Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases.

Certain autoimmune diseases as well as asthma have increased in recent decades, particularly in developed countries. The hygiene hypothesis has been the prevailing model to account for this increase; however, epidemiology studies also support the contribution of diet and obesity to inflammatory diseases. Diet affects the composition of the gut microbiota, and recent studies have identified various molecules and mechanisms that connect diet, the gut microbiota, and immune responses. Herein, we discuss the effects of microbial metabolites, such as short chain fatty acids, on epithelial integrity as well as immune cell function. We propose that dysbiosis contributes to compromised epithelial integrity and disrupted immune tolerance. In addition, dietary molecules affect the function of immune cells directly, particularly through lipid G-protein coupled receptors such as GPR43.

SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an early-onset, autosomal recessive form of demyelinating neuropathy. The clinical manifestations include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. The gene mutated in CMT4C disease, SH3TC2/KIAA1985, was recently identified; however, the function of the protein it encodes remains unknown. We have generated knockout mice where the first exon of the Sh3tc2 gene is replaced with an enhanced GFP cassette. The Sh3tc2(DeltaEx1/DeltaEx1) knockout animals develop progressive peripheral neuropathy manifested by decreased motor and sensory nerve conduction velocity and hypomyelination. We show that Sh3tc2 is specifically expressed in Schwann cells and localizes to the plasma membrane and to the perinuclear endocytic recycling compartment, concordant with its possible function in myelination and/or in regions of axoglial interactions. Concomitantly, transcriptional profiling performed on the endoneurial compartment of peripheral nerves isolated from control and Sh3tc2(DeltaEx1/DeltaEx1) animals uncovered changes in transcripts encoding genes involved in myelination and cell adhesion. Finally, detailed analyses of the structures composed of compact and noncompact myelin in the peripheral nerve of Sh3tc2(DeltaEx1/DeltaEx1) animals revealed abnormal organization of the node of Ranvier, a phenotype that we confirmed in CMT4C patient nerve biopsies. The generated Sh3tc2 knockout mice thus present a reliable model of CMT4C neuropathy that was instrumental in establishing a role for Sh3tc2 in myelination and in the integrity of the node of Ranvier, a morphological phenotype that can be used as an additional CMT4C diagnostic marker.

Constraints on the permeability structure of alluvial aquifers from the poro-elastic inversion of multi-frequency P-wave velocity logs

We have explored the possibility of obtaining first-order permeability estimates for saturated alluvial sediments based on the poro-elastic interpretation of the P-wave velocity dispersion inferred from sonic logs. Modern sonic logging tools designed for environmental and engineering applications allow one for P-wave velocity measurements at multiple emitter frequencies over a bandwidth covering 5 to 10 octaves. Methodological considerations indicate that, for saturated unconsolidated sediments in the silt to sand range and typical emitter frequencies ranging from approximately 1 to 30 kHz, the observable velocity dispersion should be sufficiently pronounced to allow one for reliable first-order estimations of the permeability structure. The corresponding predictions have been tested on and verified for a borehole penetrating a typical surficial alluvial aquifer. In addition to multifrequency sonic logs, a comprehensive suite of nuclear and electrical logs, an S-wave log, a litholog, and a limited number laboratory measurements of the permeability from retrieved core material were also available. This complementary information was found to be essential for parameterizing the poro-elastic inversion procedure and for assessing the uncertainty and internal consistency of corresponding permeability estimates. Our results indicate that the thus obtained permeability estimates are largely consistent with those expected based on the corresponding granulometric characteristics, as well as with the available evidence form laboratory measurements. These findings are also consistent with evidence from ocean acoustics, which indicate that, over a frequency range of several orders-of-magnitude, the classical theory of poro-elasticity is generally capable of explaining the observed P-wave velocity dispersion in medium- to fine-grained seabed sediments

The Upper Oligocene of Montgat (Catalan Coastal Ranges, Spain): new age constraints to the western Mediterranean Basin opening

The Oligocene deposits of Montgat are integrated in a small outcrop made up of Cenozoic and Mesozoic rocks located in the Garraf-Montnegre horst, close to the major Barcelona fault. The Oligocene of Montgat consists of detrital sediments of continental origin mainly deposited in alluvial fan environments; these deposits are folded and affected by thrusts and strike-slip faults. They can be divided in two lithostratigraphic units separated by a minor southwest-directed thrust: (i) the Turó de Montgat Unit composed of litharenites and lithorudites with high contents of quartz, feldspar, plutonic and limestone rock fragments; and (ii) the Pla de la Concòrdia Unit composed of calcilitharenites and calcilithorudites with high contents of dolosparite and dolomicrite rock fragments. The petrological composition of both units indicates that sediments were derived from the erosion of Triassic (Buntsandstein, Muschelkalk and Keuper facies), Jurassic and Lower Cretaceous rocks (Barremian to Aptian in age). Stratigraphic and petrological data suggest that these units correspond to two coalescent alluvial fans with a source area located northwestwards in the adjoining Collserola and Montnegre inner areas. Micromammal fossils (Archaeomys sp.) found in a mudstone layer of the Pla de la Concòrdia Unit assign a Chattian age (Late Oligocene) to the studied materials. Thus, the Montgat deposits are the youngest dated deposits affected by the contractional deformation that led to the development of the Catalan Intraplate Chain. Taking into account that the oldest syn-rift deposits in the Catalan Coastal Ranges are Aquitanian in age, this allows to precise that the change from a compressive to an extensional regime in this area took place during latest Oligocene-earliest Aquitanian times. This age indicates that the onset of crustal extension related to the opening of the western Mediterranean Basin started in southern France during latest Eocene-early Oligocene and propagated southwestward, affecting the Catalan Coastal Ranges and the northeastern part of the Valencia trough during the latest Chattian-earliest Aquitanian times.

Stochastic delay equations with non-negativity constraints driven by fractional Brownian motion

In this note we prove an existence and uniqueness result for the solution of multidimensional stochastic delay differential equations with normal reflection. The equations are driven by a fractional Brownian motion with Hurst parameter H > 1/2. The stochastic integral with respect to the fractional Brownian motion is a pathwise Riemann¿Stieltjes integral.

Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone.

The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue-inducer cells with stromal lymphoid tissue-organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue-inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin alpha(1)beta(2) signaling. Thus, crosstalk between lymphoid tissue-inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.

The Upper Oligocene of Montgat (Catalan Coastal Ranges, Spain): new age constraints to the western Mediterranean Basin opening

The Oligocene deposits of Montgat are integrated in a small outcrop made up of Cenozoic and Mesozoic rocks located in the Garraf-Montnegre horst, close to the major Barcelona fault. The Oligocene of Montgat consists of detrital sediments of continental origin mainly deposited in alluvial fan environments; these deposits are folded and affected by thrusts and strike-slip faults. They can be divided in two lithostratigraphic units separated by a minor southwest-directed thrust: (i) the Turó de Montgat Unit composed of litharenites and lithorudites with high contents of quartz, feldspar, plutonic and limestone rock fragments; and (ii) the Pla de la Concòrdia Unit composed of calcilitharenites and calcilithorudites with high contents of dolosparite and dolomicrite rock fragments. The petrological composition of both units indicates that sediments were derived from the erosion of Triassic (Buntsandstein, Muschelkalk and Keuper facies), Jurassic and Lower Cretaceous rocks (Barremian to Aptian in age). Stratigraphic and petrological data suggest that these units correspond to two coalescent alluvial fans with a source area located northwestwards in the adjoining Collserola and Montnegre inner areas. Micromammal fossils (Archaeomys sp.) found in a mudstone layer of the Pla de la Concòrdia Unit assign a Chattian age (Late Oligocene) to the studied materials. Thus, the Montgat deposits are the youngest dated deposits affected by the contractional deformation that led to the development of the Catalan Intraplate Chain. Taking into account that the oldest syn-rift deposits in the Catalan Coastal Ranges are Aquitanian in age, this allows to precise that the change from a compressive to an extensional regime in this area took place during latest Oligocene-earliest Aquitanian times. This age indicates that the onset of crustal extension related to the opening of the western Mediterranean Basin started in southern France during latest Eocene-early Oligocene and propagated southwestward, affecting the Catalan Coastal Ranges and the northeastern part of the Valencia trough during the latest Chattian-earliest Aquitanian times.

Radiometric age constraints on mineral growth, metamorphism, and tectonism of the Gummfluh klippe, Brianconnais domain of the Prealpes, Switzerland

A combined Ar-40/Ar-39, K/Ar, Rb/Sr and stable isotope study has been made of white micas from the Gummfluh klippe (Brianconnais domain of the Prealpes), Switzerland. The klippe consists mainly of Mesozoic to early Tertiary carbonate rocks metamorphosed from anchizonal to epizonal conditions. At the base of the klippe is a 10-50 m thick, ductilely deformed marble mylonite containing deformed authigenic quartz segregations. Stable isotope measurements of the coexisting calcite (deltaO-18SMOW=24.5) and quartz (deltaO-18SMOW=28.4) from the mylonite indicate relatively low temperatures (< 300-degreesC) during mylonitization. Analyses of white mica separates of varying size fractions from the mylonitic rocks by K/Ar and Rb/Sr techniques yield ages between 57 and 103 Ma. This variation is correlated with two parameters, the size of the mineral fraction, and the proportion of 2M1 (more phengitic) to 1M (more muscovitic) polytype in the sample. The K/Ar and Rb/Sr ages are generally younger in the smaller size fractions, which also containless 2M1 phengite. High precision Ar-40/Ar-39 age spectra from different size fractions of these micas record three distinct components, a small Hercynian component (ca. 200-300 Ma), a significant Eoalpine component (64-80 Ma) forming Ar-40/Ar-39 age plateaus, and a very minor Tertiary component (ca. 20-40 Ma). Characterization of the samples by SEM indicates the presence of two white mica populations, a coarser grained, deformed, detrital mica that probably corresponds to the 2M1 phengite and a finer grained neoformed 1M mica. Collectively these observations suggest that the Gummfluh samples contain a mixture of detrital phengites of Hercynian age together with neocrystallized muscovites grown during the late Eoalpine metamorphic event followed by minor argon loss during the Tertiary. The main geologic episode recorded in the Ar-40/Ar-39 age spectra of white micas in the mylonite is of Late Cretaceous/Early Tertiary age (64-80 Ma), representing the first reliable Eoalpine ages ever to be reported from the Prealpes. Contrary to tectonic models, the marble mylonite at the base of the Gummfluh klippe appears to be a Cretaceous thrust plane and not the thrust surface formed during transport of the klippe into its present position from the Penninic Alps during the Tertiary. The late Cretaceous thrust developed during marine sedimentation at a depth of 800 m below the seafloor at temperatures of approximately 280-degrees-C, facilitated by warm fluids along the tectonic discontinuity.

Distinct effects of inflammation on gliosis, osmohomeostasis, and vascular integrity during amyloid beta-induced retinal degeneration.

In normal retinas, amyloid-β (Aβ) accumulates in the subretinal space, at the interface of the retinal pigment epithelium, and the photoreceptor outer segments. However, the molecular and cellular effects of subretinal Aβ remain inadequately elucidated. We previously showed that subretinal injection of Aβ(1-42) induces retinal inflammation, followed by photoreceptor cell death. The retinal Müller glial (RMG) cells, which are the principal retinal glial cells, are metabolically coupled to photoreceptors. Their role in the maintenance of retinal water/potassium and glutamate homeostasis makes them important players in photoreceptor survival. This study investigated the effects of subretinal Aβ(1-42) on RMG cells and of Aβ(1-42)-induced inflammation on retinal homeostasis. RMG cell gliosis (upregulation of GFAP, vimentin, and nestin) on day 1 postinjection and a proinflammatory phenotype were the first signs of retinal alteration induced by Aβ(1-42). On day 3, we detected modifications in the protein expression patterns of cyclooxygenase 2 (COX-2), glutamine synthetase (GS), Kir4.1 [the inwardly rectifying potassium (Kir) channel], and aquaporin (AQP)-4 water channels in RMG cells and of the photoreceptor-associated AQP-1. The integrity of the blood-retina barrier was compromised and retinal edema developed. Aβ(1-42) induced endoplasmic reticulum stress associated with sustained upregulation of the proapoptotic factors of the unfolded protein response and persistent photoreceptor apoptosis. Indomethacin treatment decreased inflammation and reversed the Aβ(1-42)-induced gliosis and modifications in the expression patterns of COX-2, Kir4.1, and AQP-1, but not of AQP-4 or GS. Nor did it improve edema. Our study pinpoints the adaptive response to Aβ of specific RMG cell functions.

Early diagenesis of bone and tooth apatite in fluvial and marine settings: Constraints from combined oxygen isotope, nitrogen and REE analysis

Fossil bones and teeth of Late Pleistocene terrestrial mammals from Rhine River gravels (RS) and the North Sea (NS), that have been exposed to chemically and isotopically distinct diagenetic fluids (fresh water versus seawater), were investigated to study the effects of early diagenesis on biogenic apatite. Changes in phosphate oxygen isotopic composition (delta O-18(PO4)), nitrogen content (wt.% N) and rare earth element (REE) concentrations were measured along profiles within bones that have not been completely fossilized, and in skeletal tissues (bone, dentine, enamel) with different susceptibilities to diagenetic alteration. Early diagenetic changes of elemental and isotopic compositions of apatite in fossil bone are related to the loss of the stabilizing collagen matrix. The REE concentration is negatively correlated with the nitrogen content, and therefore the amount of collagen provides a sensitive proxy for early diagenetic alteration. REE patterns of RS and NS bones indicate initial fossilization in a fresh water fluid with similar REE compositions. Bones from both settings have nearly collagen-free, REE-, U-, F- and Sr-enriched altered outer rims, while the collagen-bearing bone compacta in the central part often display early diagenetic pyrite void-fillings. However, NS bones exposed to Holocene seawater have outer rim delta O-18(PO4) values that are 1.1 to 2.6 parts per thousand higher compared to the central part of the same bones (delta O-18(PO4) = 18.2 +/- 0.9 parts per thousand, n = 19). Surprisingly, even the collagen-rich bone compacta with low REE contents and apatite crystallinity seems altered, as NS tooth enamel (delta O-18(PO4) =15.0 +/- 0.3 parts per thousand, n=4) has about 3%. lower delta O-18(PO4) values, values that are also similar to those of enamel from RS teeth. Therefore, REE concentration, N content and apatite crystallinity are in this case only poor proxies for the alteration of delta O-18(PO4) values. Seawater exposure of a few years up to 8 kyr can change the delta O-18(PO4) values of the bone apatite by > 3 parts per thousand. Therefore, bones fossilized in marine settings must be treated with caution for palaeoclimatic reconstructions. However, enamel seems to preserve pristine delta O-18(PO4) values on this time scale. Using species-specific calibrations for modern mammals, a mean delta O-18(H2O) value can be reconstructed for Late Pleistocene mammalian drinking water of around -9.2 +/- 0.5 parts per thousand, which is similar to that of Late Pleistocene groundwater from central Europe. (c) 2008 Elsevier B.V. All rights reserved.

Mobile Robot Local Predictive Control under Perception Constraints

This research extends a previously developed work concerning about the use of local model predictive control in mobile robots. Hence, experimental results are presented as a way to improve the methodology by considering aspects as trajectory accuracy and time performance. In this sense, the cost function and the prediction horizon are important aspects to be considered. The platformused is a differential driven robot with a free rotating wheel. The aim of the present work is to test the control method by measuring trajectory tracking accuracy and time performance. Moreover, strategies for the integration with perception system and path planning are also introduced. In this sense, monocular image data provide an occupancy grid where safety trajectories are computed by using goal attraction potential fields

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.