Atypical responses to morphine in mice: a possible relationship to anorexia nervosa?

According to our previously proposed auto-addiction hypothesis of chronic anorexia nervosa, patients become addicted to an initial period of dieting through endogenous opioid mediated mechanisms. Morphine causes hyperactivity and anorexia in the mouse, symptoms of anorexia nervosa but responses opposite to those of most species including rats and normal human subjects. This suggests that the atypical opioid systems in the mouse may resemble those of the chronic anorexia nervosa patient in contrast to those of most species including the normal human. Characterization of this atypical opioid system may be useful in understanding the pathophysiology of anorexia nervosa.     

Is it possible to produce succinic acid at a low pH?

Bio-based succinate is still a matter of special emphasis in biotechnology and adjacent research areas. The vast majority of natural and engineered producers are bacterial strains that accumulate succinate under anaerobic conditions. Recently, we succeeded in obtaining an aerobic yeast strain capable of producing succinic acid at low pH. Herein, we discuss some difficulties and advantages of microbial pathways producing "succinic acid" rather than "succinate." It was concluded that the peculiar properties of the constructed yeast strain could be clarified in view of a distorted energy balance. There is evidence that in an acidic environment, the majority of the cellular energy available as ATP will be spent for proton and anion efflux. The decreased ATP:ADP ratio could essentially reduce the growth rate or even completely inhibit growth. In the same way, the preference of this elaborated strain for certain carbon sources could be explained in terms of energy balance. Nevertheless, the opportunity to exclude alkali and mineral acid waste from microbial succinate production seems environmentally friendly and cost-effective.     

Amino acid sensing mechanisms: an Achilles heel in cancer?

The act of increasing mass, either in non-dividing cells or in dividing cells seeking to provide new material for daughter cells, depends upon the continued presence of extracellular nutrients in order to conserve mass. For amino acid nutrients, it appears that their insufficiency for new protein synthesis is actively monitored by both prokaryotic and eukaryotic cells, eliciting appropriate cellular responses that may depend not only on bulk nutrient supply, but also on the abundance of specific amino acids.     

Mycorrhizal responses to biochar in soil – concepts and mechanisms

Experiments suggest that biomass-derived black carbon (biochar) affects microbial populations and soil biogeochemistry. Both biochar and mycorrhizal associations, ubiquitous symbioses in terrestrial ecosystems, are potentially important in various ecosystem services provided by soils, contributing to sustainable plant production, ecosystem restoration, and soil carbon sequestration and hence mitigation of global climate change. As both biochar and mycorrhizal associations are subject to management, understanding and exploiting interactions between them could be advantageous. Here we focus on biochar effects on mycorrhizal associations. After reviewing the experimental evidence for such effects, we critically examine hypotheses pertaining to four mechanisms by which biochar could influence mycorrhizal abundance and/or functioning. These mechanisms are (in decreasing order of currently available evidence supporting them): (a) alteration of soil physico-chemical properties; (b) indirect effects on mycorrhizae through effects on other soil microbes; (c) plant–fungus signaling interference and detoxification of allelochemicals on biochar; and (d) provision of refugia from fungal grazers. We provide a roadmap for research aimed at testing these mechanistic hypotheses.     

γ-Aminobutyric acid and related amino acids in plant immune responses: Emerging mechanisms of action

The entanglement between primary metabolism regulation and stress responses is a puzzling and fascinating theme in plant sciences. Among the major metabolites found in plants, γ-aminobutyric acid (GABA) fulfils important roles in connecting C and N metabolic fluxes through the GABA shunt. Activation of GABA metabolism is known since long to occur in plant tissues following biotic stresses, where GABA appears to have substantially different modes of action towards different categories of pathogens and pests. While it can harm insects thanks to its inhibitory effect on the neuronal transmission, its capacity to modulate the hypersensitive response in attacked host cells was proven to be crucial for host defences in several pathosystems. In this review, we discuss how plants can employ GABA's versatility to effectively deal with all the major biotic stressors, and how GABA can shape plant immune responses against pathogens by modulating reactive oxygen species balance in invaded plant tissues. Finally, we discuss the connections between GABA and other stress-related amino acids such as BABA (β-aminobutyric acid), glutamate and proline.     

Histamine in cardiac sympathetic ganglia: a novel neurotransmitter?

Although ganglia in the heart are well known to be cholinergic, many other neurotransmitters and neuropeptides also influence (and are produced in) cardiac neurons, including adrenergic and purinergic compounds. Recently, histamine was suggested as a possible neurotransmitter in cardiac tissue. Although histamine does elicit many effects in the heart, does it stand up to rigorous scrutiny and fulfill certain criteria that are used to define neurotransmitters?     

Neurodegenerative mutants in Drosophila: a means to identify genes and mechanisms involved in human diseases?

There are 50 ways to leave your lover (Simon 1987) but many more to kill your brain cells. Several neurodegenerative diseases in humans, like Alzheimer’s disease, have been intensely studied but the underlying cellular and molecular mechanisms are still unknown for most of them. For those syndromes where associated gene products have been identified their biochemistry and physiological as well as pathogenic function is often still under debate. This is in part due to the inherent limitations of genetic analyses in humans and other mammals and therefore experimentally accessible invertebrate in vivo models, such as Caenorhabditis elegans and Drosophila melanogaster, have recently been introduced to investigate neurodegenerative syndromes. Several laboratories have used transgenic approaches in Drosophila to study the human genes associated with neurodegenerative diseases. This has added substantially to our understanding of the mechanisms leading to neurodegenerative diseases in humans. The isolation and characterization of Drosophila mutants, which display a variety of neurodegenerative phenotypes, also provide valuable insights into genes, pathways, and mechanisms causing neurodegeneration. So far only about two dozen such mutants have been described but already their characterization reveals an involvement of various cellular functions in neurodegeneration, ranging from preventing oxidative stress to RNA editing. Some of the isolated genes can already be associated with human neurodegenerative diseases and hopefully the isolation and characterization of more of these mutants, together with an analysis of homologous genes in vertebrate models, will provide insights into the genetic and molecular basis of human neurodegenerative diseases.     

The cardiac cycle—a model

This easy-to-construct model makes use of the redundant kymograph and illustrates dramatically the cardiac cycle     

Antitumor vaccines: is it possible to prevent a tumor?

The main medical use of vaccines is to induce a state of immunity in healthy individuals to protect them from deadly or dangerous diseases. In the field of cancer immunology, however, vaccines are being used in patients as therapy, often with a very poor success rate against advanced disease. This paper reviews recent preclinical evidence in favor of the prophylactic use of immunological approaches to cancer. Successful attempts at immunological cancer prevention in HER-2/neu transgenic mice are described as an example. The specific properties of the HER-2/neu gene product as a tumor antigen, and the nature of the immune responses induced by effective preventive treatments are reviewed. Although the very high rate of mammary carcinoma prevention in mice has generated enthusiasm, it should not be forgotten that such treatments, when administered to healthy humans at risk of cancer, may carry the risk of inducing autoimmunity. These issues can be addressed in preclinical studies in appropriate animal models.     

Linking variability in climate to wetland habitat suitability: is it possible to forecast regional responses from simple climate measures?

Wetlands Ecology and Management - Temporary wetlands have value to both ecological and social systems. Interactions between local climate and the surrounding landscape result in patterns of...     

What is in a model?

After reading contradictory claims of model status for some insect species, we feel a brief discussion of the topic may be useful. Here, we document a few examples where clarity on model status seems to be lacking, briefly review work on widely recognized models, and offer criteria for including any given species as a model organism.     

What are the evolutionary origins of stomatal responses to abscisic acid in land plants?

The evolution of active stomatal closure in response to leaf water deficit, mediated by the hormone abscisic acid (ABA), has been the subject of recent debate. Two different models for the timing of the evolution of this response recur in the literature. A single‐step model for stomatal control suggests that stomata evolved active, ABA‐mediated control of stomatal aperture, when these structures first appeared, prior to the divergence of bryophyte and vascular plant lineages. In contrast, a gradualistic model for stomatal control proposes that the most basal vascular plant stomata responded passively to changes in leaf water status. This model suggests that active ABA‐driven mechanisms for stomatal responses to water status instead evolved after the divergence of seed plants, culminating in the complex, ABA‐mediated responses observed in modern angiosperms. Here we review the findings that form the basis for these two models, including recent work that provides critical molecular insights into resolving this intriguing debate, and find strong evidence to support a gradualistic model for stomatal evolution.     

Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

During the past several decades, many risk factors for cerebrovascular and cardiovascular disease have been identified. More recently, it has been appreciated that inadequate nutrition and/or other intrauterine factors during fetal development may play an important role in the genesis of these conditions. An additional stress factor that may "program" the fetus for disease later in life is chronic hypoxia. In studies originally designed to examine the function of developing cerebral arterial function in response to long-term hypoxia (LTH), it has become clear that many cellular and subcellular changes may have important implications for later life. Here we review some of the significant alterations in fetal cerebral artery structure and function induced by high-altitude (3,820 m, 12,470 ft) LTH ( approximately 110 days). LTH is associated with augmentation or upregulation of presynaptic functions, including responses to perivascular (i.e., sympathetic) nerve stimulation, and structural maturational changes. In contrast, many postsynaptic functions related to the Ca(2+)-dependent contractile pathway tend to be downregulated, whereas elements of the Ca(2+)-independent contraction pathway are upregulated. The results emphasize the role of high-altitude LTH in modulating many aspects of electromechanical and pharmacomechanical coupling in the developing cerebral vasculature. A complicating factor is that the regulation of cerebrovascular tone by Ca(2+)-dependent and Ca(2+)-independent pathways changes significantly as a function of maturational age. In addition to highlighting independent regulation of various elements of the signal transduction cascade, the studies demonstrate the potential for LTH to program the fetus for cerebrovascular and other disease as an adult.     

Urocortin: a cardiac protective peptide?

Urocortin (UCN), a member of the corticotropin-releasing hormone (CRH)-related peptides, has been reported to play biologically diverse roles in several systems such as cardiovascular, reproductive, appetite, stress, inflammatory responses, etc. In heart, it was reported to have protective effects. On the other hand, it was also reported to have cardiac inotropic and hypertrophic effects and hence to cause cardiac remodeling. This paper will review the effects of UCN in cardiac system.     

Cardiovascular responses to water drinking: does osmolality play a role?

Water drinking activates the autonomic nervous system and induces acute hemodynamic changes. The actual stimulus for these effects is undetermined but might be related to either gastric distension or to osmotic factors. In the present study, we tested whether the cardiovascular responses to water drinking are related to water's relative hypoosmolality. Therefore, we compared the cardiovascular effects of a water drink (7.5 ml/kg body wt) with an identical volume of a physiological (0.9%) saline solution in nine healthy subjects (6 male, 3 female, aged 26 +/- 2 years), while continuously monitoring beat-to-beat blood pressure (finger plethysmography), cardiac intervals (electrocardiography), and cardiac output (thoracic impedance). Total peripheral resistance was calculated as mean blood pressure/cardiac output. Cardiac interval variability (high-frequency power) was assessed by spectral analysis as an index of cardiac vagal tone. Baroreceptor sensitivity was evaluated using the sequence technique. Drinking water, but not saline, decreased heart rate (P = 0.01) and increased total peripheral resistance (P < 0.01), high-frequency cardiac interval variability (P = 0.03), and baroreceptor sensitivity (P = 0.01). Neither water nor saline substantially increased blood pressure. These responses suggest that water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiac vagal tone. That these effects were absent after drinking physiological saline indicate that the cardiovascular responses to water drinking are influenced by its hypoosmotic properties.