combination of dipping of meat pieces in 40% sodium lactate solution and packaging under MA1. Copyright © 2014 John Wiley & Sons, Ltd.

PED, known also as PED/PEA-15, is a Death Effector Domain (DED)-family member of 15 kDa having a variety of effects on cell growth and metabolism [1,2]. PED has a broad anti-apoptotic action, being able to inhibit both the intrinsic and the extrinsic apoptotic pathways [3,4,5,6]. Inhibition of the extrinsic pathway is accomplished through its DED, which likely acts as a competitive inhibitor for pro-apoptotic molecules during the assembly of the death-inducing signaling complex (DISC) [1,7]. To data, although PED has been reported to be over-expressed in a number of different cancer types, such as gliomas, squamous carcinoma, breast, lung cancer, and B cells chronic lymphocytic leukemia, the mechanisms that regulate its expression have not been fully addressed [3,5,8,9]. PED interacts with different molecules, among these ERK 1/2, altering their nuclear localization by sequestering them into the cytosol [10] . PED is present in the cells in either an unphosphorylated or a phosphorylated form. Phosphorylation occurs at Ser104 by protein kinase C (PKC), and on Ser116 by AKT or calcium calmodulin kinase II (CamK II) [11,12]. Interestingly, PED may interact with ERK1/2 only in its unphosphorylated form and it is associated to an increased ERK 1/2 phosphorylation [12]. Based on its phosphorylation status, PED might play a role as either a tumor-promoter factor (in the phosphorylated form) or tumor-suppressor (in the unphosphorylated form) factor [12]. To get further insights on the role of PED in cancer, we aimed to find new PED interactors. Using Tandem Affinity Purification (TAP), we previously identified and characterized, among others, Rac1, a member of mammalian Rho GTPase protein family, as a PED-interacting protein. PED-Rac1 interaction resulted in the modulation of cell migration/invasion processes in lung cancer cells through ERK1/2 pathway [13]. Another attractive PED-interacting protein was Hsc70 (Heat Shock cognate protein of 70 KDa), a chaperone protein, reported to be involved in a multitude of housekeeping chaperoning functions including folding of nascent polypeptides, protein translocation across membranes, prevention of protein aggregation under stress conditions, disassembly of clathrin coated vesicles and also in chaperone-mediated autophagy (CMA) [14,18]. CMA is a uniquely selective form of autophagy by which specific cytosolic proteins are transported one-by-one across the lysosomal membrane for degradation [14,15]-]. CMA is constitutively active in many cell types, but it is maximally activated under stress conditions (inducible CMA) such as nutritional stress, starvation or cellular stresses leading to protein damage [14]. CMA is selective for a subset of cytosolic soluble proteins. The selectivity is determined by the presence of a recognition-targeting motif in the amino acid sequence of the substrate proteins. All CMA substrates contain in their amino acid sequence a pentapeptide motif biochemically related to KFERQ, known as the CMA targeting motif [17]. The KFERQ sequence is recognized in the cytosol by Hsc70. Hsc70 not only targets the CMA substrate to the lysosomal membrane, where it can interact with the CMA receptor the lysosome-associated protein type 2A (LAMP-2A), but, along with its cochaperones it likely facilitates substrate unfolding, which is require for substrate translocation across the lysosomal membrane [14,18, 21]. In this manuscript we describe the interaction of PED with Hsc70 and demonstrate that Hsc70 targets the unphosphorylated PED for CMA.

PED (phosphoprotein enriched in diabetes) is a death-effector domain (DED) family member with a broad anti-apoptotic action. PED inhibits the assembly of the death-inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non-small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed in different lung tumour types. Western blotting performed with specimens from NSCLC-affected patients showed that PED was strongly up-regulated (>6 fold) in the areas of tumour compared to adjacent normal tissue. Furthermore, PED expression levels in NSCLC cell lines correlated with their resistance to tumour necrosis factor related apoptosis-inducing ligand (TRAIL)-induced cell death. The involvement of PED in the refractoriness to TRAIL-induced cell death was investigated by silencing PED expression in TRAIL-resistant NSCLC cells with small interfering (si) RNAs: transfection with PED siRNA, but not with cFLIP siRNA, sensitized cells to TRAIL-induced cell death. In conclusion, PED is specifically overexpressed in lung tumour tissue and contributes to TRAIL resistance.

Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc.) 8+ as the most upregulated T-UCR in BlCa tissues, although its expression was lower than in pericancerous bladder tissues. These results were confirmed on BlCa tissues by real-time PCR and by in situ hybridization. Although uc.8+ is located within intron 1 of CASZ1, a zinc-finger transcription factor, the transcribed non-coding RNA encoding uc.8+ is expressed independently of CASZ1. In vitro experiments evaluating the effects of uc.8+ silencing, showed significantly decreased capacities for cancer cell invasion, migration, and proliferation. From this, we proposed and validated a model of interaction in which uc.8+ shuttles from the nucleus to the cytoplasm of BlCa cells, interacts with microRNA (miR)-596, and cooperates in the promotion and development of BlCa. Using computational analysis, we investigated the miR-binding domain accessibility, as determined by base-pairing interactions within the uc.8+ predicted secondary structure, RNA binding affinity, and RNA species abundance in bladder tissues and showed that uc.8+ is a natural decoy for miR-596. Thus uc.8+ upregulation results in increased expression of MMP9, increasing the invasive potential of BlCa cells. These interactions between evolutionarily conserved regions of DNA suggest that natural selection has preserved this potentially regulatory layer that uses RNA to modulate miR levels, opening up the possibility for development of useful markers for early diagnosis and prognosis as well as for development of new RNA-based cancer therapies.

NEMO/IKKγ is the regulatory subunit of the IκB Kinase (IKK) complex, required for the activation of the NF-κB pathway, which is involved in a variety of key processes, including immunity, inflammation, differentiation, and cell survival. Termination of NF-κB activity on specific -κB responsive genes, which is crucial for the resolution of inflammatory responses, can be achieved by direct degradation of the chromatin-bound NF-κB subunit RelA/p65, a process mediated by a protein complex that contains Copper Metabolism Murr1 Domain 1 (COMMD1). In this study, we identify COMMD7, another member of the COMMDs protein family, as a novel NEMO-interacting protein. We show that COMMD7 exerts an inhibitory effect on NF-κB activation upon TNFα stimulation. COMMD7 interacts with COMMD1 and together they cooperate to down-regulate NF-κB activity. Accordingly, termination of TNFα-induced NF-κB activity on the -κB responsive gene, Icam1, is defective in cells silenced for COMMD7 expression. Furthermore, this impairment is not greatly increased when we silence the expression of both COMMD7 and COMMD1 indicating that the two proteins participate in the same pathway of termination of TNFα-induced NF-κB activity. Importantly, we have demonstrated that COMMD7's binding to NEMO does not interfere with the binding to the IKKs, and that the disruption of the IKK complex through the use of the NBP competitor impairs the termination of NF-κB activity. We propose that an intact IKK complex is required for the termination of NF-κB-dependent transcription and that COMMD7 acts as a scaffold in the IKK-mediated NF-κB termination.

SUMMARY Secular variation ‘master’ curves are built up using geomagnetic historical observations or archaeomagnetic data from a limited area and their use is usually restricted to regions of around 1000 km radius. Relocation of data within this distance is a common practice to enable comparison of data, although the errors due to such process are rarely taken into account. A detailed analysis of the distribution of relocating geomagnetic data has been done using three popular sets of geomagnetic models (IGRF-9, GUFM and CALS7K-2). This study improves the error analysis of relocating geomagnetic directions made up to date and expands it to geomagnetic intensities. Maximum errors correlate with the non-dipole to dipole field ratio. Archaeomagnetists could use this analysis to valuate the error introduced by reducing data.

Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. The crystallized trimeric glycoprotein gB of herpes simplex virus has been described as a postfusion conformation, and several studies prove that like other class III fusion proteins, gB undergoes a pH-dependent switch between the pre- and postfusion conformations. Using several biophysical techniques, we show that peptides corresponding to the long helix of the gB postfiision structure interfere with the membrane fusion event, likely hampering the conformational rearrangements from the pre- to the postfusion structures. Those peptides represent good candidates for further design of peptidomimetic antagonists capable of blocking the fusion process.

Results are presented for a paleodirectional and paleointensity study of 16 Popocatepetl lava flows. Popocatepetl is a tall, active, dacitic-andesitic stratovolcano; it forms the southern end of a N-S-trending Quaternary volcanic range at the eastern edge of the Basin of Mexico. Studied units are mainly andesites and one trachyandestite, and all possess similar trace- and rare-earth-element compositions. Rock-magnetic experiments show that remanence is carried in most cases by Ti-poor titanomagnetite, resulting from oxy-exsolution of original titanomagnetite during flow cooling. Unblocking temperature spectra and high coercivities point to "small" pseudo-single domain magnetic grains for these (titano)magnetites. Single-component, linear demagnetization plots were observed in most cases. A strong, lightning-produced magnetization overprint was detected for one site. Combining the new paleomagnetic data provides a mean paleodirection of I = 35.4degrees, D = 345.7degrees, k = 21, alpha(95) = 8.5degrees, N = 15 for the Popocatepetl volcano region. All studied flows yield normal polarity magnetization, which supports a maximum age within the Brunhes chron.

This research was designed to determine whether different formulations of proteinaceous foams would help to retain a higher content of olive oil. The amount of olive oil absorbed, retained and released by these foams was calculated and texture tests were performed. X-ray microtomographical (μCT) analysis was also used to study the structure of the foams quantified by image analysis. Furthermore, the information gained from the μCT analysis i.e. the geometric parameters mentioned above, provided the required information to characterise and to investigate if any, the correlation among the microstructures and textural properties of the proteinaceous foam samples. The results from this study do not only prove that the percentage of absorbed, retained and released olive oil of this protein foams is highly affected by their formulation but also showed that a correlation exists among some of the microstructural and mechanical parameters of the proteinaceous foams.

Recent advances in the understanding of cellular and molecular mechanisms of the pathogenesis of several diseases offer the possibility to address novel molecular targets for an improved diagnosis and therapy. In fact, in order to fulfill their function, macromolecular drugs, reporter molecules, and imaging agents often require to be delivered into specific intracellular compartments, usually the cytoplasm or the nucleus. From a medical perspective, biological membranes represent a critical hindrance due to their barrier-like behaviour not easily circumvented by many pharmacologically-active molecules. Therefore, identifying strategies for membrane translocation is essential. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). These peptides, which are able to efficiently translocate macromolecules through the plasma membrane, have attracted a lot of attention, and new translocating peptides are continuously described. In this review, we will focus on the viral derived peptides, and in particular those derived by viral entry proteins that may be useful as delivery vehicles due to their intrinsic properties of inducing membrane perturbation.

Recent studies have shown that copy number variants (CNVs) are important sources of variability of mammalian genomes. We applied a cross species array comparative genome hybridization (aCGH) experiment using as reference the cattle genome to investigate, for the first time, variability in the sheep and goat genomes derived from copy number variation and identified 431 and 358 CNVs, respectively. A comparison of these results to those obtained in other mammals for similar experiments is reported. The identified CNVs could be important in determining phenotypic and production differences between and within breeds. Further studies will be carried out to evaluate the identified CNVs from both functional and evolutionary points of view.

During neuropathological conditions such as infections and degenerative diseases, astrocytes can be activated by infiltrating immune cells. Activated astrocytes can produce chemokines, cytokines and adhesion molecules. In this study, the production of IL-6 and adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin by human astroglioma cells stimulated with Gram-negative surface components was investigated. Haemophilus influenzae type b porin P2 and its selected active peptide, loop L7, were found to induce MEK1-MEK2/ mitogen-activated protein kinase phosphorylation in U87-MG cells as demonstrated by ELISA, and up-regulate cellular adhesion molecule and interleukin-6 (IL-6) production as shown by RT-PCR and ELISA. Using two potent and selective inhibitors of MEK activation by Raf-1 (PD-098059) and p38 (SB-203580), it was also demonstrated that both ERK1/2 and p38 pathways play key roles in the production of IL-6 as well as in ICAM-1, VCAM-1 and E-selectin expression by Hib porin.

Background ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 to induce apoptosis in malignant cells and has shown promise as an effective anti-leukemic agent in pediatric preclinical tests. This study focuses on the effects of ABT-737 on leukemia cells with MLL rearrangement and identifies some of the biological correlates of its activity. Procedure Cells were cultured in the presence of increasing concentrations of ABT-737 alone or in combination with other agents. After 4 days in culture, cell growth inhibition was measured by Alamar blue assay. The expression and activation of potential intracellular targets of ABT-737 activity were determined by Western blot analysis. Results Significant Bcl-2 expression was detected in all infant leukemia cells investigated. ABT-737 induced cell death in all cell lines studied although the IC50 values differed somewhat between cell lines. Western blot analysis identified the effects of ABT-737 on survival and apoptosis-regulatory proteins PARP, caspase-8, and cytochrome-c. Drug combination studies indicated synergy with distinct anti-neoplastic agents, including the multi-tyrosine kinase inhibitor sunitinib. This effective drug synergy appears to be mediated by the combined inhibition of Bcl-2 and intracellular signaling pathways. Conclusions We describe the in vitro studies to demonstrate the activity and drug combinability of ABT-737 against MLL rearranged leukemia cells. In addition, identification of the molecular changes that occur in the presence of ABT-737 provides information regarding effective target validation and target modulation analyses in future clinical trials. Pediatr Blood Cancer 2011;56:353–360. © 2010 Wiley-Liss, Inc.

PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms

Swapnil Gaikwad,1 Avinash Ingle,1 Aniket Gade,1 Mahendra Rai,1 Annarita Falanga,3 Novella Incoronato,2 Luigi Russo,2 Stefania Galdiero,3 Massimilano Galdiero2 1Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, Maharashtra, India; 2Department of Experimental Medicine, Division of Microbiology, II University of Naples, 3Department of Pharmacy, University of Naples “Federico II”, DFM and Institute of Biostructures and Bioimages, Naples, Italy Abstract: The interaction between silver nanoparticles and viruses is attracting great interest due to the potential antiviral activity of these particles, and is the subject of much research effort in the treatment of infectious diseases. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with herpes simplex virus types 1 and 2 and with human parainfluenza virus type 3. We show that production of silver nanoparticles from different fungi is feasible, and their antiviral activity is dependent on the production system used. Silver nanoparticles are capable of reducing viral infectivity, probably by blocking interaction of the virus with the cell, which might depend on the size and zeta potential of the silver nanoparticles. Smaller-sized nanoparticles were able to inhibit the infectivity of the viruses analyzed. Keywords: silver nanoparticles, antiviral, herpes simplex virus, parainfluenza virus

L'elaborato prende in esame le principali questioni filosofiche legate al problema del pensiero postumanista. Si parte, pertanto, da un'analisi storico-filosofica dei differenti postumanesimi, per mettere in risalto le numerose affinità strutturali che i suddetti presentano con il pensiero metafisico occidentale e i modelli teorici animanti il dibattito bioetico.

The organic fraction of airborne particulate matter includes a wide variety of organic compounds, but the present research focus is on Polycyclic Aromatic Hydrocarbons (PAHs) and their nitrated derivatives (nitro-PAHs) because of the well-known health risk associated with these organics. In order to identify and assess the sources of hydrocarbon inputs into the environment n-alkanes content and the relative carbon preference index were utilized. Special consideration was given to nitro-PAHs. The aim of this work was to demonstrate the presence in atmosphere of nitro-PAHs not usually studied, which may be responsible for part of the high direct-acting mutagenic activity of unknown origin observed for the airborne particulate material. Of the 38 particulate-associated nitro-PAH compounds measured, 21 were described for the first time and 17 were detected in real samples, although those 21 nitro-PAHs were reported as positional isomers of corresponding PAHs, with the position of the NO2 group not determined.

The stable component of the natural remanent magnetization (NRM) of the Upper Triassic “Calcari con Selce” limestone formation at Marsico Nuovo (Lagonegro Basin, Southern Italy) has an inclination which is about 45° too steep for the expected paleogeographic position. In order to explain this abnormal magnetization direction, several rock magnetic properties such as the dependence of susceptibility on temperature and alternating field frequency, anisotropy of low field susceptibility, anisotropy of anhysteretic remanent magnetization (ARM) and characteristics of acquisition and thermal decay of isothermal remanent magnetization (IRM) have been investigated. Strong inverse fabrics of both susceptibility and ARM have been recognized, which are due to magnetite in the superparamagnetic state on the one hand and in the stable single domain grain size on the other hand. Although internal deformation in the investigated rocks has not been reported in the geological literature, this may be the cause of the observed anisotropies. The anisotropy is probably responsible for the anomalous NRM directions of these limestones.

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3′ untranslated region of the protein tyrosine phosphatase μ (PTPμ). Previous studies indicated that PTPμ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 over-expression induced a downregulation of PTPμ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPμ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPμ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.

Fatty acid profile of lipids in animal origin products (AOP) for human food regimen plays an important role for its effects on consumer health. Over time ‘lard’ has played an useful function in the composition of a ration for human diets. A revaluation of biochemical effects of ‘lard ', as a source of biomolecules with nutritional and extranutritional properties, is in progress. The Autochthonous Genetic Types, especially ancient types (AAGT), can be considered in future a particularly useful source of this AOP. 'Casertana' pig, known since ancient times, deserves AAGT title. The study was carried out on 'fresh lard' taken at the level of 4th ÷ 6th lumbar vertebra from 50 ‘Casertana’ pigs (21 castrated males and 29 females) bred at Experimental Station of ConSDABI (Circello, Benevento). The acidic fraction was extracted by Folch method and analyzed, as methyl esteres, by gas-chromatography. The acidic fraction considered consists of: palmitic, palmitoleic, margaric, eptadecenoic, stearic, oleic, C18:1 cis,12, linoleic, γ-linolenic and linolenic fatty acid and CLA, the more representative is C18:2 cis9, trans11 and the other 6 isomers were detected in traces. The effect of sex, year and month of slaughtering (covariates), age and refrigerated carcass weight was always significant (P

Three piston cores (C1067, C1201, C1202) from the continental shelf and slope in the Salerno Gulf and Cilento offshore preserve small-scale, long-term change of Earth's past magnetic field (Palaeo Secular Variation) between about 115 ka B.P and the present. The cores overlap as follows: C1201 spans the most recent 25 ka and overlaps C1067 and C1202, which respectively cover much of the last approximately 115 ka B.P. Cores C1067 and C1202 lack the record from about 20 ka to about 11 ka B.P., an absence that is due to slope erosional processes. The palaeomagnetic field behaviour, when correlated to curves of global relative palaeomagnetic field intensity and dated records of PSV for western Europe and Great Britain, coupled with discreet tephrochronology and geochronology dating (C14), allow us to compile a chronology for the combined cores. The resulting chronology for the first most recent 44 ka has application for placing time constraints on the marine geology and stratigraphy of the margin of the eastern Tyrrhenian Sea. So far, catastrophic events such as large-scale submarine slumps, volcanic eruptions, turbidite deposition, and abrupt changes in sedimentation rate have been documented. In particular, the changes in sedimentation rate seem to be linked to global rapid sea-level pulses and climatic events that induced concurrent reduction and/or abundance in the sediment supply from the adjacent coastal margin.

PED/PEA-15 (PED) is a death effector domain family member of 15 kDa with a broad antiapoptotic function found overexpressed in a number of different human tumors, including lung cancer. To date, the mechanisms that regulate PED expression are unknown. Therefore, we address this point by the identification of microRNAs that in non–small cell lung cancer (NSCLC) modulate PED levels. In this work, we identify miR-212 as a negative regulator of PED expression. We also show that ectopic expression of this miR increases tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced cell death in NSCLC cells. In contrast, inhibition of endogenous miR-212 by use of antago-miR results in increase of PED protein expression and resistance to TRAIL treatment. Besides, in NSCLC, we show both in vitro and in vivo that PED and miR-212 expressions are inversely correlated, that is, PED is upregulated and miR-212 is rarely expressed. In conclusion, these findings suggest that miR-212 should be considered as a tumor suppressor because it negatively regulates the antiapoptotic protein PED and regulates TRAIL sensitivity. Cancer Res; 70(9); 3638–46. ©2010 AACR.

NEMO/IKKγ is the regulatory subunit of the IκB Kinase (IKK) complex, required for the activation of the NF-κB pathway, which is involved in a variety of key processes, including immunity, inflammation, differentiation, and cell survival. Termination of NF-κB activity on specific -κB responsive genes, which is crucial for the resolution of inflammatory responses, can be achieved by direct degradation of the chromatin-bound NF-κB subunit RelA/p65, a process mediated by a protein complex that contains Copper Metabolism Murr1 Domain 1 (COMMD1). In this study, we identify COMMD7, another member of the COMMDs protein family, as a novel NEMO-interacting protein. We show that COMMD7 exerts an inhibitory effect on NF-κB activation upon TNFα stimulation. COMMD7 interacts with COMMD1 and together they cooperate to down-regulate NF-κB activity. Accordingly, termination of TNFα-induced NF-κB activity on the -κB responsive gene, Icam1, is defective in cells silenced for COMMD7 expression. Furthermore, this impairment is not greatly increased when we silence the expression of both COMMD7 and COMMD1 indicating that the two proteins participate in the same pathway of termination of TNFα-induced NF-κB activity. Importantly, we have demonstrated that COMMD7's binding to NEMO does not interfere with the binding to the IKKs, and that the disruption of the IKK complex through the use of the NBP competitor impairs the termination of NF-κB activity. We propose that an intact IKK complex is required for the termination of NF-κB-dependent transcription and that COMMD7 acts as a scaffold in the IKK-mediated NF-κB termination.

The application of technologies, dipping treatments and packaging under modified atmosphere conditions, to prolong the shelf life of fresh pork sausages were assessed. The work was divided into two subsequent experimental trials. The first trial was aimed to select the concentration of essential oils. For this purpose, bay with nutmeg oils and fennel with black pepper oils were properly combined to dip of meat according to Two Central Composite Designs (CCD). The second trial was aimed to combine the meat dipping with the optimal concentrations of oils and sodium lactate solution (60%). All samples were packaged under modified atmosphere (MAP: 30% CO2 70% N2). Total Aerobic Bacteria and sensory quality were monitored during the refrigerated storage and the shelf life was calculated as the lowest value between microbiological acceptability limit (MAL) and sensory acceptability limit (SAL). Results of two steps showed that an increase of sausage shelf life could be obtained combining more technologies. In particular, the shelf life of about 18 days was obtained combining the dipping of meat first in sodium lactate solution then in optimal concentrations of essential oils (1.25% fennel and 2.5% black pepper; 2.5% bay and 1.25% nutmeg), compared to the untreated samples that recorded a shelf life of two days. Practical application: The shelf life extension of fresh meat products like sausages that generally have a short shelf life, represents a challenge for food companies. Short shelf life causes problems to food distribution, increases the food loss with relevant impact also on the environment. Therefore, the use of technological options to be used during processing and packaging could have important economic feedback.

Summary Mean directions of magnetization from Mounts Arso (Ischia Island, Gulf of Naples), Etna and Vesuvius lava flows have been determined based on very stringent linearity criteria. These indicate that, regardless of the source volcano, the lava flow mean directions of magnetization form a common path, the SISVC (Southern Italy Secular Variation Curve). This curve enables a reassessment of the age of eruption of several lavas. A date of AD 1169 is demonstrated to be the only possible time of emplacement for one Etna lava flow previously assigned an age of AD 812/1169. It is also demonstrated that two Etna lava flows, which, according to the literature, were emplaced in AD 1536 and 1595 respectively, were actually both emplaced around AD 1037. Three other Etna lava flows, one ascribed to AD 1566 and two to AD 1595, were actually emplaced between AD 1169 and 1284/85. The same time window also holds for a Vesuvius lava flow for which only an upper time threshold was previously available. Only one of the studied flows needs further sampling and analysis to verify whether this flow has been affected by a complete remagnetization or has an erroneous historical dating. The applied procedure seems to be the most appropriate one in carrying out palaeomagnetic surveys of lava flows, as also suggested by the broad agreement with some 17th and 19th century measurements of the geomagnetic field in Rome, relocated to Etna, and is likely to improve knowledge of past history of a volcano significantly.

In the last few years, biomedical research has been boosted by the technological development of analytical instrumentation generating a large volume of data. Such information has increased in complexity from basic (i.e., blood samples) to extensive sets encompassing many aspects of a subject phenotype, and now rapidly extending into genetic and, more recently, radiomic information. Radiogenomics integrates both aspects, investigating the relationship between imaging features and gene expression. From a methodological point of view, radiogenomics takes advantage of non-conventional data analysis techniques that reveal meaningful information for decision-support in cancer diagnosis and treatment. This survey is aimed to review the state-of-the-art techniques employed in radiomics and genomics with special focus on analysis methods based on molecular and multimodal probes. The impact of single and combined techniques will be discussed in light of their suitability in correlation and predictive studies of specific oncologic diseases.

With the expansion of the production and applications of multiwalled carbon nanotubes (MWCNTs) in several industrial and science branches, the potential adverse effects on human health have attracted attention. Numerous studies have been conducted to evaluate how chemical functionalization may affect MWCNT effects; however, controversial data have been reported, showing either increased or reduced toxicity. In particular, the impact of carboxylation on MWCNT cytotoxicity is far from being completely understood. The aim of this work was the evaluation of the modifications induced by carboxylated-MWCNTs (MWCNTs-COOH) on cell surface and the study of cell-MWCNT-COOH interactions by means of field emission scanning electron microscope (FESEM). Human pulmonary epithelial cells (A549) were incubated with MWCNTs-COOH for different exposure times and concentrations (10 μg/mL for 1, 2, 4 h; 5, 10, 20 μg/mL for 24 h). At short incubation time, MWCNTs-COOH were easily observed associated with plasma membrane and in contact with microvilli. After 24 h exposure, FESEM analysis revealed that MWCNTs-COOH induced evident changes in the cellular surface in comparison to control cells: treated cells showed blebs, holes and a depletion of the microvilli density in association with structure modifications, such as widening and/or lengthening. In particular, an increase of cells showing holes and microvilli structure alterations was observed at 20 μg/mL concentration. FESEM analysis showed nanotube agglomerates, of different sizes, entering into the cell with two different mechanisms: inward bending of the membrane followed by nanotube sinking, and nanotube internalization directly through holes. The observed morphological microvilli modifications, induced by MWCNTs-COOH, could affect epithelial functions, such as the control of surfactant production and secretion, leading to pathological conditions, such as alveolar proteinosis. More detailed studies will be, however, necessary to examine in depth the effects induced by MWCNTs-COOH and, in particular, the timing of the MWCNT-COOH-cell interaction.

PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70 kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms.

Pre–B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial–mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β. Here we show that, in addition to inhibiting primary tumor growth, PREP1 is a novel EMT inducer and prometastatic transcription factor. In human non-small cell lung cancer (NSCLC) cells, PREP1 overexpression is sufficient to trigger EMT, whereas PREP1 down-regulation inhibits the induction of EMT in response to TGF-β. PREP1 modulates the cellular sensitivity to TGF-β by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation through mechanisms dependent, at least in part, on PREP1-mediated transactivation of a regulatory element in the SMAD3 first intron. Along with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator protein 1 components including the proinvasive Fos-related antigen 1 (FRA-1) oncoprotein. Both FRA-1 and PBX1 are required for the mesenchymal changes triggered by PREP1 in lung tumor cells. Finally, we show that the PREP1-induced mesenchymal transformation correlates with significantly increased lung colonization by cells overexpressing PREP1. Accordingly, we have detected PREP1 accumulation in a large number of human brain metastases of various solid tumors, including NSCLC. These findings point to a novel role of the PREP1 homeoprotein in the control of the TGF-β pathway, EMT, and metastasis in NSCLC.

Background: The aim of this study was to evaluate the value of CA15-3 for the diagnostic integration of molecular imaging findings performed with hybrid positron emission tomography and computed tomography (PETCT) technology. Methods: We retrospectively selected 45 patients with a median age of 60 years (range 39–85 years) and a previous history of breast cancer (BC) who had already been treated with surgery and other treatments. Three measurements of CA15-3 were collected within 1 year before PETCT examination, at 6–9 months 3–6 months and 0–3 months before PETCT. The prolonged clinical outcome or imaging follow-up was used to define disease relapse. An increase in tumor marker value was compared with PETCT findings and disease relapse. Sensitivity and specificity for both tests were calculated with respect to clinical outcome. Results: Disease relapse was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3 expression levels were significantly higher in BC patients with multiple metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels showed an increase in CA15-3 3–6 months before PETCT could identify BC patients at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a median time of 158 days compared to patients who were negative for both tests and who were free from disease for at least 1 year. Conclusions: Our results showed that serial increases in CA15-3 can be used to predict positive PETCT results in BC patients during follow-up. Increased levels of CA15-3 may be considered an early warning sign in patients needing accurate molecular imaging investigations, as they are at higher risk of recurrence. In cases of elevated levels, multiple lesions or liver involvement may exist. Also, patients receiving chemotherapeutic or anti-hormonal treatment who have negative PETCT scans and increased CA15-3 serum levels should be considered at risk for relapse, because the CA15-3-linked biochemical signal of the presence of a tumor can predict positive metabolic imaging.