Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

Towards a plug&play solution for real-time precise positioning on mass-market devices

Despite pedestrian and vehicle navigation are the key applications enabled by the development of GNSS technology, the best approach to obtain accurate, reliable, continuous and robust PVT (Position-Velocity-Timing) solutions for this purpose has yet to be identified. The real limiting factor is the environment in which the users usually navigate: e.g. multipath effects and cycle slips in harsh urban environments strongly affect, respectively, pseudorange measurements and the continuity of carrier-phase observations. Therefore, positioning services relying on code-based algorithms cannot always meet the required accuracy - which varies depending on the targeted use case -; on the other hand, phase-based approaches as Real-Time Kinematic (RTK) and Precise Point Positioning (PPP) require strong effort to deal with the ambiguity term and its reinitialization when cycle slips occur. These problems are amplified when GNSS measurements from Android smartphone are considered due to the low-cost, linearly polarized and multi-purpose antenna which inevitably impacts on the quality of GNSS observables. This paper focuses on the performance analysis of GNSS POWER - an algorithm based on the loosely coupling between Single Point Positioning (SPP) solutions and variometric velocity - combined with IGS SSR corrections to increase the accuracy achievable in a real-time stand-alone solution. The integration of SSR corrections within GNSS POWER algorithm is validated in both static and kinematic scenarios using high-end GNSS receivers and Andorid smartphones. The results demonstrated the advantages of using SSR corrections on SPP and GNSS POWER solutions also on Android devices opening to new applications of real-time stand-alone positioning approaches on mass-market devices

Use of the KlADH4 promoter for ethanol-dependent production of recombinant human serum albumine in Kluyveromyces lactis

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity which is specifically induced by ethanol. The promoter of this gene was used for the expression of heterologous proteins in K. lactis, a very promising organism which can be used as an alternative host to Saccharomyces cerevisiae due to its good secretory properties. In this paper we report the ethanol-driven expression in K. lactis of the bacterial beta-glucuronidase and of the human serum albumin (HSA) genes under the control of the KlADH4 promoter. In particular, we studied the extracellular production of recombinant HSA (rHSA) with integrative and replicative vectors and obtained a significant increase in the amount of the protein with multicopy vectors, showing that no limitation of KlADH4 trans-acting factors occurred in the cells. By deletion analysis of the promoter, we identified an element (UASE) which is sufficient for the induction of KlADH4 by ethanol and, when inserted in the respective promoters, allows ethanol-dependent activation of other yeast genes, such as PGK and LAC4. We also analyzed the effect of medium composition on cell growth and protein secretion. A clear improvement in the production of the recombinant protein was achieved by shifting from batch cultures (0.3 g/liter) to fed-batch cultures (1 g/liter) with ethanol as the preferred carbon source

Advances in Catalytic Routes for the Homogeneous Green Conversion of the Bio-Based Platform 5-Hydroxymethylfurfural

5-Hydroxymethylfufural (HMF) is an intriguing platform molecule that can be obtained from biomasses and that can lead to the production of a wide range of products, intermediates, or monomers. The presence of different moieties in HMF (hydroxy, aldehyde, furan ring) allows to carry out different transformations such as selective oxidations and hydrogenations, reductive aminations, etherifications, decarbonylations, and acetalizations. This is a great chance in a biorefinery perspective but requires the development of active and highly selective catalysts. In this view, homogeneous catalysis can lead to efficient conversion of HMF at mild reaction conditions. This Review discussed the recent achievements in homogeneous catalysts development and application to HMF transformations. The effects of metal nature, ligands, solvents, and reaction conditions were reported and critically reviewed. Current issues and future chances have been presented to drive future studies toward more efficient and scalable processes

Indirect Self-Modulation Instability Measurement Concept for the AWAKE Proton Beam

AWAKE, the Advanced Proton-Driven Plasma Wakefield Acceleration Experiment, is a proof-of-principle R&D experiment at CERN using a 400 GeV/c proton beam from the CERN SPS (longitudinal beam size sigma_z = 12 cm) which will be sent into a 10 m long plasma section with a nominal density of approx. 7x10^14 atoms/cm3 (plasma wavelength lambda_p = 1.2mm). In this paper we show that by measuring the time integrated transverse profile of the proton bunch at two locations downstream of the AWAKE plasma, information about the occurrence of the self-modulation instability (SMI) can be inferred. In particular we show that measuring defocused protons with an angle of 1 mrad corresponds to having electric fields in the order of GV/m and fully developed self-modulation of the proton bunch. Additionally, by measuring the defocused beam edge of the self-modulated bunch, information about the growth rate of the instability can be extracted. If hosing instability occurs, it could be detected by measuring a non-uniform defocused beam shape with changing radius. Using a 1 mm thick Chromox scintillation screen for imaging of the self-modulated proton bunch, an edge resolution of 0.6 mm and hence a SMI saturation point resolution of 1.2 m can be achieved.Comment: 4 pages, 4 figures, EAAC conference proceeding

Evaluating the user experience of acoustic data transmission A study of sharing data between mobile devices using sound

Users of smart devices frequently need to exchange data with people nearby to them. Yet despite the availability of various communication methods, data exchange between co-located devices is often complicated by technical and user experience barriers. A potential solution to these issues is the emerging technology of device-to-device acoustic data transmission. In this work, we investigate the medium-specific properties of sound as a data exchange mechanism, and question how these contribute to the user experience of sharing data. We present a user study comparing three wireless communication technologies (acoustic data transmission, QR codes and Bluetooth), when used for a common and familiar scenario: peer-to-peer sharing of contact information. Overall, the results show that acoustic data transmission provides a rapid means of transferring data (mean transaction time of 2.4 s), in contrast to Bluetooth (8.3 s) and QR (6.3 s), whilst requiring minimal physical effort and user coordination. All QR code transactions were successful on the first attempt; however, some acoustic (5.6%) and Bluetooth (16.7%) transactions required multiple attempts to successfully share a contact. Participants also provided feedback on their user experience via surveys and semi-structured interviews. Perceived transaction time, physical effort, and connectivity issues. Specifically, users expressed frustration with Bluetooth due to device selection issues, and with QR for the physical coordination required to scan codes. The findings indicate that acoustic data transmission has unique advantages in facilitating information sharing and interaction between co-located users

Creating Non-Believed Memories for Recent Autobiographical Events

A recent study showed that many people spontaneously report vivid memories of events that they do not believe to have occurred [1]. In the present experiment we tested for the first time whether, after powerful false memories have been created, debriefing might leave behind nonbelieved memories for the fake events. In Session 1 participants imitated simple actions, and in Session 2 they saw doctored video-recordings containing clips that falsely suggested they had performed additional (fake) actions. As in earlier studies, this procedure created powerful false memories. In Session 3, participants were debriefed and told that specific actions in the video were not truly performed. Beliefs and memories for all critical actions were tested before and after the debriefing. Results showed that debriefing undermined participants' beliefs in fake actions, but left behind residual memory-like content. These results indicate that debriefing can leave behind vivid false memories which are no longer believed, and thus we demonstrate for the first time that the memory of an event can be experimentally dissociated from the belief in the event's occurrence. These results also confirm that belief in and memory for an event can be independently-occurring constructs

Gait-related frequency modulation of beta oscillatory activity in the subthalamic nucleus of parkinsonian patients

Background: Abnormal beta band activity in the subthalamic nucleus (STN) is known to be exaggerated in patients with Parkinson's disease, and the amplitude of such activity has been associated with akinetic rigid symptoms. New devices for deep brain stimulation (DBS) that operate by adapting the stimulation parameters generally rely on the detection of beta activity amplitude modulations in these patients. Movement-related frequency modulation of beta oscillatory activity has been poorly investigated, despite being an attractive variable for extracting information about basal ganglia activity. Objective: We studied the STN oscillatory activity associated with locomotion and proposed a new approach to extract movement related information from beta band activity. Methods: We recorded bilateral local field potential of the STN in eight parkinsonian patients implanted with DBS electrodes during upright quiet standing and unperturbed walking. Neurophysiological recordings were combined with kinematic measurements and individual molecular brain imaging studies. We then determined the information carried by the STN oscillatory activity about locomotion and we identified task-specific biomarkers. Results: We found a gait-related peak frequency modulation of the beta band of STN recordings of parkinsonian patients. This novel biomarker and the associated power modulations were highly informative to detect the walking state (with respect to standing) in each single patient. Conclusion: Frequency modulation in the human STN represents a fundamental aspect of information processing of locomotion. Our information-driven approach could significantly enrich the spectrum of Parkinson's neural markers, with input signals encoding ongoing tasks execution for an appropriate online tuning of DBS delivery