Scintillation counter with MRS APD light readout

START, a high-efficiency and low-noise scintillation detector for ionizing particles, was developed for the purpose of creating a high-granular system for triggering cosmic muons. Scintillation light in START is detected by MRS APDs (Avalanche Photo-Diodes with Metal-Resistance-Semiconductor structure), operated in the Geiger mode, which have 1 mm^2 sensitive areas. START is assembled from a 15 x 15 x 1 cm^3 scintillating plastic plate, two MRS APDs and two pieces of wavelength-shifting optical fiber stacked in circular coils inside the plastic. The front-end electronic card is mounted directly on the detector. Tests with START have confirmed its operational consistency, over 99% efficiency of MIP registration and good homogeneity. START demonstrates a low intrinsic noise of about 10^{-2} Hz. If these detectors are to be mass-produced, the cost of a mosaic array of STARTs is estimated at a moderate level of 2-3 kUSD/m^2.Comment: 6 pages, 5 figure

Post-sigh sleep apneas in mice: Systematic review and data-driven definition

Sleep apneas can be categorized as post-sigh (prevailing in non-rapid eye movement sleep) or spontaneous (prevailing in rapid eye movement sleep) according to whether or not they are preceded by an augmented breath (sigh). Notably, the occurrence of these apnea subtypes changes differently in hypoxic/hypercapnic environments and in some genetic diseases, highlighting the importance of an objective discrimination. We aim to: (a) systematically review the literature comparing the criteria used in categorizing mouse sleep apneas; and (b) provide data-driven criteria for this categorization, with the final goal of reducing experimental variability in future studies. Twenty-two wild-type mice, instrumented with electroencephalographic/electromyographic electrodes, were placed inside a whole-body plethysmographic chamber to quantify sleep apneas and sighs. Wake\u2013sleep states were scored on 4-s epochs based on electroencephalographic/electromyographic signals. Literature revision showed that highly different criteria were used for post-sigh apnea definition, the intervals for apnea occurrence after sigh ranging from 1 breath up to 20 s. In our data, the apnea occurrence rate during non-rapid eye movement sleep was significantly higher than that calculated before the sigh only in the 1st and 2nd 4-s epochs following a sigh. These data suggest that, in mice, apneas should be categorized as post-sigh only if they start within 8 s from a sigh; the choice of shorter or longer time windows might underestimate or slightly overestimate their occurrence rate, respectively

Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting

Purpose: Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. Methods: Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points. Results: Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively]. Conclusion: These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome

Study objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies

Z boson production in p+Pb collisions at sNN√=5.02 TeV measured with the ATLAS detector

The ATLAS Collaboration has measured the inclusive production of Z bosons via their decays into electron and muon pairs in p+Pb collisions at √ sNN = 5.02 TeV at the Large Hadron Collider. The measurements are made using data corresponding to integrated luminosities of 29.4 nb−1 and 28.1 nb−1 for Z → ee and Z → µµ, respectively. The results from the two channels are consistent and combined to obtain a cross section times the Z → `` branching ratio, integrated over the rapidity region |y ∗ Z | < 3.5, of 139.8 ± 4.8 (stat.) ± 6.2 (syst.) ± 3.8 (lumi.) nb. Differential cross sections are presented as functions of the Z boson rapidity and transverse momentum, and compared with models based on parton distributions both with and without nuclear corrections. The centrality dependence of Z boson production in p+Pb collisions is measured and analyzed within the framework of a standard Glauber model and the model’s extension for fluctuations of the underlying nucleon-nucleon scattering cross sectionFil: Aad, G.. Aix-Marseille Université; FranciaFil: Abbott, B.. Oklahoma State University; Estados UnidosFil: Abdallah, J.. Academia Sinica; ChinaFil: Abdinov, O.. Azerbaijan Academy of Sciences; AzerbaiyánFil: Aben, R.. University of Amsterdam; Países BajosFil: Alconada Verzini, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Alonso, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Arduh, Francisco Anuar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Dova, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Monticelli, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Wahlberg, Hernan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Otero y Garzon, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Piegaia, Ricardo Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Reisin, Hernan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sacerdoti, Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Zieminska, D.. Indiana University; Estados UnidosFil: Zimine, N. I.. Joint Institute for Nuclear Research ; RusiaFil: Zimmermann, C.. Universität Mainz; AlemaniaFil: Zimmermann, S.. Albert-Ludwigs-Universität; AlemaniaFil: Zinonos, Z.. Georg-August-Universität; AlemaniaFil: Zinser, M.. Universität Mainz; AlemaniaFil: Ziolkowski, M.. Universität Siegen ; AlemaniaFil: Živković, L.. University of Belgrade; SerbiaFil: Zobernig, G.. University of Wisconsin; Estados UnidosFil: Zoccoli, A.. Università di Bologna; ItaliaFil: Nedden, M. zur. Humboldt University; AlemaniaFil: Zurzolo, G.. Università di Napoli; ItaliaFil: Zwalinski, L.. Cern - European Organization For Nuclear Research; SuizaFil: The ATLAS Collaboration. No especifica

Neural control of fasting-induced torpor in mice

Torpor is a peculiar mammalian behaviour, characterized by the active reduction of metabolic rate, followed by a drop in body temperature. To enter torpor, the activation of all thermogenic organs that could potentially defend body temperature must be prevented. Most of these organs, such as the brown adipose tissue, are controlled by the key thermoregulatory region of the Raphe Pallidus (RPa). Currently, it is not known which brain areas mediate the entrance into torpor. To identify these areas, the expression of the early gene c-Fos at torpor onset was assessed in different brain regions in mice injected with a retrograde tracer (Cholera Toxin subunit b, CTb) into the RPa region. The results show a network of hypothalamic neurons that are specifically activated at torpor onset and a direct torpor-specific projection from the Dorsomedial Hypothalamus to the RPa that could putatively mediate the suppression of thermogenesis during torpor

Age-related cognitive and motor decline in a mouse model of CDKL5 deficiency disorder is associated with increased neuronal senescence and death

open20noThis work was supported by grants to E.C. and M.G. from Telethon (GGP19045) and from the Italian parent Association “CDKL5 insieme verso la cura”, and to M.G. from the Association “l’Albero di Greta”, from the International Foundation for CDKL5 Research (IFCR 2019), from the CDKL5 Program of Excellence - LouLou Fundation (CDKL5-17-106-01) and from the Association Française du Syndrome de Rett (ASFR 2017).CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. Children affected by CDD display a clinical phenotype characterized by early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. Although the clinical aspects associated with CDKL5 mutations are well described in children, adults with CDD are still under-characterized. Similarly, most animal research has been carried out on young adult Cdkl5 knockout (KO) mice only. Since age represents a risk factor for the worsening of symptoms in many neurodevelopmental disorders, understanding age differences in the development of behavioral deficits is crucial in order to optimize the impact of therapeutic interventions. Here, we compared young adult Cdkl5 KO mice with middle-aged Cdkl5 KO mice, at a behavioral, neuroanatomical, and molecular level. We found an age-dependent decline in motor, cognitive, and social behaviors in Cdkl5 KO mice, as well as in breathing and sleep patterns. The behavioral decline in older Cdkl5 KO mice was not associated with a worsening of neuroanatomical alterations, such as decreased dendritic arborization or spine density, but was paralleled by decreased neuronal survival in different brain regions such as the hippocampus, cortex, and basal ganglia. Interestingly, we found increased β-galactosidase activity and DNA repair protein levels, γH2AX and XRCC5, in the brains of older Cdkl5 KO mice, which suggests that an absence of Cdkl5 accelerates neuronal senescence/death by triggering irreparable DNA damage. In summary, this work provides evidence that CDKL5 may play a fundamental role in neuronal survival during brain aging and suggests a possible worsening with age of the clinical picture in CDD patients.openGennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E.Gennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E