Serotoninergic and Circadian Systems: Driving Mammary Gland Development and Function

Since lactation is one of the most metabolically demanding states in adult female mammals, beautifully complex regulatory mechanisms are in place to time lactation to begin after birth and cease when the neonate is weaned. Lactation is regulated by numerous different homeorhetic factors, all of them tightly coordinated with the demands of milk production. Emerging evidence support that among these factors are the serotonergic and circadian clock systems. Here we review the serotoninergic and circadian clock systems and their roles in the regulation of mammary gland development and lactation physiology. We conclude by presenting our hypothesis that these two systems interact to accommodate the metabolic demands of lactation and thus adaptive changes in these systems occur to maintain mammary and systemic homeostasis through the reproductive cycles of female mammals

Exploring disruption through the lens of an adapted Five Senses Framework

This quasi-experimental research design surveyed 688 students through a self-administered online survey to specifically explore relations between student self-assessed capabilities (Lizzio Five Senses, 2006), overall program satisfaction, withdrawal behaviours, demographics and year of study in their university courses during an emergency COVID-19 lockdown experience. Importantly, this research offers a more nuanced view of the Five Senses and confirms their importance as a university strategy for student success. These findings offer further granularity into the complex set of relations that impact decisions around satisfaction, persistence, and capability in higher education and support previous research by Lizzio and Wilson (2008) indicating students’ perceptions of purpose is the strongest predictor of satisfaction, lower anxiety and lower course withdrawal. Ultimately, the paper suggests as higher education looks towards future possible disruptions due to climate, health or political realities, equipping and fostering a strong sense of purpose, connectedness, and resourcefulness as well as sense of capability and academic culture will buffer and support students to persevere. In addition, this research suggests that those students who may have weak associations with these senses merit additional attention

Does STAT5a Have an Effect on BMAL1 Levels in Mammary Epithelial Cells?

The mammary gland is a very important organ for reproduction in mammals because it produces milk which serves as the primary source of nutrients for newly-born offspring. Previous studies suggest that its development is regulated by circadian clocks, biochemical oscillators that generate circadian rhythms (the body’s internal clock). The circadian system plays a major role in homeostasis, coordinating the body’s internal physiology and synchronizing it with the external environment. Our lab showed that levels of the BMAL1 protein, a core clock component, increased in the mammary gland at the onset of lactation. Treatment of mammary epithelial cells (HC11) with the hormone prolactin significantly increased BMAL1 levels. We hypothesize that the secretion of prolactin during lactogenesis induces expression of BMAL1 in the mouse mammary gland through the STAT5a signaling pathway. The objective of the project was to determine the effect of different amounts of STAT5a protein on BMAL1 levels with and without prolactin treatment. For this experiment, western blot analysis was used to measure STAT5a and BMAL1 levels in wild type HC11 cells and in HC11 cell lines that were genetically modified to: 1) express very high levels of STAT5a (STAT5a-OE), 2) express a mutant form of STAT5a that is inactive (STAT5a-dnl), and 3) delete the BMAL1 gene (BMAL1 KO). Our first round of analysis showed that overexpressing STAT5a increased BMAL1 protein levels, especially in cells differentiated by prolactin. Results from this experiment would allow us to better understand the relationship between mammary gland development and the circadian system

Relationship Between Sleep Quality, Depression Symptoms, and Blood Glucose in Pregnant Women

Sleep quality during pregnancy affects maternal/child health. We aimed to assess changes in sleep quality during pregnancy and determine its relationship to maternal mood, blood glucose, and work schedule among primiparous women. We conducted a prospective/longitudinal/observational study. Ninety-two pregnant women were recruited from Midwestern hospital. Mood and sleep quality data were collected using Edinburgh Postnatal Depression Scale/Pittsburgh Sleep Quality Index at Gestational Weeks 22 and 32. Forty-three women completed the study. Twenty-six women (63%) were African American and the mean age was 23.64 (SD = 3.82) years. Rate of poor sleep quality increased during pregnancy with 25% of women had scores indicative of depression symptoms. Poor sleep quality score was related to mood scores (p < .05) and work schedule. Blood glucose was not significantly related to sleep duration. In conclusion, poor sleep quality during pregnancy was associated with poor mood and work schedule, suggesting that interventions targeting mental health and lifestyles are needed

Prospectus, November 30, 2005

https://spark.parkland.edu/prospectus_2005/1028/thumbnail.jp

Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep

Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive (‐ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30–90 or 60–90 resulted in increased numbers of VTA TH‐ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T‐treated ewes, which was primarily accounted for by greater numbers of TH‐ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T‐treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH‐ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH‐ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.We report a sex difference in ventral tegmental area (VTA) dopamine cells in the adult sheep with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive cells in males than females. Moreover, prenatal exposure to excess T during gestational days 30–90 or 60–90 caused increased numbers of VTA TH‐immunoreactive cells in adult ewes compared to control females. Sex differences were also demonstrated in the substantia nigra, but prenatal T had no effect on TH in this area. Results indicate that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels in the VTA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111123/1/ejn12871.pd

Kmt2c mutations enhance HSC self-renewal capacity and convey a selective advantage after chemotherapy

The myeloid tumor suppressor KMT2C is recurrently deleted in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly therapy-related MDS/AML (t-MDS/t-AML), as part of larger chromosome 7 deletions. Here, we show that KMT2C deletions convey a selective advantage to hematopoietic stem cells (HSCs) after chemotherapy treatment that may precipitate t-MDS/t-AML. Kmt2c deletions markedly enhance murine HSC self-renewal capacity without altering proliferation rates. Haploid Kmt2c deletions convey a selective advantage only when HSCs are driven into cycle by a strong proliferative stimulus, such as chemotherapy. Cycling Kmt2c-deficient HSCs fail to differentiate appropriately, particularly in response to interleukin-1. Kmt2c deletions mitigate histone methylation/acetylation changes that accrue as HSCs cycle after chemotherapy, and they impair enhancer recruitment during HSC differentiation. These findings help explain why Kmt2c deletions are more common in t-MDS/t-AML than in de novo AML or clonal hematopoiesis: they selectively protect cycling HSCs from differentiation without inducing HSC proliferation themselves

Delayed Lactogenesis II is Associated With Lower Sleep Efficiency and Greater Variation in Nightly Sleep Duration in the Third Trimester

Background: Metabolic and hormonal disturbances are associated with sleep disturbances and delayed onset of lactogenesis II. Research aims: The aim of this study was to measure sleep using wrist actigraphy during gestation weeks 22 and 32 to determine if sleep characteristics were associated with blood glucose, body mass index, gestational related disease, delayed onset of lactogenesis II, or work schedule. Methods: Demographic data were collected at study intake from primiparous women who wore a wrist actigraph during gestation weeks 22 (n = 50) and 32 (n = 44). Start and end sleep time, total nighttime sleep, sleep efficiency, wake after sleep onset, and sleep fragmentation were measured. Night to night variability was assessed with the root mean square of successive difference. Blood glucose levels, body mass index, and gestational disease data were abstracted from medical charts. Timing of lactogenesis II was determined by survey. Results: Between gestation week 22 and 32, sleep efficiency decreased and fragmentation increased (p < .05). During gestation week 32, blood glucose was negatively correlated with sleep duration, and positively related to fragmentation (p < .05). Women who experienced delayed lactogenesis II had lower sleep efficiency and greater fragmentation (p < .05), and greater night-to-night variability in sleep start and end time, efficiency, and duration during gestation week 32 (p < .05). Conclusion: Women with better sleep efficiency and more stable nightly sleep time are less likely to experience delayed onset of lactogenesis II. Interventions to improve sleep may improve maternal health and breastfeeding adequacy

Recurrent mutation in the crystallin alpha A gene associated with inherited paediatric cataract

© 2016 Javadiyan et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Cataract is a major cause of childhood blindness worldwide. The purpose of this study was to determine the genetic cause of paediatric cataract in a South Australian family with a bilateral lamellar paediatric cataract displaying variable phenotypes. Case presentation: Fifty-one genes implicated in congenital cataract in human or mouse were sequenced in an affected individual from an Australian (Caucasian) family using a custom Ampliseq library on the Ion Torrent Personal Genome Machine. Reads were mapped against the human genome (hg19) and variants called with the Torrent Suite software. Variants were annotated to dbSNP 137 using Ion Reporter (IR 1.6.2) and were prioritised for validation if they were novel or rare and were predicted to be protein changing. We identified a previously reported oligomerization disrupting mutation, c.62G > A (p.R21Q), in the Crystallin alpha A (CRYAA) gene segregating in this three generation family. No other novel or rare coding mutations were detected in the known cataract genes sequenced. Microsatellite markers were used to compare the haplotypes between the family reported here and a previously published family with the same segregating mutation. Haplotype analysis indicated a potential common ancestry between the two South Australian families with this mutation. The work strengthens the genotype-phenotype correlations between this functional mutation in the crystallin alpha A (CRYAA) gene and paediatric cataract. Conclusion: The p.R21Q mutation is the most likely cause of paediatric cataract i