It is now generally accepted that the motor system is not purely dedicated to the control of behavior, but also has cognitive functions. Mirror neurons have provided a new perspective on how sensory information regarding others’ actions and gestures is coupled with the internal cortical motor representation of them. This coupling allows an individual to enrich his interpretation of the social world through the activation of his own motor representations. Such mechanisms have been highly preserved in evolution as they are (...) present in humans, apes and monkeys. Recent neuroanatomical data showed that there are two different connectivity patterns in mirror neuron networks in the macaque: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and the new data show that it is connected with limbic structures. The mouth mirror sector seems to be wired not only for ingestive behaviors but also for orofacial communicative gestures and vocalizations. Notably, the hand and mouth mirror networks partially overlap, suggesting the importance of hand-mouth synergies not only for sensorimotor transformation, but also for communicative purposes in order to better convey and control social signals. (shrink)

In the mammalian brain dopamine systems play a central role in the control of movement, hormone release, emotional balance and reward. Alteration of dopaminergic neurotransmission is involved in Parkinson's disease and other movement disorders, as well as in some psychotic syndromes. This review summarises recent findings, which shed some light on signals and cellular interactions involved in the specification and maturation of the dopaminergic function during neurogenesis. In particular we will focus on three major issues: (1) the differentiation of (...) dopaminergic neurones triggered by direct contact with the midbrain floor plate cells through the action of sonic hedgehog; (2) the neurotrophic factors acting on dopaminergic neurones; and (3) the role of target striatal cells on the survival and the axonal growth of developing or grafted dopaminergic neurones. (shrink)

The vertebrate nervous system performs the most complex functions of any organ system. This feat is mediated by dedicated assemblies of neurons that must be precisely connected to one another and to peripheral tissues during embryonic development. Motor neurons, which innervate muscle and regulate autonomic functions, form an integral part of this neural circuitry. The first part of this review describes the remarkable progress in our understanding of motor neuron differentiation, which is arguably the best understood model of (...) neuronal differentiation to date. During development, the coordinate actions of inductive signals from adjacent non‐neural tissues initiate the differentiation of distinct motor neuron subclasses, with specific projection patterns, at stereotypical locations within the neural tube. Underlying this specialisation is the expression of specific homeodomain proteins, which act combinatorially to confer motor neurons with both their generic and subtype‐specific properties. Ensuring that specific motor neuron subtypes innervate the correct target structure, however, requires precise motor axon guidance mechanisms. The second half of this review focuses on how distinct motor neuron subtypes pursue highly specific projection patterns by responding differentially to spatially discrete attractive and repulsive molecular cues. The tight link between motor neuron specification and axon pathfinding appears to be established by the dominant role of homeodomain proteins in dictating the ways that navigating motor axons interpret the plethora of guidance cues impinging on growth cones. BioEssays 23:582–595, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre‐mRNAs encoding neuronal‐specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track‐binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal genes are turned on in both non‐neuronal and neuronal cells, restricted expression of PTB in non‐neuronal cells diverts their mRNAs (...) to nonsense‐mediated decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron. BioEssays 30:1–4, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The noncoding RNA 7SK is a critical regulator of transcription by adjusting the activity of the kinase complex P‐TEFb. Release of P‐TEFb from 7SK stimulates transcription at many genes by promoting productive elongation. Conversely, P‐TEFb sequestration by 7SK inhibits transcription. Recent studies have shown that 7SK functions are particularly important for neuron development and maintenance and it can thus be hypothesized that 7SK is at the center of many signaling pathways contributing to neuron function. 7SK activates neuronal gene (...) expression programs that are key for terminal differentiation of neurons. Proteomics studies revealed a complex protein interactome of 7SK that includes several RNA‐binding proteins. Some of these novel 7SK subcomplexes exert non‐canonical cytosolic functions in neurons by regulating axonal mRNA transport and fine‐tuning spliceosome production in response to transcription alterations. Thus, a picture emerges according to which 7SK acts as a multi‐functional RNA scaffold that is integral for neuron homeostasis. (shrink)

It has been convincingly shown that peptides play important roles in the regulation and maintenance of a variety of tissues and organs in living animals. However, little is known concerning the potential role of peptides as signaling molecules in developmental processes. In Hydra, there is circumstantial evidence that small diffusible molecules act as morphogens in the regulation of patterning processes. In order to view the entire spectrum of peptide signaling molecules, we initiated a project aiming at the systematic identification of (...) peptide signaling molecules in Hydra. In this review, we describe three peptide signaling molecules and one family of peptides that function as signaling molecules in the processes of axial pattern formation and neuron differentiation in Hydra. These peptides are produced by epithelial cells and are therefore termed “epitheliopeptides”. We discuss the importance of epitheliopeptides in developmental processes within a subset of hydrozoans. (shrink)

We use a spiking neural network model of working memory capable of performing the spatial delayed response task to investigate two drugs that affect WM: guanfacine and phenylephrine. In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the (...) model. In particular, applying GFC causes increased activity in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased activity in these same neurons. Interestingly, these differential effects emerge from network-level interactions because GFC and PHE affect all neurons equally. We compare our model to both electrophysiological data from neurons in monkey dorsolateral prefrontal cortex and to behavioral evidence from monkeys performing the DRT. (shrink)

AbstractmRNA stability is increasingly recognized as being essential for controlling the expression of a wide variety of transcripts during neuronal development and synaptic plasticity. In this context, the role of AU‐rich elements (ARE) contained within the 3′ untranslated region (UTR) of transcripts has now emerged as key because of their high incidence in a large number of cellular mRNAs. This important regulatory element is known to significantly modulate the longevity of mRNAs by interacting with available stabilizing or destabilizing RNA‐binding proteins (...) (RBP). Thus, in parallel with the emergence of ARE, RBP are also gaining recognition for their pivotal role in regulating expression of a variety of mRNAs. In the nervous system, the member of the Hu family of ARE‐binding proteins known as HuD, has recently been implicated in multiple aspects of neuronal function including the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. Through its ability to interact with ARE and stabilize multiple transcripts, HuD has now emerged as an important regulator of mRNA expression in neurons. The present review is designed to provide a comprehensive and updated view of HuD as an RBP in the nervous system. Additionally, we highlight the role of HuD in multiple aspects of a neuron's life from early differentiation to changes in mature neurons during learning paradigms and in response to injury and regeneration. Finally, we describe the current state of knowledge concerning the molecular and cellular events regulating the expression and activity of HuD in neurons. BioEssays 28: 822–833, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the (...) neocortex and, more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the differentiation of CSMN for therapeutic benefit. (shrink)

Peptides serve as important signalling molecules in development and differentiation in the simple metazoan Hydra. A systematic approach (The Hydra Peptide Project) has revealed that Hydra contains several hundreds of peptide signalling molecules, some of which are neuropeptides and others emanate from epithelial cells. These peptides control biological processes as diverse as muscle contraction, neuron differentiation, and the positional value gradient. Signal peptides cause changes in cell behaviour by controlling target genes such as matrix metalloproteases. The abundance (...) of peptides in Hydra raises the question of whether, in early metazoan evolution, cell–cell communication was based mainly on these small molecules rather than on the growth‐factor‐like cytokines that control differentiation and development in higher animals. BioEssays 23:420–427, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

An historical review of the concepts of self-consciousness is presented, highlighting the important role of the body (particularly, body perception but also body action) and the social other in the construction of self-consciousness. More precisely, body perception, especially intermodal sensory perception including kinesthetic perception, is involved in the construction of a sense of self allowing self-nonself differentiation. Furthermore, the social other, through very early social and emotional interactions, provides meaning to the infant’s perception and contributes to the development of (...) his/her symbolization capacities. This is a necessary condition for body image representation and awareness of a permanent self in a time-space continuum (invariant over time and space). Self-image recognition impairments in the mirror are also discussed regarding a comprehensive developmental theory of self-consciousness. Then, a neuropsychological and neurophysiological approach to self-consciousness reviews the role of complex brain activation/integration pathways and the mirror neuron system in self-consciousness. Finally, this article offers new perspectives on self-consciousness evaluation using the mirror as an experimental paradigm to study self- and other- image and body recognition. (shrink)

The self, Joseph LeDoux tells us, is “the totality of the living organism”. Most disciplines in the natural sciences focus on only one or two levels of organization. Indeed, Dmitri Mendeleev figured out the periodic table of the elements without knowing any of the underlying quantum mechanics or stereochemistry. There are, however, at least a dozen levels of organization within the neurosciences — and, if we use a metaphor, we temporarily create yet another. This leads to considerable confusion and arguments (...) at cross purposes over whether learning is an alteration at the level of gene expression, ion channels, synapses, neurons or circuits. Each neuron has thousands of synapses, which produce currents that summate to form an impulse train. But only rarely is the activity of a single neuron sufficient to cause a perception or trigger an action. Neurons usually act as members of ‘committees’ — what Donald Hebb in 1949 called cellassemblies. Just as in academia, one individual may function in different committees on different occasions. A concept, including any explicit memory that we can talk about, is probably formed by such a committee. Implicit memories are less differentiated — they are part of the ‘feltwork’, together with motivations and emotions, that biases the choice of one’s next act. In this well-written 400-page appreciation of behavioural neuroscience, LeDoux argues that synapses are the seat of self. He says, in effect, that you are your memories; that it is the uniqueness of an array of synaptic strengths that distinguishes one twin from another. Fair enough, but why not instead focus on one’s unique array of ion channels? Or neurons, because a neuron is the closest thing we have to a computational unit? Or one’s unique arrangement of those overlapping, redundant hebbian committees? None of these make for a catchy book title, but relating other things to the synapses proves to be a good way of covering a lot of fascinating material at the overlying levels, including a few updates to LeDoux’s earlier book The Emotional Brain. (shrink)

The target article discusses a model of how brain circuits mediate social behaviors such as imitation and mindreading. Hurley suggests potential mechanisms for development of shared circuits. We propose that empirical studies can be designed to differentiate the influence of genetic and learning-based factors on the development of shared circuits. We use the mirror neuron system as a model system.

Prior work proposes a view of development of purpose and source of meaning in life as a more or less temporally distal project ideal self-situation in terms of which intermediate situations are experienced and prospects evaluated. This work considers Augustine on ensoulment alongside current work into self as adapted routines to common social regularities of the sort that Augustine found deficient. How can we account for such diversity of self-reported value orientation in terms of common structural dynamics differently developed, embodied (...) and enacted over the life course? This work in progress represents divergent views as different sorts of error theory, and hypothesizes that differential development of spindle neural projections underlies different accounts of error for attentive self-correction through iterative attenuation. Some implications for AI augmentation and value alignment of autonomous agents developed on such a model are briefly entertained. (shrink)

The concepts of hope and its absence, hopelessness, are seen as crucial in palliative care for people with motor neurone disease. A primary measure in psychological research on hopelessness in people with motor neurone disease is the Beck Hopelessness Scale. This scale can be understood as being conceptually based on the philosophical standard account of hope, which understands hope as an intentional expectancy. This essay argues that this is a misconstruction of hopelessness in palliative care. Rather, pre-intentional hope is essential (...) for palliative care of people with motor neurone disease. Pre-intentional hope enables the formation of intentional hopes and is intrinsically relational. Finally, it is argued that the absence of pre-intentional hope should not be subjected to psychiatric diagnosis, for example, in the form of demoralization disorder. (shrink)

This paper focuses on the ethical dilemmas created by advanced technology that would allow patients with motor neurone disease to be sustained by artificial ventilation. The author attempts to support the patient's right to informed choice, arguing from the perspective of autonomy as a first order principle. The counter arguments of caregiver burden and financial restraints are analysed. In the UK, where active euthanasia is not legalized, the dilemma of commencing ventilation is seen to be outweighed by the problems of (...) withdrawing this treatment. The lack of accurate data and protocols that would clarify the current situation is emphasized and the conclusion takes the form of a recommendation for further research. (shrink)

Studies on the ethical culture of organizations have mainly focused on ethical culture at the organizational level. This study explores ethical culture at the team level because this can add a more detailed understanding of the ethics of an organization, which is necessary for more customized and effective management interventions. To find out whether various teams within an organization can have different ethical cultures, we employ the differentiation perspective and conduct a survey of 180 teams from one organization. The (...) results show that there are significant differences between the ethical cultures of teams. These differences are relevant given the different relationships that were established between high and low clusters of team ethical culture and two outcome variables. The results also show that the dimensions of ethical cultures among teams have different patterns, which indicates the usefulness of using a multidimensional scale for capturing further differences among team ethical cultures. (shrink)

Studies on the ethical culture of organizations have mainly focused on ethical culture at the organizational level. This study explores ethical culture at the team level because this can add a more detailed understanding of the ethics of an organization, which is necessary for more customized and effective management interventions. To find out whether various teams within an organization can have different ethical cultures, we employ the differentiation perspective and conduct a survey of 180 teams from one organization. The (...) results show that there are significant differences between the ethical cultures of teams. These differences are relevant given the different relationships that were established between high and low clusters of team ethical culture and two outcome variables. The results also show that the dimensions of ethical cultures among teams have different patterns, which indicates the usefulness of using a multidimensional scale for capturing further differences among team ethical cultures. (shrink)

Studies on the ethical culture of organizations have mainly focused on ethical culture at the organizational level. This study explores ethical culture at the team level because this can add a more detailed understanding of the ethics of an organization, which is necessary for more customized and effective management interventions. To find out whether various teams within an organization can have different ethical cultures, we employ the differentiation perspective and conduct a survey of 180 teams from one organization. The (...) results show that there are significant differences between the ethical cultures of teams. These differences are relevant given the different relationships that were established between high and low clusters of team ethical culture and two outcome variables. The results also show that the dimensions of ethical cultures among teams have different patterns, which indicates the usefulness of using a multidimensional scale for capturing further differences among team ethical cultures. (shrink)

In this third installment of his series on key, underappreciated ideas in Ayn Rand's epistemology, the author discusses the nature of differentiation and integration as the functional essence of consciousness and applies that insight to various cognitive and noncognitive processes of awareness, with a special emphasis on logic and illogic. He offers an extended analysis of the fallacies of “Frozen Abstraction” and “False Alternative,” as well as critiques of a long-standing Objectivist conflation of falsity and contradiction and a relatively (...) more recent Objectivist error, the fallacy of “genuine awareness.”. (shrink)

Central to the differentiation and patterning of the Drosophila oocyte is the asymmetric intracellular localization of numerous mRNA and protein molecules involved in developmental signalling. Recent advances have identified some of the molecules mediating oocyte differentiation, specification of the anterior pole of the embryo, and determination of the embryonic germ line. This work is considered in the context of the classical model of the germ plasm as a cytoplasmic determinant for germ cell formation.

In modern academic career systems there are a large number of entry positions, much smaller numbers of intermediate positions, and still fewer full professorships. We examine how this system has developed in Germany, the country where the modern academic system was introduced, tracing the historical development of academic positions since the early 19th century. We show both a differentiation and professionalization. At first, professorships and private lecturer positions were the only formal positions, but later, lower formal academic positions emerged. (...) Over the whole period, the share of higher academic positions steadily decreased. This differentiation process was closely connected to professionalization: remuneration through salaries was extended from professors to almost everyone working in the German academic system. We propose that the process of differentiation and professionalization was induced by the expansion and democratization of higher education. Finally, our study shows that the opportunities for PhDs to obtain salaried doctoral positions have increased since the 1950s. On the other hand, opportunities for PhDs to become a professor or obtain another tenured job have decreased since the 1980s due to a slowdown of higher education expansion. (shrink)

Worship as the work of the people of God does not arise in a vacuum. It is contextual and cultural. In the areas of the world, long designated as the mission field, many developments were transported to countries in the global south and imposed on local peoples. This was true of the arrival of Presbyterians who came to settle in southern Africa. Presbyterians imported two differing traditions of worship, the evangelical and the liturgical, and introduced them to the indigenous peoples (...) they encountered. They were adopted without adaptation and have largely followed their European ancestors and contemporaries. Africans have largely followed their missionary mentors but have found ways of subverting these traditions by forming a new tradition by blending aspects of each and adding their own African brand of Spirit inspired and led. worship while their mentors pay only lip service to their African colleagues. Contribution: This article highlights the historical continuities in the worship of a mainline Church of European Origin (CEO) with their ecclesiastical and ecumenical source(s). This is in discontinuity with the worship traditions of African Christian communities, which are less formal and tend to incline towards the charismatic and Pentecostal traditions with their freedom of expression of faith rather than the more cerebral forms of expression. (shrink)

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder of motor neurones. Although the genetic basis of familial forms of ALS has been well explored, the molecular basis of sporadic ALS is less well understood. Recent evidence has linked sporadic ALS with the failure to edit key residues in ionotropic glutamate receptors, resulting in excessive influx of calcium ions into motor neurones which in turn triggers cell death. Here we suggest that edited AMPA glutamate (GluR2) receptor subunits serve as gatekeepers (...) for motor neurone survival. BioEssays 30:1185–1192, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Hepatocellular carcinoma represents the third leading cause of cancer-related death. Because HCC is multicentric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors taken from zebrafish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. (...) In such a trial the patients, with “intermediate” and “advanced” HCC according to Barcelona Clinic Liver Cancer/American Association for the Study of Liver Diseases guidelines, presented benefit in terms of performance status and objective tumoral response, with some cases of complete response, that is, sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of alpha-fetoprotein... (shrink)

The neural crest is a transient population of multipotent progenitors arising at the lateral edge of the neural plate in vertebrate embryos. After delamination and migration from the neuroepithelium, these cells contribute to a diverse array of tissues including neurons, smooth muscle, craniofacial cartilage, bone cells, endocrine cells and pigment cells. Considerable progress in recent years has furthered our understanding at a molecular level of how this important group of cells is generated and how they are assigned to specific lineages. (...) Here we review a number of recent studies supporting a role for Wnt signaling in neural crest induction, differentiation, and apoptosis. We also summarize the timing of expression of a number of Wnt ligands and receptors with respect to neural crest induction. BioEssays 25:317–325, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In Primitive Classification, Durkheim suggests using the notion of affectivity to explain the emergence of various social structures. This bold attempt to extend the role of affectivity in sociological thinking has been rejected by most social scientists. By greatly elaborating Durkheim's outline for a sociology of emotions, however, this essay suggests that there is a fruitful way to use affectivity in macrosociological theory. This model allows us to develop in a new way Durkheim's description of structural differentiation and stratification (...) in The Division of Labor in Society. (shrink)

Individuals differ considerably in their emotion experience. Some experience emotions in a highly differentiated manner, clearly distinguishing among a variety of negative and positive discrete emotions. Others experience emotions in a relatively undifferentiated manner, treating a range of like-valence terms as interchangeable. Drawing on self-regulation theory, we hypothesised that individuals with highly differentiated emotion experience should be better able to regulate emotions than individuals with poorly differentiated emotion experience. In particular, we hypothesised that emotion differentiation and emotion regulation would (...) be positively related in the context of intense negative emotions, where the press for emotion regulation is generally greatest. To test this hypothesis, participants' negative and positive emotion differentiation was assessed using a 14-day diary protocol. Participants' regulation of negative and positive emotions was assessed using laboratory measures. As predicted, negative emotion differentiation was positively related to the frequency of negative emotion regulation, particularly at higher levels of emotional intensity. (shrink)

The “community effect” is necessary for tissue differentiation. In the Xenopus muscle paradigm, e‐FGF has been identified as a candidate community factor. Standley et al.1 now show that the community effect, mediated through FGF signalling, continues to be important at later stages of development in the posterior part of the embryo. In this region, the paraxial mesoderm is still undergoing segmentation into somites, which are the site of early skeletal muscle formation. Indeed, somitogenesis, together with the read‐out of the (...) Hox code, which confers anteroposterior positional identity, is regulated by FGF signalling. This raises the question of the co‐ordination between these events and the community effect which orchestrates myogenesis. BioEssays 25:13–16, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

T‐bet and Eomes are two related transcription factors (TFs) that regulate the differentiation of cytotoxic lymphocytes such as Natural Killer (NK) cells and CD8 T cells. Recent genome‐wide analyses suggest they have complementary roles in instructing the transcriptional program of NK cells, although their DNA binding sites appear to be very similar. In this essay, we discuss the mechanisms that could specify their action, addressing their expression profile, the cofactors they interact with, as well as their roles in the (...) epigenetic regulation of chromatin accessibility. Based on the recent literature on these TFs, we propose different models to describe how they regulate gene expression in NK cells at steady state, or in the context of activation or exhaustion. We also discuss recent findings in the field of CD8 T cell differentiation and residency, where Eomes and T‐bet appear to be major regulators, and the parallels that can be drawn between mechanisms of NK and CD8 T cell differentiation and trafficking. (shrink)

There are many obvious morphological and behavioural differences between male and female Drosophila, whose differing phenotypes are produced by a hierarchy of sex determination genes. These genes have been well characterised at the genetic and molecular level. Similarly, a number of sex‐specific differentiation genes have been characterised, such as the chorion and vitelline membrane genes in females and the sex peptide and other accessory gland proteins in males. Despite the depth of these parallel studies, there is only one example (...) of a direct link between the sex determination pathway and the downstream sex differentiation genes, namely the regulation of the female‐specific yolk protein genes. The yolk proteins are synthesised in the fat body and ovarian follicle cells of the adult female and are subsequently transported to the oocyte where they are stored for utilization during embrygenesis. The expression of the yolk protein genes is not entirely controlled by the sex determination hierarchy, as several different regulatory pathways must interact to direct their correct sexual, temporal and spatial regulation during development. (shrink)

The development of factor markets has opened Chinese agriculture for the penetration of capitalism. This new round of rural transformation—China’s agrarian transition— raises the agrarian question in the Chinese context. This study investigates how capitalist forms and relations of production transform agricultural production and the peasantry class in rural China. The authors identify six forms of nonpeasant agricultural production, compare the labor regimes and direct producers’ socioeconomic statuses across these forms, and evaluate the role of China’s land-rights institution in shaping (...) these forms. The empirical investigation presents three main findings: Peasant differentiation : capitalist forms of agricultural production differentiate peasants into a variety of new class positions. Market-based stratification: producers in capitalist agriculture are primarily stratified by their positions in labor and land markets; their socioeconomic statuses are linked with their varying degrees of proletarianization. Institutional mediation: rural China’s dual-track land system plays a crucial role in shaping the diverse and unique forms of capitalist production. (shrink)