121 research outputs found

    Key stages in mammary gland development: The mammary end bud as a motile organ

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    In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-β acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed

    A simplistic pedagogical formulation of a thermal speed distribution using a relativistic framework

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    A novel pedagogical technique is presented that can be used in the undergraduate (UG) class to formulate a relativistically extended Kinetic Theory of Gases and thermal speed distribution, while assuming the basic thermal symmetry arguments of the famous Maxwell-Boltzmann distribution as presented at the UG level. The adopted framework can be used by students to understand the physics in a thermally governed system at high temperature and speeds, without having to indulge in high level tensor based mathematics, as has been done by the previous works in the subject. Our approach, a logical extension of that proposed by Maxwell, will first recapitulate what is taught and known in the UG class and then present a methodology inspired from the Maxwell-Boltzmann framework that will help students to understand and derive the physics of relativistic thermal systems. The methodology uses simple tools well known to undergraduates and involves a component of computational techniques that can be used to involve students in this exercise. We have tried to place the current work in a larger perspective in regard to the earlier works done and emphasize on it's simplicity and accessibility to students. Towards the end, interesting implications of the relativistically extended distribution are presented and compared with the Maxwell-Boltzmann results at various temperatures.Comment: 13 pages, 5 figures, Publication accepted in Pramana - Journal of Physics (Indian Academy of Sciences). Revised version has an additional section, discussing previous work on relativistic Kinetic Theory in section 2.1 and comparison with these in section 6. Arguments for formulating a relativistic thermal speed distributions have been enriched and made more clear and categorical in section

    Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CPG of the rat spinal cord in vitro.

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    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 \u3bcM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits

    Visuospatial Integration: Paleoanthropological and Archaeological Perspectives

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    The visuospatial system integrates inner and outer functional processes, organizing spatial, temporal, and social interactions between the brain, body, and environment. These processes involve sensorimotor networks like the eye–hand circuit, which is especially important to primates, given their reliance on vision and touch as primary sensory modalities and the use of the hands in social and environmental interactions. At the same time, visuospatial cognition is intimately connected with memory, self-awareness, and simulation capacity. In the present article, we review issues associated with investigating visuospatial integration in extinct human groups through the use of anatomical and behavioral data gleaned from the paleontological and archaeological records. In modern humans, paleoneurological analyses have demonstrated noticeable and unique morphological changes in the parietal cortex, a region crucial to visuospatial management. Archaeological data provides information on hand–tool interaction, the spatial behavior of past populations, and their interaction with the environment. Visuospatial integration may represent a critical bridge between extended cognition, self-awareness, and social perception. As such, visuospatial functions are relevant to the hypothesis that human evolution is characterized by changes in brain–body–environment interactions and relations, which enhance integration between internal and external cognitive components through neural plasticity and the development of a specialized embodiment capacity. We therefore advocate the investigation of visuospatial functions in past populations through the paleoneurological study of anatomical elements and archaeological analysis of visuospatial behaviors

    Cheetah mothers' vigilance: looking out for prey or for predators?

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    Free-living cheetah ( Acinonyx jubatus ) cubs are killed by a number of predators, thus vigilance in cheetah mothers may be a form of anti-predator behaviour as well as a means of locating prey. Mothers' vigilance during the day was closely associated with measures of hunting but not with measures of anti-predator behaviour. In contrast, mothers' vigilance at kills was not related to hunting but was related to anti-predator behaviour. Both forms of vigilance decreased as cubs grew older. Vigilance during the day increased with litter size which supports a model of ‘shared’ parental investment (Lazarus and Inglis 1986) because after prey had been located and caught by mothers, cubs shared the prey between them. Vigilance at kills did not increase with litter size when cubs were young; in these situations predators stole cheetahs' prey and rarely chased cubs so, at most, only a single cub would be taken. Mothers' anti-predator behaviour away from kills did increase with litter size at young cub ages however; more cubs are killed in these circumstances the greater is the size of the litter. When cubs were older and could outrun predators, neither vigilance at kills nor anti-predator behaviour increased with litter size. These results strongly support two models of ‘unshared’ investment (Lazarus and Inglis 1986) and demonstrate, not only that superficially similar behaviour has different functions in different contexts, but that parental investment is shaped by the type of benefits accrued from it.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46879/1/265_2004_Article_BF00300681.pd

    A brain-inspired cognitive system that mimics the dynamics of human thought

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    In recent years, some impressive AI systems have been built that can play games and answer questions about large quantities of data. However, we are still a very long way from AI systems that can think and learn in a human-like way. We have a great deal of information about how the brain works and can simulate networks of hundreds of millions of neurons. So it seems likely that we could use our neuroscientific knowledge to build brain-inspired artificial intelligence that acts like humans on similar timescales. This paper describes an AI system that we have built using a brain-inspired network of artificial spiking neurons. On a word recognition and colour naming task our system behaves like human subjects on a similar timescale. In the longer term, this type of AI technology could lead to more flexible general purpose artificial intelligence and to more natural human-computer interaction

    Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis

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    Visualizing the Human Subcortex Using Ultra-high Field Magnetic Resonance Imaging

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