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A single locus on the X chromosome codes for androgen receptor (AR) although this gene is subject to alternative splicing. AR is expressed in multiple tissues in males and females and is essential for reproductive success in the male. Since male and female mice are viable following naturally occurring and engineered loss of function with male mice infertile as anticipated, functional deletion of AR in pigs was hypothesized to provide a genetic containment strategy for males with edited genomes. In addition, deletion of AR might be a method to manage boar taint, hence contributing to a perceived improvement in animal welfare. The CRISPR/Cas9 technology was used to edit either exon 2 or exon 5 of the pig AR gene. Although pregnancies were established following embryo transfer of edited embryos, they were not maintained beyond day 25. Furthermore, normal M:F sex ratios were present in edited blastocysts and 19-day fetuses, but all fetuses recovered on day 21 or later were female. The pig AR gene differs from the mouse in having a U2 spliceosome component encoded in the intronic region. Hence, the absence of fetal survival beyond day 25 may be due to interference with the U2 component rather than AR.

Genome editing using programmable nucleases has revolutionized biomedical research. CRISPR-Cas9 mediated zygote genome editing enables high efficient production of knockout animals suitable for studying development and relevant human diseases. Here we report efficient disabling pancreatogenesis in pig embryos via zygotic co-delivery of Cas9 mRNA and dual sgRNAs targeting the PDX1 gene, which when combined with chimeric-competent human pluriopotent stem cells may serve as a suitable platform for the xeno-generation of human tissues and organs in pigs.

Suppose $ X $ is a compact connected metric space and $ f\colon X \to X $ is a metric coarse expanding conformal map in the sense of Haïssinsky-Pilgrim. We show that if $ X $ contains a homeomorphic copy of the letter 'Y', then the Hausdorff dimension of $ X $ is greater than one. As an application, we show that for a semi-hyperbolic rational map $ f $ its Julia set $ \mathcal{J}_f $ is quasi-symmetric equivalent to a space having Hausdorff dimension 1 if and only if $ \mathcal{J}_f $ is homeomorphic to a circle or a closed interval. [ABSTRACT FROM AUTHOR]

The present study investigated the potential role of the composition of dietary fatty acids in the regulation of biological rhythms, such as the sleep architecture, core body temperature and leukocyte clock gene expression, in subjects fed meals rich in palmitic acid (PA) or oleic acid (OA). Eleven males participated in two sessions of indirect calorimetry in a whole-room metabolic chamber. In each session, subjects consumed three meals rich in PA (44·3 % of total fat as PA and 42·3 % as OA) or OA (11·7 % of total fat as PA and 59·3 % as OA) in the metabolic chamber. The ratio of PA to OA in plasma was significantly lower and fat oxidation was significantly higher during 24 h of indirect calorimetry in the session with meals rich in OA than in that with meals rich in PA. The duration of slow wave sleep (SWS) was shorter, the latency of SWS was longer and the nadir of core body temperature after bedtime was later in the session with meals rich in PA than in that with meals rich in OA. The peak in CRY1 gene expression was earlier and its amplitude was higher in the session with meals rich in PA than in that with meals rich in OA. In healthy young males, meals rich in PA decreased fat oxidation and disrupted biological rhythms, particularly the sleep architecture and core body temperature during sleep, more than meals rich in OA. [ABSTRACT FROM AUTHOR]

Exposure to continuous light at night, including night-shift work or a nocturnal lifestyle, is emerging as a novel deleterious factor for weight gain and obesity. Here, we examined whether a single bout of bright light (BL) exposure at night affects energy metabolism via changes in circadian rhythm and nocturnal melatonin production. Ten healthy young men were randomized to a two-way crossover experimental design protocol: control (< 50 lux) and BL (approximately 10000 lux) conditions, with at least seven days of interval. The participants were exposed to each condition for 3 h (21:00–24:00) before sleep (0 lux, 00:00–07:00) in a room-type metabolic chamber. On each experimental night (21:00–07:00), energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured to determine the energy metabolism. BL exposure prior to bedtime altered biological rhythms, disrupted the nocturnal decline in body temperature, and suppressed the melatonin level before sleeping, resulting in an increase in sleep latency. Indirect calorimetry data revealed that BL exposure significantly decreased the fat oxidation and increased the RQ, an indicator of the carbohydrate-to-fat oxidation ratio, throughout the whole period (light exposure and sleep). We revealed that acute BL exposure prior to bedtime exacerbated circadian rhythms and substrate oxidations, suggesting that chronic BL exposure at night may lead to obesity risk due to disturbances in circadian rhythms and macronutrient metabolism. [ABSTRACT FROM AUTHOR]