The Role of Aquaporin RWC3 in Drought Avoidance in Rice

The above article appeared     

Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an in vitro model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a “self-generated” gradient mechanisms that accelerates the extension of the sprout.     

Rank Diversity of Languages: Generic Behavior in Computational Linguistics

Statistical studies of languages have focused on the rank-frequency distribution of words. Instead, we introduce here a measure of how word ranks change in time and call this distribution rank diversity. We calculate this diversity for books published in six European languages since 1800, and find that it follows a universal lognormal distribution. Based on the mean and standard deviation associated with the lognormal distribution, we define three different word regimes of languages: “heads” consist of words which almost do not change their rank in time, “bodies” are words of general use, while “tails” are comprised by context-specific words and vary their rank considerably in time. The heads and bodies reflect the size of language cores identified by linguists for basic communication. We propose a Gaussian random walk model which reproduces the rank variation of words in time and thus the diversity. Rank diversity of words can be understood as the result of random variations in rank, where the size of the variation depends on the rank itself. We find that the core size is similar for all languages studied.     

The Dynamics of an Avoidance Behavior by Ixodid Ticks to Liquid Water

Life stages of different tick species avoid walking on a wet surface surrounding a dry patch by systematically returning to the dry each time they contact the wet surface beyond the border with the tip of a first leg tarsus. Sequential analysis of the border behaviors shows that repetitive contact with the water increases the probability of walks astride the border. Ticks accept this unilateral contact with the water for longer intervals and eventually walk on to the wet surface after a combination of a short patch walk followed by a border walk which is longer than the foregoing ones. Staying time on a small circular patch is shorter than on a large one, arising probably from faster adaptation of peripheral receptors following a higher frequency of border contacts. However, an equal number of border reactions on patches of different sizes and shapes suggests that a counter in the CNS may also influence dry patch departure.     

The Empirical Analysis of Cigarette Tax Avoidance and Illicit Trade in Vietnam, 1998-2010

Illicit trade carries the potential to magnify existing tobacco-related health care costs through increased availability of untaxed and inexpensive cigarettes. What is known with respect to the magnitude of illicit trade for Vietnam is produced primarily by the industry, and methodologies are typically opaque. Independent assessment of the illicit cigarette trade in Vietnam is vital to tobacco control policy. This paper measures the magnitude of illicit cigarette trade for Vietnam between 1998 and 2010 using two methods, discrepancies between legitimate domestic cigarette sales and domestic tobacco consumption estimated from surveys, and trade discrepancies as recorded by Vietnam and trade partners. The results indicate that Vietnam likely experienced net smuggling in during the period studied. With the inclusion of adjustments for survey respondent under-reporting, inward illicit trade likely occurred in three of the four years for which surveys were available. Discrepancies in trade records indicate that the value of smuggled cigarettes into Vietnam ranges from $100 million to $300 million between 2000 and 2010 and that these cigarettes primarily originate in Singapore, Hong Kong, Macao, Malaysia, and Australia. Notable differences in trends over time exist between the two methods, but by comparison, the industry estimates consistently place the magnitude of illicit trade at the upper bounds of what this study shows. The unavailability of annual, survey-based estimates of consumption may obscure the true, annual trend over time. Second, as surveys changed over time, estimates relying on them may be inconsistent with one another. Finally, these two methods measure different components of illicit trade, specifically consumption of illicit cigarettes regardless of origin and smuggling of cigarettes into a particular market. However, absent a gold standard, comparisons of different approaches to illicit trade measurement serve efforts to refine and improve measurement approaches and estimates.     

Sex Differences in Exploration Behavior and the Relationship to Harm Avoidance

Venturing into novel terrain poses physical risks to a female and her offspring. Females have a greater tendency to avoid physical harm, while males tend to have larger range sizes and often outperform females in navigation-related tasks. Given this backdrop, we expected that females would explore a novel environment with more caution than males, and that more-cautious exploration would negatively affect navigation performance. Participants explored a novel, large-scale, virtual environment in search of five objects, pointed in the direction of each object from the origin, and then navigated back to the objects. We found that females demonstrated more caution while exploring as reflected in the increased amounts of pausing and revisiting of previously traversed locations. In addition, more pausing and revisiting behaviors led to degradation in navigation performance. Finally, individual levels of trait harm avoidance were positively associated with the amount of revisiting behavior during exploration. These findings support the idea that the fitness costs associated with long-distance travel may encourage females to take a more cautious approach to spatial exploration, and that this caution may partially explain the sex differences in navigation performance.     

The Shade Avoidance Syndrome in Arabidopsis: The Antagonistic Role of Phytochrome A and B Differentiates Vegetation Proximity and Canopy Shade

Light limitation caused by dense vegetation is one of the greatest threats to plant survival in natural environments. Plants detect such neighboring vegetation as a reduction in the red to far-red ratio (R:FR) of the incoming light. The low R:FR signal, perceived by phytochromes, initiates a set of responses collectively known as the shade avoidance syndrome, intended to reduce the degree of current or future shade from neighbors by overtopping such competitors or inducing flowering to ensure seed production. At the seedling stage these responses include increased hypocotyl elongation. We have systematically analyzed the Arabidopsis seedling response and the contribution of phyA and phyB to perception of decreased R:FR, at three different levels of photosynthetically active radiation. Our results show that the shade avoidance syndrome, induced by phyB deactivation, is gradually antagonized by phyA, operating through the so-called FR-High Irradiance Response, in response to high FR levels in a range that simulates plant canopy shade. The data indicate that the R:FR signal distinguishes between the presence of proximal, but non-shading, neighbors and direct foliar shade, via a intrafamily photosensory attenuation mechanism that acts to suppress excessive reversion toward skotomorphogenic development under prolonged direct vegetation shade.     

Computational Modeling of Single-Cell Migration: The Leading Role of Extracellular Matrix Fibers

Cell migration is vitally important in a wide variety of biological contexts ranging from embryonic development and wound healing to malignant diseases such as cancer. It is a very complex process that is controlled by intracellular signaling pathways as well as the cell’s microenvironment. Due to its importance and complexity, it has been studied for many years in the biomedical sciences, and in the last 30 years it also received an increasing amount of interest from theoretical scientists and mathematical modelers. Here we propose a force-based, individual-based modeling framework that links single-cell migration with matrix fibers and cell-matrix interactions through contact guidance and matrix remodelling. With this approach, we can highlight the effect of the cell’s environment on its migration. We investigate the influence of matrix stiffness, matrix architecture, and cell speed on migration using quantitative measures that allow us to compare the results to experiments.     

The Role of Compassion in Altruistic Helping and Punishment Behavior

Compassion, the emotional response of caring for another who is suffering and that results in motivation to relieve suffering, is thought to be an emotional antecedent to altruistic behavior. However, it remains unclear whether compassion enhances altruistic behavior in a uniform way or is specific to sub-types of behavior such as altruistic helping of a victim or altruistic punishment of a transgressor. We investigated the relationship between compassion and subtypes of altruistic behavior using third-party paradigms where participants 1) witnessed an unfair economic exchange between a transgressor and a victim, and 2) had the opportunity to either spend personal funds to either economically a) help the victim or b) punish the transgressor. In Study 1, we examined whether individual differences in self-reported empathic concern (the emotional component of compassion) was associated with greater altruistic helping or punishment behavior in two independent samples. For participants who witnessed an unfair transaction, trait empathic concern was associated with greater helping of a victim and had no relationship to punishment. However, in those who decided to punish the transgressor, participants who reported greater empathic concern decided to punish less. In Study 2, we directly enhanced compassion using short-term online compassion meditation training to examine whether altruistic helping and punishment were increased after two weeks of training. Compared to an active reappraisal training control group, the compassion training group gave more to help the victim and did not differ in punishment of the transgressor. Together, these two studies suggest that compassion is related to greater altruistic helping of victims and is not associated with or may mitigate altruistic punishment of transgressors.     

The Role of Behavior in Temperature Acclimation and Tolerance in Ectotherms

A review of field and laboratory investigations suggests thatmany ectothermic vertebrates can exploit the spatiotemporaldistribution of environmental temperatures to maximize energyutilization and to enhance survivability. Diel and seasonalcycles in thermal preference, acclimation rate, thermal toleranceand heat-hardening may well be adapted to temporal variationsin environmental temperature. In addition, many ectoiherms behaviorallyexploit thermal heterogeneity in the environment. Such behavioraladaptations are synergistic with various degrees of physiologicalregulation. Voluntary brief exposures to temperatures that wouldbe lethal upon prolonged exposure can result in heat-hardening.Heat-hardening, distinct from acclimation to high temperature,is a short-term increase in thermal tolerance while toleranceacclimation is a longer lasting response within normal rangesof environmental temperatures; both are reversible nongeneticresponses. The physiological and ecological significance ofbehaviorally mediated heat-hardening may be greater than previouslyrealized and suggest new approaches for future study.     

Social Transmission of Avoidance Behavior under Situational Change in Learned and Unlearned Rats

Background

Rats receive information from other conspecifics by observation or other types of social interaction. Such social interaction may contribute to the effective adaptation to changes of environment such as situational switching. Learning to avoid dangerous places or objects rapidly occurs with even a single conditioning session, and the conditioned memory tends to be sustained over long periods. The avoidance is important for adaptation, but the details of the conditions under which the social transmission of avoidance is formed are unknown. We demonstrate that the previous experience of avoidance learning is important for the formation of behaviors for social transmission of avoidance and that the experienced rats adapt to a change of situation determined by the presence or absence of aversive stimuli. We systematically investigated social influence on avoidance behavior using a passive avoidance test in a light/dark two-compartment apparatus.

Methodology/Principal Findings

Rats were divided into two groups, one receiving foot shocks and another with no aversive experience in a dark compartment. Experienced and inexperienced rats were further divided into subjects and partners. In Experiment 1, each subject experienced (1) interaction with an experienced partner, (2) interaction with an inexperienced partner, or (3) no interaction. In Experiment 2, each subject experienced interaction with a partner that received a shock. The entering latency to a light compartment was measured. The avoidance behavior of experienced rats was inhibited by interaction with inexperienced or experienced partners in a safely-changed situation. The avoidance of experienced rats was reinstated in a dangerously-changed situation by interaction with shocked rats. In contrast, the inexperienced rats were not affected by any social circumstances.

Conclusions/Significance

These results suggest that transmitted information among rats can be updated under a situational change and that the previous experience is crucial for social enhancement and inhibition of avoidance behavior in rats.     

Prenatal Stress and Adaptive Behavior of Offspring: The Role of Placental Serotonin

Doklady Biochemistry and Biophysics - The effect of mild prenatal stress in mice, leading to an increase in the placental serotonin level, on the formation of adaptive behavior in male offspring at...     

Predation Risk Avoidance by Terrestrial Amphibians: The Role of Prey Experience and Vulnerability to Native and Exotic Predators

We studied avoidance, by four amphibian prey species (Rana luteiventris, Ambystoma macrodactylum, Pseudacris regilla, Tarichia granulosa), of chemical cues associated with native garter snake (Thamnophis elegans) or exotic bullfrog (R. catesbeiana) predators. We predicted that avoidance of native predators would be most pronounced, and that prey species would differ in the intensity of their avoidance based on relative levels of vulnerability to predators in the wild. Adult R. luteiventris (presumably high vulnerability to predation) showed significant avoidance of chemical cues from both predators, A. macrodactylum (intermediate vulnerability to predation) avoided T. elegans only, while P. regilla (intermediate vulnerability to predation) and T. granulosa (low vulnerability to predation) showed no avoidance of either predator. We assessed if predator avoidance was innate and/or learned by testing responses of prey having disparate levels of prior exposure to predators. Wild‐caught (presumably predator‐exposed) post‐metamorphic juvenile R. luteiventris and P. regilla avoided T. elegans cues, while laboratory‐reared (predator‐naive) conspecifics did not; prior exposure to R. catesbeiana was not related to behavioural avoidance among adult or post‐metamorphic juvenile wild‐reared A. macrodactylum and P. regilla. These results imply that (i) some but not all species of amphibian prey avoid perceived risk from garter snake and bullfrog predators, (ii) the magnitude of this response probably differs according to prey vulnerability to predation in the wild, and (iii) avoidance tends to be largely learned rather than innate. Yet, the limited prevalence and intensity of amphibian responses to predation risk observed herein may be indicative of either a relatively weak predator–prey relationship and/or the limited importance of predator chemical cues in this particular system.     

Environmental Smoking and Smoking Onset in Adolescence: The Role of Dopamine-Related Genes. Findings from Two Longitudinal Studies

Although environmental smoking (i.e., paternal and maternal smoking, sibling smoking, and peer smoking) is one of the most important factors for explaining adolescent smoking behavior, not all adolescents are similarly affected. The extent to which individuals are vulnerable to smoking in their environment might depend on genetic factors. The aim of this study was to examine the interplay between environmental smoking and genes encoding components of the dopaminergic system (i.e., dopamine receptor D2, D4, and dopamine transporter DAT1) in adolescent smoking onset. Data from two longitudinal studies were used. Study 1 consisted of 991 non-smoking early adolescents (mean age = 12.52, SD = .57) whereas study 2 consisted of 365 non-smoking middle to late adolescents (mean age = 14.16, SD = 1.07) who were followed for 16 and 48 months, respectively. Logistic regression analyses were conducted using Mplus. In study 1, we found positive associations between parents'' and friends'' smoking at the first measurement and smoking status 16 months later. In study 2 we found a positive association between friends'' smoking and smoking onset 48 months later. Neither study demonstrated any interaction effects of the DRD2, DRD4, or DAT1 genotypes. In conclusion, the effects of environmental smoking on smoking onset are similar for adolescent carriers and non-carriers of these specific genes related to the dopaminergic system.     

Deciding Not to Decide: Computational and Neural Evidence for Hidden Behavior in Sequential Choice

Understanding the cognitive and neural processes that underlie human decision making requires the successful prediction of how, but also of when, people choose. Sequential sampling models (SSMs) have greatly advanced the decision sciences by assuming decisions to emerge from a bounded evidence accumulation process so that response times (RTs) become predictable. Here, we demonstrate a difficulty of SSMs that occurs when people are not forced to respond at once but are allowed to sample information sequentially: The decision maker might decide to delay the choice and terminate the accumulation process temporarily, a scenario not accounted for by the standard SSM approach. We developed several SSMs for predicting RTs from two independent samples of an electroencephalography (EEG) and a functional magnetic resonance imaging (fMRI) study. In these studies, participants bought or rejected fictitious stocks based on sequentially presented cues and were free to respond at any time. Standard SSM implementations did not describe RT distributions adequately. However, by adding a mechanism for postponing decisions to the model we obtained an accurate fit to the data. Time-frequency analysis of EEG data revealed alternating states of de- and increasing oscillatory power in beta-band frequencies (14–30 Hz), indicating that responses were repeatedly prepared and inhibited and thus lending further support for the existence of a decision not to decide. Finally, the extended model accounted for the results of an adapted version of our paradigm in which participants had to press a button for sampling more information. Our results show how computational modeling of decisions and RTs support a deeper understanding of the hidden dynamics in cognition.     

Computational ligand-based rational design: Role of conformational sampling and force fields in model development

A significant number of drug discovery efforts are based on natural products or high throughput screens from which compounds showing potential therapeutic effects are identified without knowledge of the target molecule or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compound's structure and physicochemical attributes to its biological activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compounds with improved biological attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quantitative structure-activity relationships (QSAR) yielding quantitative estimates of activities based on physiochemical properties, and to similarity searching, which explores compounds with similar properties as well as various combinations of the above. A number of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is molecular mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression analysis to neural networks, from which the SAR is determined. Accordingly, for effective application of LBDD for SAR determinations it is important that the compounds be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modelling is largely based on use of the appropriate empirical force field for the molecules being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations associated with empirical energy functions and conformational sampling methods.     

Vibration Sensitivity and a Computational Theory for Prey-Localizing Behavior in Sand Scorpions

As burrowing, nocturnal predators of small arthropods, sandscorpions have evolved exquisite sensitivity to vibrationalinformation that comes to them through the substrate they liveon, dry sand. Over distances of a few decimeters, sand conductslow velocity (50 m/sec) surface (Rayleigh) waves of sufficientamplitude and bandwidth (200<f<500 Hz) to be biologicallydetectable. Eight acceleration-sensitive receptors (slit sensilla)at the tips of the scorpion's circularly arranged legs detectsurface waves generated by prey movements or "juddering" signalsfrom other scorpions. From this input alone, direction of thedisturbance source is calculated up to 20 cm distance. By ablatingslit sensilla in various combinations on the eight legs, thecontribution each makes in computing target location can beassessed. Other behavioral experiments show that differentialtiming of surface wave arrival at each sensor is most likelythe cue that determines target location. Given the simplicityof this sensory system, a computational theory to account forwave source localization has been developed using a populationof second-order neurons, each receiving excitatory input fromone vibration receptor and inhibition from the triad of receptorsopposite to it in the eight-element array. Input from a passingsurface wave opens and closes a time widow, the width of whichdetermines the firing probability of second-order neurons. Targetdirection is encoded as the relative excitation of these neurons,and stochastic optimization tunes the relative strengths ofexcitatory and inhibitory inputs for accuracy of response. Theexcellent agreement between predictions of the model and observedbehavior of sand scorpions confirms a simple theory for computationalmapping of surface vibration space.     

Evidence for a Pro-Proliferative Feedback Loop in Prostate Cancer: The Role of Epac1 and COX-2-Dependent Pathways

Objective

In human prostate cancer cells, a selective Epac agonist, 8-CPT-2Me-cAMP, upregulates cell proliferation and survival via activation of Ras-MAPK and PI- 3-kinase-Akt-mTOR signaling cascades. Here we examine the role of inflammatory mediators in Epac1-induced cellular proliferation by determining the expression of the pro-inflammatory markers p-cPLA2, COX-2, and PGE₂ in prostate cancer cells treated with 8-CPT-2Me-cAMP.

Methods

We employed inhibitors of COX-2, mTORC1, and mTORC2 to probe cyclic AMP-dependent pathways in human prostate cancer cells. RNAi targeting Epac1, Raptor, and Rictor was also employed in these studies.

Results

8-CPT-2Me-cAMP treatment caused a 2–2.5-fold increase of p-cPLA2^S505, COX-2, and PGE₂ levels in human prostate cancer cell lines. Pretreatment of cells with the COX-2 inhibitor SC-58125 or the EP4 antagonist AH-23848, or with an inhibitor of mTORC1 and mTORC2, Torin1, significantly reduced the Epac1-dependent increase of p-cPLA2 and COX-2, p-S6-kinase^T389, and p-AKT^S473. In addition, Epac1-induced protein and DNA synthesis were greatly reduced upon pretreatment of cells with either COX-2, EP4, or mTOR inhibitors. Transfection of prostate cancer cells with Epac1 dsRNA, Raptor dsRNA, or Rictor dsRNA profoundly reduced Epac1-dependent increases in p-cPLA2 and COX-2.

Conclusion

We show that Epac1, a downstream effector of cAMP, functions as a pro-inflammatory modulator in prostate cancer cells and promotes cell proliferation and survival by upregulating Ras-MAPK, and PI 3-kinase-Akt-mTOR signaling.