A Global Geomorphologic Map of Saturn's Moon Titan.

Titan has an active methane-based hydrologic cycle1 that has shaped a complex geologic landscape2, making its surface one of most geologically diverse in the solar system. Despite the different materials, temperatures, and gravity fields between Earth and Titan, many surface features are similar between the two worlds and can be interpreted as products of the same geologic processes3. However, Titan's thick and hazy atmosphere has hindered the identification of geologic features at visible wavelengths and the study of surface composition4. Here we identify and map the major geologic units on Titan's surface using radar and infrared data from the Cassini orbiter spacecraft. Correlations between datasets enabled us to produce a global map even where data sets were incomplete. The spatial and superposition relations between major geologic units reveals the likely temporal evolution of the landscape and gives insight into the interacting processes driving its evolution. We extract the relative dating of the various geological units by observing their spatial superposition in order to get information on the temporal evolution of the landscape. Dunes and lakes are relatively young, while hummocky/mountainous terrains are the oldest on Titan. Our results also show that Titan's surface is dominated by sedimentary/depositional processes with significant latitudinal variation, with dunes at the equator, plains at mid-latitudes and labyrinth terrains and lakes at the poles.

Using velocity-pressure loops in the operating room: a new approach of arterial mechanics for cardiac afterload monitoring under general anesthesia.

Cardiac afterload is usually assessed in the ascending aorta and can be defined by the association of peripheral vascular resistance (PVR), total arterial compliance (Ctot), and aortic wave reflection (WR). We recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta. The aim of this study was to 1) describe the arterial mechanic properties by studying the velocity-pressure relations according to cardiovascular risk (low-risk and high-risk patients) in the ascending and descending thoracic aorta and 2) analyze the association between the VP loop (GALA and ß-angle) and cardiac afterload parameters (PVR, Ctot, and WR). PVR, Ctot, WR, and VP loop parameters were measured in the ascending and descending thoracic aorta in 50 anesthetized patients. At each aortic level, the mean arterial pressure (MAP), cardiac output (CO), and PVR were similar between low-risk and high-risk patients. In contrast, Ctot, WR, GALA, and ß-angle were strongly influenced by cardiovascular risk factors regardless of the site of measurement along the aorta. The GALA angle was inversely related to aortic compliance, and the ß-angle reflected the magnitude of wave reflection in both the ascending and descending aortas (P < 0.001). Under general anesthesia, the VP loop can provide new visual insights into arterial mechanical properties compared with the traditional MAP and CO for the assessment of cardiac afterload. Further studies are necessary to demonstrate the clinical utility of the VP loop in the operating room.NEW & NOTEWORTHY Our team recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta under general anesthesia. However, the evaluation of cardiac afterload at this location is unusual. The present study shows that VP loop parameters can describe the components of cardiac afterload both in the ascending and descending thoracic aorta in the operating room. Aging and cardiovascular risk factors strongly influence VP loop parameters. The VP loop could provide continuous visual additional information on the arterial system than the traditional mean arterial pressure and cardiac output during the general anesthesia.

New software dedicated to virtual mazes for human cognitive investigations.

BACKGROUND: Compared to previous neuropsychological investigations with standard paper-pen tests limited to test complex spatial learning and memory processes, 3-D virtual immersive technology might offer new tools for research purposes and for diagnosis in patients suffering from mild cognitive impairment or dementia. COMPARISON WITH EXISTING METHODS: Current software proposes a customizable VR environment combined with an analyser module based on regions of interest and some parameters of analysis or pre-calibrated VR mazes with raw data. NEW METHOD: We attempted to create the VRmaze software offering either turnkey mazes with automatic tracking and analysis, or more complex and specific virtual mazes for human brain-behavioural research adaptable to all desired settings and parameters of analysis. The software combines 3D pre-calibrated VR tests or free customizable VR tests with digitized neuropsychological 2D standard and validated tests or tasks. RESULTS: We have tested an ERAM, a MWM and a reverse T-maze on 44 healthy subjects, showing gender differences in terms of navigation strategy. We have observed that the choice of benchmarks, instructions, and experimental parameters influence the performances. CONCLUSION: VRmaze software offers a translational approach for research units that wish to combine animal models and patient evaluations as well as complex 3D tasks and standardized neuropsychological tests combined with an automatic analysis opening a large perspective in the neurosciences to investigate cognitive functions. A clinical module with preconfigured 2- and 3-D tasks should offer clinicians an easy way to evaluate their patients routinely.

The critical role of vestibular graviception during cognitive-motor development.

Earth's gravity acts both as a mechanical stimulus on the body and as a sensory stimulus to the vestibular organ, which is transmitted into the brain. The vestibular system has been recently highlighted as the cornerstone of the multisensory cortex and of the dorsal hippocampus related to spatial cognition. Consequently, we have hypothesized that the vestibular sensory perception of gravity by the otoliths might also play a crucial role during the first stages of development in both sensorimotor and cognitive functions and the construction and perception of the 'self' and related functions of orientation and navigation. We have investigated an original mouse model (Head Tilted mice, B6Ei.GL-Nox3het/J) suffering from a selective congenital absence of vestibular otolithic gravisensors. We report that mouse pups suffered from a delay in the acquisition of sensorimotor reflexes, spatial olfactory guidance, path integration, and ultrasonic communication, while maternal care remained normal. We demonstrate that development has a critical period dependent on the vestibular otolithic sensory perception of gravity, probably temporally between the somesthetic and visual critical periods. The symptoms expressed by the congenital otolithic-deficient mice are similar to validated mouse models of autism and highlight the significance of vestibular graviception in the pathophysiology of development.

Norepinephrine reduces arterial compliance less than phenylephrine when treating general anesthesia-induced arterial hypotension.

INTRODUCTION: During general anesthesia, arterial hypotension is frequent and may be an important contributor to perioperative morbidity. We assessed the effect of a 5 µg bolus of Norepinephrine (NA) when compared with 50 µg bolus of Phenylephrine (PE) administered to treat hypotension during maintenance anesthesia, on MAP, derived cardiac output and arterial stiffness parameters. METHODS: Patients scheduled for a neurosurgical procedure under general anesthesia were prospectively included. Monitoring included invasive blood pressure, esophageal Doppler, and arterial tonometer used to estimate central aortic pressure with arterial stiffness parameters, such as augmentation index (Aix). After initial resuscitation, hypotensive episodes were corrected by a bolus administration of NA or PE in a peripheral venous line. RESULTS: There were 269 bolus administrations of vasopressors (149 NA, 120 PE) in 47 patients with no adverse effects detected. A decrease in stroke volume (SV) was observed with PE compared with NA (-18 ± 9% vs. -14 ± 7%, P < 0.001). This decrease was associated with an increase in Aix, which was greater for PE than for NA (+10 ± 8% vs. +6 ± 6%, P < 0.0001), and a decrease in total arterial compliance greater for PE compared to NA (Ctot = SV/Central Pulse Pressure) (-35 ± 9% vs. -29 ± 10%, P < 0.001). DISCUSSION: This study suggests that 5 µg of NA administered as a bolus in a peripheral venous line could treat general anesthesia-induced arterial hypotension with a smaller decrease in SV and arterial compliance when compared to PE.

Spectral properties of Titan's impact craters imply chemical weathering of its surface.

We examined the spectral properties of a selection of Titan's impact craters that represent a range of degradation states. The most degraded craters have rims and ejecta blankets with spectral characteristics that suggest that they are more enriched in water ice than the rims and ejecta blankets of the freshest craters on Titan. The progression is consistent with the chemical weathering of Titan's surface. We propose an evolutionary sequence such that Titan's craters expose an intimate mixture of water ice and organic materials, and chemical weathering by methane rainfall removes the soluble organic materials, leaving the insoluble organics and water ice behind. These observations support the idea that fluvial processes are active in Titan's equatorial regions.

Viewpoint: effective stakeholder communication in agriculture: together we stand, divided we fall!

Substantial improvements of agricultural systems are necessary to meet the future requirements of humanity. However, current agricultural knowledge and information systems are generally not well suited to meet the necessary improvements in productivity and sustainability. For more effective application of research output, research producers and research consumers should not be considered as separate individuals in the knowledge chain but as collaborating partners creating synergy. The current paper investigates the relationships between scientists and stakeholders and identifies approaches to increase the effectiveness of their communication. On-farm research has proven to be an effective means of improving exploitation of research output at farm level because it connects all relevant partners in the process. Furthermore, pilot farms can act as an effective platform for communication and dissemination. Regional networks of pilot farms should be established and connected across regions.

MELODIE: a whole-farm model to study the dynamics of nutrients in dairy and pig farms with crops.

In regions of intensive pig and dairy farming, nutrient losses to the environment at farm level are a source of concern for water and air quality. Dynamic models are useful tools to evaluate the effects of production strategies on nutrient flows and losses to the environment. This paper presents the development of a new whole-farm model upscaling dynamic models developed at the field or animal scale. The model, called MELODIE, is based on an original structure with interacting biotechnical and decisional modules. Indeed, it is supported by an ontology of production systems and the associated programming platform DIESE. The biotechnical module simulates the nutrient flows in the different animal, soil and crops and manure sub-models. The decision module relies on an annual optimization of cropping and spreading allocation plans, and on the flexible execution of activity plans for each simulated year. These plans are examined every day by an operational management sub-model and their application is context dependent. As a result, MELODIE dynamically simulates the flows of carbon, nitrogen, phosphorus, copper, zinc and water within the whole farm over the short and long-term considering both the farming system and its adaptation to climatic conditions. Therefore, it is possible to study both the spatial and temporal heterogeneity of the environmental risks, and to test changes of practices and innovative scenarios. This is illustrated with one example of simulation plan on dairy farms to interpret the Nitrogen farm-gate budget indicator. It shows that this indicator is able to reflect small differences in Nitrogen losses between different systems, but it can only be interpreted using a mobile average, not on a yearly basis. This example illustrates how MELODIE could be used to study the dynamic behaviour of the system and the dynamic of nutrient flows. Finally, MELODIE can also be used for comprehensive multi-criterion assessments, and it also constitutes a generic and evolving framework for virtual experimentation on animal farming systems.

Extended Hopfield models for combinatorial optimization.

The extended Hopfield neural network proposed by Abe et al. for solving combinatorial optimization problems with equality and/or inequality constraints has the drawback of being frequently stabilized in states with neurons of ambiguous classification as active or inactive. We introduce in the model a competitive activation mechanism and we derive a new expression of the penalty energy allowing us to reduce significantly the number of neurons with intermediate level of activations. The new version of the model is validated experimentally on the set covering problem. Our results confirm the importance of instituting competitive activation mechanisms in Hopfield neural-network models.

Molecular variation in the nucleoprotein gene (ORF7) of the porcine reproductive and respiratory syndrome virus (PRRSV).

The nucleoprotein gene (ORF7) of 15 European isolates of porcine reproductive and respiratory syndrome virus (PRRSV) was sequenced and compared with corresponding sequences of other PRRSV isolates (2 European and 13 American) and one isolate each of other arteriviruses (the lactate dehydrogenase elevating virus (LDV), the simian haemorrhagic fever virus (SHFV) and the equine arteritis virus (EAV)). Their phylogenetic relationships were established using neighbour-joining and parsimony methods. Four lineages (PRRSV, LDV, SHFV and EAV) were discriminated. Two genotypes of PRRSV, European and American, could be further identified. The European genotype of PRRSV was highly conserved. Analysis of the nucleotide and amino acid substitutions in PRRSV ORF7 revealed four stable regions, probably conserved because of their requirement for nucleocapsid function and/or structure. No constant mutations accumulation in the ORF7 could be determined precisely when either synonymous or non-synonymous mutations were studied. Passage of the European PRRSV in vivo had little influence on the ORF7 sequence: only a small number of synonymous substitutions in ORF7 was detectable, confirming its low variability.

The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells.

Delivery of newly synthesized membrane-spanning proteins to the apical plasma membrane domain of polarized MDCK epithelial cells is dependent on yet unidentified sorting signals present in the luminal domains of these proteins. In this report we show that structural information for apical sorting of transmembrane neurotrophin receptors (p75(NTR)) is localized to a juxtamembrane region of the extracellular domain that is rich in O-glycosylated serine/threonine residues. An internal deletion of 50 amino acids that removes this stalk domain from p75(NTR) causes the protein to be sorted exclusively of the basolateral plasma membrane. Basolateral sorting stalk-minus p75(NTR) does not occur by default, but requires sequences present in the cytoplasmic domain. The stalk domain is also required for apical secretion of a soluble form of p75(NTR), providing the first demonstration that the same domain can mediate apical sorting of both a membrane-anchored as well as secreted protein. However, the single N-glycan present on p75(NTR) is not required for apical sorting of either transmembrane or secreted forms.

Antigenic variability of porcine reproductive and respiratory syndrome (PRRS) virus isolates. Influence of virus passage in pig.

In order to study the antigenic variability of porcine reproductive and respiratory syndrome virus (PRRSV), 18 European and Canadian field isolates were analysed with a panel of 15 monoclonal antibodies (MAbs) raised against five different European and one Canadian PRRSV isolates. The antigenic pattern of these isolates was used to infer their phylogenetic relationships. Isolates which had the same reactivity pattern were gathered together so that five antigenic profiles were analysed. The pairwise distances between these groups were defined based on antigenic pattern differences. Two main antigenic groups were obtained, discriminating between the European and the Canadian populations, as illustrated by the great distance observed between European and Canadian isolates (D = 0.5619 +/- 0.0625) compared to the distance between European isolates (D = 0.1524 +/- 0.0735). The distance matrix allowed also the construction of a tree diagram. Bootstrap analysis was performed to test the confidence in the branching. The tree diagram confirmed the distinction between the European and the Canadian PRRSV populations. Antigenic variability between an isolate and its progeny recovered after one or two passages in vivo was examined on six isolates. It was restricted to the GP3 protein of the virus.

The neural cell adhesion molecule expresses a tyrosine-independent basolateral sorting signal.

Transmembrane isoforms of the neural cell adhesion molecule, N-CAM (N-CAM-140 and N-CAM-180), are vectorially targeted from the trans-Golgi network to the basolateral domain upon expression in transfected Madin-Darby canine kidney cells (Powell, S. K., Cunningham, B. A., Edelman, G. M., and Rodriguez-Boulan, E. (1991) Nature 353, 76-77). To localize basolateral targeting information, mutant forms of N-CAM-140 were constructed and their surface distribution analyzed in Madin-Darby canine kidney cells. N-CAM-140 deleted of its cytoplasmic domain shows a non-polar steady state distribution, resulting from delivery from the trans-Golgi network to both the apical and basolateral surfaces. This result suggests that entrance into the basolateral pathway may occur without cytoplasmic signals, implying that apical targeting from the trans-Golgi network is not a default mechanism but, rather, requires positive sorting information. Subsequent construction and analysis of a nested set of C-terminal deletion mutants identified a region of 40 amino acids (amino acids 749-788) lacking tyrosine residues required for basolateral targeting. Addition of these 40 amino acids is sufficient to restore basolateral targeting to both the non-polar cytoplasmic deletion mutant of N-CAM as well as to the apically expressed cytoplasmic deletion mutant of the p75 low affinity neurotrophin receptor (p75(NTR)), indicating that this tyrosine-free sequence is capable of functioning independently as a basolateral sorting signal. Deletion of both cytoplasmic and transmembrane domains resulted in apical secretion of N-CAM, demonstrating that the ectodomain of this molecule carries recessive apical sorting information.

Vesicular transport: implications for cell polarity.

In polarized cells intracellular sorting of plasma membrane proteins occurs to a large extent at the trans-Golgi network, giving rise to vesicles destined for distinct plasma membrane domains. This review discusses the several pathways, both direct and indirect, which lead to protein incorporation into the correct cell surface, as well as the mechanisms involved. Proteins contain signals which direct their incorporation into the distinct vesicles destined for plasma membrane microdomains. Specific coat proteins are involved in vesicle assembly and are likely to play a role in the generation of discrete vesicle populations. Molecules involved in vesicle docking and fusion may also add specificity to the targeting process.

A competitive activation neural network model for the weighted minimum vertex covering.

We give a generalization of a neural network model originally developed to solve the minimum cardinality vertex covering problem, in order to solve the weighted version of the problem. The model is governed by a modified activation rule and we show that it has some important properties, namely convergence and irredundant covers at stable states. We present experimental results that confirm the effectiveness of the model.

Epithelial cell polarity: new perspectives.

All epithelial cells possess two distinct plasma membrane domains. The apical and basolateral domains differ in protein and lipid composition, and this allows the cell to perform a variety of vectorial functions. Structures involved in generating and maintaining these distinct membrane domains include the tight junction, which serves to restrict lateral diffusion within the membrane, and the cortical cytoskeleton, which can selectively bind and retain transmembrane proteins at a particular surface. A major means to generating membrane asymmetry lies in the ability of the cell to sort apical and basolateral proteins and target them to appropriate destinations. This sorting occurs predominantly at two intracellular sites: the trans-Golgi network, and the basolateral endosome. Constitutive protein traffic in epithelial cells has recently been shown to be regulated via classical signal transduction pathways involving heterotrimeric G proteins and protein kinases. The diversion of apical and basolateral proteins into specific pathways can be mediated by signals contained within these proteins. Apical sorting information is thought to be localized in the luminal domain of transmembrane proteins, and in the case of proteins anchored to the membrane via a GPI anchor, apical sorting information is provided by the lipid moiety. In contrast, basolateral signals have been identified in the cytoplasmic domain of transmembrane proteins. Shared similarities between basolateral signals and those required for endocytosis have suggested that these two sorting processes are mechanistically related.

Effects of bombesin, of a new bombesin agonist (BIM187) and a new antagonist (BIM189) on food intake in rats, in relation to cholecystokinin.

To study the mechanism by which bombesin induces satiety, we studied the effect of two new peptides, BIM187, a bombesin agonist, and BIM189, a bombesin antagonist, on food intake in rats fed 6 h a day. BIM187 at 4 micrograms/kg, significantly reduced food intake at 30 min, but did not change the total 6-h food intake. BIM189 (10 mg/kg), had no effect on food intake when administered alone, even at high doses (20 mg/kg). BIM189 selectively reduced bombesin-induced satiety but had no effect on satiety induced by BIM187. To examine the extent to which the satiety effect of bombesin or related peptides depends on the release of cholecystokinin (CCK), we studied the ability of CCK antagonists, BIM18216 and L364718, to reduce satiety induced by bombesin and BIM187. Neither BIM18216 nor L364718 alone had an effect on the 30-min food intake. They were not able to reverse the effect of bombesin on food intake. In our model, bombesin seems to act on satiety by a mechanism independent of CCK.

Identification of allergenic epitopes on Der f I, a major allergen of Dermatophagoides farinae, using monoclonal antibodies.

The antigenic and allergenic structure of Der f I, a major allergen of the house dust mite Dermatophagoides farinae (Df) was investigated by means of a panel of 11 selected monoclonal antibodies (mAb) obtained from BALB/c mice immunized with purified Der f I. The species specificity of these mAb, tested with Der f I and Der p I--the homologous allergen from Dermatophagoides pteronyssinus--was generally restricted to Der f I since 10 out of 11 mAb reacted only with this allergen. Epitope specificity of the mAb was determined by both competitive inhibition and sandwich ELISA experiments. The results indicated the presence of at least four non-overlapping, non-repeated antigenic sites on Der f I, which were recognized by one or several mAb (sites A, B, C and D). Comparative epitope specificity studies between human IgE antibodies and mice mAb were performed, on sera and basophils of Df sensitive patients, using different inhibition assays (ELISA and histamine release experiments). The degree of inhibition varied between the patients and upon the assay design. Most of the mAb tested were found to significantly inhibit the binding of human IgE to Der f I (p less than 0.01) when compared with Der p I specific mAb as a control. The mAb reacting with site A was found to be the most potent inhibitor, presenting a mean inhibition of up to 56% in ELISA as well as in histamine release experiments. The results show that both human IgE antibodies and mAb can be directed against identical or closely related epitopes of Der f I. Therefore anti-Der f I mAb constitute immunologic probes in further allergenic epitope and peptide analysis of this major mite allergen.