Amount-dependent temporal discounting?

Amount-dependent temporal discounting has been demonstrated for human choice between outcomes differing in amount and delay. In the only study to date with non-humans, Grace reported no evidence for amount-dependent temporal discounting with pigeons in a concurrent-chains procedure. The present experiments repeated Grace's procedure but with modifications to enhance the discrimination between small and large magnitude outcomes. In Experiment 1, sensitivity of pigeons' initial-link choice to the terminal link delay ratio was greater with large reinforcer durations in the terminal links than with small reinforcer durations. This result is consistent with a greater rate of temporal discounting for larger reinforcers (the reverse of the result for humans), but can also be explained as enhanced discrimination of delay ratios with larger reinforcer durations. The results of a second experiment supported Grace's conclusion that amount-dependent temporal discounting does not characterize pigeons' choice in concurrent chains. Because reinforcer amount was held constant between choice alternatives in the present experiments and that of Grace, but varied in the human studies, our results question whether prior demonstrations of amount-dependent discounting reflect the effects of reinforcer delay or of reinforcer amount. Differences in the procedures used to study discounting in humans (titration procedures) and non-humans (concurrent chains) may contribute to the divergent results across species.     

Delay discounting: trait variable?

Delay discounting refers to the tendency for outcomes that are remote in time to have less value than more immediate outcomes. Steep discounting of delayed outcomes is associated with a variety of social maladies. The degree of sensitivity to delayed outcomes may be a stable and pervasive individual characteristic. In analyses of archival data, the present study found positive correlations between the degree of delay discounting for one outcome (as measured by the Area Under the Curve), and the degree of discounting for other outcomes. Along with additional evidence reviewed, these data suggest that delay discounting may be considered a personality trait. Recent research in epigenetics, neuroscience, and behavior suggests delay discounting may prove to be a beneficial target for therapeutic attempts to produce global reductions in impulsivity related to delay discounting.     

Commodity specific rates of temporal discounting: Does metabolic function underlie differences in rates of discounting?

Discounting rates vary as a function of commodity type. Previous studies suggest five potential characteristics of the commodity that could explain these differences: type of reinforcer (primary or secondary), if the commodity is perishable, if the commodity is satiable, if the commodity can be directly consumed, and immediacy of consumption. This paper suggests that these characteristics may best be viewed as related to a more fundamental characteristic: metabolic processing. In order to explore the possibility that metabolic processing underlies changes in discount rates, the difference in discounting between food, money, music CDs, DVDs, and books are compared. Music CDs, DVDs, and books share many characteristics in common with food, including gaining value through a physiological process, but are not directly metabolized. Results are consistent with previous findings of commodity specific discount rates and show that metabolic function plays a role in determining discount rates with those commodities that are metabolized being discounted at a higher rate. These results are interpreted as evidence that the discount rate for different commodities lies along a continuum with those that serve an exchange function rather than a direct function (money) anchoring the low end and those that serve a direct metabolic function capping the high end (food, alcohol, drugs).     

Do high rates of cigarette consumption increase delay discounting? A cross-sectional comparison of adolescent smokers and young-adult smokers and nonsmokers

The present report attempts to help clarify the causal or consequent relation between frequently reported high rates of delay discounting (DD) associated with cigarette-smoking status in adults. Delay-discount functions of adolescent smokers and young-adult smokers and nonsmokers from two earlier studies [Reynolds, B., Karraker, K., Horn, K., Richards, J.B., 2003. Delay and probability discounting as related to different stages of adolescent smoking and non-smoking. Behav. Process. 64, 333-344; Reynolds, B., Richards, J.B., Horn, K., Karraker, K., 2004. Delay discounting and probability discounting as related to cigarette smoking status in adults. Behav. Process. 65, 35-42] were cross-sectionally compared. If a high rate of DD is a predisposing factor to future smoking status, adolescent and young-adult smokers were expected to have similar rates of DD, but both groups were expected to have higher rates of discounting than young-adult nonsmokers. Alternatively, if a high rate of cigarette consumption over an extended period is related to increases in DD, young-adult smokers were expected to discount more than adolescent smokers and young-adult nonsmokers. Results supported the hypothesis that a high rate of cigarette consumption is related to higher rates of DD, rather than the alternative hypothesis that smokers are predisposed with higher rates of DD. Also, after combining adolescent and young-adult smokers, self-reported number of cigarettes consumed per day was positively correlated with rate of DD; however, reported length of smoking history was not correlated with DD. Possible neurological mechanisms leading to increased discounting are discussed.     

Syntheses and spectroscopic properties of α- and β-phosphatidylcholines and phosphatidylethanolamines

The widely used partial synthesis of phospholipids via deacylation of naturally occurring phospholipids, followed by reacylation with fatty acid anhydrides, is accompanied by phosphoryl migration. The resulting mixture of α- and β-phospholipids was separated by short-column chromatography. Milder acylation procedures in which no phosphoryl migration occurs, were developed. 1,2-Dilinoleoyl-sn-glycero-3-phosphocholine was prepared in 50% yield by acylation of sn-glycero-3-phosphocholine (GPC) with N-linoleoylimidazole. Detailed NMR and infrared spectra of α- and β-phosphatidylcholines (PCs) and -ethanolamines (PEs) are reported and the differences between isomers discussed.     

Phenotypic plasticity and longevity in plants and animals: cause and effect?

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.     

Dogmatisms and Catechisms — Ethics and Companion Animals

Abstract

The current reconsideration of the place in nature of human beings unfortunately continues to be an acrimonious one. All too often the debate is more akin to a warlike encounter where each side attempts to gain control or the upper hand than a search for points of agreement. Given this context, it is important to entertain views that emanate from different cultural traditions as a way to infuse the debate with new life. Students of Native American culture have consistently pointed out that the essential concepts of life balance and reciprocity represented there may serve as useful points of consideration as we struggle with the appropriate relationships with animals and nature. This article presents a representative Zuni story, told by Governor Robert E. Lewis, that illustrates these notions.     

DCCP and DICP： Construction and Analyses of Databases for Copper- and Iron-Chelating Proteins

Copper and iron play important roles in a variety of biological processes, especially when being chelated with proteins. The proteins involved in the metal binding, transporting and metabolism have aroused much interest. To facilitate the study on this topic, we constructed two databases （DCCP and DICP） containing the known copper- and iron-chelating proteins~ which are freely available from the website http：//sdbi.sdut.edu.cn/en. Users can conveniently search and browse all of the entries in the databases. Based on the two databases, bioinformatic analyses were performed, which provided some novel insights into metalloproteins.     

Biosynthesis of geraniol and nerol and their β-d-glucosides in Perlargonium graveolens and Rosa dilecta

1. 3R-[2-(14)C]Mevalonate was incorporated into geranyl and neryl beta-d-glucosides in petals of Rosa dilecta in up to 10.6% yield, and the terpenoid part was specifically and equivalently labelled in the moieties derived from isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate. A similar labelling pattern, with incorporations of 0.06-0.1% was found for geraniol or nerol formed in leaves of Pelargonium graveolens The former results provide the best available evidence for the mevalonoid route to regular monoterpenes in higher plants. 2. Incorporation studies with 3RS-[2-(14)C,(4R)-4-(3)H(1)]-mevalonate and its (4S)-isomer showed that the pro-4R hydrogen atom of the precursor was retained and the pro-4S hydrogen atom was eliminated in both alcohols and both glucosides. These results suggest that the correlation of retention of the pro-4S hydrogen atom of mevalonate with formation of a cis-substituted double bond, such as has been found in certain higher terpenoids, does not apply to the biosynthesis of monoterpenes. It is proposed that either nerol is derived from isomerization of geraniol or the two alcohols are directly formed by different prenyltransferases. Possible mechanisms for these processes are discussed. 3. The experiments with [(14)C,(3)H]mevalonate also show that in these higher plants, as has been previously found in animal tissue and yeast, the pro-4S hydrogen atom of mevalonate was lost in the conversion of isopentenyl pyrophosphate into 3,3-dimethylallyl pyrophosphate.     

Zinc and diabetes — clinical links and molecular mechanisms

Zinc is an essential trace element crucial for the function of more than 300 enzymes and it is important for cellular processes like cell division and apoptosis. Hence, the concentration of zinc in the human body is tightly regulated and disturbances of zinc homeostasis have been associated with several diseases including diabetes mellitus, a disease characterized by high blood glucose concentrations as a consequence of decreased secretion or action of insulin. Zinc supplementation of animals and humans has been shown to ameliorate glycemic control in type 1 and 2 diabetes, the two major forms of diabetes mellitus, but the underlying molecular mechanisms have only slowly been elucidated. Zinc seems to exert insulin-like effects by supporting the signal transduction of insulin and by reducing the production of cytokines, which lead to beta-cell death during the inflammatory process in the pancreas in the course of the disease. Furthermore, zinc might play a role in the development of diabetes, since genetic polymorphisms in the gene of zinc transporter 8 and in metallothionein (MT)-encoding genes could be demonstrated to be associated with type 2 diabetes mellitus. The fact that antibodies against this zinc transporter have been detected in type 1 diabetic patients offers new diagnostic possibilities. This article reviews the influence of zinc on the diabetic state including the molecular mechanisms, the role of the zinc transporter 8 and MT for diabetes development and the resulting diagnostic and therapeutic options.     

siRNA, miRNA and HIV： promises and challenges

Small interfering RNA （siRNA） and microRNA （miRNA） are small RNAs of 18-25 nucleotides （nt） in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex （RISC） and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 （HIV-1） which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi （RNA interference）. On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells＇ antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs （vmiRNAs）.     

Toxoplasmosis and Epilepsy — Systematic Review and Meta Analysis

Background

Toxoplasmosis is an important, widespread, parasitic infection caused by Toxoplasma gondii. The chronic infection in immunocompetent patients, usually considered as asymptomatic, is now suspected to be a risk factor for various neurological disorders, including epilepsy. We aimed to conduct a systematic review and meta-analysis of the available literature to estimate the risk of epilepsy due to toxoplasmosis.

Methods

A systematic literature search was conducted of several databases and journals to identify studies published in English or French, without date restriction, which looked at toxoplasmosis (as exposure) and epilepsy (as disease) and met certain other inclusion criteria. The search was based on keywords and suitable combinations in English and French. Fixed and random effects models were used to determine odds ratios, and statistical significance was set at 5.0%.

Principal findings

Six studies were identified, with an estimated total of 2888 subjects, of whom 1280 had epilepsy (477 positive for toxoplasmosis) and 1608 did not (503 positive for toxoplasmosis). The common odds ratio (calculated) by random effects model was 2.25 (95% CI 1.27–3.9), p = 0.005.

Conclusions

Despite the limited number of studies, and a lack of high-quality data, toxoplasmosis should continue to be regarded as an epilepsy risk factor. More and better studies are needed to determine the real impact of this parasite on the occurrence of epilepsy.     

Defining and measuring autophagosome flux—concept and reality

The autophagic system is involved in both bulk degradation of primarily long-lived cytoplasmic proteins as well as in selective degradation of cytoplasmic organelles. Autophagic flux is often defined as a measure of autophagic degradation activity, and a number of methods are currently utilized to assess autophagic flux. However, despite major advances in measuring various molecular aspects of the autophagic machinery, we remain less able to express autophagic flux in a highly sensitive, robust, and well-quantifiable manner. Here, we describe a conceptual framework for defining and measuring autophagosome flux at the single-cell level. The concept discussed here is based on the theoretical framework of metabolic control analysis, which distinguishes between the pathway along which there is a flow of material and the quantitative measure of this flow. By treating the autophagic system as a multistep pathway with each step characterized by a particular rate, we are able to provide a single-cell fluorescence live-cell imaging-based approach that describes the accurate assessment of the complete autophagosome pool size, the autophagosome flux, and the transition time required to turn over the intracellular autophagosome pool. In doing so, this perspective provides clarity on whether the system is at steady state or in a transient state moving towards a new steady state. It is hoped that this theoretical account of quantitatively measuring autophagosome flux may contribute towards a new direction in the field of autophagy, a standardized approach that allows the establishment of systematic flux databases of clinically relevant cell and tissue types that serve as important model systems for human pathologies.Abbreviations: CMA, chaperone-mediated autophagy; GFP, green fluorescent protein; J, flux; LC3, microtubule-associated protein 1 light chain 3; n_A, number of autophagosomes; τ, transition time; TEM, transmission electron microscopyThe autophagic system is involved in both bulk degradation of primarily long-lived cytosolic proteins as well as in the selective degradation of cytoplasmic organelles. In the past few years the assessment and evaluation of this complete system including its dynamics has received growing attention, as our understanding of autophagosome turnover and kinetic behavior has progressed. Autophagic flux is often defined as a measure of autophagic degradation activity, and a number of methods are currently suggested for assessing autophagic flux, many of which infer whether or not autophagic flux is occuring.¹ However, although we have advanced in the methodological approach to assess whether or not a change in autophagic flux is occurring, and whether autophagic flux goes up or down, we remain less able to express this change in a sensitive, robust, and well-quantifiable manner. Moreover, although the development of novel reporter assays enabled the identification of pharmacological regulators of autophagy, highly sensitive assays that characterize the extent and dynamics of this regulation quantitatively remain a challenge in the in vitro, and even more so the in vivo, environment. Based on the well-established metabolic control analysis approach,^2,3 where the use of the term flux has been reserved for the rate of flow along a metabolic pathway, we describe a methodological concept that allows the definition and measurement of autophagosome flux at the single cell level in a sensitive and quantifiable manner. Here, we treat the autophagic system as a multistep pathway with each step characterized by a particular rate. We distinguish between the vesicular machinery of the autophagic system, and the cargo that is being degraded within this system. Autophagosome flux, the subject of this paper, is the rate of flow along the vesicular pathway, whereas substrate clearance flux is the rate of cargo degradation within the vesicular system. This distinction makes it possible not only to describe whether or not the vesicular part of the autophagic system is at steady state, but also to quantitatively assess autophagosome flux and to calculate the transition time of the system required to turn over its autophagosome pool. The concept described here makes it possible to quantify and to compare treatment interventions or different cellular systems with one another in terms of change in autophagosome pool size, autophagosome flux, and pool size turnover as well as in the responsiveness and sensitivity to the treatment intervention.We will start with our quantitative definition of autophagosome flux and describe a methodological concept for measuring this flux. We will then briefly describe 3 of the major current and predominantly used approaches to measuring autophagic degradation activity, and, by juxtaposing them against our definition of autophagosome flux, attempt to indicate the major inherent challenges to these techniques. We will then describe a step-by-step methodology that describes the accurate assessment of i) the complete autophagosome pool size, ii) the steady state, iii) autophagosome flux, and iv) the transition time. Since our definition of autophagosome flux requires a dynamic assessment over time, this conceptual approach shows how to acquire data that describe both the existence of a steady state and the variables that characterize the steady state, such as the steady-state number of autophagosomes and the associated flux in terms of the change in this number per time per cell. We hope that this approach will provide a robust tool for generating numerical data that are sensitive enough to allow us to change flux incrementally, say by 5%, that allows a comparison of fluxes and steady states of different cellular systems, with the benefit of using data that directly reflect the intracellular autophagosome pool. It is moreover envisaged that the approach described here may contribute towards a standardized means for the establishment of flux databases of clinically relevant cell and tissue types that serve as important model systems for, for example, neurodegenerative disorders, cancer, or heart disease.^4-6 Finally, this concept may lay the foundation for future control analyses, to unravel the degree of control as opposed to regulation that the different steps in the autophagic pathway exert over the autophagosome flux.     

Journal of Ethnobiology and Ethnomedicine – achievements and perspectives

Last summer we officially launched the Journal of Ethnobiology and Ethnomedicine, published by BioMedCentral, with the aim of establishing a serious, peer-reviewed, open-access online journal that focuses on the multidisciplinary, interdisciplinary, and transdisciplinary fields of ethnobiology and ethnomedicine, drawing on approaches and methods from both the social and biological sciences. The strong start vindicates the widely held belief that the journal responds to a real need within the research community. The success of the journal has been most gratifying. The steady influx of submissions of high scientific standards illustrates the strong demand for a dynamic, proactive, and open-minded scientific journal in these research areas. Our aim has been to dedicate JEE to the "scientific communities" worldwide, particularly those in the developing countries.     

Rise and Demise of Bioinformatics? Promise and Progress

The field of bioinformatics and computational biology has gone through a number of transformations during the past 15 years, establishing itself as a key component of new biology. This spectacular growth has been challenged by a number of disruptive changes in science and technology. Despite the apparent fatigue of the linguistic use of the term itself, bioinformatics has grown perhaps to a point beyond recognition. We explore both historical aspects and future trends and argue that as the field expands, key questions remain unanswered and acquire new meaning while at the same time the range of applications is widening to cover an ever increasing number of biological disciplines. These trends appear to be pointing to a redefinition of certain objectives, milestones, and possibly the field itself.