Cancer progression: a single cell perspective

Tumor tissues are constituted by a dynamic diversity of malignant and non-malignant cells, which shape a puzzling biological ecosystem affecting cancer biology and response to treatments. Over the course of the tumoral disease, cancer cells acquire genotypic and phenotypic changes, allowing them to improve cellular fitness and overcome environmental and treatment constraints. This progression is depicted by an evolutionary process in which single cells expand as a result of an interaction between single-cell changes and the lovelopments have made it possible to depict the development of cancer at the single-cell level, offering a novel method for understanding the biology of this complex disease. Here, we review those complex interactions from the perspective of single cells and introduce the concept of omics for single-cell studies. This review emphasizes the evolutionary dynamics that control cancer progression and the capacity of single cells to escape the local environment and colonize distant sites. We are assisting a rapid progression of studies carried out at the single-cell level, and we survey relevant single-cell technologies looking at multi-omics studies. These path for precision medicine in cancer

Ceramide-induced BOK promotes mitochondrial fission in preeclampsia

Mitochondria are in a constant balance of fusing and dividing in response to cellular cues. Fusion creates healthy mitochondria, whereas fission results in removal of non-functional organelles. Changes in mitochondrial dynamics typify several human diseases. However, the contribution of mitochondrial dynamics to preeclampsia, a hypertensive disorder of pregnancy characterized by placental cell autophagy and death, remains unknown. Herein, we show that the mitochondrial dynamic balance in preeclamptic placentae is tilted toward fission (increased DRP1 expression/activation and decreased OPA1 expression). Increased phosphorylation of DRP1 (p-DRP1) in mitochondrial isolates from preeclamptic placentae and transmission electron microscopy corroborated augmented mitochondrial fragmentation in cytotrophoblast cells of PE placentae. Increased fission was accompanied by build-up of ceramides (CERs) in mitochondria from preeclamptic placentae relative to controls. Treatment of human choriocarcinoma JEG3 cells and primary isolated cytrophoblast cells with CER 16:0 enhanced mitochondrial fission. Loss- and gain-of-function experiments showed that Bcl-2 member BOK, whose expression is increased by CER, positively regulated p-DRP1/DRP1 and MFN2 expression, and localized mitochondrial fission events to the ER/MAM compartments. We also identified that the BH3 and transmembrane domains of BOK were vital for BOK regulation of fission. Moreover, we found that full-length PTEN-induced putative kinase 1 (PINK1) and Parkin, were elevated in mitochondria from PE placentae, implicating mitophagy as the process that degrades excess mitochondria fragments produced from CER/BOK-induced fission in preeclampsia. In summary, our study uncovered a novel CER/BOK-induced regulation of mitochondrial fission and its functional consequence for heightened trophoblast cell autophagy in preeclampsia

Total- and semi-bare noble metal nanoparticles@silica core@shell catalysts for hydrogen generation by formic acid decomposition

Catalysts are involved in a number of established and emerging chemical processes as well as in environmental remediation and energy conversion. Nanoparticles (NPs) can offer several advantages over some conventional catalysts, such as higher efficiency and selectivity. Nowadays, versatile and scalable nanocatalysts that combine activity and stability are still lacking. Here, we report a comprehensive investigation on the production and characterization of hybrid nano-architectures bringing a partial or total bare surface together with their catalytic efficiency evaluation on, as a proof-of-concept, the formic acid decomposition reaction. In this regard, formic acid (FA) is a convenient and safe hydrogen carrier with appealing features for mobile applications, fuel cells technologies, petrochemical processes and energetic applications. Thus, the design of robust catalysts for FA dehydrogenation is strongly demanded. Due to this, we produced and evaluated nano-architectures with various equilibrium between the size-increase of the active part and the barer catalytic surface. Overall, this work paves the way for the development of new approaches for green energy storage and safe delivery

Anomalies Observed in VLF and LF Radio Signals on the Occasion of the Western Turkey Earthquake (Mw = 5.7) on May 19, 2011

VLF radio signals lie in the 10 - 60 kHz frequency band. These radio signals are used for worldwide navigation support, time signals and for military purposes. They are propagated in the earth-ionosphere wave-guide mode along great circle propagation paths. So, their propaga-tion is strongly affected by the ionosphere conditions. LF signals lie in 150 - 300 kHz frequency band. They are used for long way broadcasting by the few (this type of broadcasting is going into disuse) transmitters located in the world. These radio signals are characterized by the ground wave and the sky wave propagation modes [1]. The first generates a stable signal that propagates in the channel Earth-troposphere and is affected by the surface ground and troposphere condition. The second instead gives rise to a signal which varies greatly between day and night, and between summer and winter, and which propagates using the lower ionosphere as a reflector; its propagation is mainly affected by the ionosphere condi-tion, particularly in the zone located in the middle of the transmitter-receiver path. The propagation of the VLF/LF radio signals is affected by different factors such as the meteorological condition, the solar bursts and the geo-magnetic activity. At the same time, variations of some parameters in the ground, in the atmosphere and in the ionosphere occurring during the preparatory phase of earthquakes can produce disturbances in the above men-tioned signals. As already reported by many previous studies [2-18] the disturbances are classified as anoma-lies and different methods of analysis as the residual dA/ dP [15], the terminator time TT [9], the Wavelet spectra and the Principal Component Analysis have been used [6,7]. Here the analysis carried out on LF and VLF radio signals using three different methods on the occasion of a strong earthquake occurred recently in Turkey is pre-sented

Pro-apoptotic and size-reducing effects of protein corona-modulating nano-architectures enclosing platinum prodrug in in vivo oral carcinoma

The selective and localized delivery of active agents to neoplasms is crucial to enhance the chemotherapeutic efficacy while reducing the associated side effects. The encapsulation of chemotherapeutics in nanoparticles decorated with targeting agents is a strategy of special interest to improve drug delivery. However, serum protein adsorption often compromises the in vivo efficiency of targeting agents, leading to protein corona formation that interferes with the targeting process. Here, the enhanced efficacy of hybrid nano-architectures enclosing a platinum prodrug and decorated with a customized peptide (NAs-cisPt-Tf2) is demonstrated by employing alternative in vivo models of oral carcinoma. The peptide binds to transferrin and modulates the protein corona formation on NAs-cisPt-Tf2, supporting the identification of its receptor. Optimized chorioallantoic membrane cancer models (CAMs) enabled a thorough assessment of the tumor-suppressing effect of NAs-cisPt-Tf2 as well as the quantitative evaluation of angiogenesis and cell cycle associated mechanisms. The treatment strategy resulted in a significant tumor volume reduction coupled with anti-angiogenic and pro-apoptotic effects inferred from the downregulation of the vascular endothelial growth factor gene and increased expression of cleaved caspase-3. Overall, this study provides a potentially effective tumor-targeted approach for a non-invasive management of oral carcinoma

Wavelet analysis of the LF radio signals collected by the European VLF/LF network from July 2009 to April 2011

In 2008, a radio receiver that works in very low frequency (VLF; 20-60 kHz) and LF (150-300 kHz) bands was developed by an Italian factory. The receiver can monitor 10 frequencies distributed in these bands, with the measurement for each of them of the electric field intensity. Since 2009, to date, six of these radio receivers have been installed throughout Europe to establish a ‘European VLF/LF Network’. At present, two of these are into operation in Italy, and the remaining four are located in Greece, Turkey, Portugal and Romania. For the present study, the LF radio data collected over about two years were analysed. At first, the day-time data and the night-time data were separated for each radio signal. Taking into account that the LF signals are characterized by ground-wave and sky-wave propagation modes, the day-time data are related to the ground wave and the night-time data to the sky wave. In this framework, the effects of solar activity and storm activity were defined in the different trends. Then, the earthquakes with M ≥5.0 that occurred over the same period were selected, as those located in a 300-km radius around each receiver/transmitter and within the 5th Fresnel zone related to each transmitter-receiver path. Where possible, the wavelet analysis was applied on the time series of the radio signal intensity, and some anomalies related to previous earthquakes were revealed. Except for some doubt in one case, success appears to have been obtained in all of the cases related to the 300 km circles in for the ground waves and the sky waves. For the Fresnel cases, success in two cases and one failure were seen in analysing the sky waves. The failure occurred in August/September, and might be related to the disturbed conditions of the ionosphere in summer

Analisi della suscettibilità da frana a scala di bacino (Bacino del Fiume Arno, Toscana-Umbria, Italia)

In questa nota vengono presentati i metodi applicati e i risultati ottenuti in una recente analisi della pericolosità da frana, condotta sul territorio del Bacino del Fiume Arno nell’ambito di una convenzione tra l’Autorità di Bacino e il Dipartimento di Scienze della Terra dell’Università di Firenze (2002-2005). Tutti i dati acquisiti, confluiti in una banca dati GIS, sono stati sintetizzati in carte tematiche e in una carta inventario delle frane. La sovrapposizione dei fattori predisponenti selezionati (pendenza, litologia, uso del suolo, curvatura di profilo e area drenata) ha permesso di definire le unità elementari per il trattamento statistico (Unità Territoriali Omogenee: UTO). La valutazione della pericolosità è stata estesa alle aree prive di movimenti franosi utilizzando metodi statistici multivariati implementati in Reti Neurali Artificiali. L’area di studio è stata suddivisa in cinque Macroaree morfologicamente e geologicamente omogenee: per ogni Macroarea, i predittori neurali sono stati addestrati su un opportuno sottoinsieme di dati, applicando poi i migliori all’intero data-set al fine di generare valori previsti dell’indice di suscettibilità per ogni UTO. Infine, i valori di uscita sono stati riclassificati in differenti livelli di pericolosità in base a criteri di soglia e validati per confronto con l’inventario. Una percentuale di area in frana compresa tra l’81 e il 96% risulta correttamente classificata dalla previsione nelle varie Macroare

Present status and preliminary results of the VLF/LF radio recording European network installed in 2009.

In January 2009 a European network of receivers able to measure the electric field intensity from various VLF/LF broadcasting stations located throughout Europe, was installed. Five new receivers constructed by an Italian enterprise have been delivered to Greece, Romania, Turkey and to the Italian team. The motivation of this effort is to study the possible connections between the preparatory phase of earthquakes and perturbations in the transmitted radio signals. The receivers can be reached via ftp and gsm mobile connection, thus allowing a real time data collection. We present here the status of the network and the various testing steps performed in order to achieve a correct set up. We show how antennas variations, receivers locations and changes of selected frequencies affect the performances of the whole network. After this necessary testing period, several LF/VLF radio signals are now simultaneously and continuously being sampled by the five receivers. As a preliminary result we inspect also specific cases in which an anomaly in the radio signals is clearly related to the transmitter or to the receiver (e.g. meteorological conditions around the sampling site). At a basic level, the analysis adopted consists in a simple statistical evaluation of the signals by comparing the instantaneous values to the trend of the signal