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Identifying Breast Cancer Treatment Biomarkers Using Transcriptomics
Published in Shazia Rashid, Ankur Saxena, Sabia Rashid, Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Genomic biomarkers like somatic structural variations (Tubio, 2015) can help in zooming in to the change-maker genes in cancer. Previously studies have shown that structural variations in circadian genes like Per3 can increase the risk of breast cancer (Zhu et al., 2005). Therefore, it’s worth looking at structural variations like insertions, deletions, copy number variations, and translocations in trying to understand the links between what is happening in the genome and how it is affecting the transcriptome.
Sleep deprivation therapy: A rapid-acting antidepressant
Published in S.R. Pandi-Perumal, Meera Narasimhan, Milton Kramer, Sleep and Psychosomatic Medicine, 2017
The results showed a significant and marked loss in rhythmicity in the top-ranked cyclic genes in MDD patients compared to controls and provided the first direct evidence of dysregulation in clock gene expression across six brain regions. The findings were independent of medication and cause of death. Dysregulated genes included the core circadian clock genes (i.e., BMAL1, PER1, PER2, PER3, Rev-Erbα, DBP, DEC1, and DEC2), which are essential to modulating virtually all rhythms throughout the body.84
Neurobiology of Mood Disorders
Published in Dr. Ather Muneer, Mood Disorders, 2018
The SCN neurons house the circadian molecular hub, while the clock itself is composed of a series of transcriptional and translational feedback loops that result in the rhythmic expression of clock genes on a timescale of just over 24 hours. In the primary feedback loop, the transcription factors, Circadian Locomotor Output Cycles Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), heterodimerize and bind to E-box containing sequences in a number of genes including the three Period (PER) genes (PER1, PER2 and PER3) and two Cryptochrome (CRY) genes (CRY1 and CRY2). Over time PER and CRY proteins dimerize in the cytosol and are shuttled back into the nucleus where CRY proteins can directly inhibit the activity of CLOCK and BMAL1. In addition to this feedback loop, the CLOCK and BMAL1 proteins regulate the expression of Rev-erbα and ROR (retinoic acid-related orphan nuclear receptors) which in turn can repress or activate BMAL1 transcription respectively, through action at the Rev-Erb/ROR response element in the promoter. There are several key proteins which regulate the timing of the molecular clock through phosphorylation, sumoylation and other mechanisms. The enzymes, casein kinases, phosphorylate the PER, CRY and BMAL1 proteins altering their stability and nuclear entry; glycogen synthase kinase 3 beta (GSK3β) also phosphorylates the PER2 protein facilitating its nuclear entry.8 As alluded to above many controlling kinases, phosphatases and secondary feedback loops act on the molecular clock, contributing to great intricacy to the circadian apparatus. Significantly, circadian transcription factors are involved in the regulation and functioning of several other clock-controlled genes, which partake in a whole range of homeostatic actions in every body system. As will become clear in the ensuing sections, these sub-cellular mechanisms regulate the key physiological functions of the body in a circadian fashion.
Dim light melatonin onset following simulated eastward travel is earlier in young males genotyped as PER35/5 than PER34/4
Published in Chronobiology International, 2022
Lovemore Kunorozva, Dale E. Rae, Laura C. Roden
While the only sleep-related difference between the two groups following the day of resynchronisation was that the PER35/5 group had a slightly shorter sleep onset latency, the changes in total sleep time, sleep efficiency and wake after sleep onset time measured in the PER35/5 group between the two sleep opportunities may reflect an earlier shift towards habitual sleep quality markers measured before the trial. This means that the PER34/4 individuals may experience impaired sleep duration and efficiency during the early part of their sleep opportunity due to attempting to sleep during their wake maintenance zone (Dijk and Czeisler 1994; Lavie 1986; Sletten et al. 2015), as a result of the misalignment between their sleep time and circadian clock. Measurement of sleep patterns over at least another five days, however, would provide better insight as to the extent which PER3 VNTR genotype might impact resynchronisation of sleep patterns. Furthermore, since the sleepiness scores of the two groups both during the first day of resynchronisation and during the second constant routine period were similar, it is possible that, as discussed below, the acute effects of sleep deprivation induced by the first constant routine (>28 h of continued wakefulness), may mask underlying circadian disruption-related effects on sleep characteristics or daytime sleepiness in the immediate period after simulated eastward travel.
Atrazine neural and reproductive toxicity
Published in Toxin Reviews, 2022
Hamidreza Sadeghnia, Sara Shahba, Alireza Ebrahimzadeh-Bideskan, Shabnam Mohammadi, Amir Mohammad Malvandi, Abbas Mohammadipour
It also alters genes associated with neuroendocrine such as CYP17A1, phosphodiesterase 10 A (PDE10A), LH, thyroid hormone receptor alpha (THRA), and adenylate cyclase 1 (ADCY1) (Weber et al. 2013, Wirbisky et al. 2015). In addition, alterations in period 1 (PER1) and period 3 (PER3) have already been reported after embryonic exposure to atrazine. PER1 and PER3 have been shown to play a role in regulating circadian rhythm (Wirbisky et al. 2016a). This herbicide has also been shown to change zebrafish's defensive and social behaviors by decreasing brain acetylcholinesterase (AChE) activity (Schmidel et al. 2014). As studies show, there is a close relationship between the cholinergic system and social stress, anxiety, depression, and resilience (Mineur et al. 2013). Thus, atrazine seems to have the potential to induce behavioral changes in humans.
Time-of-day effects on objective and subjective short-term memory task performance
Published in Chronobiology International, 2021
Anna Ceglarek, Magdalena Hubalewska-Mazgaj, Koryna Lewandowska, Barbara Sikora-Wachowicz, Tadeusz Marek, Magdalena Fafrowicz
The effect of the homeostatic process (the accumulation of sleep pressure throughout the day Goel et al. 2009) was not observed, regardless of the chronotype. Currently, research shows that PER3 polymorphism is more related to the homeostatic process, in a way that PER3 5/5 carriers were more prone to the accumulation of sleep pressure (Archer et al. 2018). Our results revealed no differences between chronotypes in the evening hours in both objective and subjective performance – the only disparity between chronotypes was in accuracy; however, it was independent of the time-of-day. We have shown that with a moderately demanding task and with well-rested participants, the effect of the homeostatic process and synchrony effect are not visible. The results of the current study, as well as Schmidt et al. (2015), demonstrated that tasks with low and medium cognitive load don’t show the synchrony effect.