Inherited Cardiomyopathies: Genetics and Clinical Genetic Testing

Inherited cardiomyopathies are major causes of morbidity and mortality and include a group of cardiac disorders such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), left ventricular noncompaction (LVNC), and restrictive cardiomyopathy (RCM). These diseases have a substantial genetic component and predispose to sudden cardiac death. Since the first gene was identified as a disease-causing gene for HCM over two decades ago, more than eighty genes have been identified to be associated with inherited cardiomyopathies and genetic testing has become prevalent in making clinical diagnosis. With the advent of next-generation sequencing technology, genetic panel testing of inherited cardiomyopathies has become feasible and cost efficient. In this review, we summarize the individual cardiomyopathies with the emphasis on cardiomyopathy genetics and genetic testing

Correction to: Identification of novel Y chromosome encoded transcripts by testis transcriptome analysis of mice with deletions of the Y chromosome long arm.

Following publication of the original article [1], the following error was reported: The actin control panel in Fig. 3 of this paper is reproduced from Fig. 7 of Touré et al, 2004 [2] by kind permission of the Genetics Society of America. Touré et al, 2004 used Northern blotting to show that the Y-linked genes Ssty1 and Ssty2 have reduced expression in a range of mouse genotypes with deletions on the Y chromosome long arm. This paper shows that two novel genes, Sly and Asty are also present on mouse Yq and have reduced expression in these deleted genotypes. A further companion paper was published in Human Molecular Genetics (Ellis et al, 2005 [3]) showing that X-linked genes are upregulated in the various deleted genotypes. Since two of the genotypes concerned are sterile and very hard to generate, all the Northern blot experiments in these papers were performed on a single membrane that was stripped and re-probed with a range of different X- and Y-linked genes. The same beta-actin loading control image thus necessarily applies to all the data presented, and was shown in all three papers. We regret that this was not mentioned appropriately in the Methods and figure legends at the time of publication

Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex

KELT-7b: A hot Jupiter transiting a bright V=8.54 rapidly rotating F-star

We report the discovery of KELT-7b, a transiting hot Jupiter with a mass of $1.28 \pm 0.18$ MJ, radius of $1.53_{-0.047}^{+0.046}$ RJ, and an orbital period of $2.7347749 \pm 0.0000039$ days. The bright host star (HD33643; KELT-7) is an F-star with $V=8.54$, Teff $=6789_{-49}^{+50}$ K, [Fe/H] $=0.139_{-0.081}^{+0.075}$, and $\log{g}=4.149 \pm 0.019$. It has a mass of $1.535_{-0.054}^{+0.066}$ Msun, a radius of $1.732_{-0.045}^{+0.043}$ Rsun, and is the fifth most massive, fifth hottest, and the ninth brightest star known to host a transiting planet. It is also the brightest star around which KELT has discovered a transiting planet. Thus, KELT-7b is an ideal target for detailed characterization given its relatively low surface gravity, high equilibrium temperature, and bright host star. The rapid rotation of the star ($73 \pm 0.5$ km/s) results in a Rossiter-McLaughlin effect with an unusually large amplitude of several hundred m/s. We find that the orbit normal of the planet is likely to be well-aligned with the stellar spin axis, with a projected spin-orbit alignment of $\lambda=9.7 \pm 5.2$ degrees. This is currently the second most rapidly rotating star to have a reflex signal (and thus mass determination) due to a planetary companion measured.Comment: Accepted to The Astronomical Journa

The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans

Animal research suggests that the consolidation of fear and extinction memories depends on N-methyl D-aspartate (NMDA)- type glutamate receptors. Using a fear conditioning and extinction paradigm in healthy normal volunteers, we show that postlearning administration of the NMDA partial agonist D-cycloserine (DCS) facilitates fear memory consolidation, evidenced behaviorally by enhanced skin conductance responses, relative to placebo, for presentations of a conditioned stimulus (CS) at a memory test performed 72 h later. DCS also enhanced CS-evoked neural responses in a posterior hippocampus/collateral sulcus region and in the medial prefrontal cortex at test. Our data suggest a role for NMDA receptors in regulating fear memory consolidation in humans

Dynamic causal modelling of effective connectivity during perspective taking in a communicative task

Previous studies have shown that taking into account another person's perspective to guide decisions is more difficult when their perspective is incongruent from one's own compared to when it is congruent. Here we used dynamic causal modelling (DCM) for functional magnetic resonance imaging (fMRI) to investigate effective connectivity between prefrontal and posterior brain regions in a task that requires participants to take into account another person's perspective in order to guide the selection of an action. Using a new procedure to score model evidence without computationally costly estimation, we conducted an exhaustive search for the best of all possible models. The results elucidate how the activity in the areas from our previously reported analysis (Dumontheil et al., 2010) are causally linked and how the connections are modulated by both the social as well as executive task demands of the task. We find that the social demands modulate the backward connections from the medial prefrontal cortex (MPFC) more strongly than the forward connections from the superior occipital gyrus (SOG) and the medial temporal gyrus (MTG) to the MPFC. This was also the case for the backward connection from the MTG to the SOG. Conversely, the executive task demands modulated the forward connections of the SOG and the MTG to the MPFC more strongly than the backward connections. We interpret the results in terms of hierarchical predictive coding

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells