Altered expression of antioxidant enzymes and autophagic proteins in transglutaminase 2 knockout mice

""Background. Transglutaminases (TGs) are ubiquitous calcium-dependent acyl-transferases, catalysing post-translational protein modifications. Among the family members, TG2 (or "tissue" transglutaminase) acts as a multifunctional protein regulating cell processes, including autophagy [1,2]. . TG2 is highly expressed in the nervous tissue and reportedly involved in neurodegenerative disorders [3]. Indeed, the pathophysiology of these diseases includes insoluble aggregate formation, and covalent cross-linking of pathogenic proteins by TG2 has been suggested. Another hallmark of neurodegeneration is dysregulated autophagy, thus making the role played by TG2 in this cellular process especially relevant. Interestingly, conditions promoting TG2 activity, such as low GTP and high calcium levels, associated with oxidative stress, occur in neurodegeneration. . The present study aims to clarify the role of TG2 in redox balance and autophagy. To this purpose, the expression levels of antioxidant enzymes and pro-autophagic proteins were investigated in various brain regions and liver of TG2-\\\/- mice. . . Materials and methods. Expression of antioxidant enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), catalase (CAT) and glutathione peroxidase 1 (GPX1), and autophagic proteins (Beclin1, LC3 and AMBRA1) were evaluated by Western blotting (WB) and immunohistochemistry in selected brain areas (neocortex, hippocampus, brainstem, and cerebellum) and liver of 12-month-old TG2-\\\/- and wild-type mice.. . Results. WB and immunohistochemical data reveal altered expression patterns of antioxidant enzymes in both liver and brain tissues. Of particular interest is the statistically significant decrease of CAT and SOD2 in the cerebellum and hippocampus of TG2-\\\/- mice, while unchanged levels of these proteins are detected in the neocortex and brainstem. In the knockout liver, even more dramatic reduction of CAT and SOD2 expression is found, while SOD1 is intriguingly upregulated. Concerning the effect of TG2 deletion on autophagy, Beclin1 is down-regulated in the neocortex and hippocampus of knockout mice.. . Conclusions. Overall, our data on TG2-\\\/- mice support the involvement of the transamidating enzyme in controlling redox balance of different organs, and in regulating autophagic flux [1-3]. The specific decrease in the peroxisomal enzyme CAT and in the mitochondrial protein SOD2 emphasizes the role of these organelles in oxidative stress management and their interplay in cell metabolism. Moreover, region-based differences in the effect of TG2 deletion may reflect multiple functions related to the organ, tissue and cell type.. "

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an up- regulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition in- dexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) “Dino Amadori”, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

Calibration of the LIGO strain data was performed with a GstLAL-based calibration software pipeline (Viets et al. 2018). Calibration of the Virgo strain data was performed with C-based software (Acernese et al. 2022b). Data quality products and event-validation results were computed using the DMT (https://labcit.ligo.caltech.edu/~jzweizig/DMT-Project. html), DQR (https://docs.ligo.org/detchar/data-quality-report/), DQSEGDB (Fisher et al. 2021), gwdetchar (Macloed et al. 2021a), hveto (Smith et al. 2011), iDQ (Essick et al. 2020), and Omicron (Robinet et al. 2020) software packages and contribut- ing software tools. Analyses relied upon the LALSuite software library (LIGO Scientific Collaboration 2018). PESummary was used to postprocess and collate parameter estimation results (Hoy & Raymond 2021). For an exhaustive list of the software used for searching the GW signals and characterizing their source, see Abbott et al. (2021c). Plots were prepared with Matplotlib (Hunter 2007), seaborn (Waskom 2021), GWSumm (Macleod et al. 2021b), and GWpy (Macleod et al. 2021c). NumPy (Harris et al. 2020) and SciPy (Virtanen et al. 2020) were used in the preparation of the manuscript. This material is based upon work supported by NSF’s LIGO Laboratory which is a major facility fully funded by the National Science Foundation. The authors also gratefully acknowledge the support of the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max- Planck-Society (MPS), and the State of Niedersachsen/ Germany for support of the construction of Advanced LIGO and construction and operation of the GEO 600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowl- edge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS), and the Netherlands Organization for Scientific Research (NWO) for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación (AEI), the Spanish Ministerio de Ciencia e Innovación and Ministerio de Universidades, the Conselleria de Fons Europeus, Universitat i Cultura and the Direcció General de Política Universitaria i Recerca del Govern de les Illes Balears, the Conselleria d'Innovació, Universitats, Ciència i Societat Digital de la Generalitat Valenciana and the CERCA Programme Generalitat de Catalunya, Spain, the National Science Centre of Poland and the European Union – European Regional Development Fund; Foundation for Polish Science (FNP), the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Social Funds (ESF), the European Regional Development Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the French Lyon Institute of Origins (LIO), the Belgian Fonds de la Recherche Scientifique (FRS- FNRS), Actions de Recherche Concertées (ARC) and Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO), Belgium, the Paris Île-de-France Region, the National Research, Development and Innovation Office Hungary (NKFIH), the National Research Foundation of Korea, the Natural Science and Engineering Research Council Canada, Canadian Founda- tion for Innovation (CFI), the Brazilian Ministry of Science, Technology, and Innovations, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP-SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan, the United States Department of Energy, and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, INFN, and CNRS for provision of computational resources. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to- Core Program A, Advanced Research Networks, JSPS Grant- in-Aid for Scientific Research (S) 17H06133 and 20H05639, JSPS Grant-in-Aid for Transformative Research Areas (A) 20A203: JP20H05854, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF), Computing Infrastruc- ture Project of Global Science experimental Data hub Center (GSDC) at KISTI, Korea Astronomy and Space Science Institute (KASI), and Ministry of Science and ICT (MSIT) in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the National Science and Technology Council (NSTC) in Taiwan under grants including the Rising Star Program and Science Vanguard Research Program, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK.Peer reviewe

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Thyroid pathologies in nuclear medicine

The presented work describes the thyroid pathologies and the nuclear-medical diagnostic approach, in order to obtain a differential diagnosis and the monitoring of various neoplasms; specifically, it describes the importance of radiometabolic treatment with iodine 131, after thyroidectomy surgery. Through a study conducted in patients suffering from thyroid disease, undergoing metabolic radiotherapy, it is shown that, with equal distribution of radioiodine, uptake with at least 3700 MBq of therapeutic dose is obtained. All this can be seen through the whole body scintigraphic framework, obtained through the use of the double-headed gamma camera with collimators for high emission energies. Radiometabolic treatment is effective in patients with a high risk of relapse, while radioiodine treatment is not recommended in low-risk patients.</jats:p

Nuclear medicine in the pediatric field

The work presented describes the main ways of preparing radiopharmaceuticals and carrying out nuclear-medical examinations in pediatric patients. Through the differences in the execution of the tests, the importance of dosimetry is revealed, i.e. the diagnostic reference levels, in which the percentage of activity that must be administered to the child on the basis of that introduced in the adult is indicated. Through a study performed on pediatric patients, subjected to nuclear-medical investigations, the validity of the LDRs is reported according to the scheme in tab. 6 (EANM-EUROPEAN ASSOCIATION OF NUCLEAR MEDICINE). Through a study conducted in pediatric patients, subjected to medical - nuclear investigations, the importance of the dose is noted in order to obtain greater benefits in the patient and high quality images for diagnostic purposes. By carrying out pediatric-radiopharmaceutical calculations, it is possible to reproduce the aforementioned, ie an optimization of the dose. Using body surface area Child's body surface area (m2) _______________________________ = 0.53g: 1.8 g = 29% - 2.9 mCi Adult's body surface area (m2) Using organ weight Target organ weight of child (g) = 93 g: 310g = 30% - 3.0 mCi Target organ weight of adult (g)</jats:p