Factors associated with long-term pessary use

Vaginal pessary is a well-established pelvic organ prolapse (POP) treatment, but little evidence about long-term use is available. Our aim was to report the duration of use and investigate predictors of long-term pessary use for POP. We hypothesized that younger, healthier women and women who experienced complications would have shorter duration of use

Hawberry (Crataegus monogyna Jaqc.) extracts inhibit lipid oxidation and improve consumer liking of ready-to-eat (RTE) pork patties

The objective of this work was to study the effectiveness of extracts from hawberry (Crataegus monogyna Jacq.) to inhibit lipid oxidation and odor deterioration during processing of ready-to-eat (RTE) pork patties subjected to roasting (180 °C/16 min), chilling (10 days/+3 °C) and reheating in microwave (600 mW/1 min). Acetone extracts of hawberry were chosen based on their total phenolic content (1281.1 ± 84.8 mg gallic acid equivalent (GAE)/100 g fruit) and in vitro antiradical activity (DPPH) (53.33 ± 15.40 g equivalent Trolox per g of fruits). Pork patties treated with increasing concentrations of hawberry extract, 200 and 800 ppm GAE (T2 and T8, respectively) and a control group (T0) of samples, were analyzed for TBARS, volatile carbonyls and odor liking in a consumer test. Hawberry extracts significantly improved the oxidative stability of cooked pork patties keeping TBARS and hexanal counts at basal levels during the whole process. The addition of hawberry phenolic-rich extracts significantly improved the degree of consumer satisfaction regarding the odor of patties. In conclusion, the hawberry extract displayed potential usage as an ingredient with antioxidant properties for the manufacture of high-quality RTE meat products. © 2017, Association of Food Scientists & Technologists (India)

Biomarkers of the Endocannabinoid System in Substance Use Disorders

Despite substance use disorders (SUD) being one of the leading causes of disability and mortality globally, available therapeutic approaches remain ineffective. The difficulty in accurately characterizing the neurobiological mechanisms involved with a purely qualitative diagnosis is an obstacle to improving the classification and treatment of SUD. In this regard, identifying central and peripheral biomarkers is essential to diagnosing the severity of drug dependence, monitoring therapeutic efficacy, predicting treatment response, and enhancing the development of safer and more effective pharmacological tools. In recent years, the crucial role that the endocannabinoid system (ECS) plays in regulating the reinforcing and motivational properties of drugs of abuse has been described. This has led to studies characterizing ECS alterations after exposure to various substances to identify biomarkers with potential diagnostic, prognostic, or therapeutic utility. This review aims to compile the primary evidence available from rodent and clinical studies on how the ECS components are modified in the context of different substance-related disorders, gathering data from genetic, molecular, functional, and neuroimaging experimental approaches. Finally, this report concludes that additional translational research is needed to further characterize the modifications of the ECS in the context of SUD, and their potential usefulness in the necessary search for biomarkers

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

<p>Abstract</p> <p>Background</p> <p>Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy.</p> <p>Methods</p> <p>To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC.</p> <p>Results</p> <p>The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression.</p> <p>Conclusion</p> <p>This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.</p

Insights from the first flaring activity of a high synchrotron peaked blazar with X-ray polarization and VHE gamma rays

Abe, K. et al.-- Full list of authors: MAGIC Collaboration; Abe, K.; Abe, S.; Abhir, J.; Abhishek, A.; Acciari, V. A.; Aguasca-Cabot, A.; Agudo, I.; Aniello, T.; Ansoldi, S.; Antonelli, L. A.; Arbet Engels, A.; Arcaro, C.; Asano, K.; Babić, A.; Barres de Almeida, U.; Barrio, J. A.; Barrios-Jiménez, L.; Batković, I.; Baxter, J.; Becerra González, J.; Bednarek, W.; Bernardini, E.; Bernete, J.; Berti, A.; Besenrieder, J.; Bigongiari, C.; Biland, A.; Blanch, O.; Bonnoli, G.; Bošnjak, Ž.; Bronzini, E.; Burelli, I.; Campoy-Ordaz, A.; Carosi, A.; Carosi, R.; Carretero-Castrillo, M.; Castro-Tirado, A. J.; Cerasole, D.; Ceribella, G.; Chai, Y.; Chilingarian, A.; Cifuentes, A.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; D'Ammando, F.; D'Amico, G.; da Vela, P.; Dazzi, F.; de Angelis, A.; de Lotto, B.; de Menezes, R.; Delfino, M.; Delgado, J.; Delgado Mendez, C.; di Pierro, F.; di Tria, R.; di Venere, L.; Dinesh, A.; Dominis Prester, D.; Donini, A.; Dorner, D.; Doro, M.; Eisenberger, L.; Elsaesser, D.; Escudero, J.; Fariña, L.; Foffano, L.; Font, L.; Fröse, S.; Fukazawa, Y.; García López, R. J.; Garczarczyk, M.; Gasparyan, S.; Gaug, M.; Giesbrecht Paiva, J. G.; Giglietto, N.; Giordano, F.; Gliwny, P.; Godinović, N.; Gradetzke, T.; Grau, R.; Green, D.; Green, J. G.; Günther, P.; Hadasch, D.; Hahn, A.; Hassan, T.; Heckmann, L.; Herrera Llorente, J.; Hrupec, D.; Imazawa, R.; Israyelyan, D.; Itokawa, T.; Jiménez Martínez, I.; Jiménez Quiles, J.; Jormanainen, J.; Kankkunen, S.; Kayanoki, T.; Kerszberg, D.; Khachatryan, M.; Kluge, G. W.; Kobayashi, Y.; Konrad, J.; Kouch, P. M.; Kubo, H.; Kushida, J.; Láinez, M.; Lamastra, A.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, R.; López-Moya, M.; López-Oramas, A.; Loporchio, S.; Lorini, A.; Lyard, E.; Majumdar, P.; Makariev, M.; Maneva, G.; Manganaro, M.; Mangano, S.; Mannheim, K.; Mariotti, M.; Martínez, M.; Maruševec, P.; Mas-Aguilar, A.; Mazin, D.; Menchiari, S.; Mender, S.; Miceli, D.; Miranda, J. M.; Mirzoyan, R.; Molero González, M.; Molina, E.; Mondal, H. A.; Moralejo, A.; Nakamori, T.; Nanci, C.; Neustroev, V.; Nickel, L.; Nievas Rosillo, M.; Nigro, C.; Nikolić, L.; Nilsson, K.; Nishijima, K.; Njoh Ekoume, T.; Noda, K.; Nozaki, S.; Okumura, A.; Paiano, S.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Peresano, M.; Persic, M.; Pihet, M.; Pirola, G.; Podobnik, F.; Prada Moroni, P. G.; Prandini, E.; Principe, G.; Rhode, W.; Ribó, M.; Rico, J.; Righi, C.; Sahakyan, N.; Saito, T.; Saturni, F. G.; Schmuckermaier, F.; Schubert, J. L.; Sciaccaluga, A.; Silvestri, G.; Sitarek, J.; Sliusar, V.; Sobczynska, D.; Stamerra, A.; Strišković, J.; Strom, D.; Strzys, M.; Suda, Y.; Tajima, H.; Takahashi, M.; Takeishi, R.; Temnikov, P.; Terauchi, K.; Terzić, T.; Teshima, M.; Truzzi, S.; Tutone, A.; Ubach, S.; van Scherpenberg, J.; Ventura, S.; Verna, G.; Viale, I.; Vigliano, A.; Vigorito, C. F.; Vitale, V.; Vovk, I.; Walter, R.; Wersig, F.; Will, M.; Yamamoto, T.; Yeung, P. K. H.; Other Groups; Collaborations; Liodakis, I.; Middei, R.; Kiehlmann, S.; Gesu, L. D.; Kim, D. E.; Ehlert, S. R.; Saade, M. L.; Kaaret, P.; Maksym, W. P.; Chen, C. T.; de La Calle Pérez, I.; Perri, M.; Verrecchia, F.; Domann, O.; Dürr, S.; Feige, M.; Heidemann, M.; Koppitz, O.; Manhalter, G.; Reinhart, D.; Steineke, R.; Lorey, C.; McCall, C.; Jermak, H. E.; Steele, I. A.; Fallah Ramazani, V.; Otero-Santos, J.; Morcuende, D.; Aceituno, F. J.; Casanova, V.; Sota, A.; Jorstad, S. G.; Marscher, A. P.; Pauley, C.; Sasada, M.; Kawabata, K. S.; Uemura, M.; Mizuno, T.; Nakaoka, T.; Akitaya, H.; Myserlis, I.; Gurwell, M.; Keating, G. K.; Rao, R.; Angelakis, E.; Kraus, A.Context. Blazars exhibit strong variability across the entire electromagnetic spectrum, including periods of high-flux states commonly known as flares. The physical mechanisms in blazar jets responsible for flares remain poorly understood to date.Aims. Our aim is to better understand the emission mechanisms during blazar flares using X-ray polarimetry and broadband observations from the archetypical TeV blazar Mrk 421, which can be studied with higher accuracy than other blazars that are dimmer and/or located farther away.Methods. We studied a flaring activity from December 2023 that was characterized from radio to very high-energy (VHE; E > 0.1 TeV) gamma rays with MAGIC, Fermi-LAT, Swift, XMM-Newton, and several optical and radio telescopes. These observations included, for the first time for a gamma-ray flare of a blazar, simultaneous X-ray polarization measurements with IXPE, in addition to optical and radio polarimetry data. We quantify the variability and correlations among the multi-band flux and polarization measurements, and describe the varying broadband emission within a theoretical scenario constrained by the polarization data.Results. We find substantial variability in both X-rays and VHE gamma rays throughout the campaign, with the highest VHE flux above 0.2 TeV occurring during the IXPE observing window, and exceeding twice the flux of the Crab Nebula. However, the VHE and X-ray spectra are on average softer, and the correlation between these two bands is weaker than those reported in the previous flares of Mrk 421. IXPE reveals an X-ray polarization degree significantly higher than that at radio and optical frequencies, similar to previous results for Mrk 421 and other high synchrotron peaked blazars. Differently to past observations, the X-ray polarization angle varies by ∼100° on timescales of days, and the polarization degree changes by more than a factor of 4. The highest X-ray polarization degree, analyzed in 12 h time intervals, reaches 26 ± 2%, around which an X-ray counter-clockwise hysteresis loop is measured with XMM-Newton. It suggests that the X-ray emission comes from particles close to the high-energy cutoff, hence possibly probing an extreme case of the Turbulent Extreme Multi-Zone model for which the chromatic trend in the polarization may be more pronounced than theoretically predicted. We model the broadband emission with a simplified stratified jet model throughout the flare. The polarization measurements imply an electron distribution in the X-ray emitting region with a very high minimum Lorentz factor (γ ′ min ≳ 10 4 ), which is expected in electron-ion plasma, as well as a variation of the emitting region size of up to a factor of 3 during the flaring activity. We find no correlation between the fluxes and the evolution of the model parameters, which indicates a stochastic nature of the underlying physical mechanism that likely explains the lack of a tight X-ray/VHE correlation during this flaring activity. Such behavior would be expected in a highly turbulent electron-ion plasma crossing a shock front. © The Authors 2025A. Arbet Engels: project management, P.I. of MAGIC observations, organization of multi-wavelength observations and data analysis, MAGIC analysis, correlation analysis, theoretical modeling and interpretation, paper drafting; I. Liodakis: organization of multi-wavelength observations and data analysis; L. Heckmann: project management, MAGIC and Fermi-LAT data analysis, variability analysis, theoretical interpretation, paper drafting; D. Paneque: organization of the MWL observations, theoretical interpretation, paper drafting; The rest of the authors have contributed in one or several of the following ways: design, construction, maintenance and operation of the instrument(s) used to acquire the data; preparation and/or evaluation of the observation proposals; data acquisition, processing, calibration and/or reduction; production of analysis tools and/or related Monte Carlo simulations; overall discussions about the contents of the draft, as well as related refinements in the descriptions. We would like to thank the Instituto de Astrofísica de Canarias for the excellent working conditions at the Observatorio del Roque de los Muchachos in La Palma. The financial support of the German BMBF, MPG and HGF; the Italian INFN and INAF; the Swiss National Fund SNF; the grants PID2019-104114RB-C31, PID2019-104114RB-C32, PID2019-104114RB-C33, PID2019-105510GB-C31, PID2019-107847RB-C41, PID2019-107847RB-C42, PID2019-107847RB-C44, PID2019-107988GB-C22, PID2022-136828NB-C41, PID2022-137810NB-C22, PID2022-138172NB-C41, PID2022-138172NB-C42, PID2022-138172NB-C43, PID2022-139117NB-C41, PID2022-139117NB-C42, PID2022-139117NB-C43, PID2022-139117NB-C44 funded by the Spanish MCIN/AEI/ 10.13039/501100011033 and “ERDF A way of making Europe”; the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1-400/18.12.2020 and the Academy of Finland grant nr. 320045 is gratefully acknowledged. This work was also been supported by Centros de Excelencia “Severo Ochoa” y Unidades “María de Maeztu” program of the Spanish MCIN/AEI/ 10.13039/501100011033 (CEX2019-000920-S, CEX2019-000918-M, CEX2021-001131-S) and by the CERCA institution and grants 2021SGR00426 and 2021SGR00773 of the Generalitat de Catalunya; by the Croatian Science Foundation (HrZZ) Project IP-2022-10-4595 and the University of Rijeka Project uniri-prirod-18-48; by the Deutsche Forschungsgemeinschaft (SFB1491) and by the Lamarr-Institute for Machine Learning and Artificial Intelligence; by the Polish Ministry Of Education and Science grant No. 2021/WK/08; and by the Brazilian MCTIC, CNPq and FAPERJ. The Fermi LAT Collaboration acknowledges generous ongoing support from a number of agencies and institutes that have supported both the development and the operation of the LAT as well as scientific data analysis. These include the National Aeronautics and Space Administration and the Department of Energy in the United States, the Commissariat à l’Energie Atomique and the Centre National de la Recherche Scientifique / Institut National de Physique Nucléaire et de Physique des Particules in France, the Agenzia Spaziale Italiana and the Istituto Nazionale di Fisica Nucleare in Italy, the Ministry of Education, Culture, Sports, Science and Technology (MEXT), High Energy Accelerator Research Organization (KEK) and Japan Aerospace Exploration Agency (JAXA) in Japan, and the K. A. Wallenberg Foundation, the Swedish Research Council and the Swedish National Space Board in Sweden. Additional support for science analysis during the operations phase is gratefully acknowledged from the Istituto Nazionale di Astrofisica in Italy and the Centre National d’Études Spatiales in France. This work performed in part under DOE Contract DE-AC02-76SF00515. The corresponding authors of this manuscript, namely Axel Arbet-Engels, Lea Heckmann and David Paneque, acknowledge support from the Deutsche Forschungs gemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC-2094 – 390783311. The Imaging X-ray Polarimetry Explorer (IXPE) is a joint US and Italian mission. The US contribution is supported by the National Aeronautics and Space Administration (NASA) and led and managed by its Marshall Space Flight Center (MSFC), with industry partner Ball Aerospace (contract NNM15AA18C). The Italian contribution is supported by the Italian Space Agency (Agenzia Spaziale Italiana, ASI) through contract ASI-OHBI-2017-12-I.0, agreements ASI-INAF-2017-12-H0 and ASI-INFN-2017.13-H0, and its Space Science Data Center (SSDC), and by the Istituto Nazionale di Astrofisica (INAF) and the Istituto Nazionale di Fisica Nucleare (INFN) in Italy. This research used data products provided by the IXPE Team (MSFC, SSDC, INAF, and INFN) and distributed with additional software tools by the High-Energy Astrophysics Science Archive Research Center (HEASARC), at NASA Goddard Space Flight Center (GSFC). I. L. and S.K. were funded by the European Union ERC-2022-STG – BOOTES – 101076343. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them Some of the data are based on observations collected at the Observatorio de Sierra Nevada; which is owned and operated by the Instituto de Astrofísica de Andalucía (IAA-CSIC); and at the Centro Astronómico Hispano en Andalucía (CAHA); which is operated jointly by Junta de Andalucía and Consejo Superior de Investigaciones Científicas (IAA-CSIC). The research at Boston University was supported in part by National Science Foundation grant AST-2108622, NASA Fermi Guest Investigator grants 80NSSC21K1917 and 80NSSC22K1571, and NASA Swift Guest Investigator grant 80NSSC22K0537. This research was conducted in part using the Mimir instrument, jointly developed at Boston University and Lowell Observatory and supported by NASA, NSF, and the W.M. Keck Foundation. We thank D. Clemens for guidance in the analysis of the Mimir data. This study used observations conducted with the 1.8m Perkins Telescope (PTO) in Arizona (USA), which is owned and operated by Boston University. This work was supported by NSF grant AST-2109127. We acknowledge the use of public data from the Swift data archive. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA. This work has made use of data from the Joan Oró Telescope (TJO) of the Montsec Observatory (OdM), which is owned by the Catalan Government and operated by the Institute for Space Studies of Catalonia (IEEC). The Submillimeter Array is a joint project between the Smithsonian Astrophysical Observatory and the Academia Sinica Institute of Astronomy and Astrophysics and is funded by the Smithsonian Institution and the Academia Sinica. We recognize that Maunakea is a culturally important site for the indigenous Hawaiian people; we are privileged to study the cosmos from its summit. The 100 m radio telescope at Effelsberg is operated by the Max-Planck-Institut für Radioastronomie (MPIfR) on behalf of the Max-Planck-Society. Observations with the 100 m telescope have received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 101004719 (ORP). The Liverpool Telescope is operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2019-000920-S).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation ( CEX2019-000918-M).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

The utility of superficial abdominal reflex in the initial diagnosis of scoliosis: a retrospective review of clinical characteristics of scoliosis with syringomyelia

<p>Abstract</p> <p>Background</p> <p>With increasing use of magnetic resonance imaging (MRI), underlying syringomyelia is increasingly found in patients with presumed idiopathic scoliosis. To determine the indications for MRI in the differential diagnosis of scoliosis, several clinical characteristics of syringomyelia have been reported. Neurological signs, particularly abnormal superficial abdominal reflex (SAR), are important in establishing the initial diagnosis of scoliosis. However, the prevalence of abnormal SAR in patients with scoliosis and the sensitivity of this sign in predicting syringomyelia are not well known. We aimed to determine the diagnostic utility of SAR and other characteristics of syringomyelia in patients with scoliosis.</p> <p>Methods</p> <p>We reviewed the medical records of 93 patients with scoliosis, 90 of whom underwent corrective surgery. All patients underwent MRI to determine the presence of syringomyelia. Mean age at surgery was 12.5 years. Abnormal SAR was defined as unilateral or bilateral absence or hyporeflexia of SAR. We calculated indices of diagnostic utility of abnormal SAR for non-idiopathic scoliosis and for syringomyelia. Abnormal SAR, left thoracic curve pattern, gender, and curve flexibility were compared between scoliosis with syringomyelia and idiopathic scoliosis. Logistic regression analysis was performed with the existence of syringomyelia as the dependent variable and curve flexibility as the independent variable.</p> <p>Results</p> <p>Abnormal SAR was observed in 20 patients (prevalence 22%). All 6 patients with myopathic scoliosis displayed bilateral absence of SAR. The sensitivity of abnormal SAR for non-idiopathic scoliosis was 38%, with 96% specificity, 90% PPV (positive predictive value), and 60% NPV (negative predictive value). Syringomyelia was identified in 9 of the 93 patients (9.7%); 8 of these had abnormal SAR. The sensitivity of abnormal SAR for syringomyelia in presumed idiopathic scoliosis was 89%, with 95% specificity, 80% PPV, and 98% NPV. Gender, abnormal neurological findings, and curve flexibility differed significantly between patients with syringomyelia and those with idiopathic scoliosis (P < 0.05). In the logistic regression model, the area under the receiver operating characteristic (ROC) curve was 0.79 and the cut-off value of curve flexibility for syringomyelia was 50% (P = 0.08).</p> <p>Conclusion</p> <p>Abnormal SAR was a useful indicator not only for syringomyelia, but also for myogenic scoliosis.</p

Immunolocalization of cell wall polymers in grapevine (Vitis vinifera) internodes under nitrogen, phosphorus or sulfur deficiency

Abstract The impact on cell wall (CW) of the deficiency in nitrogen (–N), phosphorus (–P) or sulphur (–S), known to impair essential metabolic pathways, was investigated in the economically important fruit species Vitis vinifera L. Using cuttings as an experimental model a reduction in total internode number and altered xylem shape was observed. Under –N an increased internode length was also seen. CW composition, visualised after staining with calcofluor white, Toluidine blue and ruthenium red, showed decreased cellulose in all stresses and increased pectin content in recently formed internodes under –N compared to the control. Using CW-epitope specific monoclonal antibodies (mAbs), lower amounts of extensins incorporated in the wall were also observed under –N and –P conditions. Conversely, increased pectins with a low degree of methyl-esterification and richer in long linear 1,5-arabinan rhamnogalacturonan-I (RG-I) side chains were observed under –N and –P in mature internodes which, in the former condition, were able to form dimeric association through calcium ions. –N was the only condition in which 1,5-arabinan branched RG- content was not altered, as –P and –S older internodes showed, respectively, lower and higher amounts of this polymer. Higher xyloglucan content in older internodes was also observed under –N. The results suggest that impairments of specific CW components led to changes in the deposition of other polymers to promote stiffening of the CW. The unchanged extensin amount observed under –S may contribute to attenuating the effects on the CW integrity caused by this stress. Our work showed that, in organized V. vinifera tissues, modifications in a given CW component can be compensated by synthesis of different polymers and/or alternative linking between polymers. The results also pinpoint different strategies at the CW level to overcome mineral stress depending on how essential they are to cell growth and plant development

Performance and first measurements of the MAGIC stellar intensity interferometer

S. Abe et al.In recent years, a new generation of optical intensity interferometers has emerged, leveraging the existing infrastructure of Imaging Atmospheric Cherenkov Telescopes (IACTs). The MAGIC telescopes host the MAGIC-SII system (Stellar Intensity Interferometer), implemented to investigate the feasibility and potential of this technique on IACTs. After the first successful measurements in 2019, the system was upgraded and now features a real-time, dead-time-free, 4-channel, GPU-based correlator. These hardware modifications allow seamless transitions between MAGIC’s standard very-high-energy gamma-ray observations and optical interferometry measurements within seconds. We establish the feasibility and potential of employing IACTs as competitive optical Intensity Interferometers with minimal hardware adjustments. The measurement of a total of 22 stellar diameters are reported, 9 corresponding to reference stars with previous comparable measurements, and 13 with no prior measurements. A prospective implementation involving telescopes from the forthcoming Cherenkov Telescope Array Observatory’s Northern hemisphere array, such as the first prototype of its Large-Sized Telescopes, LST-1, is technically viable. This integration would significantly enhance the sensitivity of the current system and broaden the UV-plane coverage. This advancement would enable the system to achieve competitive sensitivity with the current generation of long-baseline optical interferometers over blue wavelengths.The financial support of the German BMBF, MPG, and HGF; the Italian INFN and INAF; the Swiss National Fund SNF; the grants PID2019-104114RB-C31, PID2019-104114RB-C32, PID2019-104114RB-C33, PID2019-105510GB-C31, PID2019-107847RB-C41, PID2019-107847RB-C42, PID2019-107847RB-C44, PID2019-107988GB-C22, PID2022-136828NB-C41, PID2022-137810NB-C22, PID2022-138172NB-C41, PID2022-138172NB-C42, PID2022-138172NB-C43, PID2022-139117NB-C41, PID2022-139117NB-C42, PID2022-139117NB-C43, PID2022-139117NB-C44 funded by the Spanish MCIN/AEI/ 10.13039/501100011033 and ‘ERDF A way of making Europe’; the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1-400/18.12.2020 and the Academy of Finland grant nr. 320045 is gratefully acknowledged. This work was also been supported by Centros de Excelencia ‘Severo Ochoa’ y Unidades ‘María de Maeztu’ program of the Spanish MCIN/AEI/ 10.13039/501100011033 (CEX2019-000920-S, CEX2019-000918-M, CEX2021-001131-S) and by the CERCA institution and grants 2021SGR00426 and 2021SGR00773 of the Generalitat de Catalunya; by the Croatian Science Foundation (HrZZ) Project IP-2022-10-4595 and the University of Rijeka Project uniri-prirod-18-48; by the Deutsche Forschungsgemeinschaft (SFB1491) and by the Lamarr-Institute for Machine Learning and Artificial Intelligence; by the Polish Ministry Of Education and Science grant No. 2021/WK/08; and by the Brazilian MCTIC, CNPq and FAPERJ. Funded/Co-funded by the European Union (ERC, MicroStars, 101076533).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2019-000920-S).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2019-000918-M).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice

It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long-term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin-1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin-1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin-1 receptor knockout mice. Neurogenesis can be increased in wild-type but not neurokinin-1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain-derived neurotrophic factor are also two-fold higher in neurokinin-1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus-dependent learning and memory but found no clear enhancement in neurokinin-1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain-derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain-derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.This research was supported by the Wellcome Trust, a European Community Marie Curie fellowship to S.M. and a Boehringer Ingelheim Fonds Predoctoral Fellowship to M.P. C.A.G. is on the Wellcome Trust Four-year PhD in Neuroscience at UCL.Peer reviewe