Dietary fat and corticosterone levels are contributing factors to meal anticipation

Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content

Vertex importance extension of betweenness centrality algorithm

Variety of real-life structures can be simplified by a graph. Such simplification emphasizes the structure represented by vertices connected via edges. A common method for the analysis of the vertices importance in a network is betweenness centrality. The centrality is computed using the information about the shortest paths that exist in a graph. This approach puts the importance on the edges that connect the vertices. However, not all vertices are equal. Some of them might be more important than others or have more significant influence on the behavior of the network. Therefore, we introduce the modification of the betweenness centrality algorithm that takes into account the vertex importance. This approach allows the further refinement of the betweenness centrality score to fulfill the needs of the network better. We show this idea on an example of the real traffic network. We test the performance of the algorithm on the traffic network data from the city of Bratislava, Slovakia to prove that the inclusion of the modification does not hinder the original algorithm much. We also provide a visualization of the traffic network of the city of Ostrava, the Czech Republic to show the effect of the vertex importance adjustment. The algorithm was parallelized by MPI (http://www.mpi-forum.org/) and was tested on the supercomputer Salomon (https://docs.it4i.cz/) at IT4Innovations National Supercomputing Center, the Czech Republic.808726

Armor or Withdraw? Likely Litigation and Potential Adjudication of Shoreland Conflicts Along Michigan\u27s Shifting Great Lake Coasts

Michigan enjoys along its inland seas, the Laurentian Great Lakes, one of the longest coastlines in the U.S. Much of that shoreline is privately owned. Because of a confluence of development pressures and irrepressible physical dynamics, growing numbers of Great Lakes shoreland properties, built on shifting sandy shores, are at heightened risk of loss from coastal storm surge, inundation, erosion, and shoreline recession. In response, property owners are installing extensive hardened shoreline armoring structures like seawalls and revetments to arrest those erosional processes. Those structures, however, will substantially impair, if not ultimately destroy, the state’s natural coastal beaches and other shoreland resources, as well as accelerate erosion of neighboring shoreland properties. The clash of imperatives to protect shoreland properties versus conserve coastal resources signifies a wicked dilemma the State cannot avoid: armor or withdraw? More precisely, should we allow the armoring of Michigan’s Great Lakes shorelines in an attempt to fix in place shoreland properties, at great and ongoing private and public expense, and ultimately risk the loss of public trust resources? Or should we allow—and should we compel shoreland property owners to allow—natural processes to proceed, even though doing so will increase the rate at which privately owned shorelands naturally convert into state-owned submerged bottomlands? We cannot hope to simultaneously protect both the beach and the beach house along naturally receding Great Lakes shorelines; we must choose which interest to prioritize first, recognizing the cost of doing so by losing the other. In addition to the complex physical dynamics at play along Michigan’s Great Lakes coasts, there are evolving legal complexities as well. The State, as sovereign, enjoys police power authorities that encompass coastal shoreland management. The State has also long recognized the applicability of the public trust doctrine to its Great Lakes shores, and its constitution mandates the protection of natural resources. This article first analyzes current Michigan law to determine how those doctrines and mandates apply to Great Lakes shoreline armoring, particularly in terms of what to prioritize. Based on that assessment, we conclude that Michigan’s courts, legislature, and people have consistently and clearly prioritized protecting and conserving Great Lakes natural coastal resources above developing or impairing them for private use, except when such development truly serves larger public trust interests. In contrast, the administrative rules now used to execute those protections prioritize protecting the private beach house first, even at the expense of destroying the natural beach and impairing other public trust interests. This administrative approach was not inevitable— indeed it may be unlawful—and it has created strong expectations on the part of shoreland property owners, heightening the likelihood of litigation. The article then analyzes current Michigan law to determine how the courts might resolve disputes between property owners hoping to armor the shore and State or local constraints on such armoring. Here we find that while the Michigan courts have resolved a number of key questions regarding coastal shorelands, there is no caselaw addressing directly the lawfulness of shoreline armoring. Based on our review of relevant caselaw, we conclude the courts are not likely to find that the State lacks authority to regulate—or prohibit altogether—shoreline armoring to protect coastal resources. There is conflicting caselaw, however, upon which the courts could rely to find either that the current regulatory regime provides adequate protection of coastal resources, or alternatively that it is deficient. Finally, beyond questions of regulatory authority, the courts are not likely to find that reinvigorated regulatory efforts to prevent the destruction and impairment of public trust coastal resources from armoring—even those resulting in the accelerated loss of private properties—violate constitutional protections, especially if State reforms are undertaken with deliberation and care. If the courts conclude that current regulatory efforts are lawful and require no greater protection, then Michigan will likely see much of its Great Lakes shorelines armored and its natural coastal beaches destroyed. If they conclude that current regulatory efforts are deficient (or if they approve of reinvigorated protection efforts), however, then private shoreland properties may be lost to the lakes. Such losses cannot be avoided forever, especially along naturally receding shorelines, but they might occur sooner than would happen absent attempts to arrest shoreline erosion with armoring. As with most wicked policy dilemmas, the best response may not be at either extreme—always armor or always withdraw—but somewhere in between. Crafting that hybrid approach, and the appropriate rules for applying it, will be the most challenging course to navigate

Sleep homeostasis during daytime food entrainment in mice

24h rhythms of physiology and behavior are driven by the environment and an internal endogenous timing system. Daily restricted feeding (RF) in nocturnal rodents during their inactive phase initiates food anticipatory activity (FAA) and a reorganisation of the typical 24h sleep-wake structure. Here, we investigate the effects of daytime feeding, where food access was restricted to 4h during the light period ZT4-8 (Zeitgeber time; ZT0 is lights on), on sleep-wake architecture and sleep homeostasis in mice. Following 10 days of RF, mice were returned to ad libitum feeding. To mimic the spontaneous wakefulness associated with FAA and daytime feeding, mice were then sleep deprived between ZT3-6. While the amount of wake increased during FAA and subsequent feeding, total wake time over 24h remained stable as the loss of sleep in the light phase was compensated for by an increase in sleep in the dark phase. Interestingly, sleep which followed spontaneous wake episodes during the dark period and the extended period of wake associated with FAA, exhibited lower levels of slow-wave activity (SWA) when compared to baseline or after sleep deprivation, despite a similar duration of waking. This suggests an evolutionary mechanism of reducing sleep drive during negative energy balance to enable greater arousal for food seeking behaviors. However, the total amount of sleep and SWA accumulated during the 24h was similar between baseline and RF. In summary, our study suggests that despite substantial changes in the daily distribution and quality of wake induced by RF, sleep homeostasis is maintained.</p

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Circadian Behaviour in Neuroglobin Deficient Mice

Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night

How Coupling Determines the Entrainment of Circadian Clocks

Autonomous circadian clocks drive daily rhythms in physiology and behaviour. A network of coupled neurons, the suprachiasmatic nucleus (SCN), serves as a robust self-sustained circadian pacemaker. Synchronization of this timer to the environmental light-dark cycle is crucial for an organism's fitness. In a recent theoretical and experimental study it was shown that coupling governs the entrainment range of circadian clocks. We apply the theory of coupled oscillators to analyse how diffusive and mean-field coupling affects the entrainment range of interacting cells. Mean-field coupling leads to amplitude expansion of weak oscillators and, as a result, reduces the entrainment range. We also show that coupling determines the rigidity of the synchronized SCN network, i.e. the relaxation rates upon perturbation. %(Floquet exponents). Our simulations and analytical calculations using generic oscillator models help to elucidate how coupling determines the entrainment of the SCN. Our theoretical framework helps to interpret experimental data

Neuropeptide Signaling Differentially Affects Phase Maintenance and Rhythm Generation in SCN and Extra-SCN Circadian Oscillators

Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2, play important roles in the functioning of the SCN pacemaker. Mice lacking VPAC2 receptors (Vipr2−/−) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. Within the brain, the SCN is not the only site containing endogenous circadian oscillators, nor is it the only site of VPAC2 receptor expression; both VPAC2 receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. The functional role of VPAC2 receptors in rhythm generation and maintenance in these tissues is, however, unknown. We used wild type (WT) and Vipr2−/− mice expressing a luciferase reporter (PER2::LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC2 receptor. Vipr2−/− SCN cultures expressed significantly lower amplitude PER2::LUC oscillations than WT SCN. Surprisingly, in Vipr2−/− Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2−/− cultures was reset by cull/culture procedure. These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2−/− mice, the ability of these oscillators to resist phase shifts is compromised. These deficiencies may contribute towards the aberrant behavior and metabolism associated with Vipr2−/− animals. Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting