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Prostate cancer antigen 3 ( PCA3 ) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2 , a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.

Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) \"clinical-pathological AD\" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) \"pathological AD\" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE<3.2); and III) \"normal aging\" (N)--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.

This work shows a sustainable methodology for the synthesis of biogenic materials designed for the removal and photodegradation of rhodamine B (RhB), a highly dangerous environmental pollutant that induces reproductive toxicity. The classical synthesis of MCM-41-ordered mesoporous materials was modified using biocompatible rice husk as the silica template. Iron was incorporated and the so-prepared biogenic photocatalysts were characterized by X-ray diffraction, N2 adsorption–desorption isotherms, transmission electron microscopy, diffuse reflectance UV-Vis, surface pH, cyclic voltammetry, and Fourier transform infrared spectral analysis of pyridine adsorption. The photocatalytic performance of the materials was evaluated following the removal by adsorption and the photon-driven degradation of RhB. The adsorption capacity and photocatalytic activity of the biogenic materials were correlated with their properties, including iron content, texture, surface content, and electrochemical properties. The best biogenic material boosted the degradation rates of RhB under UV irradiation up to 4.7 and 2.2 times greater than the direct photolysis and the benchmark semiconductor TiO2-P25. It can be concluded that the use of rice husks for the synthesis of biogenic Fe-modified mesoporous materials is a promising strategy for wastewater treatment applications, particularly in the removal of highly toxic organic dyes.

Impacts of climate change and air pollutants are a growing concern. Reliable and accessible monitoring systems to assess air quality and climate extremes are essential to inform decision-makers and increase awareness of citizens. Approaches from Volunteered Geography play a pivotal role both in research and empowerment by new low-cost technologies. Recently, the spread of GeoICT and micro-sensors are offering opportunities for mobile environmental mapping. In general, official stations acquire data with high accuracy and reliability; in contrast low-cost mobile devices increase the spatio-temporal resolution of air sampling but with lower accuracy. Aims of study are i) assessing accuracy of temperature values from Sodaq Air and MeteoTracker devices; ii) assessing accuracy on PM 2.5 acquisition for Sodaq Air; iii) geovisualizing three months of environmental monitoring in the city of Padua. Accuracy assessment for air temperature was performed by using a calibrated thermometer; PM 2.5 from Sodaq Air were compared with an official air quality station. Preliminary results on dynamic mobile mapping indicate that temperature values from MeteoTracker present good accuracy, while those from Sodaq Air showed bias of approximately +2.5 °C. Air quality data from the latter seems to present, in this phase of development, some limitations, since comparative analysis with official air quality station indicates 93% of overestimation, on average. On the other hand, the environmental campaign with mobile mapping devices at urban scale highlights the capability of geovisualizing hotspots and densifying georeferenced data acquisition over space and time. Further software/hardware implementation and applied research are required with various devices in different environmental conditions to improve data quality and reliability.

The specific genes and molecules that drive physiological angiogenesis differ from those involved in pathological angiogenesis, suggesting distinct mechanisms for these seemingly related processes. Unveiling genes and pathways preferentially associated with pathologic angiogenesis is key to understanding its mechanisms, thereby facilitating development of novel approaches to managing angiogenesis-dependent diseases. To better understand these different processes, we elucidated the transcriptome of the mouse retina in the well-accepted oxygen-induced retinopathy (OIR) model of pathological angiogenesis. We identified 153 genes changed between normal and OIR retinas, which represent a molecular signature relevant to other angiogenesis-dependent processes such as cancer. These genes robustly predict the survival of breast cancer patients, which was validated in an independent 1,000-patient test cohort (40% difference in 15-year survival; p = 2.56 x 10-21). These results suggest that the OIR model reveals key genes involved in pathological angiogenesis, and these may find important applications in stratifying tumors for treatment intensification or for angiogenesis-targeted therapies.

Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR ≥1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak ≤ II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.

The experimental fusion reactor ITER will feature two (or three) heating neutral beam injectors (NBI) capable of delivering 33(or 50) MW of power into the plasma. A NBI consists of a plasma source for production of negative ions (extracted negative ion current up to 329 A/m 2 in H and 285 A/m 2 in D) then accelerated up to 1 MeV for one hour. The negative ion beam is neutralized, and the residual ions are electrostatically removed before injection. The beamline was designed for a beam divergence between 3 and 7 mrad. The ion source in ITER NBIs relies on RF-driven, Inductively-Coupled Plasmas (ICP), based on the prototypes developed at IPP Garching; RF-driven negative-ion beam sources have never been employed in fusion devices up to now. The recent results of SPIDER, the full size ITER NBI ion source operating at NBTF in Consorzio RFX, Padova, measure a beamlet divergence minimum of 12mrad and highlighted beam spatial non-uniformity. SPIDER results confirmed the experimental divergence found in smaller prototype sources, which is larger compared to filament-arc ion sources. Although prototype experiments have shown that the extracted current requirement can be achieved with minor design improvements, the beamlet divergence is expected to marginally achieve the design value of 7 mrad, which in multi-grid long accelerators results in unexpected heat loads over the accelerator grids. A contributor to the beam divergence is the energy/temperature of the extracted negative ions, so it is believed that plasma differences between the two source types play a role. Research is focused on the plasma parameters in the ion source. One RF driver, identical to the ones used in SPIDER, installed in a relatively small-scale experimental set-up, inherently more flexible than large devices, is starting operations devoted to the investigation of the properties of RF-generated plasmas, so as to contribute to the assessment of negative ion precursors, and of their relationship with the plasma parameters, particularly when enhancing plasma confinement. The scientific questions, that have arisen from the preliminary results of SPIDER, guided the design of the test stand, which are described in this contribution, together with the diagnostic systems and related simulation tools. The test stand, which shares with the larger experiment all the geometrical features and constraints, will allow technological developments and optimized engineering solutions related to the ICP design for the ITER NBIs.

The immunogenicity and reactogenicity of two influenza vaccines were evaluated in a randomised, double-blind trial in north-east Italy during winter 2005–2006. Of 238 adult subjects (18–60 years of age) with underlying chronic diseases, 120 received MF59-adjuvanted subunit vaccine (Sub/MF59) and 118 received conventional subunit vaccine (Subunit). At 4 weeks post-vaccination, geometric mean titres (GMT) were significantly ( P < 0.001) increased for both groups. For the A/H3N2 and B strains, significantly ( P < 0.02) higher GMT were reported for the Sub/MF59 group. The mean-fold increase in titre, the percentage of subjects with at least a four-fold titre increase and the seroprotection rate (≥1:40) were also higher in the Sub/MF59 group, with the seroprotection rate and four-fold titre increase achieving significance ( P = 0.002 and P = 0.02, respectively) for the A/H3N2 strain. Our results suggest that adults affected by chronic diseases can mount a satisfactory immune response to influenza vaccines, and that these vaccines are well tolerated. Addition of the MF59-adjuvant, however, enhances the immunogenicity of subunit influenza vaccine, conferring superior protection than a conventional subunit vaccine in this population, who are at high-risk of influenza-related complications.

The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.

Polyoxometalates (POMs) were used, together with chitosan (CS), to obtain hybrid nanoaggregates. Three representative POMs were efficiently assembled into nanoparticles of few hundred nm diameter, featuring entangled ribbons substructure. In order to establish suitable preparation and stability conditions, the assemblies were characterized in solution by UV–Vis spectroscopy, dynamic light scattering and ζ-potential. The nanoparticles were tested against E.   coli (10 6  CFU/ml) in aqueous solution, showing a synergic activity of the heteropolyacid H 5 PMo 10 V 2 O 40 and CS. For such components, a highly porous and antibacterial film was obtained upon lyophilisation of the colloidal mixture.