A rapid assessment of stimulus properties of morphine

The difficulty in assessing stimulus properties of drugs becomes apparent when the test drug, like morphine, carries both aversive and reinforcing effects at certain doses. Mice (ICR Crj strain) were trained in a passive avoidance conditioning using a two-compartment shuttle-box. On alternate days, morphine (3.0 mg/kg) was paired with shock in one compartment and saline with shock in the other compartment. A total of 3 morphine/saline pairings were given. Animals were then tested 7 times, one test per day, with saline and different doses of morphine (0.75, 1.12, 1.32, 0.93, 1.50, 3.0 mg/kg) to reveal the stimulus properties of morphine. The preference for the morphine-conditioned safe compartment after morphine injections was used to indicate that the animals associated some “stimulus” or “motivational” properties of morphine with the cues of the safe compartment. The animals discriminated very well between saline and low doses of morphine on the one hand and higher doses of morphine (close to that given during conditioning) on the other. The discontinuity between injections responded to as saline and those responded to as morphine was virtually complete between 1.12 and 1.32 mg/kg of morphine. These findings demonstrate that the present method can be used to establish an association between some stimulus properties of morphine and avoidance of shock. Accordingly, the successful discrimination of the animals between the two compartments revealed some stimulus properties of morphine.     

Behavioral evidence for dopaminergic supersensitivity after chronic haloperidol

Chronic administration for 16 days of haloperidol (in increasing doses up to 20 mg/kg/day) results in a supersensitivity of dopamine receptors. This supersensitivity is manifested by an enhanced stereotypy and aggression in response to small, otherwise ineffective, doses of apomorphine. Maximum aggression is observed 7 days after the last dose of haloperidol when 2.5 mg/Kg of apomorphine is administered. In addition, “wet shakes”, reminiscent of withdrawal from morphine, are observed in these animals after the cessation of the haloperidol administration. These shakes are blocked by morphine. These results may be interpreted to mean that “wet shakes” and drug induced aggression are the results of hyperactivity of the dopaminergic system.     

Ethanol suppression of naloxone-induced withdrawal in morphine-dependent rats

The technique of morphine pellet implantation was used to produce physical dependence on morphine in male rats. The number of “wet dog” shakes occurring within a period of 30 minutes during naloxone-precipitated (1.0 mg/kg, s.c.) withdrawal in four-day morphine implanted rats was determined after either acute or chronic treatment with ethanol. An acute dose of ethanol administered prior to withdrawal had no significant effect on the withdrawal response whereas chronic administration of ethanol during the development of dependence on morphine significantly suppressed the naloxone-precipitated withdrawal response to 44–57 percent of the control response. Analysis of brain and plasma for morphine concentration four days following dependence development showed no significant differences between morphine controls and those animals treated with both morphine and ethanol. Pentobarbital, another central nervous system depressant, demonstrated no effect on the withdrawal response, whether administered acutely or chronically during the development of dependence.     

Anaphylactic shock and lethal anaphylaxis caused by compound amino acid solution, a nutritional treatment widely used in China

Compound amino acid solution (CAAS) is a large class of solution of amino acids’ mixture and was widely used in China. Its extensive nutritional treatment was accompanied by a substantial incidence of adverse reactions, especially life-threatening anaphylaxis. However, the adverse reactions were reported in isolated case reports only, and the reasons behind this needed further investigation. The Chinese language papers were searched from China National Knowledge Infrastructure and Wanfang database published in China from 1985 to 2010. The search terms “anaphylactic”, “anaphylaxis”, “allergic”, “allergy”, “shock”, and “adverse reaction” combined with the term “amino acid” were used. Totally 71 episodes of anaphylactic shock and seven deaths in 38 articles were analyzed. Chest distress and cool extremities were the most common clinical manifestations. Almost all patients suffered from significant hypotension. The vast majority of patients were not found to be allergic to certain substances. CAAS was inappropriately administrated in more than one-third of patients. The life-threatening anaphylaxis was prominently prevalent in pregnant women, the elderly and patients with hypersensitivity such as asthma, and patients without medicinal indication. Innovation of processing technique and establishment of more strict supervision system are an urgent need for CAAS to control its production quality and thus improve its safety in China.     

TLR4 signaling-induced heme oxygenase upregulation in the acute lung injury: role in hemorrhagic shock and two-hit induced lung inflammation

Resuscitated hemorrhagic shock is believed to promote the development of acute lung injury (ALI) by priming the immune system for an exaggerated inflammatory response to a second trivial stimulus. This work explored effects of TLR4 on hemorrhage-induced ALI and “second-hit” responses, and further explore the mechanisms involved in “second-hit” responses. Expression of HO-1, IL-10, lung W/D and MPO markedly increased at nearly all time-points examined in HSR/LPS group as compared with sham/LPS group in WT mice. In HSR/LPS mice, the induced amount of IL-10 and the expressions of HO-1 of WT mice were significantly higher compared with TLR-4d/d. This study provides in vivo evidence that pulmonary infections after LPS instillation contribute to local tissue release of pro-inflammatory mediators after HSR systemic. Activation of TLR4 might induce HO-1 expression and HO-1 modulates proinflammatory responses that are triggered via TLR4 signaling.     

Protein kinase‐mediated signalling in priming: Immune signal initiation,propagation, and establishment of long‐term pathogen resistance in plants

“Priming” in plant phytopathology describes a phenomenon where the “experience” of primary infection by microbial pathogens leads to enhanced and beneficial protection of the plant against secondary infection. The plant is able to establish an immune memory, a state of systemic acquired resistance (SAR), in which the information of “having been attacked” is integrated with the action of “being prepared to defend when it happens again.” Accordingly, primed plants are often characterized by faster and stronger activation of immune reactions that ultimately result in a reduction of pathogen spread and growth. Prerequisites for SAR are (a) the initiation of immune signalling subsequent to pathogen recognition, (b) a rapid defence signal propagation from a primary infected local site to uninfected distal parts of the plant, and (c) a switch into an immune signal‐dependent establishment and subsequent long‐lasting maintenance of phytohormone salicylic acid‐based systemic immunity. Here, we provide a summary on protein kinases that contribute to these three conceptual aspects of “priming” in plant phytopathology, complemented by data addressing the role of protein kinases crucial for immune signal initiation also for signal propagation and SAR.     

Morphine tolerance and naloxone receptor binding.

³H-naloxone specific binding studies have confirmed the induction of receptor expansion after an acute injection of morphine, as reported by Pert et al (3) as well as the lack of expansion in chronically morphinized rats shown by Klee and Streaty (4) using dihydromorphine. With a challenging test dose of morphine given to rats maintained drug free after acute and chronic regimens of morphine, the lack of expansion as measured by 3H-naloxone specific binding persisted up to at least 4 weeks. Between 4–8 weeks receptor expansion can be re-induced with a challenging test dose. This “physical binding tolerance” is dose related. That this persistant “tolerance” is not attributable to the presence of dissociable morphine remaining after the drug regimen or challenge dose can be shown by detergent extraction and exhaustive dialysis of the standard buffer homogenate preparation as well as with fresh excised tissue.     

Zebrafish “personality” influences sensitivity to magnetic fields

How animals integrate different sensory information for orientation is a complex process involving interactions between a variety of internal and external factors. Due to this complexity, each component of a suite of factors is typically studied in isolation. Here, we examine how an internal factor (personality of fish) influences the response of zebrafish (Danio rerio) to the magnetic field, while swimming in a flow chamber. Our previous work demonstrated that the orientation to the water current (rheotaxis) of zebrafish individuals is influenced by variations of the magnetic field only when fish are part of a shoal. In this study, we evaluated the rheotactic behavior of 20 fish, grouped in shoals of “proactive” or “reactive” individuals, under magnetic fields of different directions. We found that the magnetic field influenced at which water speed rheotaxis was elicited in zebrafish with “reactive” personality, but not in those with “proactive” personality. These results suggest that fish personality influences response to or weighing of sensory inputs and provides some insight on the variation in behavioral responses to environmental stimuli in both laboratory and natural settings.     

On the Mechanism of Action of H2O2 in the Cellular Stress

We propose a hypothesis according to which the reactive and reduced species of oxygen could be the intracellular inducers of the stress (or “heat-shock”) response. This hypothesis is based on the following observations on Drosphila cells: -a) the return to normoxia after 24 h anaerobiosis is suficient to induce the synthesis of the ‘heat shock’ proteins without elevation of temperature together with a rapid increase of O₂ consumption; -b) hydrogen peroxide introduced in the culture medium induces the early transcrip-tional activation of the ‘heat shock’ genes (maximal after 5 minutes); -c) hydrogen peroxide added to cellular extracts in vitro (thus acting as an intracellular metabolite) activates instantaneously the binding capacity of a ‘heat shock’ factor to a DNA ‘heat shock’ regulatory element. Thus, hydrogen peroxide, and possibly other reactive reduced species ofoxygen, could trigger the onset of the stress (or ‘heat shock’) response.     

A simulation study of three methods for estimating selective values and survival rates from recapture data

The methods ofManly (1973),Manly (1975) andManly (1977) for estimating survival rates and relative survival rates from recapture data have been compared by computer simulation. In the simulations batches of two types of animal were “released” at one point in “time” and recapture samples were taken at “daily” intervals from then on. The various methods of estimation were then used to estimate, the daily survival rates of type 1 and type 2 animals, and also the survival rate of the type 2 animals relative to the type 1 animals. Simulation experiments were designed to examine (a) the bias in estimates, (b) the relative precision of different methods of estimation, (c) the validity of confidence intervals for true parameter values, and (d) the effect on estimates of the failure of certain assumptions.     

Behavior of males in a reproductive aggregation of the banded demoiselle Calopteryx splendens (Insecta, Odonata)

The view according to which damselfly males practice two alternative reproductive tactics of access to females is critically discussed. It is widely accepted that some males (“territorial” ones) have priority as potential female partners, while others (“sneakers” or “wanderers”) are incapable of retaining an individual territory. They have a chance of mating only by intruding briefly into the area defended by a “territorial” male when a female is present there. Thus, the tactics of a “territorial” male consists in waiting for a female in its territory and copulating with it “by agreement,” whereas non-territorial males resort to forced copulations. By observation of individually marked males (48 out of 118) it was shown that every male could be regarded as “territorial” during a certain period and as a “wanderer” before and after it. Thus, no correlation between the modes of space use by a male (residence/mobility) and the characters of its external morphology and/or signal behavior appears to be possible in principle. According to the data obtained, a more plausible explanation is that the female chooses not the male but the best area for oviposition. In addition, it was ascertained that adherence to forced copulations cannot constitute successful “tactics” since they rarely result in insemination, neither by “territorial” nor “non-territorial” males. In other words, we are dealing not with certain alternative tactics (i.e., specialized adaptive mechanisms that have evolved in the species) but simply with the results of different sets of circumstances at a given moment.     

Manipulations of sensory experiences during development reveal mechanisms underlying vocal learning biases in zebra finches

Biological predispositions in learning can bias and constrain the cultural evolution of social and communicative behaviors (e.g., speech and birdsong), and lead to the emergence of behavioral and cultural “universals.” For example, surveys of laboratory and wild populations of zebra finches (Taeniopygia guttata) document consistent patterning of vocal elements (“syllables”) with respect to their acoustic properties (e.g., duration, mean frequency). Furthermore, such universal patterns are also produced by birds that are experimentally tutored with songs containing randomly sequenced syllables (“tutored birds”). Despite extensive demonstrations of learning biases, much remains to be uncovered about the nature of biological predispositions that bias song learning and production in songbirds. Here, we examined the degree to which “innate” auditory templates and/or biases in vocal motor production contribute to vocal learning biases and production in zebra finches. Such contributions can be revealed by examining acoustic patterns in the songs of birds raised without sensory exposure to song (“untutored birds”) or of birds that are unable to hear from early in development (“early‐deafened birds”). We observed that untutored zebra finches and early‐deafened zebra finches produce songs with positional variation in some acoustic features (e.g., mean frequency) that resemble universal patterns observed in tutored birds. Similar to tutored birds, early‐deafened birds also produced song motifs with alternation in acoustic features across adjacent syllables. That universal acoustic patterns are observed in the songs of both untutored and early‐deafened birds highlights the contribution motor production biases to the emergence of universals in culturally transmitted behaviors.     

Forest cover and level of protection influence the island-wide distribution of an apex carnivore and umbrella species,the Sri Lankan leopard (<Emphasis Type="Italic">Panthera pardus kotiya</Emphasis>)

Apex predators fulfil potentially vital ecological roles. Typically wide-ranging and charismatic, they can also be useful surrogates for biodiversity preservation, making their targeted conservation imperative. The Sri Lankan leopard (Panthera pardus kotiya), an endangered, endemic sub-species, is the island’s apex predator. Of potential keystone importance, this carnivore also fulfills “umbrella” and “flagship” criterion and is of high ecological and existence value. Apex predator conservation requires identifying factors underlying distribution, so we used multi-scale maximum entropy modelling with sampling bias correction to investigate a broad suite of relevant ecological, climatic and anthropogenic factors in order to identify potentially suitable leopard habitat. Presence locations were determined from 15 years of surveys, observations and verified reports. The best bias correction procedure and scale were uncertain, so we employed a novel method of using information from all models across analyses to determine top models and identify influential variables. Leopard presence was most strongly linked to the landscape proportion encompassed by Protected Areas strictly limiting human presence, with more porous Protected Areas less influential. All three forest composition and configuration metrics investigated (area weighted mean patch size, patch density and forest connectivity) were influential, with increased patch size and higher connectivity predicting better habitat suitability for leopards. Habitat suitability was also better where cropland extent and urban patch size were small. In summary, ground-level protection and natural forest extent and connectivity are of profound importance to Sri Lankan leopard distribution and are key factors in ensuring the ecological integrity of the island’s faunal assemblages.     

Studies on the mechanism of T-cell-mediated lysis: XIII. Lectin-dependent T-cell-mediated cytotoxicity is supported by Con A-coupled Sepharose beads

In an attempt to characterize the “activation” signal delivered by concanavalin A (Con A) in lectin-dependent T-cell-mediated cytotoxicity (LDCC), we attempted to determine whether there was a need for the intracellular localization of lectin within the effector cell. To preclude such internalization, Con A was insolubilized by coupling to Sepharose and was then tested for its ability to support LDCC. We found that all the preparations of Con A-Sepharose tested were effective in supporting cytolysis, suggesting that the “activation” signal for lysis could be delivered solely at the level of the effector cell membrane. Furthermore, in contrast to previous reports, we found that insolubilized Con A was mitogenic for T-cell populations.     

Interactions of thyrotropin releasing hormone and morphine sulfate in rodents.

Thyrotopin releasing hormone (TRH) produces “wet dog shakes” in rats similar to those observed during morphine withdrawal. The shaking behavior precipitated by morphine abstinence can be exacerbated by TRH administration while the other components of the morphine withdrawal syndrome remain unchanged. Morphine, chlorpromazine, apomorphine, and Δ⁹-tetrahydrocannabinol effectively block shakes induced by either TRH administration or morphine withdrawal. These results suggest the possibility that endogenous TRH may be associated with the “wet dog shakes” observed as a portion of morphine's abstinence syndrome in rats. However, TRH is unable to alter the stereospecific binding of morphine $\text{in}$$\text{vivo}$ or $\text{in}$$\text{vitro}$, and naloxone fails to potentiate the number of TRH-induced shakes. TRH has no antinociceptive properties, and it cannot alter those of morphine. These data suggest that more than one neuromechanism may be responsible for shaking behavior in rats.     

Is there an opiate receptor in the snail Megalobulimus sanctipauli? Action of morphine and naloxone

The effects of morphine sulfate (10, 15 and 20 mg/kg) or saline control (5 mg/kg) on the latency of the anterior body-lifting response to heat (avoidance response) were determined in four groups of snails Megalobulimus sanctipauli (n = 6) individually placed on a metal plate mounted on the surface of a water bath at 52 ± 1°C. The effects of pre-treatment with naloxone hydrochloride (5 mg/kg) or saline (2.5 ml/kg) control on the responses to morphine (15 mg/kg) were determined in two different groups of animals (n = 6). Administration of morphine resulted in an increase in the avoidance behavior latency with maximum effects occuring at 15 mg/kg, 10–15 min after injection. The effects of morphine disappeared within 90–120 min. Saline treatment had no detectable effects on the latency of the response to an aversive stimulus. Naloxone significantly blocked (P < 0.05, Student paired t-test) the increase in avoidance behavior latency. The present results indicate that: 1. morphine has an antinociceptive effect on the response of Megalobulimus sanctipauli to an aversive thermal stimulus; and 2. the morphine-induced “analgesia” may be caused by the stimulation of μ opiate receptors.     

When will evolution lead to deceptive signaling in the Sir Philip Sidney game?

Sir Philip Sidney games are a widely used model of simple signaling. Johnstone and Grafen [Johnstone, R.A., Grafen, A., 1993. Dishonesty and the handicap principle. Animal Behaviour 46, 759–764] present a version in which the Evolutionarily Stable Strategy (ESS) is for most signalers to “honestly” signal, with a small minority of signalers who “cheat”. This model is among the most frequently cited papers on the topic of “dishonest” signaling and supports the view that signals may be “dishonest” as long as they are “honest on average”. Using genetic algorithms, we demonstrate that another solution exists to the game, an evolutionarily stable set of Nash equilibria in which members of the set never signal and all donors give their resource. Payoffs to players using this set of strategies is greater those when playing the “dishonest” signaling ESS. We demonstrate that a random population is far more likely to evolve to this non-communicating strategy set than the “dishonest” signaling ESS. We also discuss the dynamics of biological game theory models and the advances of genetic algorithms as a heuristic solution method for these models.     

Historical and philosophical perspectives on the study of developmental bias

Throughout the recent history of research at the intersection of evolution and development, notions such as developmental constraint, evolutionary novelty, and evolvability have been prominent, but the term “developmental bias” has scarcely been used. And one may even doubt whether a unique and principled definition of bias is possible. I argue that the concept of developmental bias can still play a vital scientific role by means of setting an explanatory agenda that motivates investigation and guides the formulation of integrative explanatory frameworks. Less crucial is a definition that would classify patterns of phenotypic variation and unify variational patterns involving different traits and taxa as all being “bias.” Instead, what we should want is a concept that generates intellectual identity across various researchers, and that unites the diverse fields and approaches relevant to the study of developmental bias, from paleontology to behavioral biology. I point to some advantages of conducting research specifically under the label of “developmental bias,” compared with employing other, more common terms such as “evolvability.”