35 research outputs found

    Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

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    Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10 <sup>cre/cre</sup> Bmal1 <sup>fl/-</sup> ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4 <sup>-/-</sup> ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society

    Atypical Effect of Displacement Damage on LM124 Bipolar Integrated Circuits

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    International audienceLM124 operational amplifiers from three different manufacturers are irradiated with 60Co gamma rays and neutrons. During neutrons irradiation, one of the three integrated circuits exhibits an unexpected slew rates increase while its open loop gain and supply bias current follow the usual monotonic decrease as described in the literature. Analysis at circuit level shows that this phenomenon is due to an increase in the radiation-induced base current of the transistor used as buffer stage in the amplification chain. It is then demonstrated that a slight modification of the buffer transistor design, which is not implemented on the two other devices, enhances this phenomenon. Finally, the impact of the buffer transistor design on displacement damage and total ionizing dose response is investigated

    A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development

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    Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans

    Impact of Total Ionizing Dose on the Electromagnetic Susceptibility of a single bipolar transistor

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    International audienceSpace or military electronic components are subject to both electromagnetic fields and total ionizing dose. This paper deals with the modification in the susceptibility to 100 MHz – 1.5 GHz signals of a discrete low frequency transistor subsequently to total ionizing dose deposition. The electromagnetic susceptibility is investigated on both non-irradiated and irradiated transistors mounted in common emitter configuration. A synergy effect between near field electromagnetic interferences and total ionizing dose is observed

    Analysis of the proton-induced permanent degradation in an optocoupler

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