Sleep scoring made easy Semi-automated sleep analysis software and manual rescoring tools for basic sleep research in mice

Studying sleep behavior in animal models demands clear separation of vigilance states. Pure manual scoring is time-consuming and commercial scoring software is costly. We present a LabVIEW-based, semi-automated scoring routine using recorded EEG and EMG signals. This scoring routine is • designed to reliably assign the vigilance/sleep states wakefulness (WAKE), non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) to defined EEG/EMG episodes. • straightforward to use even for beginners in the field of sleep research. • freely available upon request. Chronic recordings from mice were used to design and evaluate the scoring routine consisting of an artifact-removal, a scoring- and a rescoring routine. The scoring routine processes EMG and different EEG frequency bands. Amplitude-based thresholds for EEG and EMG parameters trigger a decision tree assigning each EEG episode to a defined vigilance/sleep state automatically. Using the rescoring routine individual episodes or particular state transitions can be re-evaluated manually. High agreements between auto-scored and manual sleep scoring could be shown for experienced scorers and for beginners quickly and reliably. With small modifications to the software, it can be easily adapted for sleep analysis in other animal models

Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells.

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.Research in the S.P.J. laboratory is funded by Cancer Research UK (CRUK; programme grant C6/A11224), the European Research Council and the European Community Seventh Framework Programme (grant agreement no. HEALTH-F2-2010-259893; DDResponse). Core funding is provided by Cancer Research UK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives salary from the University of Cambridge, supplemented by CRUK. J.V.F. was funded by Cancer Research UK programme grant C6/A11224 and the Ataxia Telangiectasia Society. J.C. was funded by Cancer Research UK programme grant C6/A11224. D.J.A. is supported by CRUK. Research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) and ERC grant agreement no. (311166)

Boundaries and Prototypes in Categorizing Direction

Projective terms such as left, right, front, back are conceptually interesting due to their flexibility of contextual usage and their central relevance to human spatial cognition. Their default acceptability areas are well known, with prototypical axes representing their most central usage and decreasing acceptability away from the axes. Previous research has shown these axes to be boundaries in certain non-linguistic tasks, indicating an inverse relationship between linguistic and non-linguistic direction concepts under specific circumstances. Given this striking mismatch, our study asks how such inverse non-linguistic concepts are represented in language, as well as how people describe their categorization. Our findings highlight two distinct grouping strategies reminiscent of theories of human categorization: prototype based or boundary based. These lead to different linguistic as well as non-linguistic patterns

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Inherited thrombocytopenias are a heterogeneous group of disorders characterised by abnormally low platelet counts which can be associated with abnormal bleeding. Next generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease causing genes. However its full potential has not previously been utilised. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown aetiology with platelet counts varying from 11-186x109 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases which include novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia

A comprehensive targeted next-generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia.

Background: Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet counts and often disproportionate bleeding with over 30 genes currently implicated. Previously the UK-GAPP study using whole exome sequencing (WES) identified a pathogenic variant in 19 of 47 (40%) patients of which 71% had variants in genes known to cause IT. Aims: To employ a targeted next-generation sequencing platform to improve efficiency of diagnostic testing and reduce overall costs. Methods: We have developed an IT-specific gene panel as a pre-screen for patients prior to WES using the Agilent SureSelectQXT transposon-based enrichment system. Results: Thirty-one patients were analyzed using the panel-based sequencing, of which; 10% (3/31) were identified with a classified pathogenic variant, 16% (5/31) were identified with a likely pathogenic variant, 51% (16/31) were identified with variants of unknown significance, and 23% (7/31) were identified with either no variant or a benign variant. Discussion and Conclusion: Although requiring further clarification of the impact of the genetic variations, the application of an IT-specific next generation sequencing panel is an viable method of pre-screening patients for variants in known IT-causing genes prior to WES. With an added benefit of distinguishing IT from idiopathic thrombocytopenic purpura (ITP) and the potential to identify variants in genes known to have a predisposition to hematological malignancies, it could become a critical step in improving patient clinical management

The Inclusiveness and Emptiness of <i>Gong Qi</i>: A Non-Anglophone Perspective on Ethics from a Sino-Japanese Corporation

This article introduces a non-Anglophone concept of gong qi(communal vessel, 公器) as a metaphor for ‘corporation’. It contributes an endogenous perspective from a Sino-Japanese organizational context that enriches mainstream business ethics literature, otherwise heavily reliant on Western traditions. We translate the multi-layered meanings of gong qi based on analysis of its ideograms, its references into classical philosophies, and contemporary application in this Japanese multinational corporation in China. Gong qi contributes a perspective that sees a corporation as an inclusive and virtuous social entity, and also addresses the elusive, implicit, and forever evolving nature of organizational life that is rarely noticed. We propose gong qi can be applied in other organizations and wider cultural contexts to show a new way of seeing and understanding business ethics and organization. Rather than considering virtue as a list of definable individual qualities, we suggest that the metaphor of gong qi reveals how virtue can be experienced as indeterminate, yet immanently present, like the substance of emptiness. This, then allows us to see the virtue of immanence, the beauty of implicitness, and hence, the efficacy of gong qi

A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism

Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD