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Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform.

We describe the application of a microarray platform, which combines information from exon body and splice-junction probes, to perform a quantitative analysis of tissue-specific alternative splicing (AS) for thousands of exons in mammalian cells. Through this system, we have analyzed global features of AS in major mouse tissues. The results provide numerous inferences for the functions of tissue-specific AS, insights into how the evolutionary history of exons can impact on their inclusion levels, and also information on how global regulatory properties of AS define tissue type. Like global transcription profiles, global AS profiles reflect tissue identity. Interestingly, we find that transcription and AS act independently on different sets of genes in order to define tissue-specific expression profiles. These results demonstrate the utility of our quantitative microarray platform and data for revealing important global regulatory features of AS.

Alternative Splicing↗

Developmental sculpting of social phenotype and plasticity.

Early developmental variables engender behavioral and neural variation, especially in species in which embryonic environment determines gonadal sex. In the leopard gecko, Eublepharis macularius, the incubation temperature of the egg (IncT) determines gonadal sex. Moreover, IncT affects the sexual differentiation of the individual and, consequently, within-sex variation. Individuals hatched from eggs incubated at an IncT that produces predominantly males are more masculinized than same-sex counterparts from IncTs that produce predominantly females. Here we review how gonadal sex and IncT interact to affect behavioral, endocrinological, and neural phenotype in the leopard gecko and influence phenotypic plasticity following hormone administration or social experience. We discuss the hormonal dependence of sex- and IncT-dependent behavioral and neural morphological and metabolic differences and highlight the parallels between IncT effects in geckos and intrauterine position effects in rodents. We argue that the leopard gecko is an important model of how the process of sex determination can affect sexual differentiation and of selection forces underlying the evolution of sex ratios.

Animals↗

The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease.

Why do we get the stress-related diseases we do? Why do some people have flare ups of autoimmune disease, whereas others suffer from melancholic depression during a stressful period in their life? In the present review possible explanations will be given by using different levels of analysis. First, we explain in evolutionary terms why different organisms adopt different behavioral strategies to cope with stress. It has become clear that natural selection maintains a balance of different traits preserving genes for high aggression (Hawks) and low aggression (Doves) within a population. The existence of these personality types (Hawks-Doves) is widespread in the animal kingdom, not only between males and females but also within the same gender across species. Second, proximate (causal) explanations are given for the different stress responses and how they work. Hawks and Doves differ in underlying physiology and these differences are associated with their respective behavioral strategies; for example, bold Hawks preferentially adopt the fight-flight response when establishing a new territory or defending an existing territory, while cautious Doves show the freeze-hide response to adapt to threats in their environment. Thus, adaptive processes that actively maintain stability through change (allostasis) depend on the personality type and the associated stress responses. Third, we describe how the expression of the various stress responses can result in specific benefits to the organism. Fourth, we discuss how the benefits of allostasis and the costs of adaptation (allostatic load) lead to different trade-offs in health and disease, thereby reinforcing a Darwinian concept of stress. Collectively, this provides some explanation of why individuals may differ in their vulnerability to different stress-related diseases and how this relates to the range of personality types, especially aggressive Hawks and non-aggressive Doves in a population. A conceptual framework is presented showing that Hawks, due to inefficient management of mediators of allostasis, are more likely to be violent, to develop impulse control disorders, hypertension, cardiac arrhythmias, sudden death, atypical depression, chronic fatigue states and inflammation. In contrast, Doves, due to the greater release of mediators of allostasis (surplus), are more susceptible to anxiety disorders, metabolic syndromes, melancholic depression, psychotic states and infection.

Adaptation, Physiological↗

Neuroprotection from soman-induced seizures in the rodent: evaluation with diffusion- and T2-weighted magnetic resonance imaging.

Exposure to the organophosphate nerve agent soman produces seizures that in turn lead to neuropathology. This study describes the temporal and spatial evolution of brain pathology following soman-induced convulsions and the attenuation of these alterations after neuroprotective intervention with magnetic resonance imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and thalamus exhibited significant decreases (23%) in apparent diffusion coefficients (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements declined significantly at 12 h (37%) returning to near normal values by 24 h. Histopathological analyses confirmed moderate cell loss within the hippocampus and piriform cortex. Together these findings suggest that initial cell death was resolved through regional cellular remodeling. Pharmacological countermeasures were administered in the form of diazepam, a benzodiazepine anticonvulsant, or gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied immediately after soman exposure prevented acute ADC changes. However the presence of edema, using T2 measurements, was detected at 3 h within the retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34% below normal). GK-11 therapy appeared to prevent most of these changes. However at 7 days after soman, a decrease (17%) in ADC was observed in the piriform cortex. Pathology was confined to the piriform cortex suggesting that this region is more difficult to protect. This is the first report that provides temporal and spatial resolution using MRI with histological correlation of pharmacological interventions against soman-mediated seizure-induced neuropathology.

Animals↗

The common organization of the amygdaloid complex in tetrapods: new concepts based on developmental, hodological and neurochemical data in anuran amphibians.

Research over the last few years has demonstrated that the amygdaloid complex in amniotes shares basic developmental, hodological and neurochemical features. Furthermore, homolog territories of all main amygdaloid subdivisions have been recognized among amniotes, primarily highlighted by the common expression patterns for numerous developmental genes. With the achievement of new technical approaches, the study of the precise neuroanatomy of the telencephalon of the anuran amphibians has been possible, revealing that most of the structures present in amniotes are recognizable in these anamniotes. Thus, recent investigations have yielded enough results to support the notion that the organization of the anuran amygdaloid complex includes subdivisions with origin in ventral pallial and subpallial territories, a strong relationship with the vomeronasal and olfactory systems, abundant intra-amygdaloid connections, a main output center involved in the autonomic system, profuse amygdaloid fiber systems, and distinct chemoarchitecture. When all these new data about the development, connectivity and neurochemistry of the amygdaloid complex in anurans are taken into account, it becomes patent that a basic organization pattern is shared by both amniotic and anamniotic tetrapods.

Amygdala↗

Species comparative studies and cognitive development.

The comparative study of infant development and animal cognition brings to cognitive science the promise of insights into the nature and origins of cognitive skills. In this article, I review a recent wave of comparative studies conducted with similar methodologies and similar theoretical frameworks on how two core components of human cognition--object permanence and gaze following--develop in different species. These comparative findings call for an integration of current competing accounts of developmental change. They further suggest that evolution has produced developmental devices capable at the same time of preserving core adaptive components, and opening themselves up to further adaptive change, not only in interaction with the external environment, but also in interaction with other co-developing cognitive systems.

Animals↗

Continuity of the conceptual system across species.

In a recent neuroimaging study of macaque monkeys, Gil-da-Costa and colleagues reported that a distributed circuit of modality-specific properties represents macaques' conceptual knowledge of social situations. The circuit identified shows striking similarities to analogous circuits in humans that represent conceptual knowledge. This parallel suggests that a common architecture underlies the conceptual systems of different species, although with additional systems extending human conceptual abilities significantly.

Animals↗

Detecting cheaters.

Explore the source record for details and available documents.

Biological Evolution↗

Maternal behavior and developmental psychopathology.

This paper reviews recent developments in the phenomenology, neurobiology, and genetics of maternal behavior in animal model systems from an evolutionary perspective on psychopathology. Following a review of the phenomenology and neurobiology of maternal behavior, recent studies addressing the role of genetic factors in the maternal behavior of rodents were identified in a search of literature in peer-reviewed journals. Gene knockout studies were evaluated with regard to mouse strain background, method of behavioral phenotyping, and quantification of the behavioral deficits. Gene knockout data were then analyzed using a cluster analysis technique. At least nine genes have been identified that are necessary for the expression of one or more aspects of maternal behavior. These genes encode for three transcription factors: three enzymes, including dopamine beta hydroxylase and neuronal nitric oxide synthase; two receptors, including the prolactin and the estrogen alpha receptor; and one neuropeptide, oxytocin. Cluster analysis suggested possible relationships between specific genes. Gene knockout technology has provided new insights into the molecular basis of maternal behavior that are congruent with the existing neurobiological literature. Future studies of genetic and environmental influences on maternal behavior have the potential to inform models of disease pathogenesis.

Animals↗

Depersonalization: neurobiological perspectives.

Depersonalization remains a fascinating and obscure clinical phenomenon. In addition to earlier Jacksonian neurobiological adumbrations, and conventional psychodynamic accounts, views started to be expressed in the 1930s that depersonalization might be a vestigial form of behavior, and since the 1960s that it might be a phenomenon related to the temporal lobe. Recent advances in the neurobiology of the limbic system, and the application of Geschwind's concept of disconnection in the corticolimbic system, have opened the possibility of developing testable models. This paper includes a review of these ideas and of the clinical features of depersonalization, particularly of its emotional changes, suggesting that they are important for the neurobiological understanding of depersonalization. It also draws attention to clinical similarities between the experiential narratives produced by patients suffering from depersonalization and those with corticolimbic disconnections. On the basis of this, a new model is proposed according to which the state of increased alertness observed in depersonalization results from an activation of prefrontal attentional systems (right dorsolateral prefrontal cortex) and reciprocal inhibition of the anterior cingulate, leading to experiences of "mind emptiness" and "indifference to pain" often seen in depersonalization. On the other hand, a left-sided prefrontal mechanism would inhibit the amygdala resulting in dampened autonomic output, hypoemotionality, and lack of emotional coloring that would in turn, be reported as feelings of "unreality or detachment."

Adaptation, Biological↗

Evolving an integral ecology of mind.

A deliberation upon the possibility of generating a comprehensive view of 'mind as a whole' by integrating biology, psychology and sociology, and considering 'Mind' as a dynamical interplay between values existing over many levels and scales of complex systems. This view of mind as a coevolutionary whole is related to similar ecological viewpoints being developed in the fields of artificial life and multi-agent systems. A meta-model of mind is proposed which attempts to integrate the various existing views of mind from a time perspective, and positions the field in a way that we think augurs well for the potential of mind studies based upon modern complex systems science concepts.

Animals↗

The evolution of complexity in human brain development: an EEG study.

Analysis of the EEG as a signal from a deterministic non-linear system should, in principle, allow insights into the complexity of underlying brain activity. We examined the capability of this method to analyse the marked changes in brain activity during normal brain development. Resting EEGs of 54 healthy children (newborns to 14 years old) and of 12 normal adults were recorded digitally. The following parameters were calculated: correlation dimension, a measure of the complexity of the underlying system, and the first Lyapunov coefficient, indicating the system's 'unpredictability'. Analysis of variance (ANOVA) was performed with probands grouped by age. The subgroups of children older than 1 year was further examined by regression analysis. In all analysed epochs, Lyapunov coefficients were significantly positive (P < 0.0001. t-test). The presence of non-linear dynamics was asserted statistically in 64-76% of examined epochs. A highly significant increase in correlation dimension with age was found in all examined leads (P < 0.0001, ANOVA). In all age groups, marked differences in correlation dimension in different brain regions became evident (P < 0.01-0.0001, ANOVA). Evidence for the presence of non-linearity can be found even in newborns. Brain maturation was reflected in a marked and highly significant increase in correlation dimension (complexity). Our work indicates that non-linear dynamics analysis is suitable for measuring complexity of brain activity during maturation and provides age-dependent normal values as a basis for further study.

Adolescent↗

Some thoughts on the evolutionary basis for the prominent role of ATP and ADP in cellular energy metabolism.

The predominance of the adenosine triphosphate/adenosine diphosphate (ATP/ADP) couple in cellular phosphorylation reactions, including those that form the basis for cellular energy metabolism, cannot be explained on thermodynamic grounds since a variety of "high energy phosphate" compounds (including ADP itself) found in the cell would, based on thermodynamic considerations, be at least as effective as ATP in serving as a phosphoryl donor. How then did present-day organisms come to rely on the ATP/ADP couple as the principal mediator of phosphorylation reactions? The early appearance of adenine compounds in the prebiotic environment is suggested by experiments indicating that, relative to other purine or pyridimine compounds, adenine derivatives are preferentially synthesized under simulated prebiotic conditions (Ponnamperuma et al., 1963). In addition to the roles of adenine nucleotides in phosphorylation reactions, other adenine derivatives (e.g. Coenzyme A, flavin adenine dinucleotide, puridine nucleotides) are employed in a variety of metabolic roles. The principal function of the adenine moiety in these latter cases is in the binding of these derivatives to the relevant enzyme. The capability for binding of the adenine moiety appears to have arisen early in evolution and been exploited in a multitude of contexts, a suggestion consistent with observed similarities between the binding sites of several enzymes employing adenine derivatives as substrate. The early availability of suitable adenine compounds in the biosphere and development of complementary binding sites on cellular proteins, coupled with the expected advantages in having a limited number of metabolites as central mediators of endergonic and exergonic metabolism could readily have led to the observed pre-eminence of adenine nucleotides in cellular energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Evolution of central respiratory chemoreception: a new twist on an old story.

Evolution of central respiratory chemosensitivity has been linked traditionally to the need for carbon dioxide regulation that accompanied the evolution of air breathing in terresterial animals. We examined the validity of this linkage by investigating the possibility of central chemoreception in air breathing fish that diverged from the amphibian lineage long before the appearance of terrestriality. We showed that the isolated brainstem preparation of the long nose gar (Lepisosteus osseus) produces a putative motor pattern for lung ventilation, which is responsive to CO(2). These findings, together with more inferential evidence, suggest an association between air breathing and central chemosensitivity in aquatic animals that spans the major branches in vertebrate phylogeny. Furthermore, developmental observations in tadpoles suggest that the neural substrates for central chemoreception exist in proximity to that for rhythm generation. We postulate that a primitive ancestral CPG, sensitive to CO(2) is conserved and is evidenced in the intrinsic coupling of respiratory CPG and central chemoreception in modern tetrapods.

Animals↗

Survey of the adrenal homolog in teleosts.

The adrenal homolog of teleosts is not a compact organ as the adrenal glands of most vertebrates but is composed by aminergic chromaffin and interrenal steroidogenic cells located mostly inside the head kidney that, in this taxon, generally has a hematopoietic function. The two tissues can be mixed, adjacent, or completely separated and line the endothelium of the venous vessels or are located in close proximity. The chromaffin cells in some species are also present in the posterior kidney. Histological and ultrastructural work revealed cytological peculiarities of both types of cells as compared to those of other vertebrate species. In particular, the interrenal ones can show some variations in ultrastructure depending on sex, time of the year, and relation to stress events. A periodic renewal of the whole gland tissue is also sustained by some studies. Research regarding development is scanty as compared to mammals and most studies go back to the early years of the past century. The adrenal homolog of teleosts is under hormonal and neuronal control. Moreover, local paracrine interactions may play an important role in modulating a system involved in stress response and osmoregulation. Most previous studies involved a few species with the object of intensive rearing for commercial purposes; in fact cortisol, the main hormone secreted by the interrenal cells, can also influence reproduction and growth. This review summarizes data from morphocytological work and refers to other excellent reviews regarding physiology. Some of the results are compared to data available from other fishes and vertebrate classes with the aim of including them in an evolutionary and environmental framework.

Adrenal Glands↗