The NK cells phenotype and function in resected non small cell lung cancer: differences between squamous and adenocarcinoma.

The tumor microenvironment has come to light as a key player in carcinogenesis and progression. Tumors affect many host cell types, in particular immune cells. The immune system appears to select particularly fit tumor cells in the process of immuno-­editing, while the tumor cells influence the polarization of immune cells towards phenotypes that favor tumor growth and vascularization. Here we investigated the phenotype of tumor infiltrating natural killer (NK) cells, focusing on angiogenesis associated cytokines and activities in patient-­derived material from non-­small cell lung cancer (NSCLC). Samples from the tumor and adjacent normal issues, as well as peripheral blood and lung samples as well as from non-­oncologic patients with bullous emphysema were collected and rapidly processed to obtain single cell suspensions. Flow cytometry (FC) analyses were performed to evaluate specific markers (CD3, CD56, CD16) to identify NK cell subsets. We observed that in the NSCLC samples, the CD56+CD16-­ NK phenotype, associated with cytokine production, predominated in the tumor samples while the CD56dimCD16+ cytotoxic phenotype dominated in the adjacent normal tissues and in lung tissue derived from non-­oncologic patients. This was independent of tumor histotype and smoking status. We examined the angiogenic potential of tumor infiltrating NK cells by intracellular staining for production of VEGF, PlGF, IL-­8 (CXCL8), IFNand other markers. The CD56+CD16-­ subset was clearly associated with production of angiogenic cytokines in all samples. However, patients with squamous carcinoma histotypes showed remarkably and significantly higher production of angiogenic factors in tumor infiltrating, adjacent tissue and especially in peripheral blood CD56+CD16-­ NK cells than patients with adenocarcinomas. Following surgical intervention, these levels were reduced in disease-free patients. Moreover, supernatants derived from the tumor infiltrating CD56+CD16-­ NK cells were able to induce endothelial cell chemotaxis and formation of capillary-­like structures in vitro; this was particularly evident for NK cells isolated from squamous cell carcinomas. Our data suggest that squamous NSCLC tumors have a significant systemic effect on NK cells, enhancing angiogenic cytokine production in a manner dependent on the presence of disease. NK cells appear to participate in tumor neovascularization and could represent a peripheral marker for disease progression, angiogenesis and response to therapies in some tumor subsets

The NK cells phenotype and function in resected non small cell lung cancer: differences between squamous and adenocarcinoma.

The tumor microenvironment has come to light as a key player in carcinogenesis and progression. Tumors affect many host cell types, in particular immune cells. The immune system appears to select particularly fit tumor cells in the process of immuno-\uadediting, while the tumor cells influence the polarization of immune cells towards phenotypes that favor tumor growth and vascularization. Here we investigated the phenotype of tumor infiltrating natural killer (NK) cells, focusing on angiogenesis associated cytokines and activities in patient-\uadderived material from non-\uadsmall cell lung cancer (NSCLC). Samples from the tumor and adjacent normal issues, as well as peripheral blood and lung samples as well as from non-\uadoncologic patients with bullous emphysema were collected and rapidly processed to obtain single cell suspensions. Flow cytometry (FC) analyses were performed to evaluate specific markers (CD3, CD56, CD16) to identify NK cell subsets. We observed that in the NSCLC samples, the CD56+CD16-\uad NK phenotype, associated with cytokine production, predominated in the tumor samples while the CD56dimCD16+ cytotoxic phenotype dominated in the adjacent normal tissues and in lung tissue derived from non-\uadoncologic patients. This was independent of tumor histotype and smoking status. We examined the angiogenic potential of tumor infiltrating NK cells by intracellular staining for production of VEGF, PlGF, IL-\uad8 (CXCL8), IFN\uf0e3\uf020and other markers. The CD56+CD16-\uad subset was clearly associated with production of angiogenic cytokines in all samples. However, patients with squamous carcinoma histotypes showed remarkably and significantly higher production of angiogenic factors in tumor infiltrating, adjacent tissue and especially in peripheral blood CD56+CD16-\uad NK cells than patients with adenocarcinomas. Following surgical intervention, these levels were reduced in disease-free patients. Moreover, supernatants derived from the tumor infiltrating CD56+CD16-\uad NK cells were able to induce endothelial cell chemotaxis and formation of capillary-\uadlike structures in vitro; this was particularly evident for NK cells isolated from squamous cell carcinomas. Our data suggest that squamous NSCLC tumors have a significant systemic effect on NK cells, enhancing angiogenic cytokine production in a manner dependent on the presence of disease. NK cells appear to participate in tumor neovascularization and could represent a peripheral marker for disease progression, angiogenesis and response to therapies in some tumor subsets

Fluctuation theorems for non-Markovian quantum processes

Exploiting previous results on Markovian dynamics and fluctuation theorems, we study the consequences of memory effects on single realizations of nonequilibrium processes within an open system approach. The entropy production along single trajectories for forward and backward processes is obtained with the help of a recently proposed classical-like non-Markovian stochastic unravelling, which is demonstrated to lead to a correction of the standard entropic fluctuation theorem. This correction is interpreted as resulting from the interplay between the information extracted from the system through measurements and the flow of information from the environment to the open system: Due to memory effects single realizations of a dynamical process are no longer independent, and their correlations fundamentally affect the behavior of entropy fluctuations.Comment: 7 pages, 1 figur

Tomographic approach to the violation of Bell's inequalities for quantum states of two qutrits

The tomographic method is employed to investigate the presence of quantum correlations in two classes of parameter-dependent states of two qutrits. The violation of some Bell's inequalities in a wide domain of the parameter space is shown. A comparison between the tomographic approach and a recent method elaborated by Wu, Poulsen and Molmer shows the better adequacy of the former method with respect to the latter one.Comment: 9 pages, 4 figure

An ethnobotanical survey of wild edible plants of Campania (Italy)

A survey of the knowledge on edible wild plants in Campania (Italy) is presented. The checklist is based not only on literature data but also on unpublished results coming from archives of the authors. 639 records of alimentary uses related to 198 taxa are listed. Asteraceae, Lamiaceae, Brassicaceae and Rosaceae are the most represented families. The predominant biological forms are Hemycriptophytes, Terophytes and Phanerophytes. The parts of plant used as food mainly include leaves and aerial parts, followed by flowers, fruits and seeds, whereas roots and other underground parts are less frequently used. Many species are consumed in salads or soups and served in mixtures. The alimentary uses of most species are widespread in Campania, but the uses of 28 species are strictly linked to limited territories

Predittori neuropsicologici e di imaging molecolare dell'outcome cognitivo nella Malattia di Parkinson: evidenze da uno studio longitudinale su un'ampia coorte di pazienti

La Malattia di Parkinson, sebbene nota principalmente come disordine del movimento, è una patologia neurodegenerativa clinicamente eterogenea che si associa frequentemente a manifestazioni di tipo non motorio quali disfunzioni autonomiche, disturbi del tono dell’umore, disturbi del sonno, psicosi, disfunzione cognitiva e talvolta anche demenza. La demenza, in particolare, interessa nel complesso circa un terzo dei pazienti con Malattia di Parkinson e determina un importante peggioramento della qualità della vita ed una ridotta sopravvivenza del paziente, oltre ad un aumentato stress per il caregiver. I substrati neuropatologici e neurochimici della demenza in corso di Malattia di Parkinson non sono completamente conosciuti, tuttavia si ritiene comprendano la degenerazione di multiple aree cerebrali e la compromissione di diversi sistemi neurotrasmettitoriali. Nonostante numerosi fattori, di tipo demografico, genetico, clinico, o rilevati agli studi di neuroimaging, siano stati valutati nelle ultime due decadi al fine di predire lo sviluppo di demenza, attualmente non si conosce alcun test in grado di distinguere con esattezza quale categoria di pazienti con Malattia di Parkinson svilupperanno demenza. L’obiettivo del presente studio è stato valutare, in un gruppo di pazienti con Malattia di Parkinson, il ruolo predittivo del grado di degenerazione nigrostriatale misurata con SPECT con 123I-FP-CIT al baseline e della performance al baseline al test della copia dei pentagoni dell’outcome cognitivo durante un follow-up di 5 anni. Sono stati reclutati 96 pazienti con malattia di Parkinson iniziale e tutti sono stati sottoposti a SPECT con 123I-FP-CIT al baseline e ad una valutazione del grado di disabilità motoria, con l’esecuzione della Unified Parkinson’s Disease Rating Scale (UPDRS) nell’item III, e delle funzioni cognitive, con l’esecuzione del Mini Mental State Examination (MMSE), al baseline e ogni anno durante i 5 anni di follow-up. Durante il follow-up, il 18% dei pazienti ha sviluppato demenza. Tali pazienti presentavano, rispetto ai pazienti che non avrebbero sviluppato demenza, valori inferiori di captazione striatale del tracciante al baseline (p<0.01) e mostravano con una frequenza significativamente maggiore una performance errata al test della copia dei pentagoni (60% vs 20%). Significativamente diversi sono risultati inoltre il MMSE all’esordio e il punteggio della bradicinesia, entrambi maggiormente compromessi nei pazienti che avrebbero sviluppato demenza. È stata eseguita un’analisi di regressione logistica binaria considerando due variabili indipendenti: il valore di captazione striatale media, dicotomizzato in variabile binaria utilizzando come cut-off la mediana del gruppo, e il test della copia dei pentagoni. Il modello ha mostrato nel complesso la capacità di predire nel 35% dei casi lo sviluppo di demenza (p<0.001). Analogamente significativo è risultato il modello in cui venivano introdotti quali variabili la performance al test della copia dei pentagoni e la captazione media dei caudati. Tale risultato persisteva anche quando nell’analisi venivano considerati come covariate la severità del quadro motorio e la performance cognitiva al baseline. I risultati di questo studio indicano che il grado di degenerazione nigrostriatale misurata con SPECT con 123I-FP-CIT al baseline e le abilità visuospaziali e costruttive valutate con il test della copia dei pentagoni sono associate all’outcome cognitivo nei pazienti con Malattia di Parkinson, e confermano, come riscontrato da studi precedenti, che sia la degenerazione dopaminergica nigrostriatale che la disfunzione delle aree corticali posteriori, con una possibile azione sinergica, rivestono un ruolo fondamentale nel determinare il rischio di declino cognitivo nei pazienti con Malattia di Parkinson

Analysis of MAC-level throughput in LTE systems with link rate adaptation and HARQ protocols

LTE is rapidly gaining momentum for building future 4G cellular systems, and real operational networks are under deployment worldwide. To achieve high throughput performance, in addition to an advanced physical layer design LTE exploits a combination of sophisticated mechanisms at the radio resource management layer. Clearly, this makes difficult to develop analytical tools to accurately assess and optimise the user perceived throughput under realistic channel assumptions. Thus, most existing studies focus only on link-layer throughput or consider individual mechanisms in isolation. The main contribution of this paper is a unified modelling framework of the MAC-level downlink throughput of a sigle LTE cell, which caters for wideband CQI feedback schemes, AMC and HARQ protocols as defined in the LTE standard. We have validated the accuracy of the proposed model through detailed LTE simulations carried out with the ns-3 simulator extended with the LENA module for LTE

New unexpected species of Acheta (Orthoptera, Gryllidae) from the Italian volcanic Island of Pantelleria

In late April 2022, while listening to audio files from an unsupervised bioacoustic assessment of the shearwater populations (Aves, Procellariiformes) on the coast of Pantelleria island (Sicily, Italy), a cricket song of unknown attribution was heard. The first bioacoustic analyses, including FFT-based spectrograms and sound pressure envelopes, confirmed that it could not be attributed to the known sound of any Italian nor Mediterranean species of cricket. In the ensuing weeks, field research at the original station and further localities on the southern coast of Pantelleria provided photographs, living specimens, and further audio records. As soon as the photos were shared among the authors, it became clear the species belonged to the genus Acheta. Further bioacoustic analyses and morphological comparison with type specimens of Mediterranean and North-African congenerics in relevant collections and the scientific literature were conducted: they confirmed that the findings could only be attributed to a still undescribed species that escaped detection due to its impervious and unfrequented habitat. Acheta pantescus n. sp. is apparently restricted to the effusive coastal cliffs of the island of Pantelleria, a habitat whose scant extension and vulnerability require environmental protection actions such as the inclusion in a special Red List by the IUCN Italian Committe

A quantitative bioassay to determine the inhibitory potency of NGF-TrkA antagonists

In this article, we demonstrate and validate a new bioassay named the NTAB [NGF-TrkA (nerve growth factor-tropomyosin receptor kinase A) antagonist bioassay] for the determination of the inhibitory potency of NGF-TrkA antagonists, based on the inhibition of NGF-dependent proliferation of the human TF1 erythroleukemic cell line.It is well known that NGF holds great therapeutic potential due to its neurotrophic and neuroprotective properties. NGF is also involved in some pathways, however, principally driven by TrkA that, if not correctly regulated, can lead to unwanted pathological outcomes linked to pain, angiogenesis, and cancer.Indeed, there is an increasing interest, from a therapeutic perspective, in designing new effective molecules (antibodies, antibody fragments, or small molecules) able to inhibit the undesired NGF-TrkA pathway. For these reasons, there is an interest to develop functional cell-based assays for determination of the inhibition potency of compounds inhibiting the NGF-TrkA axis. The NTAB presents significant advantages over other published NGF-TrkA functional bioassays, for these reasons: (1) It is quantitative, (2) it measures a pure TrkA response, (3) it is simpler, (4) it is based on a natural biological response, and (5) it is easily scalable from a lab scale to an automated industrial assay.The NTAB assay was validated with a panel of well-characterized NGF-TrkA inhibitors, yielding characteristic dose-response curves, from which the relative strength of the inhibitors was quantitatively determined and used for comparisons. This new bioassay will be very useful to assist in the validation and prioritization of the best inhibitors among a large number of candidates

OZOGNATHUS CORNUTUS (LECONTE, 1859) (Coleoptera Anobiidae), NEW RECORD FOR ITALY

Prima segnalazione di Ozognathus cornutus (LeConte, 1859) (Coleoptera Anobiidae) in Itali