Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance

OBJECTIVE: The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Whilst the effect of these neuropeptides on individual aspects of energy homeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following ICV administration of 1nmol and 3nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight food deprived rats received an ICV injection of the anorectic peptides α-MSH, corticotrophin releasing factor (CRF) or neuromedin U (NMU). RESULTS: Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity whilst NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. Alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3nmol of the peptide. CONCLUSION: We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has demonstrated the interrelated effects of these neuropeotides on activity, energy expenditure and food intake thus facilitating comparison between the different hypothalamic systems

Slow slip source characterized by lithological and geometric heterogeneity

Slow slip events (SSEs) accommodate a significant proportion of tectonic plate motion at subduction zones, yet little is known about the faults that actually host them. The shallow depth (<2 km) of well-documented SSEs at the Hikurangi subduction zone offshore New Zealand offers a unique opportunity to link geophysical imaging of the subduction zone with direct access to incoming material that represents the megathrust fault rocks hosting slow slip. Two recent International Ocean Discovery Program Expeditions sampled this incoming material before it is entrained immediately down-dip along the shallow plate interface. Drilling results, tied to regional seismic reflection images, reveal heterogeneous lithologies with highly variable physical properties entering the SSE source region. These observations suggest that SSEs and associated slow earthquake phenomena are promoted by lithological, mechanical, and frictional heterogeneity within the fault zone, enhanced by geometric complexity associated with subduction of rough crust

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

International ocean discovery program expedition 372 preliminary report creeping gas hydrate slides and Hikurangi LWD

International Ocean Discovery Program (IODP) Expedition 372 combined two research topics, slow slip events (SSEs) on subduction faults (IODP Proposal 781A-Full) and actively deforming gas hydrate-bearing landslides (IODP Proposal 841-APL). Our study area on the Hikurangi margin, east of the coast of New Zealand, provided unique locations for addressing both research topics.SSEs at subduction zones are an enigmatic form of creeping fault behavior. They typically occur on subduction zones at depths beyond the capabilities of ocean floor drilling. However, at the northern Hikurangi subduction margin they are among the best-documented and shallowest on Earth. Here, SSEs may extend close to the trench, where clastic and pelagic sediments about 1.0-1.5 km thick overlie the subducting, seamount-studded Hikurangi Plateau. Geodetic data show that these SSEs recur about every 2 years and are associated with measurable seafloor displacement. The northern Hikurangi subduction margin thus provides an excellent setting to use IODP capabilities to discern the mechanisms behind slow slip fault behaviour

High-Resolution Studies of Mass Transport Deposits: Outcrop Perspective for Understanding Modern Submarine Slope Failure and Associated Natural Hazards

Micro- to meso-scale outcrop studies on selected field analogues allow direct calibration and testing of geophysical interpretations performed on mass transport deposits in modern continental margins, in terms of genetic processes and sliding dynamics. This comparative approach provides important information for forecasting and mitigating submarine landslide-related geohazards. The comparison of fieldwork studies (i.e., siliciclastic, carbonate and mixed, seismic-scale Eocene-Oligocene submarine mass transport deposits of the Northern Apennines in Italy, central Pyrenees in Spain and the north-western Dinarides in Italy/Slovenia) with multibeam bathymetric, seismic and drill core data from some modern analogues (i.e., offshore of New Zealand, Japan and Svalbard in Arctic Norway) is proposed in order to upscale the outcrop observations and downscale the geophysical features. Our results show that slide mass mobility is a function of the degree of internal liquefaction/fluidization, mainly achieved at the basal sliding interval and within the slide body. This is due to undrained shearing/loading-unloading of poorly-lithified sediments, and consequent development of fluid overpressure that is able to accommodate deformations at high strain rates. Structures related to these processes are observable at all scales, and represent diagnostic criteria to recognize potentially catastrophic mass transport events