The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal ...or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.
The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral ...preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POA
neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPO
neurons in mice promotes sleep with low frequency stimulation (1-4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPO
neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPO
neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPO
neurons in both sleep induction and heat loss.
We construct a family of stochastic growth models in 2 + 1 dimensions, that belong to the anisotropic KPZ class. Appropriate projections of these models yield 1 + 1 dimensional growth models in the ...KPZ class and random tiling models. We show that correlation functions associated to our models have determinantal structure, and we study large time asymptotics for one of the models.
The main asymptotic results are: (1) The growing surface has a limit shape that consists of facets interpolated by a curved piece. (2) The one-point fluctuations of the height function in the curved part are asymptotically normal with variance of order ln(
t
) for time
t
≫
1
. (3) There is a map of the (2 + 1)-dimensional space-time to the upper half-plane
H
such that on space-like submanifolds the multi-point fluctuations of the height function are asymptotically equal to those of the pullback of the Gaussian free (massless) field on
H
.
The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical ...stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states.
More than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep-wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states.
Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have ...long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state.
Subducting plates around the globe display a large variability in terms of slab geometry, including regions where smooth and little variation in subduction parameters is observed. While the vast ...majority of subduction slabs plunge into the mantle at different, but positive dip angles, the end-member case of flat-slab subduction seems to strongly defy this rule and move horizontally several hundreds of kilometers before diving into the surrounding hotter mantle. By employing a comparative assessment for the Mexican, Peruvian and Chilean flat-slab subduction zones we find a series of parameters that apparently facilitate slab flattening. Among them, trench roll-back, as well as strong variations and discontinuities in the structure of oceanic and overriding plates seem to be the most important. However, we were not able to find the necessary and sufficient conditions that provide an explanation for the formation of flat slabs in all three subduction zones. In order to unravel the origin of flat-slab subduction, it is probably necessary a numerical approach that considers also the influence of surrounding plates, and their corresponding geometries, on 3D subduction dynamics.
Two-dimensional materials with high charge carrier mobility and tunable band gaps have attracted intense research effort for their potential use in nanoelectronics. Two-dimensional π-conjugated ...polymers constitute a promising subclass because the band structure can be manipulated by varying the molecular building blocks while preserving key features such as Dirac cones and high charge mobility. The major barriers to the application of two-dimensional π-conjugated polymers have been the small domain size and high defect density attained in the syntheses explored so far. Here, we demonstrate the fabrication of mesoscale ordered two-dimensional π-conjugated polymer kagome lattices with semiconducting properties, Dirac cone structures and flat bands on Au(111). This material has been obtained by combining a rigid azatriangulene precursor and a hot dosing approach, which favours molecular diffusion and eliminates voids in the network. These results open opportunities for the synthesis of two-dimensional π-conjugated polymer Dirac cone materials and their integration into devices.
The Middle America subduction zone (MASZ) is one of the world’ most complex convergent margins as it involves the subduction of the Rivera and Cocos young oceanic plates beneath the North American ...and Caribbean plates and is bounded by the Gulf of California rift and the Panama slab window. Characterized by contorted and unusual slab geometry, irregularly distributed seismicity and volcanism, exceptionally large slow slip events (SSE) and non-volcanic tremors (NVT), this subduction system represents a great natural laboratory for better understanding geodynamic processes at a fundamental level. Based on a solid observational foundation, and incorporating the latest experimental results into a coherent geodynamical framework, we shed light on the main processes controlling the subduction system evolution in this region. The tectonics, volcanism, slab geometry and segmentation along the margin are reviewed from a geodynamical perspective. We proposed and discussed a series of evolutionary scenarios for the Mexican and Central American subduction zones, providing a coherent starting base for future geodynamical modeling studies tailored to this active margin. We discuss comparatively the recently discovered SSEs and NVTs along the MASZ, and try to differentiate among the proposed mechanisms responsible for these observations. Finally we discuss the recent seismic anisotropy observations in a geodynamic context, offering an integrated view of mantle flow pattern along the entire active margin. Although the MASZ as a whole may be considered a fairly complicated region with many unusual features and sometimes controversial interpretations, its complexity and unusual characteristics can improve our knowledge about the linkage between deep and surface processes associated with subduction zone dynamics.
► We present the main geodynamic processes along the Middle America subduction zone. ► We proposed a series of models for the Mexican and Central American subduction zones. ► We discuss comparatively the slow slip events and tremors along the subduction zone. ► We examine the seismic anisotropy observations in a geodynamic context.
Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how ...periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn-/- and Postn+/+ mice to intermittent PTH. Compared with Postn+/+, Postn-/- mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn-/- mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn-/- mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn-/- mice. In addition, primary osteoblasts from Postn-/- mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn-/- osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation.
Abstract
Acoustic pyrometry uses the variations of the speed of sound in a medium to determine its temperature. One of the assumptions at the base of this technique is that the flow velocity ...component in the direction of the acoustic path is negligible in comparison to the speed of sound. However, if the temperature of the medium is known, the acoustic pyrometry approach can be used to determine flow speed, as long as the flow is not perpendicular to the acoustic path. The combined approach of temperature and velocity determination is also known as acoustic tomography. This technique allows the determination of velocity and temperature maps in a flow region. Even though this is an interesting result, the mathematical approach to solve the velocity and temperature fields might be very complex and sensitive measurement set-up. In this study, a preliminary investigation is carried out to determine the flow velocity by starting from the time of flight of an acoustic signal moving along different acoustic paths in a constant temperature field. For this purpose, a simplified geometry is considered. The developed mathematical approach at the base of the methodology is presented in this study.
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