Olfactory cues potentiate learning of distant visuospatial information

The influence of proximal olfactory cues on place learning and memory was tested in two different spatial tasks. Rats were trained to find a hole leading to their home cage or a single food source in an array of petri dishes. The two apparatuses differed both by the type of reinforcement (return to the home cage or food reward) and the local characteristics of the goal (masked holes or salient dishes). In both cases, the goal was in a fixed location relative to distant visual landmarks and could be marked by a local olfactory cue. Thus, the position of the goal was defined by two sets of redundant cues, each of which was sufficient to allow the discrimination of the goal location. These experiments were conducted with two strains of hooded rats (Long-Evans and PVG), which show different speeds of acquisition in place learning tasks. They revealed that the presence of an olfactory cue marking the goal facilitated learning of its location and that the facilitation persisted after the removal of the cue. Thus, the proximal olfactory cue appeared to potentiate learning and memory of the goal location relative to distant environmental cues. This facilitating effect was only detected when the expression of spatial memory was not already optimal, i.e., during the early phase of acquisition. It was not limited to a particular strain.

Blood Cues Induce Antipredator Behavior in Nile Tilapia Conspecifics

In this study, we show that the fish Nile tilapia displays an antipredator response to chemical cues present in the blood of conspecifics. This is the first report of alarm response induced by blood-borne chemical cues in fish. There is a body of evidence showing that chemical cues from epidermal 'club' cells elicit an alarm reaction in fish. However, the chemical cues of these 'club' cells are restricted to certain species of fish. Thus, as a parsimonious explanation, we assume that an alarm response to blood cues is a generalized response among animals because it occurs in mammals, birds and protostomian animals. Moreover, our results suggest that researchers must use caution when studying chemically induced alarm reactions because it is difficult to separate club cell cues from traces of blood. © 2013 Barreto et al.

Ethopharmacological evaluation of the rat exposure test: A prey-predator interaction test

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT1A/5-HT2 receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs. © 2012 Elsevier B.V.

Anomalous reaction-diffusion as a model of nonexponential DNA escape kinetics

We show that data from recent experiments carried out on the kinetics of DNA escape from alpha-hemolysin nanopores [M. Wiggin, C. Tropini, C. T. Cossa, N. N. Jetha, and A. Marziali, Biophys. J. 95, 5317 (2008)] may be rationalized by a model of chain dynamics based on the anomalous diffusion of a particle moving in a harmonic well in the presence of a delta function sink. The experiments of Wiggin found, among other things, that the occasional occurrence of unusually long escape times in the distribution of chain trapping events led to nonexponential decays in the survival probability, S(t), of the DNA molecules within the nanopore. Wiggin ascribed this nonexponentiality to the existence of a distribution of trapping potentials, which they suggested was theresult of stochastic interactions between the bases of the DNA and the amino acids located on the surface of the nanopore. Based on this idea, they showed that the experimentally determined S(t) could be well fit in both the short and long time regimes by a function of the form (1+t/tau)(-alpha) (the so called Becquerel function). In our model, S(t) is found to be given by a Mittag-Leffler function at short times and by a generalized Mittag-Leffler function at long times. By suitable choice of certain parameter values, these functions are found to fit the experimental S(t) even better than the Becquerel function. Anomalous diffusion of DNA within the trap prior to escape over a barrier of fixed height may therefore provide a second, plausible explanation of the data, and may offer fresh perspectives on similar trapping and escape problems.

Optimal barrier subdivision for Kramers' escape rate

We examine the effect of subdividing the potential barrier along the reaction coordinate on Kramers' escape rate for a model potential. Using the known supersymmetric potential approach, we show the existence of an optimal number of subdivisions that maximizes the rate.

Mean first passage time approach to the problem of optimal barrier subdivision for Kramer's escape rate

We consider the effect of subdividing the potential barrier along the reaction coordinate on Kramer's escape rate for a model potential, Using the known supersymmetric potential approach, we show the existence of an optimal number of subdivisions that maximizes the rate, We cast the problem as a mean first passage time problem of a biased random walker and obtain equivalent results, We briefly summarize the results of our investigation on the increase in the escape rate by placing a blow-torch in the unstable part of one of the potential wells. (C) 1999 Elsevier Science B.V. All rights reserved.

Free Energy Barriers for Escape of Water Molecules from Protein Hydration Layer

Free energy barriers separating interfacial water molecules from the hydration layer at the surface of a protein to the bulk are obtained by using the umbrella sampling method of free energy calculation. We consider hydration layer of chicken villin head piece (HP-36) which has been studied extensively by molecular dynamics simulations. The free energy calculations reveal a strong sensitivity to the secondary structure. In particular, we find a region near the junction of first and second helix that contains a cluster of water molecules which are slow in motion, characterized by long residence times (of the order of 100 ps or more) and separated by a large free energy barrier from the bulk water. However, these ``slow'' water molecules constitute only about 5-10% of the total number of hydration layer water molecules. Nevertheless, they play an important role in stabilizing the protein conformation. Water molecules near the third helix (which is the important helix for biological function) are enthalpically least stable and exhibit the fastest dynamics. Interestingly, barrier height distributions of interfacial water are quite broad for water surrounding all the three helices (and the three coils), with the smallest barriers found for those near the helix-3. For the quasi-bound water molecules near the first and second helices, we use well-known Kramers' theory to estimate the residence time from the free energy surface, by estimating the friction along the reaction coordinate from the diffusion coefficient by using Einstein relation. The agreement found is satisfactory. We discuss the possible biological function of these slow, quasi-bound (but transient) water molecules on the surface.

GDF-15 contributes to proliferation and immune escape of malignant gliomas

Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-beta family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiologic and pathologic conditions.

Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells:selective escape of CD44high/CD24low/HER2low breast cancer stem cells

Although trastuzumab (Herceptin) has substantially improved the overall survival of patients with mammary carcinomas, even initially well-responding tumors often become resistant. Because natural killer (NK) cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to contribute to the therapeutic effects of trastuzumab, we have established a cell culture system to select for ADCC-resistant SK-OV-3 ovarian cancer and MCF7 mammary carcinoma cells. Ovarian cancer cells down-regulated HER2 expression, resulting in a more resistant phenotype. MCF7 breast cancer cells, however, failed to develop resistance in vitro. Instead, treatment with trastuzumab and polyclonal NK cells resulted in the preferential survival of individual sphere-forming cells that displayed a CD44(high)CD24(low) "cancer stem cell-like" phenotype and expressed significantly less HER2 compared with non-stem cells. Likewise, the CD44(high)CD24(low) population was also found to be more immunoresistant in SK-BR3, MDA-MB231, and BT474 breast cancer cell lines. When immunoselected MCF7 cells were then re-expanded, they mostly lost the observed phenotype to regenerate a tumor cell culture that displayed the initial HER2 surface expression and ADCC-susceptibility, but was enriched in CD44(high)CD24(low) cancer stem cells. This translated into increased clonogenicity in vitro and tumorigenicity in vivo. Thus, we provide evidence that the induction of ADCC by trastuzumab and NK cells may spare the actual tumor-initiating cells, which could explain clinical relapse and progress. Moreover, our observation that the "relapsed" in vitro cultures show practically identical HER2 surface expression and susceptibility toward ADCC suggests that the administration of trastuzumab beyond relapse might be considered, especially when combined with an immune-stimulatory treatment that targets the escape variants.

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities.

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.

Triple- and quadruple-escape peaks in HPGe detectors: Experimental observation and Monte Carlo simulation

The triple- and quadruple-escape peaks of 6.128 MeV photons from the (19)F(p,alpha gamma)(16)O nuclear reaction were observed in an HPGe detector. The experimental peak areas, measured in spectra projected with a restriction function that allows quantitative comparison of data from different multiplicities, are in reasonably good agreement with those predicted by Monte Carlo simulations done with the general-purpose radiation-transport code PENELOPE. The behaviour of the escape intensities was simulated for some gamma-ray energies and detector dimensions; the results obtained can be extended to other energies using an empirical function and statistical properties related to the phenomenon. (C) 2010 Elsevier B.V. All rights reserved.

Escherichia coli transcript cleavage factors GreA and GreB stimulate promoter escape and gene expression in vivo and in vitro.

The process of RNA chain initiation by RNA polymerases plays a central role in the regulation of transcription. In this complex phase of transcription, short oligomers are synthesized and released from the enzyme-promoter complex in a reaction termed abortive initiation. The polymerase undergoes many cycles of abortive initiation prior to completion of the initiation process, which is signaled by the translocation of the enzyme away from the promoter, release of sigma factor, and formation of an elongation complex in which the RNA is stably bound. We have studied the parameters that affect escape from the promoter by Escherichia coli RNA polymerase for the phage T7 A1 promoter, the phage T5 N25 promoter, and the chimeric promoter T5 N25antiDSR. The latter site contains a synthetic initial transcribed region that reduces its ability to synthesize RNA both in vivo and in vitro. Clearance from T5 N25antiDSR can be stimulated up to 10-fold in vitro by addition of the E. coli transcript cleavage factor GreA or GreB, but these factors have little effect on transcription from the normal T7 A1 or T5 N25 promoters. Using an E. coli strain lacking GreA and GreB, we were also able to show stimulation of transcription by the Gre factors from the T5 N25antiDSR promotor in vivo. The stimulation of RNA chain initiation by Gre factors, together with their known biochemical properties in the transcription elongation reaction, suggests some specific models for steps in the transcription initiation reaction.

A-REIT seasoned equity offerings : determinants and market reaction

The paper examines the decision by Australian Real Estate Trusts (A-REITs) to issue seasoned equity offerings from 2000 - 2008 and stock market reaction to the offerings using panel data and event study methodologies, respectively. The global financial crisis has resulted in freezing of the Australian bond markets, with several A-REITs left with seasoned equity issuance and asset sales as the only viable modes of raising additional capital. The findings review that leverage and operating risk are negative significant determinants of seasoned equity offerings; profitability and growth opportunities are positive significant determinants. Of the structure and type of properties held by the A-REIT, only stapled management structure and international operations are significant determinants. Type of properties held by A-REITs show inconsistent results. Similar to previous studies of seasoned equity offerings, we find a significant negative abnormal return associated with their announcement and no evidence of excessive leakage of information. Cross-sectional regressions show that the issued amount raised and leverage are significant factors affecting abnormal returns.