Mutations in GABRB3

Objective: To examine the role of mutations in GABRB3 encoding the b3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. Methods: We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. Results: We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands frommultiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy withmyoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies. Electrophysiologic analysis of 7 mutations in Xenopus laevis oocytes, using coexpression of wild-type or mutant beta(3), together with alpha(5) and gamma(2s) subunits and an automated 2-microelectrode voltage-clamp system, revealed reduced GABA-induced current amplitudes or GABA sensitivity for 5 of 7 mutations. Conclusions: Our results indicate that GABRB3 mutations are associated with a broad phenotypic spectrum of epilepsies and that reduced receptor function causing GABAergic disinhibition represents the relevant disease mechanism

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Structure and development of the Valmiera-Lokno Uplift – a highly elevated basement block with a strongly deformed and eroded platform cover in the East European Craton interior around the Estonian-Latvian-Russian borderland

Based on drillings, a number of geological cross-sections, and structure contour and isopach maps were composed to describe/analyse the structure and development of the Valmiera-Lokno Uplift (VLU), a basement block elevated up to 700 m with a heavily deformed and eroded platform cover in the East European Craton interior, along the regional Liepaja-Riga-Pskov Fault Zone (LRPFZ). Five isolated basement-cored anticlines (BCA), the Lokno, Haanja, Mõniste, Valmiera and Smiltene uplifts, arise in the platform cover on the VLU, whereas the downthrown LRPFZ side defines a complex monoclinal fold. The anticlines, straddling or occurring near the monocline, merge with it and thus have highly asymmetrical shapes. Thickness changes of stratigraphic units across the VLU reveal its complex history, reflecting regional tectonic activation pulses that varied noticeably even between neighbouring BCAs. In all, the latest Precambrian-earliest Ordovician initiation epoch of the VLU was followed by modest tectonic activity or a standstill period in the Middle Ordovician-Early Silurian. Intensifying tectonic movements culminated again in the prime of the Caledonian Orogeny in latest Silurian-earliest Devonian time, and faded thereafter towards the end of Early Devonian. The VLU has been reactivated occasionally since the latest Devonian and emerges as a crustal weakness in the recent movement and seismicity patterns. To decipher the origin of the VLU, hitherto factually undiscussed topics, a more detailed study of the LRPFZ, analysis of its fault pattern and kinematics alongside the regional tectonic setting/history is needed. A cursory look hints to a substantial Early Paleozoic sinistral strike-slip along the LRPFZ, allowing interpreting the VLU as a possible restraining bend structure

Ancient buried valleys in the city of Tallinn and adjacent area

The distribution, morphology, fillings, and origin of buried valleys are discussed. The direction of the valleys varies from NW to NE. Within the Viru-Harju Plateau the valleys have a more or less symmetric profile, but asymmetric profiles are dominating in the pre-klint area. They are mainly filled with glacial (till), glaciofluvial (sand, gravel, and pebbles), glacio­lacustrine (varved clay), and marine (fine-grained sand) deposits. The Tallinn valley with its tributary valleys (Saku and Sausti) and fore-klint branches (Harku, Lilleküla, and Kadriorg) looks like a river system. The fore-klint branches extend over 20 km in the Gulf of Finland. They are probably tributaries of the ancient river Pra-Neva. Most likely, the formation of valleys was continuous, starting from pre-Quaternary river erosion, and was sculptured by variable processes during the ice ages and influenced by flowing water during the interglacial periods