Oral isotretinoin is the most effective anti‐acne drug with the strongest sebum‐suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin‐induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro‐apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non‐phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne‐free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo‐cytoplasmic ratio of non‐phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin‐induced pro‐apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin‐mediated upregulation of FoxO expression.
The public sector in Egypt provides relatively generous benefits, particularly when compared to the working conditions in the predominantly informal private sector in the country. For this reason, it has been described as the employer of choice among youth in Egypt. This chapter shows a continued preference of government hiring, using the Egypt Labor Market Panel Survey (ELMPS) 2018 data. The analysis also shows that the share of the sector in employment has been declining. Inside the government, we show that the sector is becoming more educated as it consistently hires more workers with university and post-graduate education. Focusing on those employed in the government, the analysis over time shows that the sector is becoming slightly more feminized and is aging. This reflects the evolution of hiring policies in the sector. Despite an increasing presence of women in the sector, it has not reached gender parity.
Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of sleep, but does not activate sleep homeostatic mechanisms nor induce impairments in short-term memory also resulted in flies choosing warmer temperatures. To identify the underlying neuronal circuits, we used RNAi to knock down the receptor for Pigment dispersing factor, a peptide that influences circadian rhythms, temperature preference and sleep. Expressing UAS-PdfrRNAi in subsets of clock neurons prevented sleep fragmentation from increasing temperature preference. Finally, we evaluated temperature preference after flies had undergone a social jet lag protocol which is known to disrupt clock neurons. In this protocol, flies experience a 3 h light phase delay on Friday followed by a 3 h light advance on Sunday evening. Flies exposed to social jet lag exhibited an increase in temperature preference which persisted for several days. Our findings identify specific clock neurons that are modulated by sleep disruption to increase temperature preference. Moreover, our data indicate that temperature preference may be a more sensitive indicator of sleep disruption than learning and memory.
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