Effect of chronic ethanol exposure on the liver of Clock-mutant mice

In humans, chronic ethanol consumption leads to a characteristic set of changes to the metabolism of lipids in the liver that is referred to as an "alcoholic fatty liver (AFL)". In severe cases, these metabolic changes result in the enlargement and fibrillization of the liver and are considered risk factors for cirrhosis and liver cancer. Clock-mutant mice have been shown to display abnormal lipid metabolism and alcohol preferences. To further understand the potential interactions between ethanol consumption, lipid metabolism, and the circadian clock, we investigated the effect of chronic ethanol intake on the lipid metabolism of Clock-mutant mice. We found that ethanol treatment produced a number of changes in the liver of Clock-mutant mice without impacting the wild-type controls. First, we found that 8 weeks of exposure to ethanol in the drinking water increased the weight of the liver in Clock-mutant mice. Ethanol treatment also increased triglyceride content of liver in Clock-mutant and wild-type mice. This increase was larger in the mutant mice. Finally, ethanol treatment altered the expression of a number of genes related to lipid metabolism in the Clock-mutant mice. Interestingly, this treatment did not impact circadian clock gene expression in the liver of either genotype. Thus, ethanol produces a number of changes in the liver of Clock-mutant mice that are not seen in the wild-type mice. These changes are consistent with the possibility that disturbance of circadian rhythmicity associated with the Clock mutation could be a risk factor for the development of an alcoholic fatty liver

Magnetically Driven Accretion in the Kerr Metric III: Unbound Outflows

We have carried out fully relativistic numerical simulations of accretion disks in the Kerr metric. In this paper we focus on the unbound outflows that emerge self-consistently from the accretion flow. These outflows are found in the axial funnel region and consist of two components: a hot, fast, tenuous outflow in the axial funnel proper, and a colder, slower, denser jet along the funnel wall. Although a rotating black hole is not required to produce these unbound outflows, their strength is enhanced by black hole spin. The funnel-wall jet is excluded from the axial funnel due to elevated angular momentum, and is also pressure-confined by a magnetized corona. The tenuous funnel outflow accounts for a significant fraction of the energy transported to large distances in the higher-spin simulations. We compare the outflows observed in our simulations with those seen in other simulations.Comment: 33 pages, 8 figures, ApJ submitte

The distinct distribution of two Dictyostelium Talins

Although the distinct distribution of certain molecules along the anterior or posterior edge is essential for directed cell migration, the mechanisms to maintain asymmetric protein localization have not yet been fully elucidated. Here, we studied a mechanism for the distinct localizations of two Dictyostelium talin homologues, talin A and talin B, both of which play important roles in cell migration and adhesion. Using GFP fusion, we found that talin B, as well as its C-terminal actin-binding region, which consists of an I/LWEQ domain and a villin headpiece domain, was restricted to the leading edge of migrating cells. This is in sharp contrast to talin A and its C-terminal actin-binding domain, which co-localized with myosin II along the cell posterior cortex, as reported previously. Intriguingly, even in myosin II-null cells, talin A and its actin-binding domain displayed a specific distribution, co-localizing with stretched actin filaments. In contrast, talin B was excluded from regions rich in stretched actin filaments, although a certain amount of its actin-binding region alone was present in those areas. When cells were sucked by a micro-pipette, talin B was not detected in the retracting aspirated lobe where acto-myosin, talin A, and the actin-binding regions of talin A and talin B accumulated. Based on these results, we suggest that talin A predominantly interacts with actin filaments stretched by myosin II through its C-terminal actin-binding region, while the actin-binding region of talin B does not make such distinctions. Furthermore, talin B appears to have an additional, unidentified mechanism that excludes it from the region rich in stretched actin filaments. We propose that these actin-binding properties play important roles in the anterior and posterior enrichment of talin B and talin A, respectively, during directed cell migration

Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice

Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents

Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7.

c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system

PO-158 Association Of Glucose Metabolism and Physical Activity By Chronotype in Elderly Japanese Adults: There is no full text article associated with this abstract

Objective Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. Although evening chronotype has been reported to be associated with bad glucose control and low physical activity in middle-aged adults, it is not known whether it is true in elderly people. Therefore, the aim of this study was to investigate the relationship between glucose metabolism and physical activity by chronotype (circadian rhythm) in elderly Japanese adults. Methods A cross-sectional study was conducted in 178 adults (72 men and 106 women), aged 60-79 years, who were classified into three chronotype groups, ”definitely morning type (DMT)”, “moderately morning type (MMT)” and “neither type (NET)”, based on the Morningness/Eveningness Questionnaire scores (MEQ-Score). All participants were required to report their daily rhythms of behavior, such as meal time and sleep-wake cycle. Additionally, their physical activity were measured by an uniaxial accelerometer (Kenz Lifecorder EX, SUZUKEN, Nagoya, Japan). Energy intake was assessed by a brief self-administered diet-history questionnaire. Blood was drawn for biochemical analysis after an overnight fast. Results BMI and serum insulin in the DMT group was significantly higher than MMT and NET groups in male. The DMT group had a significantly shorter time interval between dinner and sleep than the other two groups, both in male and female. After adjustment for covariates (age, smoking and alcohol status, energy intakes, moderate-vigorous physical activity (MVPA) and sleep duration), the BMI, serum insulin, fasting blood glucose (FBG) and HOMA-IR in the DMT group was significantly higher than other groups. However, after adjustment for the time interval between dinner and sleep, the significant difference had disappeared. There was significant difference in terms of low-intensity physical activity between male and female. And MVPA in the DMT group, the subjects with low MVPA (<23Mets·hour/week) had higher FBG, serum insulin and HOMA-IR than the subjects with high MVPA (>23Mets·hour/week) in men, but not in women. Conclusions This study demonstrated that the DMT group with early sleep-wake lifestyle had higher BMI,  FBG, serum insulin and HOMA-IR, specially in elderly Japanese men with low MVPA, but not in women

Distribution of Faraday Rotation Measure in Jets from Active Galactic Nuclei II. Prediction from our Sweeping Magnetic Twist Model for the Wiggled Parts of AGN Jets and Tails

Distributions of Faraday rotation measure (FRM) and the projected magnetic field derived by a 3-dimensional simulation of MHD jets are investigated based on our "sweeping magnetic twist model". FRM and Stokes parameters were calculated to be compared with radio observations of large scale wiggled AGN jets on kpc scales. We propose that the FRM distribution can be used to discuss the 3-dimensional structure of magnetic field around jets and the validity of existing theoretical models, together with the projected magnetic field derived from Stokes parameters. In the previous paper, we investigated the basic straight part of AGN jets by using the result of a 2-dimensional axisymmetric simulation. The derived FRM distribution has a general tendency to have a gradient across the jet axis, which is due to the toroidal component of the magnetic field generated by the rotation of the accretion disk. In this paper, we consider the wiggled structure of the AGN jets by using the result of a 3-dimensional simulation. Our numerical results show that the distributions of FRM and the projected magnetic field have a clear correlation with the large scale structure of the jet itself, namely, 3-dimensional helix. Distributions, seeing the jet from a certain direction, show a good matching with those in a part of 3C449 jet. This suggests that the jet has a helical structure and that the magnetic field (especially the toroidal component) plays an important role in the dynamics of the wiggle formation because it is due to a current-driven helical kink instability in our model.Comment: Accepted for publication in Ap

Euglena gracilis-derived β-glucan paramylon entrains the peripheral circadian clocks in mice

Paramylon, a β-1,3-glucan storage polysaccharide derived from Euglena gracilis, has various health benefits, such as anti-obesity effects and modulation of immune function. However, whether paramylon intake affects the circadian clock remains unknown. In this study, we examined the effect of paramylon intake on the circadian clock. The results showed that the paramylon intake regulated peripheral clocks in mice. Furthermore, cecal pH and short-chain fatty acid concentrations after paramylon intake were measured. The correlation between changes in the expression of clock-related genes and alterations in the intestinal environment was confirmed. In addition, peripheral clock entrainment by paramylon intake was not observed in antibiotic-treated mice whose gut microbiota was weakened. These findings suggest that the regulation of the circadian clock by paramylon intake was mediated by changes in gut microbiota. In addition, the entraining effect of paramylon intake was also confirmed in mice bred under conditions mimicking social jetlag, which implies that paramylon intake may contribute to recovery from social jetlag. Thus, the appropriate consumption of paramylon may have a beneficial effect on health from a chrono-nutritional perspective

Numerical Examination of the Stability of an Exact Two-dimensional Solution for Flux Pile-up Magnetic Reconnection

The Kelvin--Helmholtz (KH) and tearing instabilities are likely to be important for the process of fast magnetic reconnection that is believed to explain the observed explosive energy release in solar flares. Theoretical studies of the instabilities, however, typically invoke simplified initial magnetic and velocity fields that are not solutions of the governing magnetohydrodynamic (MHD) equations. In the present study, the stability of a reconnecting current sheet is examined using a class of exact global MHD solutions for steady state incompressible magnetic reconnection, discovered by Craig & Henton. Numerical simulation indicates that the outflow solutions where the current sheet is formed by strong shearing flows are subject to the KH instability. The inflow solutions where the current sheet is formed by a fast and weakly sheared inflow are shown to be tearing unstable. Although the observed instability of the solutions can be interpreted qualitatively by applying standard linear results for the KH and tearing instabilities, the magnetic field and plasma flow, specified by the Craig--Henton solution, lead to the stabilization of the current sheet in some cases. The sensitivity of the instability growth rate to the global geometry of magnetic reconnection may help in solving the trigger problem in solar flare research.Comment: Accepted for publication in ApJ. Associated movie files and a PDF with high-resolution figures are available at http://www.pha.jhu.edu/~shirose/Craig

Chrononutrition is associated with melatonin and cortisol rhythm during pregnancy: Findings from MY-CARE cohort study

Chrononutrition has been suggested to have an entrainment effect on circadian rhythm which is crucial for metabolic health. Investigating how chrononutrition affects maternal circadian rhythm can shed light on its role during pregnancy. This study aims to determine chrononutrition characteristics of healthy primigravida during pregnancy and its association with melatonin and cortisol rhythm across gestation. A total of 70 healthy primigravidas were recruited from ten randomly selected government maternal and child clinics in Kuala Lumpur, Malaysia. During the second and third trimesters, chrononutrition characteristics including meal timing, frequency, eating window, breakfast skipping, and late-night eating were determined using a 3-day food record. Pregnant women provided salivary samples at five time-points over a 24 h period for melatonin and cortisol assay. Consistently across the second and third trimesters, both melatonin and cortisol showed a rhythmic change over the day. Melatonin levels displayed an increment toward the night whilst cortisol levels declined over the day. Majority observed a shorter eating window (≤12 h) during the second and third trimesters (66 and 55%, respectively). Results showed 23 and 28% skipped breakfast whereas 45 and 37% ate within 2 h pre-bedtime. During the third trimester, a longer eating window was associated with lower melatonin mean (β = –0.40, p = 0.006), peak (β = –0.42, p = 0.006), and AUCG (β = –0.44, p = 0.003). During both trimesters, a lower awakening cortisol level was observed in pregnant women who skipped breakfast (β = –0.33, p = 0.029; β = –0.29, p = 0.044). Only during the second trimester, breakfast-skipping was significantly associated with a greater cortisol amplitude (β = 0.43, p = 0.003). Findings suggest that certain chrononutrition components, particularly eating window and breakfast skipping have a significant influence on maternal melatonin and cortisol rhythm. Dietary intervention targeting these characteristics may be useful in maintaining maternal circadian rhythm