Specific External Stimuli Research Articles

Polymersomes: nature inspired nanometer sized compartments

Provided the right hydrophilic/hydrophobic balance can be achieved, amphiphilic block copolymers are able to assemble in water into membranes. These membranes can enclose forming spheres with an aqueous core. Such structures, known as polymer vesicles or polymersomes (from the Greek “-some” = “body of”), have sizes that vary from tens to thousands of nanometers. The wholly synthetic nature of block copolymers affords control over parameters such as the molar mass and composition which ultimately determine the structure and properties of the species in solution. By varying the copolymer molecular mass it is possible to adjust the mechanical properties and permeability of the polymersomes, while the synthetic nature of copolymers allows the design of interfaces containing various biochemically-active functional groups. In particular, non-fouling and non-antigenic polymers have been combined with hydrophobic polymers in the design of biocompatible nano-carriers that are expected to exhibit very long circulation times. Stimulus-responsive block copolymers have also been used to exploit the possibility to trigger the disassembly of polymersomes in response to specific external stimuli such as pH, oxidative species, and enzyme degradation. Such bio-inspired ‘bottom-up’ supramolecular design principles offer outstanding advantages in engineering structures at a molecular level, using the same long-studied principles of biological molecules. Thanks to their unique properties, polymersomes have already been reported and studied as delivery systems for both drugs, genes, and image contrast agents as well as nanometer-sized reactors.

The use of a shape-memory poly(ε-caprolactone)dimethacrylate network as a tissue engineering scaffold

Shape-memory polymers produced from many natural or synthetic raw polymers are able to undergo a shape transformation after exposure to a specific external stimulus. This feature enables their use in minimal-invasive surgery with a small, compact starting material switching over to a more voluminous structure in the body. The use of biomaterials in modern medicine calls for compatibility tests with cell types, encountering the biomaterial during a short-term or long-term in vivo application. We analysed the cell behaviour of L929 mouse fibroblasts, human mesenchymal stem cells, human mesothelial cells and rat mesothelial cells on a biodegradable shape-memory polymer network to assess its suitability for medical applications. Further, we investigated the differentiation capacity of mesenchymal stem cells into osteoblasts and adipocytes on the polymer and we analysed the influence of the shape-memory effect on adherent cells. The polymer was cytocompatible for all tested cell types, supporting cell viability and proliferation. The differentiation capacity of mesenchymal stem cells was supported by the polymer and shape-memory effect activation did not affect the majority of adherent cells.

Calcineurin B-Like family in Populus: comparative genome analysis and expression pattern under cold, drought and salt stress treatment

Calcium plays a critical role in regulating abiotic-stress response in plant. Calcineurin B-like (CBL) proteins have been identified as calcium sensors in the calcium signaling pathway in Arabidopsis and rice. However, molecular mechanism underlying calcium signaling remains to be elucidated, especially in poplar, a model tree species with complete sequencing of the whole genome. Here, we have characterized 10 CBL candidate genes in the genome of Populustrichocarpa (PtCBLs) and presented a comparative genomics analysis of CBLs in poplar, rice and Arabidopsis, including gene structures, conserved motifs and phylogeny. Comparative genomics analyses showed that the family in poplar appears to be rather conserved in the size and structure, and the duplication events might significantly contribute to the amplification of this gene family. Furthermore, to elucidate the functions of CBL gene members respectively in regulating plant response to external stimuli, we presented a study of CBL family in Populus euphratica (PeCBLs), a mostly salt- and drought-tolerant Populus species. Nine cDNA clones of PeCBL members were isolated from Populus euphratica and a gene specific RT-PCR was performed to investigate their expression patterns under abiotic stress treatment, such as cold, drought, and salt. A transcript analysis of CBLs in Populus euphratica under abiotic stress suggests that seven CBL gene (PeCBL1, 2, 3, 4, 5, 9, and 10) members may play an important role in correspondence to specific external stimuli. Our data will provide important evidence for further studying the functional dissection of the CBL signaling network in plant.

The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems

The mammalian JNK/p38 MAP kinase kinase kinase MEKK4 and the Saccharomyces cerevisiae Ssk2p are highly homologous. MEKK4 can replace all of the known functions of Ssk2p in yeast, including functioning in the high osmolarity glycerol (HOG) MAPK pathway and the recently described actin recovery pathway. MEKK4 and Ssk2p share a number of conserved domains and appear to be activated by a similar mechanism. Binding of an activating protein to the N-terminal region alleviates auto-inhibition and causes the kinase to auto-phosphorylate, resulting in activation. In this review we will examine the role of the MAP kinase kinase kinase isoform Ssk2p/MEKK4 in the adaptation of both yeast and mammalian systems to specific external stimuli. Recent work has provided a wealth of information about the activation, regulation, and functions of these MEKK kinases to extra-cellular signals. We will also highlight evidence supporting a role for MEKK4 in mediating actin recovery following osmotic shock in mammalian cells.

The Sir David Cuthbertson Medal Lecture Hunting for new pieces to the complex puzzle of obesity

Disentangling the neuroendocrine systems that regulate energy homeostasis and adiposity has been a long-standing challenge in pathophysiology, with obesity being an increasingly important public health problem. Adipose tissue is no longer considered a passive bystander in body-weight regulation. It actively secretes a large number of hormones, growth factors, enzymes, cytokines, complement factors and matrix proteins, at the same time as expressing receptors for most of these elements, which influence fuel storage, mobilisation and utilisation at both central and peripheral sites. Thus, an extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of adipose tissue. In addition to the already-known adipokines, such as IL, TNFα, leptin, resistin and adiponectin, more recently attention has been devoted to ‘newcomers’ to the ‘adipose tissue arena’, which include aquaporin, caveolin, visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro and in vivo experiments have provided extremely valuable information, the advances in genomics, proteomics and metabolomics are offering a level of information not previously attainable to help unlock the molecular basis of obesity. The potential and power of combining pathophysiological observations with the wealth of information provided by the human genome, knock-out models, transgenesis, DNA microarrays, RNA silencing and other emerging technologies offer a new and unprecedented view of a complex disease, conferring novel insights into old questions by identifying new pieces to the unfinished jigsaw puzzle of obesity.

The Sir David Cuthbertson Medal Lecture Hunting for new pieces to the complex puzzle of obesity

Disentangling the neuroendocrine systems that regulate energy homeostasis and adiposity has been a long-standing challenge in pathophysiology, with obesity being an increasingly important public health problem. Adipose tissue is no longer considered a passive bystander in body-weight regulation. It actively secretes a large number of hormones, growth factors, enzymes, cytokines, complement factors and matrix proteins, at the same time as expressing receptors for most of these elements, which influence fuel storage, mobilisation and utilisation at both central and peripheral sites. Thus, an extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of adipose tissue. In addition to the already-known adipokines, such as IL, TNFalpha, leptin, resistin and adiponectin, more recently attention has been devoted to 'newcomers' to the 'adipose tissue arena', which include aquaporin, caveolin, visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro and in vivo experiments have provided extremely valuable information, the advances in genomics, proteomics and metabolomics are offering a level of information not previously attainable to help unlock the molecular basis of obesity. The potential and power of combining pathophysiological observations with the wealth of information provided by the human genome, knock-out models, transgenesis, DNA microarrays, RNA silencing and other emerging technologies offer a new and unprecedented view of a complex disease, conferring novel insights into old questions by identifying new pieces to the unfinished jigsaw puzzle of obesity.

Production of Paclitaxel and the Related Taxanes by Cell Suspension Cultures of Taxus Species

Medicinal plants are the most promising source for the development of drugs, and many types of active ingredients from the plant resources have been studied in order to clarify the relationship between the chemical structure and the activity. However, it is not easy to develop drugs from those active compounds, and in many cases, the supply of active compounds can have some problems: 1) limited quantity of active compounds in plant; 2) low plant growth rate; 3) the limited localization of active ingredients in the specific organs; and 4) from the perspective of the conservation of natural resources. Therefore, the stable supply of the compounds commercially is very difficult and contains risk hedge. Plant cell culture is an attractive technology to solve these problems by securing the stable supply of the active compounds without damage to the natural plant resources. Recently, an efficient production process of anticancer drug paclitaxel by Taxus cell suspension cultures was constructed. The established Taxus cell lines produced paclitaxel and related taxanes by specific external stimuli, such as methyl jasmonate. The time-course analysis revealed that there are two regulatory steps existing in the paclitaxel biosynthesis: the taxane-ring formation step that is up-regulated by MeJA, and the acylation step at the C-13 position. By applying the data from the two-stage culture and the high-density culture, a large-scale culture process was developed with a stable paclitaxel production in the range of 140-295 mg L(-1), reaching 295 mg L(-1) at maximum.

Role of adipocytokines in metabolism and disease

Disentangling the neuroendocrine systems, which regulate energy homeostasis and adiposity, has been a long-standing challenge in pathophysiology, with obesity as an increasingly important public health problem. Adipose tissue has been considered for a long time as only a passive organ for the storage of excess energy in the form of fat. However, compelling evidence gathered during the last decades has revealed adipocytes as extremely active endocrine secretory cells playing a relevant role in the regulation of metabolism, reproduction, immunity, blood pressure, fibrinolysis, coagulation, and angiogenesis, among others. An extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of fat cells, which rely on their ability to secrete a large number of hormones, growth factors, enzymes, cytokines, complement factors, and matrix proteins, collectively termed as adipokines or adipocytokines, at the same time expressing receptors for most of these factors.

Paclitaxel production by plant-cell-culture technology.

Plant cells catalyze multiple-step reactions of secondary metabolite biosynthesis, and selectively synthesize chiral compounds with polycyclic structures. Taking advantage of this characteristic, we studied the production of the anticancer drug paclitaxel, which is currently produced in limited supply. Callus culture investigations indicate that woody plant medium supplemented with 10(-5) mol L(-1) 1-naphthylacetic acid and without the NH4+ -type ion is the best condition for growth of the callus. The accumulation of paclitaxel and related taxanes in Taxus plants is thought to be a biological response to specific external stimuli. Several signal transducers were screened; taxane biosynthesis was strongly promoted by methyl jasmonate (MeJA) and silver thiosulfate (STS) as an anti-ethylene compound. Of ten taxane-type diterpenoids isolated from T. baccata suspension-cultured cells treated with MeJA, five have a phenylisoserine side-chain at the C-13 position of the taxane skeleton. Time-course analysis revealed two regulatory steps in taxane biosynthesis: the taxane-ring formation step and the acylation step of the C-13 position. Methyl jasmonate promoted the formation of the taxane-ring. The production of paclitaxel reached a maximum level of 295 mg L(-1) in a large-scale culture of T. x media cells using a two-stage process.

Magnetic Resonance Imaging of Brain Function

Publisher Summary This chapter describes the magnetic resonance imaging (MRI) of the brain function. The rapid development of methods for noninvasive brain mapping has led to exciting advances in understanding of the human brain. Functional MRI relies on detecting the small changes in image brightness on MRI scans, associated with the hemodynamic changes in the brain, in response to a specific external stimulus or internal cognitive process. Carrying out an fMRI experiment, therefore, consists of three primary components, including presenting or otherwise cueing the stimulus, scanning the brain rapidly using MRI, and analyzing the MRI scans to detect changes in image intensity. The complex physiological processes that give rise to the signal changes observed in fMRI mean that there are a number of reasons for caution in interpreting the experimental results. The most common fast imaging method used for fMRI is echo planar imaging. This method is able to collect data from a single slice through the brain in less than 100 ms. It is found that functional MRI has been used to demonstrate the cortical changes that occur upon rehabilitation after stoke.

Intraoperative Neurophysiological Monitoring Part 4

The electrophysiological activity obtained in response to specific external stimuli reflects the status of the neuronal pathway between the stimulation and the recording sites. Unlike the spontaneous activity which represents the surface-recorded summated activity of several underlying structures, evoked activity represents the activity of specific neuronal structures and, thus, it can be used as an accurate indicator of their structural and functional integrity. In this part of the series on intraoperative monitoring we focus on evoked neurophysiological activity, such as the sensory and motor evoked potentials, and we give details on the generation, use, recording procedures, features, affecting factors, and interpretation of the signals obtained during the course of neurological, orthopedic, or vascular surgery.

Liver regeneration.

Liver regeneration after the loss of hepatic tissue is a fundamental parameter of liver response to injury. Recognized as a phenomenon from mythological times, it is now defined as an orchestrated response induced by specific external stimuli and involving sequential changes in gene expression, growth factor production, and morphologic structure. Many growth factors and cytokines, most notably hepatocyte growth factor, epidermal growth factor, transforming growth factor-alpha, interleukin-6, tumor necrosis factor-alpha, insulin, and norepinephrine, appear to play important roles in this process. This review attempts to integrate the findings of the last three decades and looks toward clues as to the nature of the causes that trigger this fascinating organ and cellular response.

Situational Specificity in Alpine‐marmot Alarm Communication

AbstractWe studied the degree to which alpine marmot(Marmota marmotaL.) alarm calls function as communication about specific external stimuli. Alpine marmots emit variable alarm calls when they encounter humans, dogs, and several species of aerial predators. The first part of the study involved observations and manipulations designed to document contextual variation in alarm calls. Alarm calls varied along several acoustic parameters, but only along one that we examined, the number of notes per call, was significantly correlated with the type of external stimulus. Marmots were more likely to emit single‐note alarm calls as their first or only call in response to an aerial stimulus, and multiple‐note alarm calls when first calling to a terrestrial stimulus. This relationship was not without exceptions; there was considerable variation in the number of notes they emitted to both aerial and terrestrial stimuli, and a single stimulus type — humans — elicited a wide range of acoustic responses. The second part of the study involved playing back three types of alarm calls to marmots and observing their responses. Marmots did not have overtly different responses to the three types of played‐back alarm calls. Our results are consistent with the hypotheses that: 1. Alarm calls do not refer to specific external stimuli; 2. Alarm calls function to communicate the degree of risk a caller experiences; and 3. Alarm calls require additional contextual cues to be properly interpreted by conspecifics.

Overwhelming Remembrance of Things Past: Proust Portrays Limbic Kindling by External Stimulus—Literary Genius Can Presage Neurobiological Patterns of Puzzling Behavior

Proust detailed inexplicable behavior long before the neurobiologists Goddard and McIntyre in 1972 demonstrated that intermittent repetition of harmless stimuli can cause "kindling" of a seizure (with or without motor convulsions). Such brief seizures can occur especially in the evolutionarily old limbic system which mediates basic drives, their concomitant emotions, and certain aspects of memory. It appears that in humans the influence of specific external stimuli that revive the memory of repeated past experiences may "kindle" a transient episode of limbic overactivation. Thereupon the normal balance between the limbic and frontal lobe systems is disturbed (for a few minutes) as are normal human decision making and control of action. Linked with such a transient frontolimbic imbalance is out-of-character behavior, psychosis (hallucinations or delusions), autonomic activation, and severe distortion of affect and of action, culminating in extreme cases in a "Limbic Psychotic Trigger Reaction," as proposed by Pontius in 1981, in motiveless homicidal acts with mostly preserved consciousness and memory for the acts.

Emotions in dream and waking event reports.

Emotions in dream and waking event reports.

Insertional mutagenesis in Arabidopsis thaliana

Recently, a number of mutant gene loci in the Arabidopsis thaliana plant genome have been identified through insertional mutagenesis. In this review, we evaluate different methods used for Agrobacterium tumefaciens-mediated T-DNA insertional mutagenesis with regard to their mutation frequencies and conclude that a major breakthrough in the isolation of genes involved in plant development has been acheived. To provide a specific example, we summarize recent progress made in the understanding of flower morphogenesis at the molecular level through the study of homeotic genes obtained via gene tagging. T-DNA gene fusion vectors are being discussed that will allow the isolation of plant regulatory sequences with particular cell or tissue specificity, or that are controlled by specific external stimuli. Finally, we report on the approaches followed to convert the maize transposons Ac/Ds into valuable gene tags for use in a heterologous host such as Arabidopsis.

The Organization of the Pre-Spawning Behaviour in the Cichlid Fish Aequidens Portalegrensis (Hensel)

This study was aimed at obtaining insight into: a) how the communicative activities carried out by this substrate laying cichlid fish during the several days lasting pre-spawning period, function in facilitating pair formation, spawning and broodcare, and b) how the behavioural mechanism controlling the performance of these activities is structured. Both sexes use largely the same activities. The causational problems were primarily approached through statistical analysis of quantitative observations, regularly made on interacting males and females between their first confrontation and spawning. On the basis of the temporal association between the various activities, the latter could be classed into three groups, or clusters, which became successively dominant in the course of the pre-spawning period. On the ground of further observations, and on the results of experiments, a closer specification of the factors underlying these clusters was attempted. It was concluded that they are primarily due to internal factors or interactions between such factors, which can however be activated by specific external stimuli. The cluster appearing in the earliest phase of the encounter is simultaneously controlled by tendencies to attack and to escape; this behaviour subserves the defense of the territory. Absence of overt aggression in the response of the female appeases the agonistic behaviour of the male and causes the appearance of behaviour of the second cluster. In the control of this cluster a sexual system is involved beside the agonistic systems. Most of the activities of this cluster are instrumental in preparing a nest site; moreover their performance is likely to have a priming effect on the sexual factor. When this factor has become dominant over the agonistic ones, the fishes concentrate their behaviour on a hard substrate and the activities of the third cluster appear, culminating in oviposition and fertilizing.

The increase in hormone-stimulated adenylate cyclase activity following Rous sarcoma virus transformation.

Rous sarcoma virus (RSV)-infected chicken embryo cells were used to study the effect of viral transformation on the hormone-stimulated synthesis of cyclic AMP. Transformation by RSV greatly increased the cells' ability to synthesize and accumulate cyclic AMP in response to the beta-adrenergic agonist isoproterenol as compared to untransformed cells. This enhancement was observed in both intact cells and in membranes prepared from these cells. The inclusion of guanosine 5'-0-(3-thiotriphosphate), a nonhydrolyzable analogue of GTP, in assays of adenylate cyclase activity did not abolish the quantitative differences between the transformed and normal cell membranes. Infection of cells by Rous-associated virus, which lacks the oncogene src, did not induce this hyperresponsiveness thus indicating the probable involvement of the src gene product in this phenomenon. The duration of the isoproterenol-induced cyclic AMP elevation was longer in the transformed than in the untransformed cells; transformed cells, unlike untransformed cells, required at least 120 min before full desensitization became established. Membranes prepared from transformed cells specifically bound more than 5 times the quantity of the beta-adrenergic radiolabeled antagonist (-)3H-dihydroalprenolol and 125I-iodocyanopindolol compared to the untransformed cell membranes. Thus, it appears that major differences between the transformed and normal phenotypes reside in the concentration of membrane beta-adrenergic receptors and the inability of RSV-transformed cells to self-limit their response to specific external stimuli.

Vitellogenesis inAcanthoscelides obtectus(Coleoptera: Bruchidae). I—Oocyte development and vitellogenin in a European strain

Oocyte development was studied in a European strain of the bean weevil, Acanthoscelides obtectus. In the experimental system used, oocyte growth begins after several hours of imaginal life. The lengths of the terminal and penultimate oocytes were measured and correlations between these measurements showed that the latter stopped growing when the former was in the phase of accelerated growth. Vitellogenin could be immunologically detected in the hemolymph of sexually mature females and was undetectable in males, larvae and in females immediately after imaginal exuviation. The moment of vitellogenin appearance in young females varies from one insect to another. It appears that no specific external stimulus is required to initiate the synthesis and incorporation of the vitellin protein in this European strain.

Gross Metabolic Changes Characteristic of the Activity of the Neonate

T HE recent experimental interest in the subject of infant activity, notably by the students of Weiss at Ohio State University and latterly of Irwin at the State University of Iowa, has been confined largely to stimulus-response relationships. Pratt, Nelson, and Sun (22) investigated differentials of bodily activity in response to several stimuli, and Pratt (20, 21), Weiss (32), Stubbs (28), and Smith (27) have extended this work by way of refinement. The study of the nature of the bodily activity of infants irrespective of specific external stimulus sources was the task of Irwin, who gave objective data regarding variations under relatively controlled conditions, originally with four infants during the first ten days (4) and later with newborns during one interval between feedings (5). The importance of time since feeding as a factor inducing bodily activity was demonstrated in these experiments. Pratt (18) obtained a very low correlation between the activity of the infant and temperature within the cabinet. Irwin (5, 6, 7) was able to show also that weight and several length and cephalic measurements of newborn infants at birth were unrelated to amount of activity shown on the stabilimeter, as were certain indices of nutritional status, body surface, and intestinal surface. Certain studies of newborn infants in the field of metabolism wherein objective measurement of bodily activity has been made have provided a means of determining the relationship of other factors to bodily activity under fairly controlled external environment. It is the purpose of this paper to present certain reinterpretations of these data in so far as they may be pertinent to the study of bodily activity of newborn infants and its physiological concomitants. That muscular activity is an important factor in heat production was recognized by the earliest workers in the field of metabolism. Rubner and Heubner (25, 26) emphasized its importance, and the classic work of Benedict and Talbot (1, 2) with infants took this factor into account. The conditions necessary for studies of basal metabolism of absolute rest and