Regulation mechanisms of human D-amino acid oxidase

The human peroxisomal FAD-dependent enzyme D-amino acid oxidase (hDAAO, EC 1.4.3.3) plays a key role in important physiological processes by catalyzing the stereospecific degradation of several D-amino acids (D-AAs). A number of studies demonstrated that a dysregulation in processes regulating D-AAs concentration is related to the mechanism(s) predisposing to several pathologies. The important role played by hDAAO in modulating D-AAs levels increased the interest for this flavoenzyme: while structural and biochemical properties have been extensively investigated, several aspects in the modulation of its functionality remain elusive. Furthermore, it has been recently suggested that DAAO could be mistargeted to the nucleus or secreted in the (mouse) intestinal lumen, where it could select the composition of gut microbiota by generating H2O2. Here, some biochemical properties of the recombinant enzyme were investigated. Moreover, we focused on mistargeting of DAAO by studying a variant lacking the N-terminal signal peptide (thus shedding light on the mechanism of microbiota selection) and two variants at position 120 (a residue belonging to a putative nuclear translocation signal): the cellular targeting of the flavoenzyme seems a way to modulate hDAAO functionality. This modulation allows hDAAO to fulfil different physiological functions, such as the control of the level of D-Ser in the brain and of other D-AAs in different tissues or the selection of microbiota in the gut

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

In 2002, the novel human gene G72 was associated with schizophrenia susceptibility. This gene encodes a small protein of 153 amino acids, named pLG72, which represents a rare case of primate-specific protein. In particular, the rs2391191 single nucleotide polymorphism (resulting in in the R30K substitution) was robustly associated to schizophrenia and bipolar disorder. In this review, we aim to summarize the results of 20 years of biochemical investigations on pLG72. The main known role of pLG72 is related to its ability to bind and inactivate the flavoenzyme d-amino acid oxidase, i.e., the enzyme that controls the catabolism of d-serine, the main NMDA receptor coagonist in the brain. pLG72 was proposed to target the cytosolic form of d-amino acid oxidase for degradation, preserving d-serine and protecting the cell from oxidative stress generated by hydrogen peroxide produced by the flavoenzyme reaction. Anyway, pLG72 seems to play additional roles, such as affecting mitochondrial functions. The level of pLG72 in the human body is still a controversial issue because of its low expression and challenging detection. Anyway, the intriguing hypothesis that pLG72 level in blood could represent a suitable marker of Alzheimer's disease progression (a suggestion not sufficiently established yet) merits further investigations

Biochemical and Biophysical Characterization of Recombinant Human 3-Phosphoglycerate Dehydrogenase

The human enzyme D-3-phosphoglycerate dehydrogenase (hPHGDH) catalyzes the reversible dehydrogenation of 3-phosphoglycerate (3PG) into 3-phosphohydroxypyruvate (PHP) using the NAD+/NADH redox cofactor, the first step in the phosphorylated pathway producing L-serine. We focused on the full-length enzyme that was produced in fairly large amounts in E. coli cells; the effect of pH, temperature and ligands on hPHGDH activity was studied. The forward reaction was investigated on 3PG and alternative carboxylic acids by employing two coupled assays, both removing the product PHP; 3PG was by far the best substrate in the forward direction. Both PHP and α-ketoglutarate were efficiently reduced by hPHGDH and NADH in the reverse direction, indicating substrate competition under physiological conditions. Notably, neither PHP nor L-serine inhibited hPHGDH, nor did glycine and D-serine, the coagonists of NMDA receptors related to L-serine metabolism. The investigation of NADH and phosphate binding highlights the presence in solution of different conformations and/or oligomeric states of the enzyme. Elucidating the biochemical properties of hPHGDH will enable the identification of novel approaches to modulate L-serine levels and thus to reduce cancer progression and treat neurological disorders

Shock identification and classification in 2D magnetohydrodynamiccompressible turbulence—Orszag–Tang vortex

Compressible magnetohydrodynamic (MHD) turbulence is a common feature of astrophysical systems such as the solar atmosphere and interstellar medium. Such systems are rife with shock waves that can redistribute and dissipate energy. For an MHD system, three broad categories of shocks exist (slow, fast, and intermediate); however, the occurrence rates of each shock type are not known for turbulent systems. Here, we present a method for detecting and classifying the full range of MHD shocks applied to the Orszag–Tang vortex. Our results show that the system is dominated by fast and slow shocks, with far less-frequent intermediate shocks appearing most readily near magnetic reconnection sites. We present a potential mechanism that could lead to the formation of intermediate shocks in MHD systems, and study the coherency and abundances of shocks in compressible MHD turbulence

A Python approach for solar data analysis: SUNDARA (SUNDish Active Region Analyser), preliminary development

This technical note describes the Python package SUNDARA (SUNDish Active Region Analyser), a sophisticated code - fully self-consistent - aimed at the data analysis of solar images. This analysis is crucial for the INAF Proposal "SunDish Project" (PI: A. Pellizzoni), active since 2018 and devoted to imaging and monitoring the solar atmosphere at high radio frequencies (at present 18 - 26 GHz) through single-dish observations with INAF radio telescopes (SRT and Medicina). SUNDARA, characterised by a very user-friendly widget, allows to automatically unearth Active Regions (ARs) across the solar disk (or on its edge) through several algorithms; these ARs are modelled through an elliptical 2D-Gaussian kernel. In little more than 5 minutes, SUNDARA produces a complete analysis of a solar map, saving a directory containing images, plots and several tables with physical information of the solar disk and ARs (brightness temperatures, fluxes and spectral indices, with respective errors). A deeper analysis (that can be completed in a few hours) is possible thanks to a Bayesian approach based on Markov Chain MonteCarlo (MCMC) simulations. Moreover, these identified ARs are automatically associate in position with the detected ARs at other observing frequencies, reported in the Heliophysics Event Knowledgebase (HEK) used by the astrophysics and solar physics communities. SUNDARA has been successfully tested on a large amount of data from solar maps implemented with the radio telescopes of the INAF Network. For the purposes of this technical note, we report only two cases (one for Medicina, and one for SRT). This Python package constitutes a crucial tool for the INAF Network to analyse solar images (the Space Weather monitoring network and forecast along the solar cycle will be soon available), and to provide a complete overview of the astrophysical phenomena

Serine metabolism during differentiation of human iPSC-derived astrocytes

: Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations

A dedicated pipeline to analyse solar data with INAF radio telescopes: SUNPIT (SUNdish PIpeline Tool)

This technical note describes SUNPIT (SUNdish PIpeline Tool) - the pipeline aimed at the imaging procedure and the data analysis of the radio solar data - and guides the user to properly reduce and analyse the solar data. SUNPIT is designed for radio data acquired with some radio telescopes of the INAF Network: the Sardinia Radio Telescope (SRT), and the Medicina Radio Telescope. The present user manual follows the development of software for solar imaging and data analysis of Active Regions (ARs), performed in the framework of the INAF Proposal "SunDish Project" (PI: A. Pellizzoni). This project has been active since 2018 with the goal of monitoring the solar atmosphere at high radio frequencies (at present 18 - 26 GHz) through single-dish observations. These solar observations will be enhanced through the upgrading of SRT with the new cryogenically cooled receivers, including a 19-feed in Q-band (33 - 50 GHz) and a 16-feed in W-band (75 - 116 GHz), in the context of the National Operative Programme (Programma Operativo Nazionale-PON); this project will provide in the near future an upgrading with the new receivers up to 116 GHz also for the Medicina and Noto Radio Telescopes, to provide the scientific community with the instrumentation suited to the study of the Universe at high radio frequencies. SUNPIT will be suitable for the data of these new forthcoming receivers, when available for the scientific community. SUNPIT produces a complete analysis of a solar map in about one hour, saving a directory which contains images, plots and several tables with the physical information of the solar disk and ARs (brightness temperatures, fluxes and spectral indices, with the respective errors). This pipeline – successfully tested – represents a crucial tool (1) to analyse solar images observed with the radio telescopes of the INAF Network, and (2) for the Space Weather monitoring network and forecast (soon available) along the solar cycle

C-band observations of supernova remnants with SRT: 2 - Calibrations

Following to the Astronomical Validation report n°6 (AV-rep-006; Egron et al. 2015) dedicated to the C-band imaging performances of SRT through the observation of two Supernova Remnants (3C157 and W44), this second note is devoted to the calibration of the resulting maps

C-band observations of supernova remnants with SRT: 1 - Imaging performances

We report on observations of Supernova Remnants (SNR) with SRT in the frame of Astronomical Validation (AV) test activities. These tests are aimed to assess single-dish imaging performances of “SRT first light receivers” coupled with Total Power (TP) backend and related hw/sw subsystems/procedures (including innovative ad hoc imaging techniques based on OTF scans)

Modelling high-resolution spatially-resolved Supernova Remnant spectra with the Sardinia Radio Telescope

Supernova Remnants (SNRs) exhibit spectra featured by synchrotron radio emission arising from the relativistic electrons, and high-energy emission from both leptonic (Bremsstrahlung and Inverse Compton) and hadronic processes (π0 mesons decay) which are a direct signature of cosmic rays acceleration. Thanks to radio single-dish imaging observations obtained in three frequency bands (1.6, 7, 22 GHz) with the Sardinia Radio Telescope (www.srt.inaf.it), we can model different SNR regions separately. Indeed, in order to disentangle interesting and peculiar hadron contributions in the high-energy spectra (gamma-ray band) and better constrain SNRs as cosmic rays emitters, it is crucial to fully constrain lepton contributions first through radio-observed parameters. In particular, the Bremsstrahlung and Inverse Compton bumps observed in gamma-rays are bounded to synchrotron spectral slope and cut-off in the radio domain. Since these parameters vary for different SNR regions and electron populations, spatially-resolved radio spectra are then required for accurate multi-wavelength modelling