Did the molecules of adaptive immunity evolve from the innate immune system?

The antigen receptors on cells of innate immune systems recognizebroadly expressed markers on non-host cells while the receptorson lymphocytes of the adaptive immune system display a higherlevel of specificity. Adaptive immunity, with its exquisitespecificity and immunological memory, has only been found inthe jawed vertebrates, which also display innate immunity. Jawlessfishes and invertebrates only have innate immunity. In the adaptiveimmune response, T and B-lymphocytes detect foreign agents orantigens using T cell receptors (TCR) or immunoglobulins (Ig),respectively. While Ig can bind free intact antigens, TCR onlybinds processed antigenic fragments that are presented on moleculesencoded in the major histocompatibility complex (MHC). MHC moleculesdisplay variation through allelic polymorphism. A diverse repertoireof Ig and TCR molecules is generated by gene rearrangement andjunctional diversity, processes carried out by the recombinaseactivating gene (RAG) products and terminal deoxynucleotidyltransferase (TdT). Thus, the molecules that define adaptiveimmunity are TCR, Ig, MHC molecules, RAG products and TdT. Nodirect predecessors of these molecules have been found in thejawless fishes or invertebrates. In contrast, the complementcascade can be activated by either adaptive or innate immunesystems and contains examples of molecules that gradually evolvedfrom non-immune functions to being part of the innate and thenadaptive immune system. In this paper we examine the moleculesof the adaptive immune system and speculate on the existenceof direct predecessors that were part of innate immunity.     

Did knuckle walking evolve twice?

Although African great apes share a similar quadrupedal locomotor behaviour, there are marked differences in hand morphology and size between the species. Hence, whilst all three species (two genera) of African ape frequently knuckle walk as adults, debate remains as to whether this behaviour is derived from a common ancestor or whether it evolved in parallel in chimpanzees and gorillas. This exploratory morphometric study of the sub-adult and adult wrist of these two genera aims to contribute to this debate. A total of twenty-seven dimensions of the lunate, triquetral, hamate and capitate of sub-adult and adult Pan troglodytes and Gorilla gorilla were analysed in order to determine whether carpal dimensions are generally ontogenetically scaled, and whether differences in growth trajectories, or length of growth, and adult morphologies can be explained by behavioural differences between the two species. Only 56% of all dimensions studied were ontogenetically scaled in sub-adults and some of these dimensions exhibit differing adult proportions between the two species. In general, the dimensions analysed fell into two categories: Pan and Gorilla either follow the same growth trajectories (Pattern A) or the Pan reduced major axis (RMA) regressions were significantly transposed above those of Gorilla (Pattern B). Additionally, it was found that Gorilla carpals appear to cease growing relatively earlier than those of Pan. While a small number of differences, notably those of the lunate, can be accounted for by differences in behaviour between the species, the majority of differences indicate heterochronic modifications of development during evolution, which correspond to kinematic differences in knuckle walking between the African great apes. In light of morphological, behavioural and ecological data currently available it is parsimonious to suggest that knuckle walking has evolved in parallel in the two lineages.     

Did language evolve in multilingual settings?

Accounts of language evolution have largely suffered from a monolingual bias, assuming that language evolved in a single isolated community sharing most speech conventions. Rather, evidence from the small-scale societies who form the best simulacra available for ancestral human communities suggests that the combination of small societal scale and out-marriage pushed ancestral human communities to make use of multiple linguistic systems. Evolutionary innovations would have occurred in a number of separate communities, distributing the labor of structural invention between populations, and would then have been pooled gradually through multilingually mediated horizontal transfer to produce the technological package we now regard as a natural ensemble.     

Can the insect nervous system synthesize ecdysteroids?

The term "neurosteroid" refers to both classic and unique steroid molecules that are synthesized from cholesterol (C) by the central and peripheral nervous systems of higher vertebrates. Therein, they accumulate and modulate nervous activity by a variety of mechanisms other than the classic steroid receptor-mediated modulation of genomic activity, although such may also be involved. Since the insect nervous system expresses ecdysteroid receptors and responds both directly and developmentally to ecdysteroids, the possibility of ecdysteroidogenesis in the pupal and adult central and peripheral nervous system of Manduca sexta and the nervous system of Drosophila melanogaster larvae was investigated. The endogenous concentrations of the critical, dietary-derived delta 5,7-sterols ergosterol and 7-dehydrocholesterol (7dC) remained 10 to 20-fold higher in the Manduca pupal and adult nervous tissues than was found in the larval hemolymph at the cessation of feeding. In addition, it was determined that the Manduca pupal nervous system, but not that of the adult, could synthesize 3H/14C-7dC or 3H-7-dehydro-25-hydroxycholesterol (3H-7d25C) from 3H/14C-cholesterol (3H/14C-C) or the polar sterol substrate 3H-25-hydroxycholesterol (3H-25C), respectively. However, none of the nervous system samples from the two species and the several stages analyzed, a small window of neural development in these insects, were capable of incorporating any of the above tracer precursor sterols into a radiolabelled ecdysteroid, i.e. less than 0.0005%. Thus, the absence of neurosteroidogenesis by the insect nervous system stands in sharp contrast to previously described nervous system steroid hormone biosynthesis by the mammalian nervous system.     

A single origin of the central nervous system?

As Denes et al. (2007) reveal in this issue, the expression profile and roles of genes that pattern the nervous system in embryos of chordates and annelids are surprisingly similar. This extraordinary conservation suggests that the patterning mechanism has been inherited largely unchanged from the bilaterian common ancestor and that the central nervous system, although dorsal in fish and ventral in worms, is an ancient characteristic of animals.     

Did the notochord evolve from an ancient axial muscle? The axochord hypothesis

The origin of the notochord is one of the key remaining mysteries of our evolutionary ancestry. Here, we present a multi‐level comparison of the chordate notochord to the axochord, a paired axial muscle spanning the ventral midline of annelid worms and other invertebrates. At the cellular level, comparative molecular profiling in the marine annelids P. dumerilii and C. teleta reveals expression of similar, specific gene sets in presumptive axochordal and notochordal cells. These cells also occupy corresponding positions in a conserved anatomical topology and undergo similar morphogenetic movements. At the organ level, a detailed comparison of bilaterian musculatures reveals that most phyla form axochord‐like muscles, suggesting that such a muscle was already present in urbilaterian ancestors. Integrating comparative evidence at the cell and organ level, we propose that the notochord evolved by modification of a ventromedian muscle followed by the assembly of an axial complex supporting swimming in vertebrate ancestors.     

How does Mycobacterium leprae target the peripheral nervous system?

Mycobacterium leprae has the capacity to invade the peripheral nervous system and cause neuropathy. The molecular mechanisms responsible have remained unknown until recently. Identification of the endoneurial laminin-2 isoform and its receptor alpha-dystroglycan as neural targets of M. leprae has not only opened up a new area of scientific inquiry into the pathogenesis of neurological damage in leprosy, but has also revealed unexpected biological properties of these important host molecules.     

Is there anything "autonomous" in the nervous system?

The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate that no element shows "autonomy" in an integrated body. Nor are they solely "passive" or generated "without mental elaboration." In addition, to be "not consciously controlled" is not a unique attribute of these components. Another term that could be proposed is "homeostatic nervous system" for providing conditions to the execution of behaviors and maintenance of the internal milieu within normal ranges. But, not all homeostatic conditions are under the direct influence of these groups of neurons, and some situations clearly impose different ranges for some variables that are adaptative (or hazardous) in the tentative of successfully coping with challenging situations. Finally, the name "nervous system for visceral control" emerges as another possibility. Unfortunately, it is not only "viscera" that represent end targets for this specific innervation. Therefore, it is commented that no quite adequate term for the sympathetic, parasympathetic, and gastrointestinal divisions has already been coined. The basic condition for a new term is that it should clearly imply the whole integrated and collaborative functions that the components have in an indivisible organism, including the neuroendocrine, immunological, and respiratory systems. Until that, we can call these parts simply by their own names and avoid terms that are more "convenient" than appropriate.     

Circadian rhythmicity and photoperiodism in the pitcher-plant mosquito: can the seasonal timer evolve independently of the circadian clock?

The two major rhythms of the biosphere are daily and seasonal; the two major adaptations to these rhythms are the circadian clock, mediating daily activities, and the photoperiodic timer, mediating seasonal activities. The mechanistic connection between the circadian clock and the photoperiodic timer remains unresolved. Herein, we show that the rhythmic developmental response to exotic light:dark cycles, usually used to infer a causal connection between the circadian clock and the photoperiodic timer, has evolved independently of the photoperiodic timer in the pitcher-plant mosquito Wyeomyia smithii across the climatic gradient of eastern North America from Florida to Canada and from the coastal plain to the mountains. We conclude that the photoperiodic timing of seasonal events can evolve independently of the daily circadian clock.     

Did brain-specific genes evolve faster in humans than in chimpanzees?

One of the most distinctive characteristics of humans among primates is the size, organization and function of the brain. A recent study has proposed that there was widespread accelerated sequence evolution of genes functioning in the nervous system during human origins. Here we test this hypothesis by a genome-wide analysis of genes that are expressed predominantly or specifically in brain tissues and genes that have important roles in the brain, identified on the basis of five different definitions of brain specificity. Although there is little overlap among the five sets of brain-specific genes, none of them supports human acceleration. On the contrary, some datasets show significantly fewer nonsynonymous substitutions in humans than in chimpanzees for brain-specific genes relative to other genes in the genome. Our results suggest that the unique features of the human brain did not arise by a large number of adaptive amino acid changes in many proteins.     

Angiotensin IV in the central nervous system

The mammalian brain harbors a renin-angiotensin system (RAS), which is independent from the peripheral RAS. Angiotensin II is a well-studied member of the RAS and exerts most of the known angiotensin-mediated effects on fluid and electrolyte homeostasis, autonomic activity, neuroendocrine regulation, and behavior. This review summarizes a mass of compelling new evidence for the biological role of an active (3-8) fragment of angiotensin II, named angiotensin IV. Angiotensin IV binds to a widely distributed binding site in the brain, but which is different from the known angiotensin II receptors AT1 and AT2. Angiotensin IV has been implicated in a number of physiological actions, including the regulation of blood flow, the modulation of exploratory behavior, and processes attributed to learning and memory. Furthermore, angiotensin IV may also be involved in neuronal development. Collectively, the available evidence suggests that angiotensin IV is a potent neuropeptide, involved in a broad range of brain functions.     

Initial patterning of the central nervous system: how many organizers?

For three-quarters of a century, developmental biologists have been asking how the nervous system is specified as distinct from the rest of the ectoderm during early development, and how it becomes subdivided initially into distinct regions such as forebrain, midbrain, hindbrain and spinal cord. The two events of 'neural induction' and 'early neural patterning' seem to be intertwined, and many models have been put forward to explain how these processes work at a molecular level. Here I consider early neural patterning and discuss the evidence for and against the two most popular models proposed for its explanation: the idea that multiple signalling centres (organizers) are responsible for inducing different regions of the nervous system, and a model first articulated by Nieuwkoop that invokes two steps (activation/transformation) necessary for neural patterning. As recent evidence from several systems challenges both models, I propose a modification of Nieuwkoop's model that most easily accommodates both classical and more recent data, and end by outlining some possible directions for future research.     

What are the characteristics of cycling cells in the adult central nervous system?

Many regions of the adult central nervous system contain cycling cells. Such cells comprise a relatively small fraction of the total population of the CNS. Work over decades has attempted to determine the normal fates of these cells and their fates under pathological conditions. The recent interest in "stem" cells and "progenitors" in the adult CNS has sparked a much revived exploration into the nature of these cells and in the signals by which they may be induced to differentiate into mature neurons or glia. This population has not yet been fully characterized, although it has become clear that this is a heterogeneous group of cells, differing in morphology, antigen expression, migratory capacity, and potential fates.     

Area 51: How do Acanthamoeba invade the central nervous system?

Acanthamoeba granulomatous encephalitis generally develops as a result of haematogenous spread, but it is unclear how circulating amoebae enter the central nervous system (CNS) and cause inflammation. At present, the mechanisms which Acanthamoeba use to invade this incredibly well-protected area of the CNS and produce infection are not well understood. In this paper, we propose two key virulence factors: mannose-binding protein and extracellular serine proteases as key players in Acanthamoeba traversal of the blood-brain barrier leading to neuronal injury. Both molecules should provide excellent opportunities as potential targets in the rational development of therapeutic interventions against Acanthamoeba encephalitis.