Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis

Energy-dependent intestinal calcium absorption is important for the maintenance of calcium and bone homeostasis, especially when dietary calcium supply is restricted. The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], is a crucial regulator of this process and increases the expression of the transient receptor potential vanilloid 6 (Trpv6) calcium channel that mediates calcium transfer across the intestinal apical membrane. Genetic inactivation of Trpv6 in mice (Trpv6(-/-)) showed, however, that TRPV6 is redundant for intestinal calcium absorption when dietary calcium content is normal/high and passive diffusion likely contributes to maintain normal serum calcium levels. On the other hand, Trpv6 inactivation impaired the increase in intestinal calcium transport following calcium restriction, however without resulting in hypocalcemia. A possible explanation is that normocalcemia is maintained at the expense of bone homeostasis, a hypothesis investigated in this study. In this study, we thoroughly analyzed the bone phenotype of Trpv6(-/-) mice receiving a normal (approximately 1%) or low (approximately 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters. When dietary supply of calcium is normal, Trpv6 inactivation did not affect growth plate morphology, bone mass and remodeling parameters in young adult or aging mice. Restricting dietary calcium had no effect on serum calcium levels and resulted in a comparable reduction in bone mass accrual in Trpv6(+/+) and Trpv6(-/-) mice (-35% and 45% respectively). This decrease in bone mass was associated with a similar increase in bone resorption, whereas serum osteocalcin levels and the amount of unmineralized bone matrix were only significantly increased in Trpv6(-/-) mice. Taken together, our findings indicate that TRPV6 contributes to intestinal calcium transport when dietary calcium supply is limited and in this condition indirectly regulates bone formation and/or mineralization.

Retrieval simulations of the vertical profiles of water vapour and other chemical species in the Martian atmosphere using PACS

Water vapour, despite being a minor constituent in the Martian atmosphere with its precipitable amount of less than 70 pr. μm, attracts considerable attention in the scientific community because of its potential importance for past life on Mars. The partial pressure of water vapour is highly variable because of its seasonal condensation onto the polar caps and exchange with a subsurface reservoir. It is also known to drive photochemical processes: photolysis of water produces H, OH, HO2 and some other odd hydrogen compounds, which in turn destroy ozone. Consequently, the abundance of water vapour is anti-correlated with ozone abundance. The Herschel Space Observatory provides for the first time the possibility to retrieve vertical water profiles in the Martian atmosphere. Herschel will contribute to this topic with its guaranteed-time key project called "Water and related chemistry in the solar system". Observations of Mars by Heterodyne Instrument for the Far Infrared (HIFI) and Photodetector Array Camera and Spectrometer (PACS) onboard Herschel are planned in the frame of the programme. HIFI with its high spectral resolution enables accurate observations of vertically resolved H2O and temperature profiles in the Martian atmosphere. Unlike HIFI, PACS is not capable of resolving the line-shape of molecular lines. However, our present study of PACS observations for the Martian atmosphere shows that the vertical sensitivity of the PACS observations can be improved by using multiple-line observations with different line opacities. We have investigated the possibility of retrieving vertical profiles of temperature and molecular abundances of minor species including H2O in the Martian atmosphere using PACS. In this paper, we report that PACS is able to provide water vapour vertical profiles for the Martian atmosphere and we present the expected spectra for future PACS observations. We also show that the spectral resolution does not allow the retrieval of several studied minor species, such as H2O2, HCl, NO, SO2, etc.

Detection of gelatinolytic activity in developing basement membranes of the mouse embryo head by combining sensitive in situ zymography with immunolabeling

Genetic evidence indicates that the major gelatinases MMP-2 and MMP-9 are involved in mammalian craniofacial development. Since these matrix metalloproteinases are secreted as proenzymes that require activation, their tissue distribution does not necessarily reflect the sites of enzymatic activity. Information regarding the spatial and temporal expression of gelatinolytic activity in the head of the mammalian embryo is sparse. Sensitive in situ zymography with dye-quenched gelatin (DQ-gelatin) has been introduced recently; gelatinolytic activity results in a local increase in fluorescence. Using frontal sections of wild-type mouse embryo heads from embryonic day 14.5-15.5, we optimized and validated a simple double-labeling in situ technique for combining DQ-gelatin zymography with immunofluorescence staining. MMP inhibitors were tested to confirm the specificity of the reaction in situ, and results were compared to standard SDS-gel zymography of tissue extracts. Double-labeling was used to show the spatial relationship in situ between gelatinolytic activity and immunostaining for gelatinases MMP-2 and MMP-9, collagenase 3 (MMP-13) and MT1-MMP (MMP-14), a major activator of pro-gelatinases. Strong gelatinolytic activity, which partially overlapped with MMP proteins, was confirmed for Meckel's cartilage and developing mandibular bone. In addition, we combined in situ zymography with immunostaining for extracellular matrix proteins that are potential gelatinase substrates. Interestingly, gelatinolytic activity colocalized precisely with laminin-positive basement membranes at specific sites around growing epithelia in the developing mouse head, such as the ducts of salivary glands or the epithelial fold between tongue and lower jaw region. Thus, this sensitive method allows to associate, with high spatial resolution, gelatinolytic activity with epithelial morphogenesis in the embryo.

Pulse-front tilt for short-wavelength lasing by means of traveling-wave plasma-excitation

Generation of coherent short-wavelength radiation across a plasma column is dramatically improved under traveling-wave excitation (TWE). The latter is optimized when its propagation is close to the speed of light, which implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles in order to increase the optical penetration of the pump into the plasma core. Pulse-front back-tilt is considered to overcome such trade-off. In fact, the TWE speed depends on the pulse-front slope (envelope of amplitude), whereas the optical penetration depth depends on the wave-front slope (envelope of phase). Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a high-magnification front-end imaging/focusing component. It is concluded that speed matching should be accomplished with minimal compressor misalignment and maximal imaging magnification.

[Disorders of the origin of the suspensory ligament in the horse: a diagnostic challenge]

Lameness in horses due to pain originating from the proximal metacarpal/metatarsal region remains a diagnostic challenge. In cases of obvious lameness the pain can be localised to this region by diagnostic anaesthesia. Because a variety of disorders can cause lameness in this region different imaging modalities including radiography, ultrasonography and scintigraphy should be used to arrive at an accurate diagnosis. Even though a precise anatomic-pathologic diagnosis can still be an enigma, because not only bone and joints, but also soft tissue structures including the proximal suspensory ligament, its origin at the proximal metacarpus/ metatarsus, its fascia, the superficial fascia, as well as the intermetacarpal/metatarsal ligaments, the accessory ligament of the deep digital flexor tendon and both digital flexor tendons may be involved. Magnet resonance tomography (MRT) shows a high diagnostic sensitivity in imaging soft tissue structures and bone. In horses MRT is still at the beginning. The MRT appearance of the proximal metacarpal/metatarsal region has not yet been evaluated in detail and there are only few anatomic studies of the origin of the suspensory ligament in horses. The first experiences showed, that more gross and histologic examinations are necessary to fully interpret MRT-images and to differentiate pathologic alterations from clinically not relevant variations.

Assessment of use of microsatellite polymorphism analysis for improving spatial distribution tracking of echinococcus multilocularis

Alveolar echinococcosis (AE)--caused by the cestode Echinococcus multilocularis--is a severe zoonotic disease found in temperate and arctic regions of the northern hemisphere. Even though the transmission patterns observed in different geographical areas are heterogeneous, the nuclear and mitochondrial targets usually used for the genotyping of E. multilocularis have shown only a marked genetic homogeneity in this species. We used microsatellite sequences, because of their high typing resolution, to explore the genetic diversity of E. multilocularis. Four microsatellite targets (EmsJ, EmsK, and EmsB, which were designed in our laboratory, and NAK1, selected from the literature) were tested on a panel of 76 E. multilocularis samples (larval and adult stages) obtained from Alaska, Canada, Europe, and Asia. Genetic diversity for each target was assessed by size polymorphism analysis. With the EmsJ and EmsK targets, two alleles were found for each locus, yielding two and three genotypes, respectively, discriminating European isolates from the other groups. With NAK1, five alleles were found, yielding seven genotypes, including those specific to Tibetan and Alaskan isolates. The EmsB target, a tandem repeated multilocus microsatellite, found 17 alleles showing a complex pattern. Hierarchical clustering analyses were performed with the EmsB findings, and 29 genotypes were identified. Due to its higher genetic polymorphism, EmsB exhibited a higher discriminatory power than the other targets. The complex EmsB pattern was able to discriminate isolates on a regional and sectoral level, while avoiding overdistinction. EmsB will be used to assess the putative emergence of E. multilocularis in Europe.

MR angiography of infrapopliteal arteries in patients with peripheral arterial occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared with selective DSA

To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease.

Solar wind reflection from the lunar surface: The view from far and near

The Moon appears bright in the sky as a source of energetic neutral atoms (ENAs). These ENAs have recently been imaged over a broad energy range both from near the lunar surface, by India's Chandrayaan-1 mission (CH-1), and from a much more distant Earth orbit by NASA's Interstellar Boundary Explorer (IBEX) satellite. Both sets of observations have indicated that a relatively large fraction of the solar wind is reflected from the Moon as energetic neutral hydrogen. CH-1's angular resolution over different viewing angles of the lunar surface has enabled measurement of the emission as a function of angle. IBEX in contrast views not just a swath but a whole quadrant of the Moon as effectively a single pixel, as it subtends even at the closest approach no more than a few degrees on the sky. Here we use the scattering function measured by CH-1 to model global lunar ENA emission and combine these with IBEX observations. The deduced global reflection is modestly larger (by a factor of 1.25) when the angular scattering function is included. This provides a slightly updated IBEX estimate of AH=0.11±0.06 for the global neutralized albedo, which is ˜25% larger than the previous values of 0.09±0.05, based on an assumed uniform scattering distribution.

Geomorphic coupling between hillslopes and channels in the Swiss Alps

The coupling relationships between hillslope and channel network are fundamental for the understanding of mountainous landscapes' evolution. Here, we applied dendrogeomorphic methods to identify the hillslope–channel relationship and the sediment transfer dynamics within an alpine catchment, at the highest possible resolution. The Schimbrig catchment is located in the central Swiss Alps and can be divided into two distinct geomorphic sectors. To the east, the Schimbrig earth flow is the largest sediment source of the basin, while to the west, the Rossloch channel network is affected by numerous shallow landslides responsible for the supply of sediment from hillslopes to channels. To understand the connectivity between hillslopes and channels and between sources and sink, trees were sampled along the main Rossloch stream, on the Schimbrig earth flow and on the Rossloch depositional area. Geomorphic observations and dendrogeomophic results indicate different mechanisms of sediment production, transfer and deposition between upper and lower segments of the channel network. In the source areas (upper part of the Rossloch channel system), sediment is delivered to the channel network through slow movements of the ground, typical of earth flow, shallow landslides and soil creep. Contrariwise, in the depositional area (lower part of the channel network), the mechanisms of sediment transfer are mainly due to torrential activity, floods and debris flows. Tree analysis allowed the reconstruction of periods of high activity during the last century for the entire catchment. The collected dataset presents a very high temporal resolution but we encountered some limitations in establishing the source-to-sink connectivity at the catchment-wide scale. Despite these uncertainties, for decennial timescales the results suggest a direct coupling between hillslopes and neighbouring channels in the Rossloch channel network, and a de-coupling between sediment sources and sink farther downstream, with connections possible only during extraordinary events.

Continuous Flow Analysis of labile iron in ice-cores

The important active and passive role of mineral dust aerosol in the climate and the global carbon cycle over the last glacial/interglacial cycles has been recognized. However, little data on the most important aeolian dust-derived biological micronutrient, iron (Fe), has so far been available from ice-cores from Greenland or Antarctica. Furthermore, Fe deposition reconstructions derived from the palaeoproxies particulate dust and calcium differ significantly from the Fe flux data available. The ability to measure high temporal resolution Fe data in polar ice-cores is crucial for the study of the timing and magnitude of relationships between geochemical events and biological responses in the open ocean. This work adapts an existing flow injection analysis (FIA) methodology for low-level trace Fe determinations with an existing glaciochemical analysis system, continuous flow analysis (CFA) of ice-cores. Fe-induced oxidation of N,N′-dimethyl-p-pheylenediamine (DPD) is used to quantify the biologically more important and easily leachable Fe fraction released in a controlled digestion step at pH ∼1.0. The developed method was successfully applied to the determination of labile Fe in ice-core samples collected from the Antarctic Byrd ice-core and the Greenland Ice-Core Project (GRIP) ice-core.

Performance evaluation of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations in planetary space research

Key performance features of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations of the chemical composition of planetary surfaces are presented. This mass spectrometer is well suited for elemental and isotopic analysis of raw solid materials with high sensitivity and high spatial resolution. In this study, ultraviolet laser radiation with irradiances suitable for ablation (< 1 GW/cm2) is used to achieve stable ion formation and low sample consumption. In comparison to our previous laser ablation studies at infrared wavelengths, several improvements to the experimental setup have been made, which allow accurate control over the experimental conditions and good reproducibility of measurements. Current performance evaluations indicate significant improvements to several instrumental figures of merit. Calibration of the mass scale is performed within a mass accuracy (Δm/m) in the range of 100 ppm, and a typical mass resolution (m/Δm) ~600 is achieved at the lead mass peaks. At lower laser irradiances, the mass resolution is better, about (m/Δm) ~900 for lead, and limited by the laser pulse duration of 3 ns. The effective dynamic range of the instrument was enhanced from about 6 decades determined in previous study up to more than 8 decades at present. Current studies show high sensitivity in detection of both metallic and non-metallic elements. Their abundance down to tens of ppb can be measured together with their isotopic patterns. Due to strict control of the experimental parameters, e.g. laser characteristics, ion-optical parameters and sample position, by computer control, measurements can be performed with high reproducibility. Copyright © 2012 John Wiley & Sons, Ltd.

Validation of network communicability metrics for the analysis of brain structural networks.

Computational network analysis provides new methods to analyze the brain's structural organization based on diffusion imaging tractography data. Networks are characterized by global and local metrics that have recently given promising insights into diagnosis and the further understanding of psychiatric and neurologic disorders. Most of these metrics are based on the idea that information in a network flows along the shortest paths. In contrast to this notion, communicability is a broader measure of connectivity which assumes that information could flow along all possible paths between two nodes. In our work, the features of network metrics related to communicability were explored for the first time in the healthy structural brain network. In addition, the sensitivity of such metrics was analysed using simulated lesions to specific nodes and network connections. Results showed advantages of communicability over conventional metrics in detecting densely connected nodes as well as subsets of nodes vulnerable to lesions. In addition, communicability centrality was shown to be widely affected by the lesions and the changes were negatively correlated with the distance from lesion site. In summary, our analysis suggests that communicability metrics that may provide an insight into the integrative properties of the structural brain network and that these metrics may be useful for the analysis of brain networks in the presence of lesions. Nevertheless, the interpretation of communicability is not straightforward; hence these metrics should be used as a supplement to the more standard connectivity network metrics.

A compilation of Western European terrestrial records 60–8 ka BP: towards an understanding of latitudinal climatic gradients

Terrestrial records of past climatic conditions, such as lake sediments and speleothems, provide data of great importance for understanding environmental changes. However, unlike marine and ice core records, terrestrial palaeodata are often not available in databases or in a format that is easily accessible to the non-specialist. As a consequence, many excellent terrestrial records are unknown to the broader palaeoclimate community and are not included in compilations, comparisons, or modelling exercises. Here we present a compilation of Western European terrestrial palaeo-records covering, entirely or partially, the 60–8-ka INTIMATE time period. The compilation contains 56 natural archives, including lake records, speleothems, ice cores, and terrestrial proxies in marine records. The compilation is limited to include records of high temporal resolution and/or records that provide climate proxies or quantitative reconstructions of environmental parameters, such as temperature or precipitation, and that are of relevance and interest to a broader community. We briefly review the different types of terrestrial archives, their respective proxies, their interpretation and their application for palaeoclimatic reconstructions. We also discuss the importance of independent chronologies and the issue of record synchronization. The aim of this exercise is to provide the wider palaeo-community with a consistent compilation of high-quality terrestrial records, to facilitate model-data comparisons, and to identify key areas of interest for future investigations. We use the compilation to investigate Western European latitudinal climate gradients during the deglacial period and, despite of poorly constrained chronologies for the older records, we summarize the main results obtained from NW and SW European terrestrial records before the LGM.

Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy

During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.

Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.