The K1.8BR spectrometer system at J-PARC

A new spectrometer system was designed and constructed at the secondary beam line K1.8BR in the hadron hall of J-PARC to investigate $\bar K N$ interactions and $\bar K$-nuclear bound systems. The spectrometer consists of a high precision beam line spectrometer, a liquid $^3$He/$^4$He/D$_2$ target system, a Cylindrical Detector System that surrounds the target to detect the decay particles from the target region, and a neutron time-of-flight counter array located $\sim$15 m downstream from the target position. Details of the design, construction, and performance of the detector components are described.Comment: 33 pages, 25 figure

Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2

During their biogenesis, 40S ribosomal subunit precursors are exported from the nucleus to the cytoplasm, where final maturation occurs. In this study, we show that the protein kinase human Rio2 (hRio2) is part of a late 40S preribosomal particle in human cells. Using a novel 40S biogenesis and export assay, we analyzed the contribution of hRio2 to late 40S maturation. Although hRio2 is not absolutely required for pre-40S export, deletion of its binding site for the export receptor CRM1 decelerated the kinetics of this process. Moreover, in the absence of hRio2, final cytoplasmic 40S maturation is blocked because the recycling of several trans-acting factors and cytoplasmic 18S-E precursor ribosomal RNA (rRNA [pre-rRNA]) processing are defective. Intriguingly, the physical presence of hRio2 but not its kinase activity is necessary for the release of hEnp1 from cytoplasmic 40S precursors. In contrast, hRio2 kinase activity is essential for the recycling of hDim2, hLtv1, and hNob1 as well as for 18S-E pre-rRNA processing. Thus, hRio2 is involved in late 40S maturation at several distinct steps

A Protein Inventory of Human Ribosome Biogenesis Reveals an Essential Function of Exportin 5 in 60S Subunit Export

A systematic search for human ribosome biogenesis factors shows conservation of many aspects of eukaryotic ribosome synthesis with the well-studied process in yeast and identifies an export route of 60S subunits that is specific for higher eukaryotes

Characterization of the intrahippocampal kainic acid model in female mice with a special focus on seizure suppression by antiseizure drugs and DMSO

ABSTRACTObjectivesAffecting around 50 million people, men and women likewise, epilepsies are among the most common neurological diseases worldwide. Despite special challenges in the medical treatment of women with epilepsy, previous research has mainly focused on males, in particular preclinical animal studies, leaving a gap that needs to be urgently addressed. The intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy (TLE) as one of the most frequently studied models in males is used for screening of novel antiepileptic therapies. In this study we investigate the IHKA model of TLE in female mice, in particular drug-resistance of hippocampal paroxysmal discharges. Furthermore, we provide evidence for anti-seizure effects of dimethyl sulfoxide (DMSO) in epileptic, but not naÏve mice.MethodsAfter injecting KA unilaterally into the hippocampus of female mice, we monitored the development of epileptiform activity in in-vivo EEG recordings, evaluated responsiveness to the commonly prescribed antiseizure drugs (ASDs) lamotrigine (LTG), oxcarbazepine (OXC) and levetiracetam (LEV) and assessed typical neuropathological alterations of the hippocampus. Moreover, the effect of different doses of DMSO was tested in the IHKA chronic epilepsy model as well as on the PTZ-induced acute seizure threshold in both female and male mice.ResultsIn the IHKA model, female mice replicated the key features of human TLE (EEG and neuropathological changes). Importantly, hippocampal paroxysmal discharges (HPDs) in female mice did not respond to commonly prescribed ASDs, thus representing a suitable model of drug-resistant seizures. The solvent DMSO caused a significant short-term reduction of HPDs, but did not affect the threshold of acute seizures.SignificanceBy characterizing the drug-resistance of HPDs in the IHKA model of TLE in female mice we have laid a foundation for future research addressing sex-specific aspects. Considering the special issues complicating the therapeutic management of women, inclusion of females in the quest for novel treatment strategies is imperative. The observed effect of DMSO on epileptiform activity underlines that its application in epilepsy research is problematic and that the choice of solvent and appropriate vehicle control is crucial.</jats:sec