Changes in Atrial Size Following PVI: Comparison of the Right and Left Atria

Background: Pulmonary vein isolation (PVI) is expected to cure atrial fibrillation (AF) and to improve atrial remodeling. However, the effects of PVI on the right atrial (RA) size have not been fully examined. We studied the effects of PVI on RA size in comparison that with the effects on LA size. Method: We studied 17 patients with drug-refractory AF (11 paroxysmal, 6 persistent). Two-dimensional echocardiography was performed at baseline and at follow-up to measure and compare RA and LA size.Results: Despite a short duration of AF in 7 patients after the PVI, all cases were maintained in sinus rhythm during the follow-up. LA and RA size were both reduced after the PVI compared with baseline measurements (LA 25.5 ± 2.9cm2 vs. 23.2 ± 3.6cm2, P < 0.05, RA 21.2 ± 2.9cm2 vs. 18.1 ± 3.0cm2, P < 0.01). The reduction ratio was more prominent in RA size (14.9%) than in LA size (8.7%)(P < 0.05). Conclusion: Atrial size was reduced following PVI for both the LA and RA, although the rate of reduction was more prominent in the RA

Identification of mutations through dominant screening for obesity using C57BL/6 substrains

The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fertilization. The screening of more than 5000 mutagenized mice established two obese pedigrees in which single nucleotide substitutions in Mc4r and Sim1 genes were identified through whole-exome sequencing. The mutation in the Mc4r gene produces a premature stop codon, and the mutant SIM1 protein lacks transcriptional activity, showing that the haploinsufficiency of SIM1 and MC4R results in obesity. We further examined the hypothalamic neuropeptide expressions in the mutant pedigrees and mice with diet-induced obesity, which showed that each obesity mouse model has distinct neuropeptide expression profiles. This forward genetic screening scheme is useful and applicable to any research field in which mouse models work

Identification of mutations through dominant screening for obesity using C57BL/6 substrains.

The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fertilization. The screening of more than 5000 mutagenized mice established two obese pedigrees in which single nucleotide substitutions in Mc4r and Sim1 genes were identified through whole-exome sequencing. The mutation in the Mc4r gene produces a premature stop codon, and the mutant SIM1 protein lacks transcriptional activity, showing that the haploinsufficiency of SIM1 and MC4R results in obesity. We further examined the hypothalamic neuropeptide expressions in the mutant pedigrees and mice with diet-induced obesity, which showed that each obesity mouse model has distinct neuropeptide expression profiles. This forward genetic screening scheme is useful and applicable to any research field in which mouse models work. Sci Rep 2016 Sep 2; 6:32453

Forward-genetics analysis of sleep in randomly mutagenized mice.

Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively. Nature 2016 Nov 17; 539(7629):378-383

Kinase signaling pathway regulates sleep quantity and depth through a distinct population of excitatory neurons

Souce dat