Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes

Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutations affecting UBE3A gene expression. Previous studies in mice revealed distinct critical periods during neurodevelopment in which reactivation of Ube3a gene expression can prevent the onset of behavioral deficits. Whether UBE3A is required for brain function throughout life is unknown. Here, we address the importance of maintaining UBE3A expression after normal brain development. Findings: Using a conditional mouse, we deleted the Ube3a gene at three ages spanning brain maturation. We assessed the consequences of Ube3a gene deletion by testing the mice in behavioral tasks previously shown to produce robust phenotypes in AS model mice. Early embryonic deletion of Ube3a recapitulated all behavioral deficits of AS mice. In contrast, Ube3a gene deletion at 3 or 12 weeks of age did not have a significant effect on most behavioral tasks and did not increase seizure sensitivity. Conclusions: Taken together, these results emphasize that UBE3A critically impacts early brain development, but plays a more limited role in adulthood. Our findings provide important considerations for upcoming clinical trials in which UBE3A gene expression is reactivated and suggest that even transient UBE3A reinstatement during a critical window of early development is likely to prevent most adverse Angelman syndrome phenotypes. However, sustained UBE3A expression into adulthood is probably needed for optimal clinical benefit

First -decay spectroscopy of and new -decay branches of

19 pags., 14 figs., 3 tabs.The  decay of the neutron-rich and was investigated experimentally in order to provide new insights into the nuclear structure of the tin isotopes with magic proton number above the shell. The -delayed -ray spectroscopy measurement was performed at the ISOLDE facility at CERN, where indium isotopes were selectively laser-ionized and on-line mass separated. Three -decay branches of were established, two of which were observed for the first time. Population of neutron-unbound states decaying via rays was identified in the two daughter nuclei of and , at excitation energies exceeding the neutron separation energy by 1 MeV. The -delayed one- and two-neutron emission branching ratios of were determined and compared with theoretical calculations. The -delayed one-neutron decay was observed to be dominant -decay branch of even though the Gamow-Teller resonance is located substantially above the two-neutron separation energy of . Transitions following the  decay of are reported for the first time, including rays tentatively attributed to . In total, six new levels were identified in on the basis of the coincidences observed in the and decays. A transition that might be a candidate for deexciting the missing neutron single-particle state in was observed in both  decays and its assignment is discussed. Experimental level schemes of and are compared with shell-model predictions. Using the fast timing technique, half-lives of the , and levels in were determined. From the lifetime of the state measured for the first time, an unexpectedly large transition strength was deduced, which is not reproduced by the shell-model calculations.M.P.-S. acknowledges the funding support from the Polish National Science Center under Grants No. 2019/33/N/ST2/03023 and No. 2020/36/T/ST2/00547 (Doctoral scholarship ETIUDA). J.B. acknowledges support from the Universidad Complutense de Madrid under the Predoctoral Grant No. CT27/16- CT28/16. This work was partially funded by the Polish National Science Center under Grants No. 2020/39/B/ST2/02346, No. 2015/18/E/ST2/00217, and No. 2015/18/M/ST2/00523, by the Spanish government via Projects No. FPA2017-87568-P, No. RTI2018-098868-B-I00, No. PID2019-104390GB-I00, and No. PID2019-104714GB-C21, by the U.K. Science and Technology Facilities Council (STFC), the German BMBF under Contract No. 05P18PKCIA, by the Portuguese FCT under the Projects No. CERN/FIS-PAR/0005/2017, and No. CERN/FIS-TEC/0003/2019, and by the Romanian IFA Grant CERN/ISOLDE. The research leading to these results has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 654002. M.Str. acknowledges the funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 771036 (ERC CoG MAIDEN). J.P. acknowledges support from the Academy of Finland (Finland) with Grant No. 307685. Work at the University of York was supported under STFC Grants No. ST/L005727/1 and No. ST/P003885/1

Decay spectroscopy at the two-proton drip line: radioactivity of the new nuclides 160Os and 156W

The radioactivity of 76160Os84 and 74156W82 that lie at the two-proton drip line have been measured in an experiment performed at the Accelerator Laboratory of the University of Jyväskylä. The 160Os nuclei were produced using fusion-evaporation reactions induced by a beam of 310 MeV 58Ni ions bombarding a 106Cd target. The 160Os ions were separated in flight using the recoil separator MARA and implanted into a double-sided silicon strip detector, which was used to measure their decays. The α decays of the ground state of 160Os (Eα = 7092(15) keV, t1/2 = 97−32+97 μs) and its isomeric state (Eα = 8890(10) keV, t1/2 = 41−9+15 μs) were measured, allowing the excitation energy of the isomer to be determined as 1844(18) keV. These α-decay properties and the excitation energy of the isomer are compared with systematics. The α decays were correlated with subsequent decays to investigate the β decays of the ground state of 156W, revealing that unlike its isotones, both low-lying isomers were populated in its daughter nuclide, 156Ta. An improved value for the half-life of the proton-decaying high-spin isomeric state in 73156Ta83 of 333−22+25 ms was obtained in a separate experiment using the same experimental systems with a 102Pd target. This result was employed to improve the precision of the half-life determined for 156W, which was measured as 157−34+57 ms

Road safety: serious injuries remain a major unsolved problem

Objective: To investigate temporal trends in the incidence, mortality, disability-adjusted life-years (DALYs), and costs of health loss caused by serious road traffic injury. Design, setting and participants: A retrospective review of data from the population-based Victorian State Trauma Registry and the National Coronial Information System on road traffic-related deaths (pre- and in-hospital) and major trauma (Injury Severity Score > 12) during 2007–2015. Main outcomes and measures: Temporal trends in the incidence of road traffic-related major trauma, mortality, DALYs, and costs of health loss, by road user type. Results: There were 8066 hospitalised road traffic major trauma cases and 2588 road traffic fatalities in Victoria over the 9-year study period. There was no change in the incidence of hospitalised major trauma for motor vehicle occupants (incidence rate ratio [IRR] per year, 1.00; 95% CI, 0.99–1.01; P = 0.70), motorcyclists (IRR, 0.99; 95% CI, 0.97–1.01; P = 0.45) or pedestrians (IRR, 1.00; 95% CI, 0.97–1.02; P = 0.73), but the incidence for pedal cyclists increased 8% per year (IRR, 1.08; 95% CI; 1.05–1.10; P < 0.001). While DALYs declined for motor vehicle occupants (by 13% between 2007 and 2015), motorcyclists (32%), and pedestrians (5%), there was a 56% increase in DALYs for pedal cyclists. The estimated costs of health loss associated with road traffic injuries exceeded $14 billion during 2007–2015, although the cost per patient declined for all road user groups. Conclusions: As serious injury rates have not declined, current road safety targets will be difficult to meet. Greater attention to preventing serious injury is needed, as is further investment in road safety, particularly for pedal cyclists.Ben Beck, Peter A Cameron, Mark C Fitzgerald, Rodney T Judson, Warwick Teague, Ronan A Lyons, Belinda J Gabb

Autism and ADHD – two ends of the same spectrum?

Abstract. Analysis of dynamics of biologically motivated neural networks allows for studying non-linear processes responsible for cognitive functions and thus provides adequate language to understand complex mental processes, including psychiatric syndromes and disorders. Problems with attention shifts that are at the roots of Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD), have been investigated using network model of Posner Visual Orienting Task (PVOT). Changing parameters that control biophysical properties of model neurons and cause network dysfunctions provides plausible explanations of many strange ASD and ADHD phenomena