Ignored Faces Produce Figural Face Aftereffects

Following adaptation to faces with contracted (or expanded) internal features, faces previously perceived as normal appear distorted in the opposite direction. This figural face aftereffect suggests face-coding mechanisms adapt to changes in the spatial relations of features and/or the global structure of faces. Here, we investigated whether the figural aftereffect requires spatial attention. Participants ignored a distorted adapting face and performed a highly demanding letter-count task. Before and after adaptation, participants rated the normality of morphed distorted faces ranging from 50% contracted through undistorted to 50% expanded. A robust aftereffect was observed. These results suggest that the figural face aftereffect can occur in the absence of spatial attention, even when the attentional demands of the relevant task are high.     

Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating

L-type Ca_V1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. Ca_V1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent Ca_V1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of Ca_V1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that Ca_V1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of Ca_V1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain Ca_V1.2 clustering, channel activity and cooperative gating. Our study suggests that Ca_V1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca²⁺ signals.     

Interactions Between DDT and River Fungi: I. Effects of p,p′-DDT on the Growth of Aquatic Hyphomycetes

Concentrations of p,p'-DDT between 0.1 and 60 mug/ml enhanced the growth rate of Heliscus submersus, and concentrations greater than 2 mug/ml had a similar effect on Tetracladium setigerum, Varicosporium elodeae, and Clavariopsis aquatica. The rate of growth of each fungus increased with increased DDT concentration.     

Spatial Electron Acceptor Variability: Implications for Assessing Bioremediation Potential

An extensive network of multilevel samplers was established in a hydrocarbon-contaminated wetland aquifer. Results of groundwater sampling for benzene, toluene, ethylbenzene, and xylenes (BTEX), and electron acceptors show that both pristine and contaminated groundwater have spatially variable chemical signatures, owing primarily to microbially mediated oxidation-reduction reactions. Due to these spatial variations, estimates of the efficiency of intrinsic bioremediation can vary significantly depending on how geochemical data are collected. Use of data collected from monitoring wells with screens longer than the vertical extent of the plume will generally underestimate the potential for intrinsic bioremediation for the most chemically active horizon of the plume. A comparison of pristine and contaminated redox patterns demonstrates that, although BTEX exerts the highest demand for electron acceptors, oxidation of natural organic matter also contributes to electron acceptor utilization. If natural and other non-BTEX losses of electron acceptors are ignored, the assimilative capacity, defined as the amount of a contaminant that can potentially be degraded with known amounts of electron acceptors, will be overestimated. Many numerical and analytical models designed to simulate biodegradation are directly or indirectly based on assimilative capacity estimates. Proper estimation of assimilative capacity is crucial if models are to accurately quantify solute concentrations over time and space.     

Seed supply, drought, and grazing determine spatio-temporal patterns of recruitment for native and introduced invasive pines in grasslands

Aim The rate of grassland invasion by trees depends on the ability of the species to invade, i.e. their invasiveness, and on the susceptibility of the environments to invasion, i.e. their invasibility. Knowledge of the invasiveness of native and introduced tree species and of the environmental factors that contribute to invasibility is necessary to understand landscape evolution and assess required management measures. Our main aim was to explore this by estimating the separate effects of propagule pressure and environmental factors on the spatio‐temporal patterns of sapling recruitment, a key stage in the tree life cycle. Location Causse Mejean calcareous plateau (southern France). Methods The effects of seed supply and environmental variables (grazing, geological substrate, and duration or intensity of drought) on the spatio‐temporal patterns of sapling recruitment were assessed for the native Scots pine (Pinus sylvestris L.) and the introduced black pine (Pinus nigra Arn. ssp. nigra). Estimates were derived by inverse modelling with data of locations and ages of 4‐ to 20‐year‐old saplings and seed‐bearing trees in 32 sites. Yearly indices of drought were derived from a soil–water content model. Results For both species, seed supply was as important as the whole set of environmental factors in explaining sapling recruitment rates. Grazing and the duration of drought from July to August decreased sapling recruitment rates, which were also lower on hard limestone than on dolomite. Dispersal distances and effective fecundities were higher for the introduced P. nigra, which was less susceptible to drought but more affected by grazing than the native P. sylvestris. In grazed grasslands, shrubs facilitated sapling establishment of both species. Main conclusions This study shows how seed supply and environmental factors shape spatio‐temporal patterns of sapling recruitment for trees invading grasslands. Implications for landscape evolution and management, of the difference in invasiveness of the two pine species and of the hierarchy of environmental factors in determining invasibility, are discussed.     

Discovery of μ-opioid selective ligands derived from 1-aminotetralin scaffolds made via metal-catalyzed ring-opening reactions

A series of 1-aminotetralin scaffolds was synthesized via metal-catalyzed ring-opening reactions of heterobicyclic alkenes. Small libraries of amides and amines were made using the amino group of each scaffold as a handle. Screening of these libraries against human opioid receptors led to the identification of (S)–(S)-5.2a as a high-affinity selective μ ligand (IC₅₀ μ = 5 nM, κ = 707 nM, δ = 3,795 nM) displaying μ-agonist/antagonist properties due to its partial agonism (EC₅₀ = 2.6 μM; E_max = 18%).     

A Simple,Quantitative Method Using Alginate Gel to Determine Rat Colonic Tumor Volume In Vivo

Many studies of the response of colonic tumors to therapeutics use tumor multiplicity as the endpoint to determine the effectiveness of the agent. These studies can be greatly enhanced by accurate measurements of tumor volume. Here we present a quantitative method to easily and accurately determine colonic tumor volume. This approach uses a biocompatible alginate to create a negative mold of a tumor-bearing colon; this mold is then used to make positive casts of dental stone that replicate the shape of each original tumor. The weight of the dental stone cast correlates highly with the weight of the dissected tumors. After refinement of the technique, overall error in tumor volume was 16.9% ± 7.9% and includes error from both the alginate and dental stone procedures. Because this technique is limited to molding of tumors in the colon, we utilized the Apc^Pirc/+ rat, which has a propensity for developing colonic tumors that reflect the location of the majority of human intestinal tumors. We have successfully used the described method to determine tumor volumes ranging from 4 to 196 mm³. Alginate molding combined with dental stone casting is a facile method for determining tumor volume in vivo without costly equipment or knowledge of analytic software. This broadly accessible method creates the opportunity to objectively study colonic tumors over time in living animals in conjunction with other experiments and without transferring animals from the facility where they are maintained.Colon cancer is the third leading cause of cancer in men and women, with more than 100,000 new cases diagnosed each year in the United States alone. This disease is not limited to humans—cancers of the colon and rectum also affect companion species, such as dogs, albeit less frequently than in humans.²⁰ Colorectal cancers generally develop from precancerous polyps, which can be detected and removed during colonoscopy screening before they become invasive cancers. However, not all precancers will become cancerous,²³ and a better understanding of early tumor growth dynamics in models of the disease can simultaneously increase the rate of detection of polyps destined to become cancerous and decrease the rate of unnecessary removal of benign polyps.Sizing of tumors creates an additional dimension beyond studies examining tumor multiplicity alone. Terminal sizing of tumors uses an eyepiece reticule under a dissection microscope to measure the maximal diameter of each tumor. However, this method likely misrepresents tumor volume for several reasons. First, tumors often are not symmetrical in shape, thereby limiting the interpretation of even multiple linear measurements. When volume calculations rely on the use of a formula, the irregular shape of solid tumors may require the testing of many different formulas to find the optimal one for that particular measurement and model.⁸ Second, if tumor sizing occurs after fixation, the original shape of the tumor can be affected. However, when tumor sizing occurs before fixation, the added time to size the tumors may result in degradation of the intestinal tissue, limiting further analysis. An alternate method of tumor sizing involves using the surrogate of tumor weight, the current ‘gold standard,’ for terminal studies. Tumor weight correlates closely with tumor size, although tumor density may vary depending on the tumor type. In addition, this technique is limited to use at the terminal time point. Methods that determine true tumor volume are powerful; those that can be applied in vivo to study the tumor longitudinally are even more compelling.It recently has been recognized that not all early colonic tumors grow; some remain static for years whereas a few spontaneously regress.²³ Importantly, the early growth profile of a tumor may correlate with its eventual fate.²³ This aspect of tumor biology is a newly emerging area that deserves deeper study. The current gold standard for determining longitudinal tumor volume is CT, given that tumor weight is available only through terminal experiments. In mice, microCT colonography can be used to detect a 16% change in tumor volume with 95% confidence in living animals.⁵ However, the cost of CT equipment limits this technology to shared facilities, and the pathogen status of these facilities may preclude returning animals to the place where they were original housed, limiting the opportunities for longitudinal study. Importantly, many institutions do not have access to microCT technology, and even if available, 3D renderings must be recreated to determine tumor volume, a process requiring specialized software and detailed computing knowledge. Furthermore, CT exposes animal subjects to radiation, which may interfere with the tumor biology. Although MRI can be used to determine tumor volume accurately in the absence of ionizing radiation, specialized scanners and software are required, and enemas or intravenous treatments are needed to visualize tumors clearly.²⁶Another imaging modality uses the surface area of signal due to proteins expressing a fluorescent marker, such as red fluorescent protein, as a surrogate for tumor volume.¹⁷ However, tumor volume measured by fluorescent surface area¹² may not accurately represent tumor volume in irregularly shaped tumors. In addition, this method necessitates a surgical procedure to orthotopically transplant fluorophore-expressing cells, raising questions of immune interactions between the recipient animal and the donor cells or to the surgery itself. If nude or immunocompromised animals are used in the procedure, the ability to study the immune aspect of tumor biology is reduced or eliminated.Alternatively, tumor volume can be estimated from endoscopic images. The study of tumors by colonoscopy has become routine for both mouse^6,10 and rat^1,15 models of the disease. In contrast to terminal assessments, colonoscopy allows tumors to be visualized in vivo over time, capturing the dynamics of tumor growth. Documentation of this aspect of tumor biology can greatly enrich studies evaluating chemopreventive or therapeutic agents.^6,15 Quantitative methods for determining tumor volume take this benefit a step further, allowing the investigation of the effects of background strain, therapeutic agents, environmental factors, or other modifiers of tumor growth pattern. One method to estimate tumor size uses the fraction of luminal cross-section occluded by tumor.² However, the colonic lumen expands as the animal grows, and its size often increases to accommodate the growing tumor, to prevent intestinal blockage. Optical methods to extrapolate tumor sizes from 2D images obtained in vivo during colonoscopy are achieved by inserting a flexible metal rod of known dimensions into the working channel of the endoscope.¹⁰ However, because colonic tumors can differ in shape (some are flat whereas others are pedunculated), area measurements may not translate accurately to tumor volume.To overcome these limitations and to add another tool to the growing cancer-research toolbox, we have developed a method using a biologically inert alginate to create negative molds of colonic tumors. These molds are filled with dental stone to achieve a positive cast of each tumor. A conversion factor then is used to calculate the volume of the original tumor from the dry weight of the dental stone cast. This procedure, which requires no specialized or expensive equipment and no complicated analytical methods, can be performed within the facility where the rats are housed and takes less than 15 min, including the 8 to 12 min during which the alginate sets. Therefore, our new method offers possibilities to study the dynamics of tumor growth in virtually any animal facility, regardless of the health status of subject animals or equipment availability.