Biological functions are causes, not effects: A critique of selected effects theories.

The theory of Selected Effects (SE) is currently the most widely accepted etiological account of function in biology. It argues that the function of any trait is the effect that past traits of that type produced that contributed to its current existence. Its proper or etiological function is whatever effect was favoured by natural selection irrespective of the trait's current effects.

A thermodynamic basis for teleological causality.

We show how distinct terminally disposed self-organizing processes can be linked together so that they collectively suppress each other's self-undermining tendency despite also potentiating it to occur in a restricted way. In this way, each process produces the supportive and limiting boundary conditions for the other. The production of boundary conditions requires dynamical processes that decrease local entropy and increase local constraints.

Cognition is entangled with metabolism: relevance for resting-state EEG-fMRI.

The brain is a living organ with distinct metabolic constraints. However, these constraints are typically considered as secondary or supportive of information processing which is primarily performed by neurons. The default operational definition of neural information processing is that (1) it is ultimately encoded as a change in individual neuronal firing rate as this correlates with the presentation of a peripheral stimulus, motor action or cognitive task.

"It's cleaner, definitely": Collaborative Process in Audio Production.

Working from vague client instructions, how do audio producers collaborate to diagnose what specifically is wrong with a piece of music, where the problem is and what to do about it? This paper presents a design ethnography that uncovers some of the ways in which two music producers co-ordinate their understanding of complex representations of pieces of music while working together in a studio. Our analysis shows that audio producers constantly make judgements based on audio and visual evidence while working with complex digital tools, which can lead to ambiguity in assessments of issues. We show how multimodal conduct guides the process of work and that complex media objects are integrated as elements of interaction by the music producers.

A degenerative process underlying hierarchic transitions in evolution.

This paper describes an evolutionary process likely involved in hierarchic transitions in biological evolution at many levels, from genetics to social organization. It is related to the evolutionary process described as contingent neutral evolution (CNE). It involves a sequence of stages initiated by the spontaneous appearance of functional redundancy.

Abandoning the code metaphor is compatible with semiotic process.

We agree with Brette's assessment that the coding metaphor has become more problematic than helpful for theories of brain and cognitive functioning. In an effort to aid in constructing an alternative, we argue that joining the insights from the dynamical systems approach with the semiotic framework of C. S.

The transition from constraint to regulation at the origin of life.

The origin of living dynamics required a local evasion of thermodynamic degradation by maintaining critical dynamical and structural constraints. Scenarios for life`s origin that fail to distinguish between constrained chemistry and regulated metabolism do not address the question of how living processes first emerge from simpler constraints on molecular interactions. We describe a molecular model system consisting of coupled reciprocal catalysis and self-assembly in which one of the catalytic bi-products tends to spontaneously self-assemble into a containing shell (analogous to a viral capsule).

Metabolic hypothesis for human altriciality.

The classic anthropological hypothesis known as the "obstetrical dilemma" is a well-known explanation for human altriciality, a condition that has significant implications for human social and behavioral evolution. The hypothesis holds that antagonistic selection for a large neonatal brain and a narrow, bipedal-adapted birth canal poses a problem for childbirth; the hominin "solution" is to truncate gestation, resulting in an altricial neonate. This explanation for human altriciality based on pelvic constraints persists despite data linking human life history to that of other species.

Colloquium paper: a role for relaxed selection in the evolution of the language capacity.

Explaining the extravagant complexity of the human language and our competence to acquire it has long posed challenges for natural selection theory. To answer his critics, Darwin turned to sexual selection to account for the extreme development of language. Many contemporary evolutionary theorists have invoked incredibly lucky mutation or some variant of the assimilation of acquired behaviors to innate predispositions in an effort to explain it.

Transient phenomena in learning and evolution: genetic assimilation and genetic redistribution.

Deacon has recently proposed that complexes of genes can be integrated into functional groups as a result of environmental changes that mask and unmask selection pressures. For example, many animals endogenously synthesize ascorbic acid (vitamin C), but anthropoid primates have only a nonfunctional version of the crucial gene for this pathway. It is hypothesized that the loss of functionality occurred in the evolutionary past when a diet rich in vitamin C masked the effect of the gene, and its loss effectively trapped the animals in a fruit-eating lifestyle.

Monkey homologues of language areas: computing the ambiguities.

The 'language-readiness' of human brains most probably resulted from modification of structures present in non-human primate brains, but identifying such homologues and the nature of their modifications has been highly problematic. In a recent article, Arbiband Bota suggest that these problems can be overcome using a neuroinformatics approach. But its assumptions ignore many non-local, activity-dependent, regressive, and allometric effects of neurodevelopment that violate assumptions of classic homology.

Socioeconomic variation in injury in children and older people: a population based study.

Objectives: To compare hospital admission rates for all causes and specific causes of injury in children and the elderly by a measure of economic deprivation.

Study Design: All emergency admissions for Welsh residents from 1997-99 were located to one of 865 electoral tracts, which were grouped into fifths using a measure of socioeconomic deprivation. Standardised admission rates for all ages and 0-14, 15-75, and 75+ year groups for each quintile were calculated with 95% confidence intervals.

Immune parameters relevant to neural xenograft survival in the primate brain.

The lack of supply and access to human tissue has prompted the development of xenotransplantation as a potential clinical modality for neural cell transplantation. The goal of the present study was to achieve a better understanding of the immune factors involved in neural xenograft rejection in primates. Initially, we quantified complement mediated cell lysis of porcine fetal neurons by primate serum and demonstrated that anti-C5 antibody treatment inhibited cell death.

Enhanced axonal growth from fetal human bcl-2 transgenic mouse dopamine neurons transplanted to the adult rat striatum.

Embryonic neurons transplanted to the adult CNS extend axons only for a developmentally defined period. There are certain intercellular factors that control the axonal extension, one of which may be the expression of the bcl-2 protein. In this study, rats with complete striatal dopamine fiber denervation received embryonic day 14 mouse ventral mesencephalon cells overexpressing human bcl-2 or control wild-type ventral mesencephalon cells.

Transplanted fetal striatum in Huntington's disease: phenotypic development and lack of pathology.

Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate-putamen (striatum).

Evolutionary perspectives on language and brain plasticity.

Our understanding of speech and language disorders may be aided by information about the constraints and predispositions contributed by neural developmental processes. As soon as we begin to look at human neuroanatomy and development from a comparative perspective, it is possible to recognize a number of ways that human brains diverge from the general pattern of other ape and monkey brains. These divergences may offer clues to language evolution.

Morris water maze analysis of 192-IgG-saporin-lesioned rats and porcine cholinergic transplants to the hippocampus.

Adults rats were lesioned with 192-IgG-saporin, an immunotoxin that targets cholinergic neurons in the basal forebrain expressing the low-affinity nerve growth factor receptor (p75). One month later, rats received E30-35 porcine cholinergic neurons bilaterally into the hippocampus, and were tested in the Morris water maze and the passive avoidance task 4.5-6 months after transplantation (in two experiments, rats were retested in the water maze) followed by histological and cellular analyses.

Pig fetal septal neurons implanted into the hippocampus of aged or cholinergic deafferented rats grow axons and form cross-species synapses in appropriate target regions.

The anatomical specificity of axon growth from fetal pig septal xenografts was studied by transplanting septal cells from E30-35 pig fetuses into cholinergic deafferented (192-IgG-saporin-infused) rats or into aged rats (> 18 months). Cell suspensions (100,000 cells/microl) were injected bilaterally into the dorsal and ventral hippocampus of immunosuppressed rats (10 mg/kg/day cyclosporine A). To assess axonal growth and synapse formation, acetylcholinesterase histochemistry, an antibody to choline acetyltransferase (ChAT), and three pig-positive/rat-negative antibodies: bovine 70kD neurofilament (NF70), human low-affinity NGF receptor (hNGFr), and human synaptobrevin (hSB) were used.

Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease.

We used brain imaging to study long-term neurodegenerative and bioadaptive neurochemical changes in a primate model of Parkinson disease. We gradually induced a selective loss of nigrostriatal dopamine neurons, similar to that of Parkinson disease, by creating oxidative stress through infusion of the mitochondrial complex 1 inhibitor MPTP for 14+/-5 months. Repeated evaluations over 3 years by positron emission tomography (PET) demonstrated progressive and persistent loss of neuronal dopamine pre-synaptic re-uptake sites; repeated magnetic resonance spectroscopy (MRS) studies indicated a 23-fold increase in lactate and macromolecules in the striatum region of the brain for up to 10 months after the last administration of MPTP.

A novel immunophilin ligand: distinct branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of Parkinson's disease.

Protection or regeneration of the dopaminergic (DA) system would be of significant therapeutic value for Parkinson's disease. Immunophilin ligands, such as FK506, can produce neurotrophic effects in vitro and in vivo, but their immunosuppressive effects make them unsuitable for neurological application. This study demonstrates that a novel, nonimmunosuppressive immunophilin ligand (V-10,367) increased the number of neurites extended by tyrosine hydroxylase positive (TH+) DA neurons in embryonic day 14 primary DA neuronal cultures.

Chronic cognitive deficits and amyloid precursor protein elevation after selective immunotoxin lesions of the basal forebrain cholinergic system.

Alzheimer's disease (AD) is the most common neurodegenerative disorder that causes cognitive deficits in the elderly. Its neuropathology is characterized by amyloid deposition and specific cholinergic degeneration. To address the link between amyloid formation and cholinergic loss, we examined histologically the amyloid precursor protein (APP) changes following selective immunolesion of the basal forebrain cholinergic system with 192 IgG-saporin in rats at 6 months post-lesion.