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Nonsense-mediated mRNA decay (NMD) protects cells from the toxic and potentially dominant effects of truncated proteins. Targeting of mRNAs with early stop codons is mediated by the ribosome and spatiotemporally aligned with translation termination. Previously we identified a novel NMD intermediate: ribosomes stalled on cleaved stop codons, raising the possibility that NMD begins even prior to ribosome removal from the stop codon. Here we show that this intermediate is the result of mRNA cleavage by the endonuclease SMG-6. Our work supports a model in which ribosomes stall secondary to SMG-6 mRNA cleavage in Caenorhabditis elegans and humans, i.e. that the novel NMD intermediate occurs after a prior ribosome elicits NMD. Our genetic analysis of C. elegans’ SMG-6 supports a central role for SMG-6 in metazoan NMD, and provides a context for evaluating its function in other metazoans.

A critical step of pre-mRNA splicing is the recruitment of U2 snRNP to the branch point sequence of an intron. U2 snRNP conformation changes extensively during branch helix formation and several RNA-dependent-ATPases are implicated in the process. However, the molecular mechanisms involved remain to be fully dissected. We took advantage of the differential nucleotide triphosphates requirements for DExD/H-box enzymes to probe their contributions to in vitro spliceosome assembly. Both ATP and GTP hydrolysis support the formation of A-complex, indicating the activity of a DEAH-enzyme because DEAD-enzymes are selective for ATP. We immunodepleted DHX15 to assess its involvement and although splicing efficiency decreases with reduced DHX15, A-complex accumulation incongruently increases. DHX15 depletion also results in the persistence of the atypical ATP-independent interaction between U2 snRNP and a minimal substrate that is otherwise destabilized in the presence of either ATP or GTP. These results lead us to hypothesize that DHX15 plays a quality control function in U2 snRNP’s engagement with an intron. In efforts to identify the RNA target of DHX15, we determined that an extended polypyrimidine tract is not necessary for disruption of the atypical interaction between U2 snRNP and the minimal substrate. We also examined U2 snRNA by RNase H digestion and identified nucleotides in the branch binding region that become accessible with both ATP and GTP hydrolysis, again implicating a DEAH-enzyme. Together, our results demonstrate that multiple ATP-dependent rearrangements are likely involved in U2 snRNP addition to the spliceosome and that DHX15 can have an expanded role in splicing.

The goal of stem cell therapy for spinal cord injury (SCI) is to restore motor function without exacerbating pain. Induced pluripotent stem cells (iPSC) may be administered by autologous transplantation, avoiding immunologic challenges. Identifying strategies to optimize iPSC-derived neural progenitor cells (hiNPC) for cell transplantation is an important objective. Herein, we report a method that takes advantage of the growth factor-like and anti-inflammatory activities of the fibrinolysis protease, tissue plasminogen activator tPA, without effects on hemostasis. We demonstrate that conditioning hiNPC with enzymatically-inactive tissue-type plasminogen activator (EI-tPA), prior to grafting into a T3 lesion site in a clinically relevant severe SCI model, significantly improves motor outcomes. EI-tPA-primed hiNPC grafted into lesion sites survived, differentiated, acquired markers of motor neuron maturation, and extended βIII-tubulin-positive axons several spinal segments below the lesion. Importantly, only SCI rats that received EI-tPA primed hiNPC demonstrated significantly improved motor function, without exacerbating pain. When hiNPC were treated with EI-tPA in culture, NMDA-R-dependent cell signaling was initiated, expression of genes associated with stemness (Nestin, Sox2) was regulated, and thrombin-induced cell death was prevented. EI-tPA emerges as a novel agent capable of improving the efficacy of stem cell therapy in SCI.

Purpose To investigate the use of an amyloid-targeting fluorescent probe, ARCAM-1, to identify amyloid-containing deposits in the retina of a transgenic mouse model of Alzheimer's disease (AD) and in human postmortem AD patients. Methods Aged APP/PS1 transgenic AD and wild-type (WT) mice were given an intraperitoneal (IP) injection of ARCAM-1 and their retinas imaged in vivo using a fluorescence ophthalmoscope. Eyes were enucleated and dissected for ex vivo inspection of retinal amyloid deposits. Additionally, formalin-fixed eyes from human AD and control patients were dissected, and the retinas were stained using ARCAM-1 or with an anti-amyloid-β antibody. Confocal microscopy was used to image amyloid-containing deposits stained with ARCAM-1 or with immunostaining. Results Four out of eight APP/PS1 mice showed the presence of amyloid aggregates in the retina during antemortem imaging. Retinas from three human AD patients stained with ARCAM-1 showed an apparent increased density of fluorescently labeled amyloid-containing deposits compared to the retinas from two healthy, cognitively normal (CN) patients. Immunolabeling confirmed the presence of amyloid deposits in both the retinal neuronal layers and in retinal vasculature. Conclusions ARCAM-1 facilitates antemortem detection of amyloid aggregates in the retina of a mouse model for AD, and postmortem detection of amyloid-containing deposits in human retinal tissues from AD patients. These results support the hypothesis of AD pathology manifesting in the eye and highlight a novel area for fluorophore development for the optical detection of retinal amyloid in AD patients. Translational relevance This paper represents an initial examination for potential translation of an amyloid-targeting fluorescent probe to a retinal imaging agent for aiding in the diagnosis of Alzheimer's disease.

Background: Electronic medical record notes have been determined to be lacking in quality, accessibility and content. Structured note templates could provide a way to improve these aspects, particularly with regard to data availability for research and quality improvement. Objective: To determine whether the implementation of a standardised template for hernia documentation can improve data completeness and timeliness. Method: Retrospective review of clinic notes of 30 patients, 15 prior to implementation of a standardised note template and 15 after implementation of the template. The number of the 21 Americas Hernia Society Quality Collaborative (AHSQC) variables which were present in the notes was recorded, as was the time that the consultation ended and the time that the note was submitted. Results: Mean number of variables collected prior to implementation of the template was 5.9 ± 1.6 vs. 20 ± 0.4 after implementation ( p < 0.001). In the pre-implementation group, 20% of the notes were completed after the day of the visit, while all of the notes in the post-implementation group were completed on the same day as the visit ( p = 0.367). Conclusion: Implementation of a structured note template resulted in significantly improved capture of specific database variables within clinical notes. Structured note templates are an effective tool to improve data capture from the clinical setting for research and quality improvement.

International audience; Natural hazards such as shallow landslides are common phenomena that disturb soil and damage forests. Quantifying the recovery of forest vegetation after a hazard is important for determining the window of susceptibility to new disturbance events, especially at high elevations, where extreme weather events are frequent and the growing season is short. Plant roots can reduce the size of this window on unstable hillslopes, by adding mechanical reinforcement (cr) to soil and increasing its matric suction, termed here as hydrological reinforcement (ch). These data are used in landslide models to calculate the Factor of Safety (FoS) of a hillslope. We calculated temporal variations in cr and ch in naturally regenerated mixed, montane forests in the French Alps. In these closed-canopy forests, open-canopy gaps were present, with understory vegetation comprising herbs, forbs and shrubs. At three altitudes (1400, 1700 and 2000 m), we dug small trenches as proxies for shallow landslide events and calculated cr before soil disturbance in both open gaps and closed forests. Then, using monthly tree root initiation and mortality data measured in rhizotrons, we calculated monthly cr for four years after the disturbance. To compare results with cr, ch was estimated using matric suction data that were measured in trenches at 1400 m for >1 year. Temporal FoS was then calculated using an infinite slope stability model.Results showed that finer, short-lived roots contributed little to soil reinforcement compared to thicker, long-lived roots. After disturbance, mean cr (over the entire soil profile) never fully recovered to the initial value at any site, although >90% recovery was observed in open gaps at 1400 m. Mean cr was slow to recover in closed forests, especially at 2000 m, where only 19% recovery occurred after 41 months. The ch in closed forests was considerable during the summer months, but marked increases in soil water moisture resulted in lower FoS, especially during December to April, when soil was near saturation. As cr changed little throughout the year, it was a more reliable contributor to slope stability. Our results show therefore, that particular attention should be paid to high elevation forests after a disturbance. Also, during the process of recovery, the highly variable soil water dynamics in closed forest can result in seasonal hotspots of vulnerability. Therefore, when tree transpiration is low, our results highlight a need for careful monitoring on steep or unstable slopes, especially in disturbed closed-canopy forests

This essay rereads the work of Yi Sang (1910–37) against the early twentieth-century revolution in aerial photographic technologies. It argues that the aerial view (and the problem of “blind sight” that attends it) functions as a dynamic organizing principle for understanding the complex network of technoscientific, political, and existential concerns driving Yi’s literary and graphic practice, across both his Japanese and his Korean works. Bringing together a comparative framework with select close readings, the essay shows how aeriality furnished Yi with a particular set of structures and signs with which to engage larger questions around the nature of seeing, the limits of objectivity and rationality, and the possibilities and politics of creative expression.

Although vegetation is increasingly used to mitigate landslide risks, how vegetation affects the temporal variability of slope stability is poorly understood, especially in earthquake-prone regions. We combined 3-year long soil moisture monitoring, measurements of soil physical properties and plant functional traits, and numerical modeling to compare slope stability under paired land uses with and without trees in tropical, sub-tropical, and temperate landslide- and earthquake-prone regions. Trees improved stability for 5-12 months per year from drawdown of soil moisture and resulted in less interannual variability in the duration of high-stability periods compared to slopes without trees. Our meta-analysis of published data also showed that slopes with woody vegetation were more stable and less sensitive to climate and soil factors than slopes with herbaceous vegetation. However, estimates of earthquake magnitude necessary to destabilize slopes at our sites suggest that large additional stabilization from trees is necessary for meaningful protection against external triggers.

UBQLN2 is one of a family of proteins implicated in ubiquitin-dependent protein quality control and integrally tied to human neurodegenerative disease. Whereas wild-type UBQLN2 accumulates in intraneuronal deposits in several common age-related neurodegenerative diseases, mutations in the gene encoding this protein result in X-linked amyotrophic lateral sclerosis/frontotemporal dementia associated with TDP43 accumulation. Using in vitro protein analysis, longitudinal fluorescence imaging and cellular, neuronal, and transgenic mouse models, we establish that UBQLN2 is intrinsically prone to self-assemble into higher-order complexes, including liquid-like droplets and amyloid aggregates. UBQLN2 self-assembly and solubility are reciprocally modulated by the protein's ubiquitin-like and ubiquitin-associated domains. Moreover, a pathogenic UBQLN2 missense mutation impairs droplet dynamics and favors amyloid-like aggregation associated with neurotoxicity. These data emphasize the critical link between UBQLN2's role in ubiquitin-dependent pathways and its propensity to self-assemble and aggregate in neurodegenerative diseases.

Background and Aims Fine roots play a major role in the global carbon cycle through respiration, exudation and decomposition processes, but their dynamics are poorly understood. Current estimates of root dynamics have principally been observed in shallow soil horizons (2.5 m) root growth occurred at two distinct periods, at bud break in spring and throughout the winter i.e., after leaf fall. In contrast, shallow roots grew mainly during the spring-summer period. Maximum root elongation rates ranged from 1 to 2 cm day−1 depending on soil depth. Most root mortality occurred in upper soil layers whereas only 10 % of fine roots below 4 m died over the study period. Fine root lifespan was longer in thicker and in deeper roots with the lifespan of the thinnest roots (0.0–0.5 mm) increasing from 129 days in the topsoil to 190 at depths > 2.5 m. Conclusions The unexpected growth of very deep fine roots during the winter months, which is unusual for a deciduous tree species, suggests that deep and shallow roots share different physiological strategies and that current estimates based on the shortest root growth periods (i.e., during spring and summer) may be underestimating root production. Although high fine root turnover rates might partially result from the minirhizotron approach used, our results help gain insight into some of the factors driving soil organic carbon content.

Background and aims: In temperate conifer forests, soil temperature is an important driver of fine root growth and winter root growth can occur during aerial dormancy. We hypothesize that in conifers, stocks of non-structural carbohydrates (NSC) in fine roots are high enough to provide energy for root growth and production throughout the year, even when photosynthesis is reduced. Methods: We measured monthly root production (i.e. the number of roots undergoing elongation) and their elongation rate (RER) in mature Picea abies for one year, along a soil temperature gradient (three altitudes of 1400, 1700 and 2000 m). Every two months we harvested needles, branches, stem, large, medium and fine roots, and quantified starch and soluble sugars in each organ using analytical methods and near infra-red spectroscopy (NIRS). Soil water potential was monitored continuously. We analysed RER data with regard to climate variables and NSC levels of the current and preceding month. Results: NIRS was a reliable method for measuring starch and soluble sugars. NSC was high in the crown and roots but very low in the trunk all year round. Soil temperature was positively correlated to RER (of the current month) between 0 and 8 °C, above which RER stabilised and was not explained by NSC levels or soil water potential. However, mean RER of fine roots in the month following the measurement of NSC was significantly and negatively correlated to soluble sugar and positively correlated with starch content. Very fine root starch content was also positively correlated with root production in the month following the starch measurement. Conclusion: Soil temperature was a major driver of fine root elongation, but at low temperatures only. At soil temperatures >8 °C, no particular driver was dominant. NSC levels were negligible in the stem and root-bases, suggesting that wood production is a major sink that depletes carbohydrates. A large pool of NSC, principally in the form of starch, existed in fine roots of P. abies, and acted as an energy supply for root production throughout the year, even when photosynthesis was limited. Soluble sugars were depleted in fine roots during the growing season, but no relationship was found between fine root production and soluble sugars. The physiological mechanism by which NSC accumulation actively or passively occurs in fine roots is not known but could be due to the symplastic pathway of phloem unloading in conifer root tips, which suggests a passive mechanism.

Background and Aims The structure of heterogeneous forests has consequences for their biophysical environment. Variations in the local climate significantly affect tree physiological processes. We hypothesize that forest structure also alters tree root elongation and longevity through temporal and spatial variations in soil temperature and water potential. Methods We installed rhizotrons in paired vegetation communities of closed forest (tree islands) and open patches (canopy gaps), along a soil temperature gradient (elevations of 1400, 1700 and 2000 m) in a heterogeneous mixed forest. We measured the number of growing tree roots, elongation and mortality every month over 4 years. Key Results The results showed that the mean daily root elongation rate (RER) was not correlated with soil water potential but was significantly and positively correlated with soil temperature between 0 and 8 degrees C only. The RER peaked in spring, and a smaller peak was usually observed in the autumn. Root longevity was dependent on altitude and the season in which roots were initiated, and root diameter was a significant factor explaining much of the variability observed. The finest roots usually grew faster and had a higher risk of mortality in gaps than in closed forest. At 2000 m, the finest roots had a higher risk of mortality compared with the lower altitudes. Conclusions The RER was largely driven by soil temperature and was lower in cold soils. At the treeline, ephemeral fine roots were more numerous, probably in order to compensate for the shorter growing season. Differences in soil climate and root dynamics between gaps and closed forest were marked at 1400 and 1700 m. but not at 2000 m, where canopy cover was more sparse. Therefore, heterogeneous forest structure and situation play a significant role in determining root demography in temperate, montane forests, mostly through impacts on soil temperature.

In the peripheral nervous system, Schwann cells (SCs) demonstrate surveillance activity, detecting injury and undergoing trans-differentiation to support repair. SC receptors that detect peripheral nervous system injury remain incompletely understood. We used RT-PCR to profile ionotropic glutamate receptor expression in cultured SCs. We identified subunits required for assembly of N-methyl-d-aspartic acid (NMDA) receptors (NMDA-Rs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and kainate receptors. Treatment of SCs with 40–100 µM glutamate or with 0.5–1.0 µM NMDA robustly activated Akt and ERK1/2. The response was transient and bimodal; glutamate concentrations that exceeded 250 µM failed to activate cell signaling. Phosphoprotein profiling identified diverse phosphorylated proteins in glutamate-treated SCs in addition to ERK1/2 and Akt, including p70 S6-kinase, glycogen synthase kinase-3, ribosomal S6 kinase, c-Jun, and cAMP response element binding protein. Activation of SC signaling by glutamate was blocked by EGTA and dizocilpine and by silencing expression of the NMDA-R NR1 subunit. Phosphoinositide 3-kinase/PI3K functioned as an essential upstream activator of Akt and ERK1/2 in glutamate-treated SCs. When glutamate or NMDA was injected directly into crush-injured rat sciatic nerves, ERK1/2 phosphorylation was observed in myelinated and nonmyelinating SCs. Glutamate promoted SC migration by a pathway that required PI3K and ERK1/2. These results identified ionotropic glutamate receptors and NMDA-Rs, specifically, as potentially important cell signaling receptors in SCs.—Campana, W. M., Mantuano, E., Azmoon, P., Henry, K., Banki, M. A., Kim, J. H., Pizzo, D. P., Gonias, S. L. Ionotropic glutamate receptors activate cell signaling in response to glutamate in Schwann cells.

Hydraulic lift (HL) is the passive movement of water through plant roots, driven by gradients in water potential. The greater soil–water availability resulting from HL may in principle lead to higher plant nutrient uptake, but the evidence for this hypothesis is not universally supported by current experiments. We grew a grass species common in North America in two-layer pots with three treatments: (1) the lower layer watered, the upper one unwatered (HL), (2) both layers watered (W), and (3) the lower layer watered, the upper one unwatered, but with continuous light 24 h a day to limit HL (no-HL). We inserted ingrowth cores filled with enriched-nitrogen organic matter (15N-OM) in the upper layer and tested whether decomposition, mineralization and uptake of 15N were higher in plants performing HL than in plants without HL. Soils in the upper layer were significantly wetter in the HL treatment than in the no-HL treatment. Decomposition rates were similar in the W and HL treatments and lower in no-HL. On average, the concentration of NH4 +-N in ingrowth cores was highest in the W treatment, and NO3 −-N concentrations were highest in the no-HL treatment, with HL having intermediate values for both, suggesting differential mineralization of organic N among treatments. Aboveground biomass, leaf 15N contents and the 15N uptake in aboveground tissues were higher in W and HL than in no-HL, indicating higher nutrient uptake and improved N status of plants performing HL. However, there were no differences in total root nitrogen content or 15N uptake by roots, indicating that HL affected plant allocation of acquired N to photosynthetic tissues. Our evidence for the role of HL in organic matter decomposition and nutrient cycling suggests that HL could have positive effects on plant nutrient dynamics and nutrient turnover.

The precise mechanisms underlying the memory-blocking properties of ethanol are unknown, in part because ethanol targets a wide array of neurotransmitter receptors and transporters. The aim of this study was to determine whether the memory loss caused by ethanol is mediated, in part, by α5 subunit-containing γ-aminobutyric acid subtype A receptors. These receptors have been implicated in learning and memory processes and are targets for a variety of neurodepressive drugs. Also, since these receptors generate a tonic inhibitory current in hippocampal pyramidal neurons, we examined whether concentrations of ethanol that block memory in vivo increased the tonic current using whole-cell patch-clamp recordings in hippocampal neurons. Null mutant mice lacking the α5 subunit (Gabra5-/-) and wild-type mice were equally impaired in contextual fear conditioning by moderate (1mg/kg) and high (1.5mg/kg) doses of ethanol. The higher dose of ethanol also reduced auditory delay fear conditioning to the same extent in the two genotypes. Interestingly, wild-type mice were more sensitive than Gabra5-/- mice to the sedative effects of low (0.5mg/kg) and moderate (1mg/kg) doses of ethanol in the open-field task. Concentrations of ethanol that impaired memory performance in vivo did not increase the amplitude of the tonic current. Together, the results suggest that the α5-subunit containing γ-aminobutyric acid subtype A receptors are not direct targets for positive modulation by ethanol nor do they contribute to ethanol-induced memory loss. In contrast, these receptors may contribute to the sedative properties of ethanol.

Cobalt–Phosphorous (Co–P) alloy thin films were prepared by electrodeposition technique from an aqueous electrolytic bath at various sodium chloride (NaCl) concentrations. The effect of sodium chloride concentration on electrochemical, structural, morphological, compositional and magnetic properties of the films was investigated by cyclic voltammetry, X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis and vibrating sample magnetometer techniques, respectively. The mechanism of formation of Co–P alloy thin films was studied using cyclic voltammetry. The compositional analysis shows that the content of phosphorous (P) increases and the content of cobalt (Co) decreases by adding NaCl. X-ray diffraction studies revealed amorphous nature for films obtained at high concentration of NaCl and hexagonal closed packed (hcp) structure for films obtained at low NaCl concentration. Magnetic properties illustrate that high value of coercivity, saturation magnetization, remanence, and saturating field were obtained at high concentration of NaCl.

Purpose The low-density lipoprotein receptor (LDLr) mediates the uptake of LDL particles enriched with cholesterol, into several tissues. In contrast to other tissues, the brain is thought to obtain cholesterol solely by de novo synthesis, yet certain brain regions such as the brainstem are highly enriched with the LDLr. The goal of the present study was to assess the role of the LDLr in maintaining cholesterol concentrations in the brainstem of wildtype and LDLr knockout (LDLr−/−) mice. Cholesterol concentrations were also measured in the cortex, which served as a reference point, due to the lower expression of the LDLr, as compared to the brainstem. Methods LDLr−/− and wildtype mice consumed an AIN-93G diet ad libitum until 7 weeks of age. After microwaving, the cortex and anterior brain stem were isolated for cholesterol analysis. Cholesterol was extracted into chloroform/methanol, derivatized in trimethylsilyl chloride and measured by gas chromatography/mass spectrometry. Results Concentrations of cholesterol in the brainstem did not differ statistically between LDLr−/− (18.8 ± 1.6 mg/g wet weight brain) and wildtype (19.1 ± 2.0). Cortical cholesterol concentrations also did not differ statistically between LDLr−/− (11.0 ± 0.4 mg/g wet weight brain) and wildtype (11.1 ± 0.2) mice. Conclusion The LDLr is not necessary for maintaining cholesterol concentrations in the cortex or brainstem, suggesting that other mechanisms are sufficient to maintain brain cholesterol concentrations.

The brain cannot synthesize n-6 or n-3 PUFAs de novo and requires their transport from the blood. Two models of brain fatty acid uptake have been proposed. One requires the passive diffusion of unesterified fatty acids through endothelial cells of the blood-brain barrier, and the other requires the uptake of lipoproteins via a lipoprotein receptor on the luminal membrane of endothelial cells. This study tested whether the low density lipoprotein receptor (LDLr) is necessary for maintaining brain PUFA concentrations. Because the cortex has a low basal expression of LDLr and the anterior brain stem has a relatively high expression, we analyzed these regions separately. LDLr knockout (LDLr(-/-)) and wild-type mice consumed an AIN-93G diet ad libitum until 7 weeks of age. After microwaving, the cortex and anterior brain stem (pons and medulla) were isolated for phospholipid fatty acid analyses. There were no differences in phosphatidylserine, phosphatidylinositol, ethanolamine, or choline glycerophospholipid esterified PUFA or saturated or monounsaturated fatty acid concentrations in the cortex or brain stem between LDLr(-/-) and wild-type mice. These findings demonstrate that the LDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFAs into the brain must exist.

Increasing pressures for food, fiber, and fuel continue to drive global land‐use changes. Efforts to optimize ecosystem services under alternative land uses are often hampered by the complex interactions and trade‐offs among them. We examined the effects of land‐use changes on ecosystem carbon storage and groundwater recharge in grasslands of Argentina and the United States to (1) understand the relationships between both services, (2) predict their responses to vegetation shifts across environmental gradients, and (3) explore how market or policy incentives for ecosystem services could affect land‐use changes. A trade‐off of ecosystem services was evident in most cases, with woody encroachment increasing carbon storage (+29 Mg C/ha) but decreasing groundwater recharge (−7.3 mm/yr) and conversions to rain‐fed cultivation driving opposite changes (−32 Mg C/ha vs. +13 mm/yr). In contrast, crops irrigated with ground water tended to reduce both services compared to the natural grasslands they replaced. Combining economic values of the agricultural products together with the services, we highlight potentials for relatively modest financial incentives for ecosystem services to abate land‐use changes and for incentives for carbon to drive land‐use decisions over those of water. Our findings also identify key opportunities and caveats for some win–win and lose–lose land‐use changes for more integrative and sustainable strategies for land management. Fil: Kim, John H.. University of Duke; Estados Unidos Fil: Jobbagy Gampel, Esteban Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina Fil: Jackson, Robert B.. University of Duke; Estados Unidos. University of Stanford; Estados Unidos

Agricultural conversion is one of the most prevalent anthropogenic uses on the terrestrial earth. Persistence of organisms in such landscapes is thought to be related to species-specific characteristics such as life history traits and dispersal distance. In an agricultural landscape in California, we examined local (farm-level) and landscape variables associated with nesting preferences of native ground-nesting bees. Compared to the known ground-nesting visitors to crops, bee community nesting on farms was depauperate. Further, more abundant and diverse communities of bees were found nesting at farms with patches of natural habitat near by than farms that were far away from natural habitat. Species responded differently to soil conditions created by farming practices, but the variability in nesting bee abundance was lower in farms near natural habitat than farms far from natural habitat. These findings suggest that most bee species are affected adversely but to varying degrees by agricultural int...

A fundamental objective of anesthesia research is to identify the receptors and brain regions that mediate the various behavioral components of the anesthetic state, including amnesia, immobility, and unconsciousness. Using complementaryin vivoandin vitroapproaches, we found that GABAAreceptors that contain the α5 subunit (α5GABAARs) play a critical role in amnesia caused by the prototypic intravenous anesthetic etomidate. Whole-cell recordings from hippocampal pyramidal neurons showed that etomidate markedly increased a tonic inhibitory conductance generated by α5GABAARs, whereas synaptic transmission was only slightly enhanced. Long-term potentiation (LTP) of field EPSPs recorded in CA1 stratum radiatum was reduced by etomidate in wild-type (WT) but not α5 null mutant (α5−/−) mice. In addition, etomidate impaired memory performance of WT but not α5−/− mice for spatial and nonspatial hippocampal-dependent learning tasks. The brain concentration of etomidate associated with memory impairmentin vivowas comparable with that which increased the tonic inhibitory conductance and blocked LTPin vitro. The α5−/− mice did not exhibit a generalized resistance to etomidate, in that the sedative-hypnotic effects measured with the rotarod, loss of righting reflex, and spontaneous motor activity were similar in WT and α5−/− mice. Deletion of the α5 subunit of the GABAARs reduced the amnestic but not the sedative-hypnotic properties of etomidate. Thus, the amnestic and sedative-hypnotic properties of etomidate can be dissociated on the basis of GABAAR subtype pharmacology.

International audience; Background and Aims: Characterising the spatial distribution of tree fine roots (diameter ≤ 2 mm) is fundamental for a better understanding of tree functioning in agroforestry ecosystems. The absorptive function of fine roots is closely associated to aboveground tree performance and the amount of competition experienced by a tree partly depends on how root spatial distribution varies with soil depth in mixed systems. We therefore compared root interception densities (RID) and fine root orientation of trees grown in an alley cropping agroforestry stand (AF) with those in a monocropped (M) tree stand. Methods: Fieldwork was conducted in two 17 year old hybrid walnut (Juglans regia × nigra cv. NG23) stands in southern France: one was an alley cropping agroforestry stand with durum wheat (Triticum turgidum L. subsp. durum) intercropped in strips between tree rows and the second was a monocropped stand with a natural understorey. One pit was dug in each stand to a depth of 1.6 m, and an additional pit was dug in the agroforestry stand to a depth of 4.0 m to examine the tree root distribution below the crop maximum rooting depth. Root intercepts were mapped on trench walls and soil cubes were sampled to assess 3D root orientation, and to establish a predictive model of root length densities (RLD).Results: In the monocropped stand, root mapping evidenced a very high RID in the top 0.5 m and a slight decrease with increasing soil depth, whereas in the agroforestry stand, RID was much lower for the same depth, but roots occupied a higher volume of soil. In the agroforestry stand, RID and RLD were higher within the tree row than in the inter-row at deeper depths. Tree fine roots in both stands were not preferentially oriented from the soil surface until a depth of 1.5 m, beneath which fine roots in the agroforestry stand were significantly more vertically oriented.Conclusions: Fine roots of intercropped walnut trees went significantly deeper indicating strong plasticity of root distribution. Deeper root systems would reduce direct competition from the crop and enable trees to access deeper water tables not available to the crop.

Data available from the Dryad Digital Repository. doi:10.5061/dryad.q5bj6; International audience; There is a fundamental trade-off between leaf traits associated with either resource acquisition or resource conservation. This gradient of trait variation, called the economics spectrum, also applies to fine roots, but whether it is consistent for coarse roots or at the plant community level remains untested. We measured a set of morphological and chemical root traits at a community level (functional parameters; FP) in 20 plant communities located along land-use intensity gradients and across three climatic zones (tropical, mediterranean and montane). We hypothesized (i) the existence of a root economics spectrum in plant communities consistent within root types (fine, < 2 mm; coarse, 2–5 mm), (ii) that variations in root FP occur with soil depths (top 20 cm of soil and 100–150 cm deep) and (iii) along land-use gradients. Root FP covaried, in line with the resource acquisition–conservation trade-off, from communities with root FP associated with resource acquisition (e.g. high specific root length, SRL; thin diameters and low root dry matter contents, RDMC) to root FP associated with resource conservation (e.g. low SRL, thick diameters and high RDMC). This pattern was consistent for both fine and coarse roots indicating a strong consistency of a trade-off between resource acquisition and conservation for plant roots. Roots had different suites of traits at different depths, suggesting a disparity in root function and exploitation capacities. Shallow, fine roots were thinner, richer in nitrogen and with lower lignin concentrations associated with greater exploitation capacities compared to deep, fine roots. Shallow, coarse roots were richer in nitrogen, carbon and soluble concentrations than deep, coarse roots. Fine root parameters of highly disturbed, herbaceous-dominated plant communities in poorer soils were associated with foraging strategies, that is greater SRL and lower RDMC and lignin concentration than those from less disturbed communities. Coarse roots, however, were less sensitive to the land-use gradient. Synthesis. This study demonstrates the existence of a general trade-off in root construction at a community level, which operates within all root types, suggesting that all plant tissues are controlled by the trade-off between resource acquisition and conservation.

Platelet endothelial cell adhesion molecule (PECAM or CD31) is a cell adhesion molecule expressed on circulating leukocytes and endothelial cells that plays an important role in mediating neutrophil and monocyte transendothelial migration in vivo. In this study, we investigated whether eosinophils, like neutrophils and monocytes, utilize PECAM for tissue recruitment to sites of allergic inflammation in vivo. Eosinophils express similar levels of PECAM as neutrophils as assessed by FACS analysis. RT-PCR studies demonstrate that eosinophils like neutrophils express the six extracellular domains of PECAM. Eosinophils exhibit homophilic binding to recombinant PECAM as assessed in a single-cell micropipette adhesion assay able to measure the biophysical strength of adhesion of eosinophils to recombinant PECAM. The strength of eosinophil adhesion to recombinant PECAM is the same as that of neutrophil binding to recombinant PECAM and can be inhibited with an anti-PECAM Ab. Although eosinophils express functional PECAM, anti-PECAM Abs did not inhibit bronchoalveolar lavage eosinophilia, lung eosinophilia, and airway hyperreactivity to methacholine in a mouse model of OVA-induced asthma in vivo. Thus, in contrast to studies that have demonstrated that neutrophil and monocyte tissue recruitment is PECAM dependent, these studies demonstrate that eosinophil tissue recruitment in vivo in this model is PECAM independent.

Background : Plants alter their environment in a number of ways. With correct management, plant communities can positively impact soil degradation processes such as surface erosion and shallow landslides. However, there are major gaps in our understanding of physical and ecological processes on hillslopes, and the application of research to restoration and engineering projects. Scope: To identify the key issues of concern to researchers and practitioners involved in designing and implementing projects to mitigate hillslope instability, we organized a discussion during the Third International Conference on Soil Bio- and Eco-Engineering: The Use of Vegetation to Improve Slope Stability, Vancouver, Canada, July 2012. The facilitators asked delegates to answer three questions: (i) what do practitioners need from science? (ii) what are some of the key knowledge gaps? (iii) what ideas do you have for future collaborative research projects between practitioners and researchers? From this discussion, ten key issues were identified, considered as the kernel of future studies concerning the impact of vegetation on slope stability and erosion processes. Each issue is described and a discussion at the end of this paper addresses how we can augment the use of ecological engineering techniques for mitigating slope instability. Conclusions: We show that through fundamental and applied research in related fields (e.g., soil formation and biogeochemistry, hydrology and microbial ecology), reliable data can be obtained for use by practitioners seeking adapted solutions for a given site. Through fieldwork, accessible databases, modelling and collaborative projects, awareness and acceptance of the use of plant material in slope restoration projects should increase significantly, particularly in the civil and geotechnical communities

1. John Kim, MD During a well baby visit, a mother of a very colicky 2-month-old baby asked me whether humans are the only species who have colicky babies. If so, what would be the evolutionary reason for this? I thought her question very interesting and would like to know if colic is a human-specific condition. Thanks for the opportunity to submit my question. # {#article-title-2} 1. Ronald G. Barr, MD 2. Martin T. Stein 1. UCSD Medical Center San Diego, Calif It is wonderful how such a parental musing can raise fundamental questions. Your patient’s mother asked two important questions: 1) Are humans the only species to have colicky babies? and 2) What is the evolutionary reason for colic; that is, is it a behavior that contributes to survival of the infant? The answer to the first question depends on what you consider colic to be. As to what might be the evolutionary reason for colic, there is no single answer, but it is subject to much fascinating speculation. To try to answer the first question, we will assume on the basis of current evidence that colic in humans is a behavioral syndrome in which there is an age-dependent increase and decrease in crying during the first 3 months after birth accounted for primarily by changes in evening crying that include prolonged and unsoothable crying bouts, many of which are “paroxysmal” or unexpected, that come and …

Combining decomposition data with process-based biogeochemical models is essential to quantify the turnover of organic carbon (C) in surface litter and soil organic matter (SOM). Long-term decomposition may be suitably analyzed by linear models (i.e., all fluxes defined by first-order kinetics), which allow the derivation of analytical expressions to estimate the loss of C and the overall apparent decay rate (kapp) through time. Here we compare eight linear models (four discrete-compartment models with one or two C pools, two models with a single time-dependent decay rate, and two models based on a continuous distribution of decay rates) and report their analytical solutions for two types of decomposition experiments: i) studies that evaluate the decomposition of a single input of fresh litter (i.e., a single cohort, as in litterbag and C labeling experiments), and ii) studies that evaluate the decomposition of soil samples with compounds of different ages (i.e., multiple cohorts, as in long-term incubations or isotope dilution experiments). We fitted analytical mass loss functions to both types of datasets and evaluated the performance of the models. For single-cohort data, continuous-decay models provide the best balance between accuracy and parsimony (R2 ¼ 0.99, lowest Akaike and Bayesian information criteria), while for multiple-cohort data the two-pool models tend to perform better (R2 ¼ 0.96), perhaps because of the strong separation of time scales in the decomposition data considered. Differences among some models are marginal, suggesting that decomposition data alone do not point to a single ‘best’ model. All models resulted in apparent decay rates that decreased markedly through time, in contrast with the assumption of constant k adopted in the single-pool exponential decay model. We also show how model parameters estimated from single cohort samples can be used to model multiple cohort decomposition, unifying both types of experimental data in one theory. Based on our results, it is possible to distinguish the temporal changes in C loss that are attributable to initial chemical composition or abiotic factors, from those associated with the presence of multiple ages in the substrate. Fil: Manzoni, Stefano. University Of Duke. Nicholas School Of Environment; Estados Unidos Fil: Piñeiro, Gervasio. University Of Duke. Nicholas School Of Environment; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina Fil: Jackson, Robert B.. University Of Duke. Nicholas School Of Environment; Estados Unidos Fil: Jobbagy Gampel, Esteban Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis ; Argentina Fil: Kim, John H.. University Of Duke; Estados Unidos Fil: Porporato, Amilcare. University Of Duke. Nicholas School Of Environment; Estados Unidos

Because groundwater is an essential resource for people and ecosystems, a better understanding is needed of the fundamental controls on recharge and its interactions with vegetation change. We analyzed >600 estimates of groundwater recharge to obtain the first global analysis of recharge and vegetation types. Globally, croplands had the highest proportion of water input (WI = precipitation + irrigation) that become recharge, followed by grasslands, woodlands, and scrublands (average proportional recharge: 0.11, 0.08, 0.06, and 0.05, respectively; P < 0.0001). A stepwise regression model revealed that WI had the strongest association with recharge overall, followed by vegetation type, potential evapotranspiration (PET), saturated hydraulic conductivity based on soil texture ( K s), and seasonality of rainfall ( R 2 = 0.29, 0.16, 0.12, 0.06, and 0.01, respectively; P < 0.0001). Recharge increased with increasing WI, K s, and seasonality of rainfall and decreased with increasing PET. Relative differences in recharge among vegetation types were larger in drier climates and clayey soils, indicating greater biological control on soil water fluxes under these conditions. To further test the relationship between recharge and vegetation, we compared global synthesis data to our parallel field estimates of recharge in paired grasslands, croplands, and woodlands across the Argentinean Pampas and the southwestern United States. Our field estimates of recharge were similar to, and followed the same pattern of, recharge under vegetation types in the synthesis data, suggesting that land-use changes will continue to alter recharge dynamics and vadose zone processes globally. The results of this study highlight the implications of land-use management for sustainable groundwater use and should also help test and improve recharge estimates in large-scale water balance and climate models.

Power generation and refrigeration accomplished by means of rotating or reciprocating machinery. One of the basic elements of rotating machinery is the rotating channel system. With the desire for ever increasing efficiency in power generation and refrigeration, higher or lower operating temperatures are achieved. It has provided motivation for the pursuit of knowledge on heat transfer and fluid flow characteristics. This paper reviews the literature pertinent to studies of fluid flow and/or heat transfer in channel flows subjected to radial rotation, parallel rotation, and coaxial revolution. Special problems unique to rotating systems are discussed and future study areas are suggested.

The high temperature crystal chemistry and oxygen permeation properties of the cation-ordered LnBaCo2 O5+δ perovskite oxides [lanthanide (Ln)=Pr, Nd, and Sm] have been investigated in comparison with the cation-disordered La0.5 Ba0.5 CoO3-δ perovskite. The LnBaCo2 O5+δ (Ln=Pr, Nd, and Sm) oxides exhibit a metal-insulator transition at T350°C in air, as evidenced by an orthorhombic to tetragonal transition. At a given temperature, the oxygen permeation flux decreases from Ln=La to Nd to Sm due to the changes in crystal symmetry and lattice strain. The oxygen permeation mechanism in the Ln=Nd is bulk-diffusion-limited rather than surface-exchange-limited for membrane thickness L1≥1 mm. Fil: Kim, John H.. University of Texas at Austin; Estados Unidos Fil: Mogni, Liliana Verónica. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina Fil: Prado, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina Fil: Caneiro, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Alonso, J. A.. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; España Fil: Manthiram, A.. University of Texas at Austin; Estados Unidos

Suramin is a trypanocidal drug that has generated recent interest as an antineoplastic agent because of its ability to inhibit the binding of growth factors to their cell surface receptors. Our studies, and others, suggest that the androgen-independent human prostatic carcinoma cell lines PC3 and DU145 proliferate via autocrine growth mechanisms mediated by transforming growth factor alpha (TGFa) and its receptor, the epidermal growth factor (EGF) receptor. The present studies were designed to evaluate the ability of suramin to inhibit PC3 and DU145 proliferation by interfering with TGFa-mediated autocrine growth. Suramin induced a dose-dependent reduction of prostatic tumor cell proliferation which was reversed by removal of suramin from the culture medium. 3H-thymidine release studies showed that suramin had little direct cytotoxicity to either cell line. These findings suggest that the effects of suramin are mediated by cytostatic, rather than cytotoxic, mechanisms. Suramin also interfered with TGFa-mediated growth mechanisms. Specifically, suramin reduced the specific binding of TGFa to PC3 and DU145 cells. Additionally, the inhibitory effect of suramin on DU145 was reversed by cultivation of cells in the presence of excess TGFa. Further investigations revealed that suramin increased the percentage of cells in the S phase of the cell cycle for both cell lines. These studies show that the inhibitory effect of suramin on PC3 and DU145 cell growth is mediated, in part, by alteration of TGFa-mediated autocrine growth mechanisms and cell cycle kinetics.

Purpose of study: To develop an experimental model of degenerative disc disease without direct intervention of the intervertebral disc (IVD). Our hypothesis was that inducing vertebral body damage at sites adjacent to the IVD would modify nutrient transport through the end plates and thus initiate degeneration in a manner relevant to degenerative disc disease in humans. Methods used: Vertebral body defects were created in lumbar motion segments of minipigs (10 experimental and 7 control levels, n=3). A high-speed drill with a diamond burr (3 to 5 mm diameter) was used to remove bone adjacent to the inferior and superior end plates of the experimental IVDs. A resorbable calcium phosphate bone cement was then packed into the defects. Spines were harvested at 3, 6 and 9 months and imaged in the sagittal plane with high-resolution magnetic resonance imaging (MRI; 7.1 T). Four blinded observers graded MRI appearance with the scheme of Thompson and coworkers (1990; 1 = nondegenerate, 5 = severely degenerate). In addition, MRI data sets were analyzed to determine changes in disc height and signal intensity for regions corresponding to the nucleus pulposus (NP) and anterior and posterior anulus fibrosus (AF). After imaging, individual motion segments were processed for routine histology (toluidine blue, hemotoxylin and eosin) and immunohistochemistry to detect matrix proteins including type II collagen and decorin. of findings: Higher MRI grades of degeneration were observed in all experimental IVD regions at 9 months after surgery. Reviewer grades were significantly higher for both NP (average of four graders = 1.8 vs. 3.8, control vs. experimental) and AF at 9 months after surgery (1.7 vs. 3.4). There was some evidence of end plate changes beginning at 3 months after surgery (1.5 vs. 2.3, control vs. experimental), which became quite dramatic at 9 months (1.4 vs. 4.5). No differences were noted in disc height between control and experimental IVDs at any region. However, decreases in MRI signal intensity (normalized to maximum values) were noted in experimental IVDs, particularly in the anterior AF (mean, 39%) and NP at 9 months (15%). Decreased signal intensity is a hallmark of IVD degeneration in the human, suggesting loss of hydration. Upon histological examination, there was evidence of inward bulging of the inner AF, end plate damage and decreased NP staining. Immunostaining demonstrated increased collagen type II in the experimental sections compared with controls, although few consistent changes were noted in the expression of decorin. Increases in the levels of both collagen type II and decorin have been demonstrated in other animal models of IVD degeneration and in human disease. Relationship between findings and existing knowledge: Overall, the changes observed in this experimental model confirm some key features of human IVD degeneration, including increased radiographic grade of degeneration, decreased MRI intensity and morphological and histological changes, such as increased staining for collagen type II and decreased staining of the NP. Holm and coworkers (1999) demonstrated that a controlled vertebral end plate defect will induce compositional and morphological evidence of disc degeneration in an animal model. Findings of the current study demonstrate that disruption of the vertebral body alone, without controlled violation of the end plate, may serve to initiate disc degeneration without direct, surgical injury of the IVD. Overall significance of findings: The mechanism for the onset of degeneration is not known but may relate to a role of vertebral body damage in altering nutrient transport across the end plate. Disclosures: No disclosures. Conflict of interest: William J. Richardson, grant research support, DePuy Orthobiologics.

The liver glycogenating action of Orinase was studied in normal, adrenalectomized and alloxan diabetic rats. The adrenalectomized rats were studied in three groups, salt maintained, cortisone maintained and cortisone plus adrenaline maintained. The alloxan diabetic rats were studied in two groups, protamine zinc insulin (P.Z.I.) maintained and uncontrolled. Of the adrenalectomized rats only those maintained on cortisone plus adrenaline responded to Orinase administration with increased liver glycogen. The alloxan diabetic animal maintained on P.Z.I. presented increased liver glycogen after Orinase administration but the untreated alloxan diabetic rat did not. This series of experiments indicated that the liver glycogenating effect seen during Orinase administration requires the participation of adrenomedullary, adrenocortical and beta cell hormones.