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1.  Antibody adsorption on the surface of water studied by neutron reflection 
mAbs  2017;9(3):466-475.
ABSTRACT
Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techniques can offer direct structural information about antibody adsorption under different conditions. The main aim of this study was to demonstrate the power of neutron reflection to unravel the amount and structural conformation of the adsorbed antibody layers at the air/water interface with and without surfactant, using a monoclonal antibody ‘COE-3′ as the model. By selecting isotopic contrasts from different ratios of H2O and D2O, the adsorbed amount, thickness and extent of the immersion of the antibody layer could be determined unambiguously. Upon mixing with the commonly-used non-ionic surfactant Polysorbate 80 (Tween 80), the surfactant in the mixed layer could be distinguished from antibody by using both hydrogenated and deuterated surfactants. Neutron reflection measurements from the co-adsorbed layers in null reflecting water revealed that, although the surfactant started to remove antibody from the surface at 1/100 critical micelle concentration (CMC) of the surfactant, complete removal was not achieved until above 1/10 CMC. The neutron study also revealed that antibody molecules retained their globular structure when either adsorbed by themselves or co-adsorbed with the surfactant under the conditions studied.
doi:10.1080/19420862.2016.1276141
PMCID: PMC5384797  PMID: 28353420
Antibody; co-adsorption; mAbs; neutron reflection; surface adsorption; structural unfolding; self-assembly; surfactant
2.  Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society 
Bevivino, Annamaria | Coiana, Alessandra | Fogazzi, Annalisa | Timelli, Fabiana | Signorini, Sandra | Lucarelli, Marco | Morelli, Patrizia | Padoan, Rita | Giordani, Barbara | Amato, Annalisa | Majo, Fabio | Ferrari, Gianluca | Quattrucci, Serena | Minicucci, Laura | Floridia, Giovanna | Fornaro, Gianna Puppo | Taruscio, Domenica | Salvatore, Marco | Seia, Manuela | Pierandrei, Silvia | Blaconà, Giovanna | Salvati, Valentina | Sette, Giovanni | Cimino, Giuseppe | Sangiuolo, Federica | Eramo, Adriana | Lucarelli, Marco | Collura, Mirella | Parisi, Elisa | Ferlisi, Annalisa | Traverso, Gabriella | Bertolino, Marcella | Termini, Lisa | Orlando, Maria A. | Di Girgenti, Caterina | Pavone, Valeria | Calamia, Maria A. | Silvestro, Maria G. | Piparo, Caterina Lo | Ficili, Francesca | Colombo, Carla | Tullis, Elizabeth | Davies, Jane C. | McKee, Charlotte | DeSouza, Cynthia | Waltz, David | Savage, Jessica | Fisher, Marc | Shilling, Rebecca | Moskowitz, Sam | Robertson, Sarah | Tian, Simon | Taylor-Cousar, Jennifer L. | Rowe, Steven M. | Beccia, Elisa | Carbone, Annalucia | Favia, Maria | Castellani, Stefano | Seia, Manuela | Angiolillo, Antonella | Colombo, Carla | Casavola, Valeria | Conese, Massimo | Padoan, Rita | Cesana, Bruno M. | Falchetti, Diego | Battistini, Fiorella | Bignamini, Elisabetta | Braggion, Cesare | Collura, Mirella | Cirilli, Natalia | Lucanto, Maria C. | Lucidi, Vincenzina | Manca, Antonio | Raia, Valeria | Rotolo, Novella | Salvatore, Donatello | Volpi, Sonia | Nazzari, Erica | Guarise, Riccardo | Mileto, Palmiro | Garbarino, Francesca | Alicandro, Gianfranco | Battezzati, Alberto | Colombo, Carla | Giordani, Barbara | Amato, Annalisa | Majo, Fabio | Ferrari, Gianluca | Quattrucci, Serena | Minicucci, Laura | Padoan, Rita | Floridia, Giovanna | Fornaro, Gianna Puppo | Taruscio, Domenica | Salvatore, Marco | Di Lullo, Antonella M. | Comegna, Marika | Amato, Felice | Iacotucci, Paola | Carnovale, Vincenzo | Cantone, Elena | Iengo, Maurizio | Castaldo, Giuseppe | Orlando, Claudio | Casale, Alida | Sepe, Angela | De Gregorio, Fabiola | De Matteo, Antonia | Castaldo, Alice | Cimbalo, Chiara | Tosco, Antonella | Raia, Valeria | Savi, Daniela | Quattrucci, Serena | Mordenti, Michela | Bonci, Enea | Troiani, Patrizia | D’Alù, Viviana | Rossi, Paolo | Varchetta, Monica | Perelli, Tamara | Bertasi, Serenella | Palange, Paolo | Cimino, Giuseppe | Tardino, Lucia | Parisi, Giuseppe F. | Portale, Anna | Franzonello, Chiara | Papale, Maria | Rotolo, Novella | Leonardi, Salvatore | Parisi, Giuseppe F. | Tardino, Lucia | Papale, Maria | Franzonello, Chiara | Pennisi, Francesca | Rotolo, Novella | Leonardi, Salvatore | Bruno, Sabina M. | Licciardello, Giulia | Pierandrei, Silvia | Ferraguti, Giampiero | Quattrucci, Serena | Lucarelli, Marco | Ferraguti, Giampiero | Sterrantino, Manuela | Bruno, Sabina M. | Pierandrei, Silvia | Testino, Giancarlo | Cimino, Giuseppe | Bertasi, Serenella | Lucarelli, Marco | Salvatore, Donatello | Padoan, Rita | Buzzetti, Roberto | Amato, Annalisa | Giordani, Barbara | Ferrari, Gianluca | Majo, Fabio | Surace, Cecilia | Lucarelli, Marco | Sofia, Valentina M. | Majo, Fabio | Cimino, Giuseppe | Pierandrei, Silvia | Ullmann, Nicola | Lucidi, Vincenzina | Novelli, Antonio | Angioni, Adriano | Comegna, Marika | Di Lullo, Antonella M. | Liguori, Renato | Manzoni, Francesca | Di Palma, Chiara | Maietta, Sabrina | Zarrilli, Federica | Amato, Felice | Sofia, Valentina M. | Surace, Cecilia | Terlizzi, Vito | Alghisi, Federico | Angiolillo, Antonella | Braggion, Cesare | Cirilli, Natalia | Colombo, Carla | Di Lullo, Antonella M. | Padoan, Rita | Quattrucci, Serena | Raia, Valeria | Tuccio, Giuseppe | Zarrilli, Federica | Novelli, Antonio | Lucidi, Vincenzina | Lucarelli, Marco | Castaldo, Giuseppe | Angioni, Adriano | Tradati, Valentina | di Stefano, Eliana | Padoan, Rita | Collura, Mirella | Dato, Patrizia | Sciarrabone, Maria G. | Fondacaro, Carmela | Termini, Lisa | Ferlisi, Annalisa | Orlando, Maria A. | Traverso, Gabriella | Bertolino, Marcella | Ficili, Francesca | Cresta, Federico | Baglioni, Valentina | Garuti, Silvia | Buffoni, Isabella | Landi, Francesca | Casciaro, Rosaria | Minicucci, Laura | Girelli, Daniela | Teri, Antonio | Sottotetti, Samantha | Biffi, Arianna | Vignati, Chiara | D’accico, Monica | Maraschini, Anna | Arghittu, Milena | Colombo, Carla | Pizzamiglio, Giovanna | Cariani, Elisa | Dolce, Daniela | Ravenni, Novella | Campana, Silvia | Camera, Erica | Castellani, Carlo | Guarise, Riccardo | Braggion, Cesare | Taccetti, Giovanni | Morelli, Patrizia | Calderone, Eleonora | Bandettini, Roberto | Guarise, Riccardo | Innocenti, Chiara Degli | Castellani, Chiara | Masi, Eleonora | Terlizzi, Vito | Cavicchi, Maria Chiara | Ferrari, Beatrice | Pezzotta, Ramona | Poli, Piercarlo | Messali, Serena | Timpano, Silvana | Padoan, Rita | Scaltriti, Erika | Pongolini, Stefano | Fiorentini, Simona | Bresci, Silvia | Corsi, Lorenzo | Guarise, Riccardo | Borchi, Beatrice | Cavallo, Annalisa | Bartalesi, Filippo | Pistolesi, Massimo | Bartoloni, Alessandro | Braggion, Cesare | Collura, Mirella | Ficili, Francesca | Termini, Lisa | Orlando, Maria A. | Traverso, Gabriella | Arcoleo, Federica | Pensabene, Tiziana | Bertolino, Marcella | Calamia, Maria A. | Ferlisi, Annalisa | Bevivino, Annamaria | Bacci, Giovanni | Armanini, Federica | Taccetti, Giovanni | Lucidi, Vincenzina | Dolce, Daniela | Morelli, Patrizia | Fiscarelli, Ersilia V. | Segata, Nicola | Mengoni, Alessio | Giordani, Barbara | Amato, Annalisa | Majo, Fabio | Ferrari, Gianluca | Quattrucci, Serena | Minicucci, Laura | Padoan, Rita | Floridia, Giovanna | Fornaro, Gianna Puppo | Taruscio, Domenica | Salvatore, Marco | Di Toppa, Maria V. | Popa, Nicoleta | Alghisi, Federico | Felicetti, Francesco | Graziano, Sonia | Ciprandi, Riccardo | Pescini, Rita | Graffigna, Guendalina | Barello, Serena | Casciaro, Rosaria | Cresta, Federico | Minicucci, Laura | Catastini, Paola | De Masi, Salvatore | Braggion, C. | Calamia, Maria A. | Ferlisi, Annalisa | Silvestro, Maria G. | Guarnuto, Lucia | Ficili, Francesca | Di Liberti, Emanuela | Patti, Valentina | Collura, Mirella | Poli, Piercarlo | Tradati, Valentina | Padoan, Rita | Castellazzi, Massimo Luca | Daccò, Valeria | Claut, Laura | Colombo, Carla | Giuliari, Matteo | Vicentini, Luana | Tilotta, Fausto | Paciaroni, Antonella | Sala, Sabino Della | Guerzoni, Cristina | Andreatta, Elisa | Dinnella, Grazia | Termini, Lisa | Pavone, Valeria | Parisi, Elisa | Ficili, Francesca | Orlando, Maria A. | Ferlisi, Annalisa | Traverso, Gabriella | Granata, Orazia M. | Aronica, Tommaso S. | Crapisi, Mimì | Fogazza, Donatella | Bertolino, Marcella | Collura, Mirella | Collura, Mirella | Alessi, Luca | Mulè, Flavia | Vitaliti, Marcello | Maresi, Mariarosaria | Orlando, Maria A. | Ferlisi, Annalisa | Traverso, Gabriella | Termini, Lisa | Bertolino, Marcella | Ficili, Francesca | De Gregorio, Fabiola | Tosco, Antonella | Casale, Alida | Sepe, Angela | Cimbalo, Chiara | Catzola, Andrea | Castaldo, Alice | Salvadori, Laura | Raia, Valeria | Salvatore, Donatello | Colangelo, Carmela | Marsicovetere, Giovanni | D’Andria, Michele | Passarella, Domenica | Genovese, Carmela | Collura, Mirella | Parisi, Elisa | Ferlisi, Annalisa | Orlando, Mari A. | Traverso, Gabriella | Termini, Lisa | Bertolino, Marcella | Di Girgenti, Caterina | Calamia, Maria A. | Silvestro, Maria G. | Barrale, Stefania | Bonaccorso, Maria R. | D’Arpa, Annalisa | Ficili, Francesca
Italian Journal of Pediatrics  2018;44(Suppl 1):6.
doi:10.1186/s13052-017-0430-4
PMCID: PMC5781055
3.  Quantile regression for genome-wide association study of flowering time-related traits in common bean 
PLoS ONE  2018;13(1):e0190303.
Flowering is an important agronomic trait. Quantile regression (QR) can be used to fit models for all portions of a probability distribution. In Genome-wide association studies (GWAS), QR can estimate SNP (Single Nucleotide Polymorphism) effects on each quantile of interest. The objectives of this study were to estimate genetic parameters and to use QR to identify genomic regions for phenological traits (Days to first flower—DFF; Days for flowering—DTF; Days to end of flowering—DEF) in common bean. A total of 80 genotypes of common beans, with 3 replicates were raised at 4 locations and seasons. Plants were genotyped for 384 SNPs. Traditional single-SNP and 9 QR models, ranging from equally spaced quantiles (τ) 0.1 to 0.9, were used to associate SNPs to phenotype. Heritabilities were moderate high, ranging from 0.32 to 0.58. Genetic and phenotypic correlations were all high, averaging 0.66 and 0.98, respectively. Traditional single-SNP GWAS model was not able to find any SNP-trait association. On the other hand, when using QR methodology considering one extreme quantile (τ = 0.1) we found, respectively 1 and 7, significant SNPs associated for DFF and DTF. Significant SNPs were found on Pv01, Pv02, Pv03, Pv07, Pv10 and Pv11 chromosomes. We investigated potential candidate genes in the region around these significant SNPs. Three genes involved in the flowering pathways were identified, including Phvul.001G214500, Phvul.007G229300 and Phvul.010G142900.1 on Pv01, Pv07 and Pv10, respectively. These results indicate that GWAS-based QR was able to enhance the understanding on genetic architecture of phenological traits (DFF and DTF) in common bean.
doi:10.1371/journal.pone.0190303
PMCID: PMC5754186  PMID: 29300788
4.  GPER-independent inhibition of adrenocortical cancer growth by G-1 involves ROS/Egr-1/BAX pathway 
Oncotarget  2017;8(70):115609-115619.
We previously demonstrated that treatment of the H295R adrenocortical cancer cell line with the non-steroidal, high-affinity GPER (G protein-coupled estrogen receptor 1) agonist G-1 reduced tumor growth in vitro and in vivo through a GPER independent action. Moreover, we observed that G-1 treatment induces cell-cycle arrest and apoptosis following a sustained ERK1/2 activation. However, the precise mechanisms causing these effects were not clarified. Starting from our preliminary published results, we performed a microarray study that clearly evidenced a strong and significative up-regulation of EGR-1 gene in H295R cells treated for 24h with micromolar concentration of G-1. The microarray findings were confirmed by RT-PCR and Western-blot analysis as well as by immunofluorescence that revealed a strong nuclear staining for EGR-1 after G-1 treatment. EGR-1 is a point of convergence of many intracellular signaling cascades that control tumor cell growth and proliferation as well as others that relate to cell death machinery. Here we found that the increased Egr-1 expression was a consequence of G-1-mediated ROS-dependent ERK activation that were promptly reversed by the presence of the antioxidant n-acetyl-cysteine. Finally, we observed that silencing EGR-1 gene expression reversed the main effects induced by G-1 in ACC cells, including upregulation of the negative regulator of cell cycle, p21Waf1/Cip1 and the positive regulator of mitochondrial apoptotic pathway, BAX, as well as the cell growth inhibition. The identified ROS/MAPK/Egr-1/BAX pathway as a potential off-target effect of the G-1 could be useful in implementing the pharmacological approach for ACC therapy.
doi:10.18632/oncotarget.23314
PMCID: PMC5777797
GPER agonist G-1; Egr-1; ROS; mitochondrial apoptotic pathway; adrenocortical cancer cell
5.  Different feeding strategies in Antarctic scavenging amphipods and their implications for colonisation success in times of retreating glaciers 
Frontiers in Zoology  2017;14:59.
Background
Scavenger guilds are composed of a variety of species, co-existing in the same habitat and sharing the same niche in the food web. Niche partitioning among them can manifest in different feeding strategies, e.g. during carcass feeding. In the bentho-pelagic realm of the Southern Ocean, scavenging amphipods (Lysianassoidea) are ubiquitous and occupy a central role in decomposition processes. Here we address the question whether scavenging lysianassoid amphipods employ different feeding strategies during carcass feeding, and whether synergistic feeding activities may influence carcass decomposition. To this end, we compared the relatively large species Waldeckia obesa with the small species Cheirimedon femoratus, Hippomedon kergueleni, and Orchomenella rotundifrons during fish carcass feeding (Notothenia spp.). The experimental approach combined ex situ feeding experiments, behavioural observations, and scanning electron microscopic analyses of mandibles. Furthermore, we aimed to detect ecological drivers for distribution patterns of scavenging amphipods in the Antarctic coastal ecosystems of Potter Cove. In Potter Cove, the climate-driven rapid retreat of the Fourcade Glacier is causing various environmental changes including the provision of new marine habitats to colonise. While in the newly ice-free areas fish are rare, macroalgae have already colonised hard substrates. Assuming that a temporal dietary switch may increase the colonisation success of the most abundant lysianassoids C. femoratus and H. kergueleni, we aimed to determine their consumption rates (g food x g amphipods−1 x day−1) and preferences of macroalgae and fish.
Results
We detected two functional groups with different feeding strategies among scavenging amphipods during carcass feeding: carcass ‘opener’ and ‘squeezer’. Synergistic effects between these groups were not statistically verified under the conditions tested. C. femoratus switched its diet when fish was not available by consuming macroalgae (about 0.2 day−1) but preferred fish by feeding up to 80% of its own mass daily. Contrary, H. kergueleni rejected macroalgae entirely and consumed fish with a maximal rate of 0.8 day−1.
Conclusion
This study reveals functional groups in scavenging shallow-water amphipods and provides new information on coastal intraguild niche partitioning. We conclude that the dietary flexibility of C. femoratus is a potential ecological driver and central to its success in the colonisation of newly available ice-free Antarctic coastal habitats.
Electronic supplementary material
The online version of this article (10.1186/s12983-017-0248-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12983-017-0248-3
PMCID: PMC5745984
Southern Ocean; King George Island/ Isla 25 de Mayo; Potter Cove; Succession; Carrion-feeding; Food web; Notothenia rossii; Notothenia coriiceps; Palmaria decipiens; Desmarestia menziesii
6.  Evidence that LDL receptor-related protein 1 (LRP1) acts as an early injury detection receptor and activates c-Jun in Schwann cells 
Neuroreport  2016;27(18):1305-1311.
Schwann cells (SCs) detect injury to peripheral nerves and transform phenotypically to respond to injury and facilitate repair. Cell-signaling pathways and changes in gene expression that drive SC phenotypic transformation in injury have been described; however, the SC receptors that detect PNS injury have not been identified. LDL receptor-related protein (LRP1) is a receptor for numerous ligands, including intracellular proteins released by injured cells and protein components of degenerated myelin. In certain cell types, including SCs, LRP1 is a cell-signaling receptor. Herein, we show that binding of the LRP1 ligand, tissue-type plasminogen activator (tPA), to cultured rat SCs induces c-Jun phosphorylation, a central event in activation of the SC Repair Program. The response to tPA was blocked by the LRP1 antagonist, receptor-associated protein (RAP). c-Jun phosphorylation also was observed when cultured rat SCs were treated with a recombinant derivative of matrix metalloproteinase-9 that contains the LRP1 recognition motif (PEX). The ability of LRP1 to induce c-Jun phosphorylation and ERK1/2 activation was confirmed using cultures of human SCs. When tPA or PEX was injected directly into crush-injured rat sciatic nerves, c-Jun phosphorylation and ERK1/2 activation were observed in SCs in vivo. The ability of LRP1 to bind proteins released in the earliest stages of PNS injury and to induce c-Jun phosphorylation support a model in which SC LRP1 functions as an injury detection receptor in the PNS.
doi:10.1097/WNR.0000000000000691
PMCID: PMC5123743  PMID: 27824728
Schwann cell; LDL receptor-related protein 1; tissue-type plasminogen activator; matrix metalloproteinase-9; repair program; c-Jun
7.  A Millifluidic System for Analysis of Daphnia magna Locomotory Responses to Water-born Toxicants 
Scientific Reports  2017;7:17603.
Aquatic toxicity testing in environmental monitoring and chemical risk assessment is critical to assess water quality for human use as well as predict impact of pollutants on ecosystems. In recent years, studies have increasingly focused on the relevance of sub-lethal effects of environmental contaminants. Sub-lethal toxicity endpoints such as behavioural responses are highly integrative and have distinct benefits for assessing water quality because they occur rapidly and thus can be used to sense the presence of toxicants. Our work describes a Lab-on-a-Chip system for the automated analysis of freshwater cladoceran Daphnia magna locomotory responses to water-born toxicants. The design combines a Lab-on-a-Chip system for Daphnia sp. culture under perfusion with time-resolved videomicroscopy and software tracking locomotory activity of multiple specimens. The application of the system to analyse the swimming behaviour of water fleas exposed to different concentrations of water-born toxicants demonstrated that Lab-on-a-Chip devices can become important research tools for behavioural ecotoxicology and water quality biomonitoring.
doi:10.1038/s41598-017-17892-z
PMCID: PMC5730546  PMID: 29242636
8.  Smart CEI Moncloa: An IoT-based Platform for People Flow and Environmental Monitoring on a Smart University Campus 
Sensors (Basel, Switzerland)  2017;17(12):2856.
Internet of Things platforms for Smart Cities are technologically complex and deploying them at large scale involves high costs and risks. Therefore, pilot schemes that allow validating proof of concepts, experimenting with different technologies and services, and fine-tuning them before migrating them to actual scenarios, are especially important in this context. The IoT platform deployed across the engineering schools of the Universidad Politécnica de Madrid in the Moncloa Campus of International Excellence represents a good example of a test bench for experimentation with Smart City services. This paper presents the main features of this platform, putting special emphasis on the technological challenges faced and on the solutions adopted, as well as on the functionality, services and potential that the platform offers.
doi:10.3390/s17122856
PMCID: PMC5751704  PMID: 29292790
Arduino; environmental monitoring; IoT; MQTT; people flow monitoring; Raspberry Pi; sensor networks; smart cities; visual analytics; Wi-Fi
9.  Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies 
Blood Advances  2017;1(25):2348-2360.
Key Points
Blockade of CD7 expression with a novel method, combined with a second-generation CAR, results in highly potent anti-CD7 CAR T cells.This practical strategy provides a new treatment option for patients with high-risk T-cell malignancies, including ETP-ALL.
Effective immunotherapies for T-cell malignancies are lacking. We devised a novel approach based on chimeric antigen receptor (CAR)–redirected T lymphocytes. We selected CD7 as a target because of its consistent expression in T-cell acute lymphoblastic leukemia (T-ALL), including the most aggressive subtype, early T-cell precursor (ETP)–ALL. In 49 diagnostic T-ALL samples (including 14 ETP-ALL samples), median CD7 expression was >99%; CD7 expression remained high at relapse (n = 14), and during chemotherapy (n = 54). We targeted CD7 with a second-generation CAR (anti-CD7–41BB-CD3ζ), but CAR expression in T lymphocytes caused fratricide due to the presence of CD7 in the T cells themselves. To downregulate CD7 and control fratricide, we applied a new method (protein expression blocker [PEBL]), based on an anti-CD7 single-chain variable fragment coupled with an intracellular retention domain. Transduction of anti-CD7 PEBL resulted in virtually instantaneous abrogation of surface CD7 expression in all transduced T cells; 2.0% ± 1.7% were CD7+ vs 98.1% ± 1.5% of mock-transduced T cells (n = 5; P < .0001). PEBL expression did not impair T-cell proliferation, interferon-γ and tumor necrosis factor–α secretion, or cytotoxicity, and eliminated CAR-mediated fratricide. PEBL-CAR T cells were highly cytotoxic against CD7+ leukemic cells in vitro and were consistently more potent than CD7+ T cells spared by fratricide. They also showed strong anti-leukemic activity in cell line– and patient-derived T-ALL xenografts. The strategy described in this study fits well with existing clinical-grade cell manufacturing processes and can be rapidly implemented for the treatment of patients with high-risk T-cell malignancies.
Visual Abstract
doi:10.1182/bloodadvances.2017009928
PMCID: PMC5729624
10.  Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors 
Purpose
To evaluate the role of the activation of mTOR (phosphorylated mTOR, p-mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well-differentiated neuroendocrine tumors.
Methods
A retrospective study was conducted on data from patients with diagnosis of neuroendocrine tumor originated from pancreas (pNET) or gastrointestinal tract (stomach, appendix, and ileus; GI-NET) made between January 2003 and December 2004 and followed up at our institution. Archival material should be available for revision according to WHO 2010 neuroendocrine tumor classification and for p-mTOR, SSTR2A, and IGF-1R immunostaining, calculating a quantitative score (QS). We evaluated clinical, pathological, and immunohistochemistry features for association with the presence of advanced disease at diagnosis and disease relapse in patients who have undergone radical surgery.
Results
Archival material from 64 patients was analyzed (37 pNETs and 27 GI-NETs). In these patients, G2 grading, low SSTR2A QS, and high p-mTOR QS were associated with advanced disease at diagnosis at multivariate analysis. Risk of recurrence in 49 patients with R0-resected tumors was higher for G2 grading, stage IIIB-IV, low IGF-1R QS, and high p-mTOR QS at univariate analysis.
Conclusions
With the limits of retrospective data, activation of m-TOR is correlated with advanced disease at diagnosis and with shorter disease-free survival after R0 resection. Validation through prospective studies is needed.
doi:10.1155/2017/7872519
PMCID: PMC5682061
11.  CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer’s disease 
Scientific Reports  2017;7:13728.
In Alzheimer’s disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected from sub-groups of AD patients to determine whether APOE genotype and CSF biomarkers influence astrocytes survival. LTP-like cortical plasticity differed between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3) genotype. Higher CSF tau levels were associated with more impaired LTP-like cortical plasticity and faster disease progression in AD patients with APOE4 but not APOE3 genotype. Apoptotic activity was higher when cells were incubated with CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on cortical plasticity, disease progression and astrocyte survival only when associated with APOE4 genotype. This is relevant for new therapeutic approaches targeting tau.
doi:10.1038/s41598-017-14204-3
PMCID: PMC5653826  PMID: 29062035
12.  Brain Ceramide Metabolism in the Control of Energy Balance 
The regulation of energy balance by the central nervous system (CNS) is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D). Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate), the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA) to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.
doi:10.3389/fphys.2017.00787
PMCID: PMC5643460
hypothalamus; lipid sensing; lipotoxicity; ceramides; energy homeostasis
13.  Performance of the ATLAS track reconstruction algorithms in dense environments in LHC Run 2 
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M. | Farthouat, P. | Fassi, F. | Fassnacht, P. | Fassouliotis, D. | Faucci Giannelli, M. | Favareto, A. | Fawcett, W. J. | Fayard, L. | Fedin, O. L. | Fedorko, W. | Feigl, S. | Feligioni, L. | Feng, C. | Feng, E. J. | Feng, H. | Fenton, M. J. | Fenyuk, A. B. | Feremenga, L. | Fernandez Martinez, P. | Fernandez Perez, S. | Ferrando, J. | Ferrari, A. | Ferrari, P. | Ferrari, R. | Ferreira de Lima, D. E. | Ferrer, A. | Ferrere, D. | Ferretti, C. | Fiedler, F. | Filipčič, A. | Filipuzzi, M. | Filthaut, F. | Fincke-Keeler, M. | Finelli, K. D. | Fiolhais, M. C. N. | Fiorini, L. | Fischer, A. | Fischer, C. | Fischer, J. | Fisher, W. C. | Flaschel, N. | Fleck, I. | Fleischmann, P. | Fletcher, R. R. M. | Flick, T. | Flierl, B. M. | Flores Castillo, L. R. | Flowerdew, M. J. | Forcolin, G. T. | Formica, A. | Förster, F. A. | Forti, A. | Foster, A. G. | Fournier, D. | Fox, H. | Fracchia, S. | Francavilla, P. | Franchini, M. | Franchino, S. | Francis, D. | Franconi, L. | Franklin, M. | Frate, M. | Fraternali, M. | Freeborn, D. | Fressard-Batraneanu, S. M. | Freund, B. | Froidevaux, D. | Frost, J. A. | Fukunaga, C. | Fusayasu, T. | Fuster, J. | Gabaldon, C. | Gabizon, O. | Gabrielli, A. | Gabrielli, A. | Gach, G. P. | Gadatsch, S. | Gadomski, S. | Gagliardi, G. | Gagnon, L. G. | Galea, C. | Galhardo, B. | Gallas, E. J. | Gallop, B. J. | Gallus, P. | Galster, G. | Gan, K. K. | Ganguly, S. | Gao, Y. | Gao, Y. S. | Garay Walls, F. M. | García, C. | García Navarro, J. E. | Garcia-Sciveres, M. | Gardner, R. W. | Garelli, N. | Garonne, V. | Gascon Bravo, A. | Gasnikova, K. | Gatti, C. | Gaudiello, A. | Gaudio, G. | Gavrilenko, I. L. | Gay, C. | Gaycken, G. | Gazis, E. N. | Gee, C. N. P. | Geisen, J. | Geisen, M. | Geisler, M. P. | Gellerstedt, K. | Gemme, C. | Genest, M. H. | Geng, C. | Gentile, S. | Gentsos, C. | George, S. | Gerbaudo, D. | Gershon, A. | Geßner, G. | Ghasemi, S. | Ghneimat, M. | Giacobbe, B. | Giagu, S. | Giannetti, P. | Gibson, S. M. | Gignac, M. | Gilchriese, M. | Gillberg, D. | Gilles, G. | Gingrich, D. M. | Giokaris, N. | Giordani, M. P. | Giorgi, F. M. | Giraud, P. F. | Giromini, P. | Giugni, D. | Giuli, F. | Giuliani, C. | Giulini, M. | Gjelsten, B. K. | Gkaitatzis, S. | Gkialas, I. | Gkougkousis, E. L. | Gkountoumis, P. | Gladilin, L. K. | Glasman, C. | Glatzer, J. | Glaysher, P. C. F. | Glazov, A. | Goblirsch-Kolb, M. | Godlewski, J. | Goldfarb, S. | Golling, T. | Golubkov, D. | Gomes, A. | Gonçalo, R. | Goncalves Gama, R. | Goncalves Pinto Firmino Da Costa, J. | Gonella, G. | Gonella, L. | Gongadze, A. | González de la Hoz, S. | Gonzalez-Sevilla, S. | Goossens, L. | Gorbounov, P. A. | Gordon, H. A. | Gorelov, I. | Gorini, B. | Gorini, E. | Gorišek, A. | Goshaw, A. T. | Gössling, C. | Gostkin, M. I. | Gottardo, C. A. | Goudet, C. R. | Goujdami, D. | Goussiou, A. G. | Govender, N. | Gozani, E. | Graber, L. | Grabowska-Bold, I. | Gradin, P. O. J. | Gramling, J. | Gramstad, E. | Grancagnolo, S. | Gratchev, V. | Gravila, P. M. | Gray, C. | Gray, H. M. | Greenwood, Z. D. | Grefe, C. | Gregersen, K. | Gregor, I. M. | Grenier, P. | Grevtsov, K. | Griffiths, J. | Grillo, A. A. | Grimm, K. | Grinstein, S. | Gris, Ph. | Grivaz, J.-F. | Groh, S. | Gross, E. | Grosse-Knetter, J. | Grossi, G. C. | Grout, Z. J. | Grummer, A. | Guan, L. | Guan, W. | Guenther, J. | Guescini, F. | Guest, D. | Gueta, O. | Gui, B. | Guido, E. | Guillemin, T. | Guindon, S. | Gul, U. | Gumpert, C. | Guo, J. | Guo, W. | Guo, Y. | Gupta, R. | Gupta, S. | Gustavino, G. | Gutierrez, P. | Gutierrez Ortiz, N. G. | Gutschow, C. | Guyot, C. | Guzik, M. P. | Gwenlan, C. | Gwilliam, C. B. | Haas, A. | Haber, C. | Hadavand, H. K. | Haddad, N. | Hadef, A. | Hageböck, S. | Hagihara, M. | Hakobyan, H. | Haleem, M. | Haley, J. | Halladjian, G. | Hallewell, G. D. | Hamacher, K. | Hamal, P. | Hamano, K. | Hamilton, A.
With the increase in energy of the Large Hadron Collider to a centre-of-mass energy of 13 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {TeV}$$\end{document}TeV for Run 2, events with dense environments, such as in the cores of high-energy jets, became a focus for new physics searches as well as measurements of the Standard Model. These environments are characterized by charged-particle separations of the order of the tracking detectors sensor granularity. Basic track quantities are compared between 3.2 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1 of data collected by the ATLAS experiment and simulation of proton–proton collisions producing high-transverse-momentum jets at a centre-of-mass energy of 13 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {TeV}$$\end{document}TeV. The impact of charged-particle separations and multiplicities on the track reconstruction performance is discussed. The track reconstruction efficiency in the cores of jets with transverse momenta between 200 and 1600 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV is quantified using a novel, data-driven, method. The method uses the energy loss, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text { d}}{} \textit{E}/d\textit{x}$$\end{document}dE/dx, to identify pixel clusters originating from two charged particles. Of the charged particles creating these clusters, the measured fraction that fail to be reconstructed is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.061 \pm 0.006\ {\text {(stat.)}} \pm 0.014\ {\text {(syst.)}}$$\end{document}0.061±0.006(stat.)±0.014(syst.) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.093 \pm 0.017\ {\text {(stat.)}}\pm 0.021\ {\text {(syst.)}}$$\end{document}0.093±0.017(stat.)±0.021(syst.) for jet transverse momenta of 200–400 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV and 1400–1600 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV, respectively.
doi:10.1140/epjc/s10052-017-5225-7
PMCID: PMC5638380
14.  Minimal residual disease in pediatric ALL 
Oncotarget  2017;8(45):78251-78252.
doi:10.18632/oncotarget.20856
PMCID: PMC5667954
ETV6-RUNX1; hyperdiploid >50; early T-cell precursor ALL; genotype; deep sequencing
15.  Origins of the Greenland shark (Somniosus microcephalus): Impacts of ice‐olation and introgression 
Ecology and Evolution  2017;7(19):8113-8125.
Abstract
Herein, we use genetic data from 277 sleeper sharks to perform coalescent‐based modeling to test the hypothesis of early Quaternary emergence of the Greenland shark (Somniosus microcephalus) from ancestral sleeper sharks in the Canadian Arctic‐Subarctic region. Our results show that morphologically cryptic somniosids S. microcephalus and Somniosus pacificus can be genetically distinguished using combined mitochondrial and nuclear DNA markers. Our data confirm the presence of genetically admixed individuals in the Canadian Arctic and sub‐Arctic, and temperate Eastern Atlantic regions, suggesting introgressive hybridization upon secondary contact following the initial species divergence. Conservative substitution rates fitted to an Isolation with Migration (IM) model indicate a likely species divergence time of 2.34 Ma, using the mitochondrial sequence DNA, which in conjunction with the geographic distribution of admixtures and Pacific signatures likely indicates speciation associated with processes other than the closing of the Isthmus of Panama. This time span coincides with further planetary cooling in the early Quaternary period followed by the onset of oscillating glacial‐interglacial cycles. We propose that the initial S. microcephalus–S. pacificus split, and subsequent hybridization events, were likely associated with the onset of Pleistocene glacial oscillations, whereby fluctuating sea levels constrained connectivity among Arctic oceanic basins, Arctic marginal seas, and the North Atlantic Ocean. Our data demonstrates support for the evolutionary consequences of oscillatory vicariance via transient oceanic isolation with subsequent secondary contact associated with fluctuating sea levels throughout the Quaternary period—which may serve as a model for the origins of Arctic marine fauna on a broad taxonomic scale.
doi:10.1002/ece3.3325
PMCID: PMC5632604
elasmobranch; Greenland shark; interspecific gene flow; introgressive hybridization; isolation with migration; Somniosus microcephalus
16.  Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients 
Scientific Reports  2017;7:11657.
The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two hypoallergenic rBet v 1 fragments were applied epicutaneously by atopy patch testing (APT) to 15 birch pollen (bp) allergic patients suffering from atopic dermatitis, 5 bp-allergic patients suffering from rhinoconjunctivitis only, 5 patients with respiratory allergy without bp allergy and 5 non-allergic individuals. Epicutaneous administration of rBet v 1 and rBet v 1 fragments led to strong and significant increases of allergen-specific T cell proliferation (CLA+ and CCR4+T cell responses) only in bp-allergic patients with a positive APT reaction. There were no relevant changes of Bet v 1-specific IgE and IgG responses. No changes were noted in allergic subjects without bp allergy and in non-allergic subjects. Epicutaneous allergen application boosts specific T cell but not antibody responses mainly in allergic, APT-positive patients suggesting IgE-facilitated allergen presentation as mechanism for its effects on systemic allergen-specific immune responses.
doi:10.1038/s41598-017-10278-1
PMCID: PMC5599525  PMID: 28912492
17.  Dogs are not better than humans at detecting coherent motion 
Scientific Reports  2017;7:11259.
The ability to perceive motion is one of the main properties of the visual system. Sensitivity in detecting coherent motion has been thoroughly investigated in humans, where thresholds for motion detection are well below 10% of coherence, i.e. of the proportion of dots coherently moving in the same direction, among a background of randomly moving dots. Equally low thresholds have been found in other species, including monkeys, cats and seals. Given the lack of data from the domestic dog, we tested 5 adult dogs on a conditioned discrimination task with random dot displays. In addition, five adult humans were tested in the same condition for comparative purposes. The mean threshold for motion detection in our dogs was 42% of coherence, while that of humans was as low as 5%. Therefore, dogs have a much higher threshold of coherent motion detection than humans, and possibly also than phylogenetically closer species that have been tested in similar experimental conditions. Various factors, including the relative role of global and local motion processing and experience with the experimental stimuli may have contributed to this result. Overall, this finding questions the general claim on dogs’ high performance in detecting motion.
doi:10.1038/s41598-017-11864-z
PMCID: PMC5595918  PMID: 28900293
18.  Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients 
The European Respiratory Journal  2017;50(2):1700050.
Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.
Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.
We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%).
ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
Awareness of clinical/radiological presentation of immunotherapy-related pneumonitis is crucial to ensure a diagnosis http://ow.ly/eIMF30bgolf
doi:10.1183/13993003.00050-2017
PMCID: PMC5593387  PMID: 28798088
19.  White-Nose Syndrome Fungus in a 1918 Bat Specimen from France  
Emerging Infectious Diseases  2017;23(9):1611-1612.
White-nose syndrome, first diagnosed in North America in 2006, causes mass deaths among bats in North America. We found the causative fungus, Pseudogymnoascus destructans, in a 1918 sample collected in Europe, where bats have now adapted to the fungus. These results are consistent with a Eurasian origin of the pathogen.
doi:10.3201/eid2309.170875
PMCID: PMC5572869  PMID: 28820367
White-nose syndrome; Pseudogymnoascus destructans; bats; Myotis bechsteinii; France; fungi
20.  Chemical Modulation of in Vivo Macrophage Function with Subpopulation-Specific Fluorescent Prodrug Conjugates 
ACS Central Science  2017;3(9):995-1005.
Immunomodulatory agents represent one of the most promising strategies for enhancing tissue regeneration without the side effects of traditional drug-based therapies. Tissue repair depends largely on macrophages, making them ideal targets for proregenerative therapies. However, given the multiple roles of macrophages in tissue homeostasis, small molecule drugs must be only active in very specific subpopulations. In this work, we have developed the first prodrug–fluorophore conjugates able to discriminate closely related subpopulations of macrophages (i.e., proinflammatory M1 vs anti-inflammatory M2 macrophages), and employed them to deplete M1 macrophages in vivo without affecting other cell populations. Selective intracellular activation and drug release enabled simultaneous fluorescence cell tracking and ablation of M1 macrophages in vivo, with the concomitant rescue of a proregenerative phenotype. Ex vivo assays in human monocyte-derived macrophages validate the translational potential of this novel platform to develop chemical immunomodulatory agents as targeted therapies for immune-related diseases.
A novel BODIPY−doxorubicin prodrug conjugate was developed for simultaneous fluorescence cell tracking and functional modulation of proinflammatory subpopulations of macrophages in vivo.
doi:10.1021/acscentsci.7b00262
PMCID: PMC5620981
21.  Long-term follow-up of MRI changes in thigh muscles of patients with Facioscapulohumeral dystrophy: A quantitative study 
PLoS ONE  2017;12(8):e0183825.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common hereditary muscular disorders. Currently FSHD has no known effective treatment and detailed data on the natural history are lacking. Determination of the efficacy of a given therapeutic approach might be difficult in FSHD given the slow and highly variable disease progression. Magnetic resonance imaging (MRI) has been widely used to qualitatively and quantitatively evaluate in vivo the muscle alterations in various neuromuscular disorders. The main aim of the present study was to investigate longitudinally the time-dependent changes occurring in thigh muscles of FSHD patients using quantitative MRI and to assess the potential relationships with the clinical findings. Thirty-five FSHD1 patients (17 females) were enrolled. Clinical assessment tools including manual muscle testing using medical research council score (MRC), and motor function measure (MFM) were recorded each year for a period ranging from 1 to 2 years. For the MRI measurements, we used a new quantitative index, i.e., the mean pixel intensity (MPI) calculated from the pixel-intensity distribution in T1 weighted images. The corresponding MPI scores were calculated for each thigh, for each compartment and for both thighs totally (MPItotal). The total mean pixel intensity (MPItotal) refers to the sum of each pixel signal intensity divided by the corresponding number of pixels. An increased MPItotal indicates both a raised fat infiltration together with a reduced muscle volume thereby illustrating disease progression. Clinical scores did not change significantly over time whereas MPItotal increased significantly from an initial averaged value of 39.6 to 41.1 with a corresponding rate of 0.62/year. While clinical scores and MPItotal measured at the start of the study were significantly related, no correlation was found between the rate of MPItotal and MRC sum score changes, MFMtotal and MFM subscores. The relative rate of MPItotal change was 2.3% (0.5–4.3)/year and was significantly higher than the corresponding rates measured for MRCS 0% (0–1.7) /year and MFMtotal 0% (0–2.0) /year (p = 0.000). On the basis of these results, we suggested that muscle MRI and more particularly the MPItotal index could be used as a reliable biomarker and outcome measure of disease progression. In slowly progressive myopathies such as FSHD, the MPItotal index might reveal subclinical changes, which could not be evidenced using clinical scales over a short period of time.
doi:10.1371/journal.pone.0183825
PMCID: PMC5571945  PMID: 28841698
22.  Determination of regulatory ionophore coccidiostat residues in feedstuffs at carry-over levels by liquid chromatography-mass spectrometry 
PLoS ONE  2017;12(8):e0182831.
In this study samples of feedstuffs were collected from different feed mills and animal farms located in central Italy and analyzed for ionophore coccidiostat residues at carry-over levels by liquid chromatography-mass spectrometry. Since unavoidable cross-contamination of feedstuffs may occur during their production as well as distribution and storage, the collection of samples covered all these different stages. Residues of lasalocid, monensin, salinomycin and maduramicin were detected in 32.4% of samples, both at production and storage level. The maximum content for unavoidable carry-over set by Regulation (EU) No 574/2011 was exceeded in 11.3% of samples. The variability of the results highlighted the different approach of each investigated feed business operator to avoid any cross-contamination in non-target feed. The method developed in this study can be able to detect ionophore coccidiostats at low concentrations consequent to carry-over.
doi:10.1371/journal.pone.0182831
PMCID: PMC5549955  PMID: 28792977
23.  Fiducial, total and differential cross-section measurements of t-channel single top-quark production in pp collisions at 8 TeV using data collected by the ATLAS detector 
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Detailed measurements of t-channel single top-quark production are presented. They use 20.2 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1 of data collected by the ATLAS experiment in proton–proton collisions at a centre-of-mass energy of 8 TeV at the LHC. Total, fiducial and differential cross-sections are measured for both top-quark and top-antiquark production. The fiducial cross-section is measured with a precision of 5.8% (top quark) and 7.8% (top antiquark), respectively. The total cross-sections are measured to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\text {tot}} (tq) = 56.7^{+4.3}_{-3.8}\;\mathrm{pb}$$\end{document}σtot(tq)=56.7-3.8+4.3pb for top-quark production and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\text {tot}} (\bar{t} q) = 32.9^{+3.0}_{-2.7}\;\mathrm{pb}$$\end{document}σtot(t¯q)=32.9-2.7+3.0pb for top-antiquark production, in agreement with the Standard Model prediction. In addition, the ratio of top-quark to top-antiquark production cross-sections is determined to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R_t=1.72 \pm 0.09$$\end{document}Rt=1.72±0.09. The differential cross-sections as a function of the transverse momentum and rapidity of both the top quark and the top antiquark are measured at both the parton and particle levels. The transverse momentum and rapidity differential cross-sections of the accompanying jet from the t-channel scattering are measured at particle level. All measurements are compared to various Monte Carlo predictions as well as to fixed-order QCD calculations where available.
doi:10.1140/epjc/s10052-017-5061-9
PMCID: PMC5589447
24.  Molecular aspects of allergens in atopic dermatitis 
Purpose of review
Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis.
Recent findings
IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach.
Summary
Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach.
doi:10.1097/ACI.0000000000000378
PMCID: PMC5540349  PMID: 28622169
allergen; allergen-specific immunotherapy; atopic dermatitis; IgE-associated allergy; micro-arrayed allergens; molecular allergology; personalized medicine
25.  Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1 
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The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.
doi:10.1140/epjc/s10052-017-5004-5
PMCID: PMC5586976

Results 1-25 (470)