Neocortical arealization: Evolution,mechanisms, and open questions

The mammalian neocortex is a structure with no equals in the vertebrates and is the seat of the highest cerebral functions, such as thoughts and consciousness. It is radially organized into six layers and tangentially subdivided into functional areas deputed to the elaboration of sensory information, association between different stimuli, and selection and triggering of voluntary movements. The process subdividing the neocortical field into several functional areas is called “arealization”. Each area has its own cytoarchitecture, connectivity, and peculiar functions. In the last century, several neuroscientists have investigated areal structure and the mechanisms that have led during evolution to the rising of the neocortex and its organization. The extreme conservation in the positioning and wiring of neocortical areas among different mammalian families suggests a conserved genetic program orchestrating neocortical patterning. However, the impressive plasticity of the neocortex, which is able to rewire and reorganize areal structures and connectivity after impairments of sensory pathways, argues for a more complex scenario. Indeed, even if genetics and molecular biology helped in identifying several genes involved in the arealization process, the logic underlying the neocortical bauplan is still beyond our comprehension. In this review, we will introduce the present knowledge and hypotheses on the ontogenesis and evolution of neocortical areas. Then, we will focus our attention on some open issues, which are still unresolved, and discuss some recent studies that might open new directions to be explored in the next few years. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 73: 411–447, 2013.     

HP1: facts,open questions,and speculation

The demonstration, over a decade ago, that HP1 is a highly conserved constituent of heterochromatin was accompanied by the explicit view that this protein plays a pivotal role in epigenetic regulation (P.B. Singh, J.R. Miller, J. Pearce, R. Kothary, R.D. Burton, R. Paro, T.C. James, and S.J. Gaunt, 1991, Nucleic Acids Res. 19, 789-794). Recent studies have confirmed this view, unveiling specific interactions of HP1 with a variety of histone and nonhistone proteins. We discuss here some of these observations, concentrating on structure-function relationships and intracellular dynamics. Integrating the available information, we also present a hypothetical model describing how HP1, acting as a bifunctional cross-linker, could organize peripheral heterochromatin and contribute in the compartmentalization of the cell nucleus.     

Law, evolution and the brain: applications and open questions

This paper discusses several issues at the intersection of law and brain science. It focuses principally on ways in which an improved understanding of how evolutionary processes affect brain function and human behaviour may improve law's ability to regulate behaviour. It explores sample uses of such 'evolutionary analysis in law' and also raises questions about how that analysis might be improved in the future. Among the discussed uses are: (i) clarifying cost-benefit analyses; (ii) providing theoretical foundation and potential predictive power; (iii) assessing comparative effectiveness of legal strategies; and (iv) revealing deep patterns in legal architecture. Throughout, the paper emphasizes the extent to which effective law requires: (i) building effective behavioural models; (ii) integrating life-science perspectives with social-science perspectives; (iii) considering the effects of brain biology on behaviours that law seeks to regulate; and (iv) examining the effects of evolutionary processes on brain design.     

Scale-up of microbial processes: impacts, tools and open questions

Industrial biotechnological production is developing rapidly worldwide. Consequently, more and novel bioprocesses need to perform optimally not only in small lab- but also in large production scales. This article shortly reviews typical impacts found when cells are exposed to micro environmental heterogeneities typically occurring in poorly mixed large scale production reactors. The current state-of-the-art of tool development is presented for analyzing these phenomena. Finally, still open questions are formulated and needs for future research are outlined to further support the expansion of biotech industries by successful research results.     

The cost of circadian desynchrony: Evidence,insights and open questions

Coordinated daily rhythms are evident in most aspects of our physiology, driven by internal timing systems known as circadian clocks. Our understanding of how biological clocks are built and function has grown exponentially over the past 20 years. With this has come an appreciation that disruption of the clock contributes to the pathophysiology of numerous diseases, from metabolic disease to neurological disorders to cancer. However, it remains to be determined whether it is the disruption of our rhythmic physiology per se (loss of timing itself), or altered functioning of individual clock components that drive pathology. Here, we review the importance of circadian rhythms in terms of how we (and other organisms) relate to the external environment, but also in relation to how internal physiological processes are coordinated and synchronized. These issues are of increasing importance as many aspects of modern life put us in conflict with our internal clockwork.

     

Endocrine mechanisms,behavioral phenotypes and plasticity: known relationships and open questions

Behavior of wild vertebrate individuals can vary in response to environmental or social factors. Such within-individual behavioral variation is often mediated by hormonal mechanisms. Hormones also serve as a basis for among-individual variations in behavior including animal personalities and the degree of responsiveness to environmental and social stimuli. How do relationships between hormones and behavioral traits evolve to produce such behavioral diversity within and among individuals? Answering questions about evolutionary processes generating among-individual variation requires characterizing how specific hormones are related to variation in specific behavioral traits, whether observed hormonal variation is related to individual fitness and, whether hormonal traits are consistent (repeatable) aspects of an individual's phenotype. With respect to within-individual variation, we need to improve our insight into the nature of the quantitative relationships between hormones and the traits they regulate, which in turn will determine how they may mediate behavioral plasticity of individuals. To address these questions, we review the actions of two steroid hormones, corticosterone and testosterone, in mediating changes in vertebrate behavior, focusing primarily on birds. In the first part, we concentrate on among-individual variation and present examples for how variation in corticosterone concentrations can relate to behaviors such as exploration of novel environments and parental care. We then review studies on correlations between corticosterone variation and fitness, and on the repeatability over time of corticosterone concentrations. At the end of this section, we suggest that further progress in our understanding of evolutionary patterns in the hormonal regulation of behavior may require, as one major tool, reaction norm approaches to characterize hormonal phenotypes as well as their responses to environments.In the second part, we discuss types of quantitative relationships between hormones and behavioral traits within individuals, using testosterone as an example. We review conceptual models for testosterone-behavior relationships and discuss the relevance of these models for within-individual plasticity in behavior. Next, we discuss approaches for testing the nature of quantitative relationships between testosterone and behavior, concluding that again reaction norm approaches might be a fruitful way forward.We propose that an integration of new tools, especially of reaction norm approaches into the field of behavioral endocrinology will allow us to make significant progress in our understanding of the mechanisms, the functional implications and the evolution of hormone–behavior relationships that mediate variation both within and among individuals. This knowledge will be crucial in light of already ongoing habitat alterations due to global change, as it will allow us to evaluate the mechanisms as well as the capacity of wild populations to adjust hormonally-mediated behaviors to altered environmental conditions.     

Phytopathology in fossil plants: New data,questions of classification

Examples of damages in fossil plants revealed using electron microscopy are considered. The formal classification of these damages is discussed.     

Allometric growth, disturbance regime, and dilemmas of controlling invasive plants: a model analysis

Disturbed communities are observed to be more susceptible to invasion by exotic species, suggesting that some attributes of the invaders may interact with disturbance regime to facilitate invasion success. Alternanthera philoxeroides, endemic to South America, is an amphibious clonal weed invading worldwide. It tends to colonize disturbed habitats such as riparian zones, floodplain wetlands and agricultural areas. We developed an analytical model to explore the interactive effects of two types of physical disturbances, shoot mowing and root fragmentation, on biomass production dynamics of A. philoxeroides. The model is based on two major biological assumptions: (1) allometric growth of root (belowground) vs. shoot (aboveground) biomass and (2) exponential regrowth of shoot biomass after mowing. The model analysis revealed that the interaction among allometric growth pattern, shoot mowing frequency and root fragmentation intensity might lead to diverse plant ‘fates’. For A. philoxeroides whose root allocation decreases with growing plant size, control by shoot mowing was faced with two dilemmas. (1) Shoot regrowth can be effectively suppressed by frequent mowing. However, frequent shoot mowing led to higher biomass allocation to thick storage roots, which enhanced the potential for faster future plant growth. (2) In the context of periodic shoot mowing, individual shoot biomass converged to a stable equilibrium value which was independent of the root fragmentation intensity. However, root fragmentation resulted in higher equilibrium population shoot biomass and higher frequency of shoot mowing required for effective control. In conclusion, the interaction between allometric growth and physical disturbances may partially account for the successful invasion of A. philoxeroides; improper mechanical control practices could function as disturbances and result in exacerbated invasion.     

The physiological ecology of vascular epiphytes: current knowledge, open questions

The current knowledge of the physiological ecology of vascular epiphytes is reviewed here with an emphasis on the most recent literature. It is argued that by far the most relevant abiotic constraint for growth and vegetative function of vascular epiphytes is water shortage, while other factors such as nutrient availability or irradiation, are generally of inferior importance. However, it is shown that the present understanding of epiphyte biology is still highly biased, both taxonomically and ecologically, and it is concluded that any generalizations are still preliminary. Future studies should include a much wider range of taxa and growing sites within the canopy to reach a better understanding how abiotic factors are limiting epiphyte growth and survival which, in turn, should affect epiphyte community composition. Finally, a more integrative approach to epiphyte biology is encouraged: physiological investigations should be balanced by studies of other possible constraints, for example, substrate instability, dispersal limitation, competition or herbivory.     

Taxus callus cultures: Initiation,growth optimization,characterization and taxol production

Callus was induced from Taxus baccata cv. Repandens Parsons ex Rehd., T. brevifolia Nutt., T. cuspidata Sieb. & Zucc., and T. x media cvs. Hicksii and Densiformis Rehd. using different concentrations of 2,4-d-(2,4-dichlorophenoxyacetic acid), IBA (indole-3-butyric acid), or NAA -naphthalene acetic acid in combination with kinetin. All cultures grew slowly following the first subculture, and a majority turned brown and ceased growth within the next six to twelve months. The callus cultures which lived, continued to grow very slowly for one to two years before the growth rate improved. Initiation of roots and shoot primordia-like structures occurred on some cultures maintained in the dark, and 16 h light/8 h dark, respectively. A fast-growing, habituated callus line (CR-1) derived from T. x media Rehd. cv. Hicksii was established from callus initiated in 1986. Supplementing the medium with casein hydrolysate and both fructose and glucose enhanced the growth rate. A great deal of heterogeneity was found among and within the callus, with respect to the amount of taxol produced. The callus exhibited levels of taxol ranging from 0.1 to 13.1 mg kg^-1 (0.0001 to 0.0131%) on a dry weight basis. Overall, the older brown-colored callus produced more taxol than the younger pale yellow-colored callus. The presence of taxol in callus samples was established by high performance liquid chromatography, its biological activity confirmed by a microtubule-stabilizing bioassay and its structure confirmed using one-and two-dimensional ¹H and ¹³C nuclear magnetic resonance spectroscopy.Abbreviations 2,4-d 2,4-dichlorophenoxyacetic acid - IBA indole-3-butyric acid - NAA -naphthaleneacetic acid - kinetin 6-furfurylaminopurine - 2iP 6-(,-dimethylallylamino)purine     

Immunologic reconstitution by interleukin-2: facts and open questions

Interleukin-2 (IL-2), one of the most potent immunoregulatory and inflammatory cytokines, is being tested in phase III clinical trials in order to demonstrate its efficacy in combination with current antiviral agents in preventing the occurrence of opportunistic infections and death in individuals infected by the human immunodeficiency virus (HIV). In the meantime, its capacity to boost the number of CD4+ T cells in peripheral blood has been confirmed by a number of individual phase I/II trials conducted in different countries by independent investigators. In the face of this remarkable result, little is known of the effects exerted by this cytokine once administered to infected individuals in terms of its impact on different immunologic functions. The recent acquisitions on the important role played by latently infected cells in in vivo infection in reinitiating HIV replication and cytopathicity once antiviral therapy is suspended or becomes suboptimal, has shed new light on the possibility of utilizing immunologic strategies, including IL-2, for eradicating the virus from latent reservoirs. Results from a clinical trial conducted at our Institute indicate a decrease in lymphocyte-associated HIV DNA after IL-2 administration, supporting this hypothesis.