A Consistent Orbital Stability Analysis for the GJ 581 System

We apply a combination of N-body modeling techniques and automated data fitting with Monte Carlo Markov Chain uncertainty analysis of Keplerian orbital models to radial velocity data to determine long term stability of the planetary system GJ 581. We find that while there are stability concerns with the 4-planet model as published by Forveille et al. (2011), when uncertainties in the system are accounted for, particularly stellar jitter, the hypothesis that the 4-planet model is gravitationally unstable is not statistically significant. Additionally, the system including proposed planet g by Vogt et al. (2012) also shows some stability concerns when eccentricities are allowed to float in the orbital fit, yet when uncertainties are included in the analysis the system including planet g also can not be proven to be unstable. We present revised reduced chi-squared values for Keplerian astrocentric orbital fits assuming 4-planet and 5-planet models for GJ~581 under the condition that best fits must be stable, and find no distinguishable difference by including planet g in the model. Additionally we present revised orbital element estimates for each assuming uncertainties due to stellar jitter under the constraint of the system being gravitationally stable.Comment: 26 pages, 8 figures, 6 tables, accepted for publication in the Astrophysical Journa

Sleep disturbances and suicide risk: A review of the literature

A growing body of research indicates that sleep disturbances are associated with suicidal ideation and behaviors. This article (1) provides a critical review of the extant literature on sleep and suicidality and (2) addresses shared underlying neurobiological factors, biological and social zeitgebers, treatment implications, and future directions for research. Findings indicate that suicidal ideation and behaviors are closely associated with sleep complaints, and in some cases, this association exists above and beyond depression. Several cross-sectional investigations indicate a unique association between nightmares and suicidal ideation, whereas the relationship between insomnia and suicidality requires further study. Underlying neurobiological factors may, in part, account for the relationship between sleep and suicide. Serotonergic neurotransmission appears to play a critical role in both sleep and suicide. Finally, it remains unclear whether or not sleep-oriented interventions may reduce risk for suicidal behaviors. Unlike other suicide risk factors, sleep complaints may be particularly amenable to treatment. As a warning sign, disturbances in sleep may thus be especially useful to research and may serve as an important clinical target for future suicide intervention efforts

Effects of High Fat Diet and Exercise on the Metabolism of Maternal Hearts during Pregnancy

Obesity has become a major concern for developed nations across the world, and the United States is the country which is most affected by this pandemic. Excess adiposity is known to cause chronic inflammation, diabetes, cancer, and cardiovascular disease: the leading cause of death for over a decade. With many women of reproductive age considered overweight or obese, the association between obesity and metabolic disorder is concerning. Positive metabolic health outcomes of offspring due to maternal exercise have been documented; however, little is known about how maternal exercise modifies high fat diet associated metabolic dysregulation upon mothers during gestation. The aim of our study was to determine whether maternal exercise before and during pregnancy would alleviate high fat diet-associated glucose and insulin resistance in high fat fed pregnant mice. Using C57BL/6 virgin female mice as a model, we fed the animals either a low fat diet (LFD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for twelve weeks, with an exercise intervention after four weeks (HFD+Ex), and pregnancy initiation after eight weeks of diet consumption. Glucose and insulin tolerance tests were performed at day 15 of gestation. Prescribed diet and exercise (or sedentary) behavior continued throughout pregnancy until animals were sacrificed at the 19th day of gestation. The HFD animals experienced a significant increase in body weight, along with increased numbers of calories consumed per day, and exercise further increased body weight and food intake. Both the HFD and the HFD+Ex animals displayed impaired glucose and insulin tolerance testing when compared with the LFD animals. Interestingly, exercise improved serum insulin levels at termination. mRNA expression of genes involved in fatty acid and glucose metabolism were upregulated in the HFD+Ex animals compared with the HFD mice. Our study exhibits that the development of adiposity from the consumption of a high fat diet prior to pregnancy leads to detrimental maternal effects during late gestation, including higher body weight, and glucose tolerance. Surprisingly, the addition of exercise did not alter dam morphology or gestational glucose tolerance; however, it did improve serum insulin levels and metabolite handling in the heart

Electron‐deficient p‐benzoyl‐l‐phenylalanine derivatives increase covalent chemical capture yields for protein–protein interactions

The photoactivatable amino acid p‐benzoyl‐l‐phenylalanine (pBpa) has been used for the covalent capture of protein–protein interactions (PPIs) in vitro and in living cells. However, this technique often suffers from poor photocrosslinking yields due to the low reactivity of the active species. Here we demonstrate that the incorporation of halogenated pBpa analogs into proteins leads to increased crosslinking yields for protein–protein interactions. The analogs can be incorporated into live yeast and upon irradiation capture endogenous PPIs. Halogenated pBpas will extend the scope of PPIs that can be captured and expand the toolbox for mapping PPIs in their native environment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149350/1/pro3621.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149350/2/pro3621_am.pd

Maternal Exercise Activates Genes Associated with Mitochondrial Biogenesis in Fetal Myocardium of Mouse

Maternal exercise during pregnancy has been shown to improve long-term metabolic health on offspring in later life. Mitochondria are the critical site of metabolism, and are inherited by maternal origin. However, the effects of maternal exercise during pregnancy on fetal mitochondrial biogenesis are not well understood. PURPOSE: To test whether maternal exercise can activate genes associate with mitochondrial biogenesis in the fetal heart. METHODS: Female C57BL/6 mice were divided into sedentary and exercise groups. The mice in the exercise group were exposed to voluntary cage-wheel from gestational day 1 through 17, at which time they were sacrificed. Litter size and individual fetal weights (3 days before birth) were taken when pregnant dams were sacrificed. All fetuses were sexed and two to three hearts from same sex within the group were pooled to study gene expression: all data were presented by group since there was no sex difference within group. RESULTS: Exercise dams ran an average of 7.22 ± 0.41km/day until mid-pregnancy and gradually decreased to low levels (1.39 ± 0.43 km/day) through the remainder of gestation. Weight gain during pregnancy was not significantly different between exercise (14.45 ± 0.99g) and sedentary (15.99 ± 1.13g) pregnant dams. There were no significant differences in litter size, sex distribution, and average fetal body weight per litter between sedentary and exercise dams. Genes associated with mitochondrial biogenesis, including Ppargc1a (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), Nrf1 (nuclear respiratory factor-1), and Nrf2 (nuclear respiratory factor-2) were significantly upregulated in fetuses from exercise dams. CONCLUSION: Although total kilometers run per day (km/day) were significantly decreased in later stage of pregnancy, maternal exercise initiated at day 1 of gestation significantly increased genes associated with mitochondria biogenesis, indicating that maternal exercise enhances mitochondrial biogenesis and mitochondrial function

A Bifunctional Amino Acid Enables Both Covalent Chemical Capture and Isolation of in Vivo Protein–Protein Interactions

In vivo covalent chemical capture by using photoactivatable unnatural amino acids (UAAs) is a powerful tool for the identification of transient protein–protein interactions (PPIs) in their native environment. However, the isolation and characterization of the crosslinked complexes can be challenging. Here, we report the first in vivo incorporation of the bifunctional UAA BPKyne for the capture and direct labeling of crosslinked protein complexes through post‐crosslinking functionalization of a bioorthogonal alkyne handle. Using the prototypical yeast transcriptional activator Gal4, we demonstrate that BPKyne is incorporated at the same level as the commonly used photoactivatable UAA pBpa and effectively captures the Gal4–Gal80 transcriptional complex. Post‐crosslinking, the Gal4–Gal80 adduct was directly labeled by treatment of the alkyne handle with a biotin‐azide probe; this enabled facile isolation and visualization of the crosslinked adduct from whole‐cell lysate. This bifunctional amino acid extends the utility of the benzophenone crosslinker and expands our toolbox of chemical probes for mapping PPIs in their native cellular environment.Using the bifunctional unnatural amino acid, BPKyne, we have developed a strategy to capture and directly label transient protein–protein interactions (PPIs) in their native environment. Click chemical functionalization post‐crosslinking with a biotin–azide probe enabled the isolation of transcriptional protein complexes from yeast cells. This amino acid will expand the toolbox for the discovery of new PPIs in live cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135955/1/cbic201600578.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135955/2/cbic201600578_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135955/3/cbic201600578-sup-0001-misc_information.pd

Age, Period, and Cohort Trends in Mood Disorder and Suicide-Related Outcomes in a Nationally Representative Dataset, 2005-2017

Drawing from the National Survey on Drug Use and Health (NSDUH; N = 611,880), a nationally representative survey of U.S. adolescents and adults, we assess age, period, and cohort trends in mood disorder and suicide-related outcomes since the mid-2000s. Rates of major depressive episode in the last year among adolescents aged 12 to 17 increased by 52% 2005-2017; major depressive episode in the last year increased 63% between 2009 and 2017 among young adults 18-25. Serious psychological distress in the last month and suicide-related outcomes (suicidal ideation, plans, attempts, and deaths by suicide) in the last year also increased among young adults 18-25 between 2008 and 2017, with less consistent and weaker increases among adults ages 26 and over. Hierarchical linear modeling analyses separating the effects of age, period, and birth cohort suggest the trends among adults are primarily due to cohort, with a steady rise in mood disorder and suicide-related outcomes over birth cohorts from the early 1980s to the late 1990s. Cultural trends contributing to an increase in mood disorders and suicidal thoughts and behaviors since the mid-2000s, including the rise of electronic communication and digital media and declines in sleep duration, may have had a larger impact on younger people, creating a cohort effect