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Sample records for sensory cell populations

  1. Uptake of 3H-thymidine by the receptor cell populations after injury of the sensory nerve fibres

    International Nuclear Information System (INIS)

    Chuchkov, Ch.N.

    1978-01-01

    The material of the study was the skin from the beak of two-day ducklings. The investigation was carried out on the 2nd, 5th, 20th and 45th day after the crushing of the sensory nerve fibres entering the capsulated Herbst receptors. Twenty four hours before the biopsy, the ducklings were injected at 6 hours intervals with 3 H-thymidine. The number of labelled index in the three cell pupulations, participating in the receptor development was determined. The cells of the subcapsular space of all control animals (with intacted suborbital nerves) have shown the highest labelled index. The index of the capsular perineural cells is about 12 times lower, while the labelled index of the Schwann receptor cells is about 10 times lower. Following the denervation, the labelled index in increasing and reaches its maximum on the 5th postoperative day. The Schwann receptor cells in comparison to the two other cell populations show the most significant deviation during the regeneration (45th day after the intervention). The investigations show that all three cell populations pass through a miotic cycle of innovation. The low labelled index of the Schwann receptors (1-2 labelled cells in 1000) is an indication of a high differentiation. One can assume that their regeneration takes place at the expense of the proper proliferation activity as well as of the differentiation of the Schwann cells from the distal section of the regenerating sensory nerve fibres. Taking into consideration the high labelled index of the other populations, it seems most probable that their regeneration takes place for the expense of their own cell populations. (A.B.)

  2. A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.

    Science.gov (United States)

    Herget, Meike; Scheibinger, Mirko; Guo, Zhaohua; Jan, Taha A; Adams, Christopher M; Cheng, Alan G; Heller, Stefan

    2013-01-01

    Mechanosensitive hair cells and supporting cells comprise the sensory epithelia of the inner ear. The paucity of both cell types has hampered molecular and cell biological studies, which often require large quantities of purified cells. Here, we report a strategy allowing the enrichment of relatively pure populations of vestibular hair cells and non-sensory cells including supporting cells. We utilized specific uptake of fluorescent styryl dyes for labeling of hair cells. Enzymatic isolation and flow cytometry was used to generate pure populations of sensory hair cells and non-sensory cells. We applied mass spectrometry to perform a qualitative high-resolution analysis of the proteomic makeup of both the hair cell and non-sensory cell populations. Our conservative analysis identified more than 600 proteins with a false discovery rate of Analysis of proteins exclusively detected in either population revealed 64 proteins that were specific to hair cells and 103 proteins that were only detectable in non-sensory cells. Statistical analyses extended these groups by 53 proteins that are strongly upregulated in hair cells versus non-sensory cells and vice versa by 68 proteins. Our results demonstrate that enzymatic dissociation of styryl dye-labeled sensory hair cells and non-sensory cells is a valid method to generate pure enough cell populations for flow cytometry and subsequent molecular analyses.

  3. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  4. Diverse coupling of neurons to populations in sensory cortex.

    Science.gov (United States)

    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  5. [Characterization of stem cells derived from the neonatal auditory sensory epithelium].

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    Diensthuber, M; Heller, S

    2010-11-01

    In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

  6. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  7. Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae.

    Science.gov (United States)

    Frye, Mitchell D; Yang, Weiping; Zhang, Celia; Xiong, Binbin; Hu, Bo Hua

    2017-02-01

    In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. SENSORY HAIR CELL REGENERATION IN THE ZEBRAFISH LATERAL LINE

    OpenAIRE

    Lush, Mark E.; Piotrowski, Tatjana

    2014-01-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing ther...

  9. Sensory Hair Cells: An Introduction to Structure and Physiology.

    Science.gov (United States)

    McPherson, Duane R

    2018-06-18

    Sensory hair cells are specialized secondary sensory cells that mediate our senses of hearing, balance, linear acceleration, and angular acceleration (head rotation). In addition, hair cells in fish and amphibians mediate sensitivity to water movement through the lateral line system, and closely related electroreceptive cells mediate sensitivity to low-voltage electric fields in the aquatic environment of many fish species and several species of amphibian.Sensory hair cells share many structural and functional features across all vertebrate groups, while at the same time they are specialized for employment in a wide variety of sensory tasks. The complexity of hair cell structure is large, and the diversity of hair cell applications in sensory systems exceeds that seen for most, if not all, sensory cell types. The intent of this review is to summarize the more significant structural features and some of the more interesting and important physiological mechanisms that have been elucidated thus far. Outside vertebrates, hair cells are only known to exist in the coronal organ of tunicates. Electrical resonance, electromotility, and their exquisite mechanical sensitivity all contribute to the attractiveness of hair cells as a research subject.

  10. Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-08-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

  11. Sensory hair cell regeneration in the zebrafish lateral line.

    Science.gov (United States)

    Lush, Mark E; Piotrowski, Tatjana

    2014-10-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling, and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. Copyright © 2014 Wiley Periodicals, Inc.

  12. SENSORY HAIR CELL REGENERATION IN THE ZEBRAFISH LATERAL LINE

    Science.gov (United States)

    Lush, Mark E.; Piotrowski, Tatjana

    2014-01-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. PMID:25045019

  13. Laser microdissection of sensory organ precursor cells of Drosophila microchaetes.

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    Eulalie Buffin

    Full Text Available BACKGROUND: In Drosophila, each external sensory organ originates from the division of a unique precursor cell (the sensory organ precursor cell or SOP. Each SOP is specified from a cluster of equivalent cells, called a proneural cluster, all of them competent to become SOP. Although, it is well known how SOP cells are selected from proneural clusters, little is known about the downstream genes that are regulated during SOP fate specification. METHODOLOGY/PRINCIPAL FINDINGS: In order to better understand the mechanism involved in the specification of these precursor cells, we combined laser microdissection, toisolate SOP cells, with transcriptome analysis, to study their RNA profile. Using this procedure, we found that genes that exhibit a 2-fold or greater expression in SOPs versus epithelial cells were mainly associated with Gene Ontology (GO terms related with cell fate determination and sensory organ specification. Furthermore, we found that several genes such as pebbled/hindsight, scabrous, miranda, senseless, or cut, known to be expressed in SOP cells by independent procedures, are particularly detected in laser microdissected SOP cells rather than in epithelial cells. CONCLUSIONS/SIGNIFICANCE: These results confirm the feasibility and the specificity of our laser microdissection based procedure. We anticipate that this analysis will give new insight into the selection and specification of neural precursor cells.

  14. Sensory hair cell death and regeneration in fishes

    Directory of Open Access Journals (Sweden)

    Jerry D. Monroe

    2015-04-01

    Full Text Available Sensory hair cells are specialized mechanotransductive receptors required for hearing and vestibular function. Loss of hair cells in humans and other mammals is permanent and causes reduced hearing and balance. In the early 1980’s, it was shown that hair cells continue to be added to the inner ear sensory epithelia in cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was documented in the chick cochlea following acoustic trauma. Since then, research using chick and other avian models has led to great insights into hair cell death and regeneration. However, with the rise of the zebrafish as a model organism for studying disease and developmental processes, there has been an increased interest in studying sensory hair cell death and regeneration in its lateral line and inner ears. Advances derived from studies in zebrafish and other fish species include understanding the effect of ototoxins on hair cells and finding otoprotectants to mitigate ototoxin damage, the role of cellular proliferation versus direct transdifferentiation during hair cell regeneration, and elucidating cellular pathways involved in the regeneration process. This review will summarize research on hair cell death and regeneration using fish models, indicate the potential strengths and weaknesses of these models, and discuss several emerging areas of future studies.

  15. Sensory Dysfunction and Sexuality in the U.S. Population of Older Adults.

    Science.gov (United States)

    Zhong, Selena; Pinto, Jayant M; Wroblewski, Kristen E; McClintock, Martha K

    2018-04-01

    first nationally representative study of sexuality and multisensory dysfunction in community-dwelling older adults. 4 of the 5 classic senses were measured with objective tests, and hearing was rated by interviewers in the context of their conversation. Medical and health care interventions that can reduce the burden of sensory dysfunction may improve older adults' sexual experience. Sensory dysfunction is associated with sexual inactivity, but not with sexual motivation. Among those who are sexually active, sensory dysfunction did not interfere with sexual expression. Improving the sexual experience of older adults requires a focus on sensory dysfunction as an impediment to sexual activity given that older adults remain sexually motivated. Zhong S, Pinto JM, Wroblewski KE, et al. Sensory Dysfunction and Sexuality in the U.S. Population of Older Adults. J Sex Med 2018;15:502-509. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  16. Biophysics of Hair Cell Sensory Systems

    NARCIS (Netherlands)

    Duifhuis, Hendrikus; Horst, Johannes; van Dijk, Pim; van Netten, Sietse

    1993-01-01

    The last decade revealed to auditory researchers that hair cells can not only detect and process mechanical energy, but are also able to produce it. Thanks to the active hair cell, ears can produce otoacoustic emissions. This book gives the newest insights into the biophysics and physiology of

  17. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Lazzari, Maurizio, E-mail: maurizio.lazzari@unibo.it; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-02-15

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L{sup −1}. Densitometric values of cONS, immunostained with anti-G {sub αolf}, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G {sub

  18. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    International Nuclear Information System (INIS)

    Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-01-01

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L"−"1. Densitometric values of cONS, immunostained with anti-G _α_o_l_f, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G _

  19. Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.

    Science.gov (United States)

    Diensthuber, Marc; Oshima, Kazuo; Heller, Stefan

    2009-06-01

    Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent

  20. Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

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    Sandeep Gupta

    2018-02-01

    Full Text Available Summary: Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC- or induced pluripotent stem cell (hiPSC-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs, which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. : In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol. Keywords: spinal cord, neurons, sensory interneurons, proprioception, mechanosensation, human embryonic stem cells, induced pluripotent stem cells, directed differentiation, primate spinal cord, mouse spinal cord

  1. Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-01-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007

  2. Think like a sponge: The genetic signal of sensory cells in sponges.

    Science.gov (United States)

    Mah, Jasmine L; Leys, Sally P

    2017-11-01

    A complex genetic repertoire underlies the apparently simple body plan of sponges. Among the genes present in poriferans are those fundamental to the sensory and nervous systems of other animals. Sponges are dynamic and sensitive animals and it is intuitive to link these genes to behaviour. The proposal that ctenophores are the earliest diverging metazoan has led to the question of whether sponges possess a 'pre-nervous' system or have undergone nervous system loss. Both lines of thought generally assume that the last common ancestor of sponges and eumetazoans possessed the genetic modules that underlie sensory abilities. By corollary extant sponges may possess a sensory cell homologous to one present in the last common ancestor, a hypothesis that has been studied by gene expression. We have performed a meta-analysis of all gene expression studies published to date to explore whether gene expression is indicative of a feature's sensory function. In sponges we find that eumetazoan sensory-neural markers are not particularly expressed in structures with known sensory functions. Instead it is common for these genes to be expressed in cells with no known or uncharacterized sensory function. Indeed, many sensory-neural markers so far studied are expressed during development, perhaps because many are transcription factors. This suggests that the genetic signal of a sponge sensory cell is dissimilar enough to be unrecognizable when compared to a bilaterian sensory or neural cell. It is possible that sensory-neural markers have as yet unknown functions in sponge cells, such as assembling an immunological synapse in the larval globular cell. Furthermore, the expression of sensory-neural markers in non-sensory cells, such as adult and larval epithelial cells, suggest that these cells may have uncharacterized sensory functions. While this does not rule out the co-option of ancestral sensory modules in later evolving groups, a distinct genetic foundation may underlie the

  3. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Science.gov (United States)

    Kupari, Jussi; Airaksinen, Matti S

    2014-01-01

    Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  4. Cell-cell junctions: a target of acoustic overstimulation in the sensory epithelium of the cochlea

    Directory of Open Access Journals (Sweden)

    Zheng Guiliang

    2012-06-01

    Full Text Available Abstract Background Exposure to intense noise causes the excessive movement of the organ of Corti, stretching the organ and compromising sensory cell functions. We recently revealed changes in the transcriptional expression of multiple adhesion-related genes during the acute phases of cochlear damage, suggesting that the disruption of cell-cell junctions is an early event in the process of cochlear pathogenesis. However, the functional state of cell junctions in the sensory epithelium is not clear. Here, we employed graded dextran-FITC, a macromolecule tracer that is impermeable to the organ of Corti under physiological conditions, to evaluate the barrier function of cell junctions in normal and noise-traumatized cochlear sensory epithelia. Results Exposure to an impulse noise of 155 dB (peak sound pressure level caused a site-specific disruption in the intercellular junctions within the sensory epithelium of the chinchilla cochlea. The most vulnerable sites were the junctions among the Hensen cells and between the Hensen and Deiters cells within the outer zone of the sensory epithelium. The junction clefts that formed in the reticular lamina were permeable to 40 and 500 but not 2,000 kDa dextran-FITC macromolecules. Moreover, this study showed that the interruption of junction integrity occurred in the reticular lamina and also in the basilar membrane, a site that had been considered to be resistant to acoustic injury. Finally, our study revealed a general spatial correlation between the site of sensory cell damage and the site of junction disruption. However, the two events lacked a strict one-to-one correlation, suggesting that the disruption of cell-cell junctions is a contributing, but not the sole, factor for initiating acute sensory cell death. Conclusions Impulse noise causes the functional disruption of intercellular junctions in the sensory epithelium of the chinchilla cochlea. This disruption occurs at an early phase of cochlear

  5. Ongoing cell death and immune influences on regeneration in the vestibular sensory organs

    Science.gov (United States)

    Warchol, M. E.; Matsui, J. I.; Simkus, E. L.; Ogilive, J. M.

    2001-01-01

    Hair cells in the vestibular organs of birds have a relatively short life span. Mature hair cells appear to die spontaneously and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. A similar regenerative mechanism also results in hair cell replacement after ototoxic damage. The cellular basis of hair cell turnover in the avian ear is not understood. We are investigating the signaling pathways that lead to hair cell death and the relationship between ongoing cell death and cell production. In addition, work from our lab and others has demonstrated that the avian inner ear contains a resident population of macrophages and that enhanced numbers of macrophages are recruited to sites of hair cells lesions. Those observations suggest that macrophages and their secretory products (cytokines) may be involved in hair cell regeneration. Consistent with that suggestion, we have found that treatment with the anti-inflammatory drug dexamethasone reduces regenerative cell proliferation in the avian ear, and that certain macrophage-secreted cytokines can influence the proliferation of vestibular supporting cells and the survival of statoacoustic neurons. Those results suggest a role for the immune system in the process of sensory regeneration in the inner ear.

  6. Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

    Science.gov (United States)

    Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Mugnaini, Enrico; Bartles, James R.

    2008-01-01

    The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca2+. In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. PMID:16909209

  7. Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

    Science.gov (United States)

    Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

    2015-12-01

    The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. © The Author 2015. Published by Oxford

  8. Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

    Science.gov (United States)

    Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

    2016-10-01

    Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

  9. Generation of Otic Sensory Neurons from Mouse Embryonic Stem Cells in 3D Culture

    Directory of Open Access Journals (Sweden)

    Michael Perny

    2017-12-01

    Full Text Available The peripheral hearing process taking place in the cochlea mainly depends on two distinct sensory cell types: the mechanosensitive hair cells and the spiral ganglion neurons (SGNs. The first respond to the mechanical stimulation exerted by sound pressure waves on their hair bundles by releasing neurotransmitters and thereby activating the latter. Loss of these sensorineural cells is associated with permanent hearing loss. Stem cell-based approaches aiming at cell replacement or in vitro drug testing to identify potential ototoxic, otoprotective, or regenerative compounds have lately gained attention as putative therapeutic strategies for hearing loss. Nevertheless, they rely on efficient and reliable protocols for the in vitro generation of cochlear sensory cells for their implementation. To this end, we have developed a differentiation protocol based on organoid culture systems, which mimics the most important steps of in vivo otic development, robustly guiding mouse embryonic stem cells (mESCs toward otic sensory neurons (OSNs. The stepwise differentiation of mESCs toward ectoderm was initiated using a quick aggregation method in presence of Matrigel in serum-free conditions. Non-neural ectoderm was induced via activation of bone morphogenetic protein (BMP signaling and concomitant inhibition of transforming growth factor beta (TGFβ signaling to prevent mesendoderm induction. Preplacodal and otic placode ectoderm was further induced by inhibition of BMP signaling and addition of fibroblast growth factor 2 (FGF2. Delamination and differentiation of SGNs was initiated by plating of the organoids on a 2D Matrigel-coated substrate. Supplementation with brain-derived neurotrophic factor (BDNF and neurotrophin-3 (NT-3 was used for further maturation until 15 days of in vitro differentiation. A large population of neurons with a clear bipolar morphology and functional excitability was derived from these cultures. Immunostaining and gene expression

  10. Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

    Directory of Open Access Journals (Sweden)

    Mauricio A. Retamal

    2017-11-01

    Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

  11. CD8 T Cell Sensory Adaptation Dependent on TCR Avidity for Self-Antigens

    DEFF Research Database (Denmark)

    Marquez, M.-E.; Ellmeier, W.; Sanchez-Guajardo, Vanesa Maria

    2005-01-01

    dephosphorylation of linker for activation of T cells and ERK upon activation. Normal TCR levels and cytokine production were restored by culturing cells in the absence of TCR/spMHC interaction, demonstrating dynamic tuning of peripheral T cell responses. The effect of avidity for self-ligand(s) on this sensory...... ZAP-YEEI cells were enhanced. Our data provide support for central and peripheral sensory T cell adaptation induced as a function of TCR avidity for self-ligands and signaling level. This may contribute to buffer excessive autoreactivity while optimizing TCR repertoire usage....

  12. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    Science.gov (United States)

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-03

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Cell density and N-cadherin interactions regulate cell proliferation in the sensory epithelia of the inner ear.

    Science.gov (United States)

    Warchol, Mark E

    2002-04-01

    Sensory hair cells in the inner ears of nonmammalian vertebrates can regenerate after injury. In many species, replacement hair cells are produced by the proliferation of epithelial supporting cells. Thus, the ability of supporting cells to undergo renewed proliferation is a key determinant of regenerative ability. The present study used cultures of isolated inner ear sensory epithelia to identify cellular signals that regulate supporting cell proliferation. Small pieces of sensory epithelia from the chicken utricle were cultured in glass microwells. Under those conditions, cell proliferation was inversely related to local cell density. The signaling molecules N-cadherin, beta-catenin, and focal adhesion kinase were immunolocalized in the cultured epithelial cells, and high levels of phosphotyrosine immunoreactivity were present at cell-cell junctions and focal contacts of proliferating cells. Binding of microbeads coated with a function-blocking antibody to N-cadherin inhibited ongoing proliferation. The growth of epithelial cells was also affected by the density of extracellular matrix molecules. The results suggest that cell density, cell-cell contact, and the composition of the extracellular matrix may be critical influences on the regulation of sensory regeneration in the inner ear.

  14. Chapter 22. Cell population kinetics

    International Nuclear Information System (INIS)

    Tubiana, M.

    1975-01-01

    The main contribution of radioisotopes to the development of a new discipline, cell population kinetics, was shown. The aim of this science is to establish, for each tissue of the organism, the life span of its component cells and the mechanisms governing its growth, its differentiation and its homeostasis with respect to outside attacks. Labelling techniques have been used to follow the cells during these various processes. The case of non-dividing cells was considered first, taking as example, the red blood cells of which the lifetime was studied, after which the case of proliferating cells was examined using 14 C- or tritium-labelled thymidine. The methods used to measure the cell cycle parameters were described: labelled-mitosis curve method, double-labelling and continuous labelling methods, proliferation coefficient measurement. Cell kinetics were shown to allow an interpretation of radiobiological data. Finally the practical value of cell kinetics research was shown [fr

  15. Respiration Gates Sensory Input Responses in the Mitral Cell Layer of the Olfactory Bulb

    Science.gov (United States)

    Short, Shaina M.; Morse, Thomas M.; McTavish, Thomas S.; Shepherd, Gordon M.; Verhagen, Justus V.

    2016-01-01

    Respiration plays an essential role in odor processing. Even in the absence of odors, oscillating excitatory and inhibitory activity in the olfactory bulb synchronizes with respiration, commonly resulting in a burst of action potentials in mammalian mitral/tufted cells (MTCs) during the transition from inhalation to exhalation. This excitation is followed by inhibition that quiets MTC activity in both the glomerular and granule cell layers. Odor processing is hypothesized to be modulated by and may even rely on respiration-mediated activity, yet exactly how respiration influences sensory processing by MTCs is still not well understood. By using optogenetics to stimulate discrete sensory inputs in vivo, it was possible to temporally vary the stimulus to occur at unique phases of each respiration. Single unit recordings obtained from the mitral cell layer were used to map spatiotemporal patterns of glomerular evoked responses that were unique to stimulations occurring during periods of inhalation or exhalation. Sensory evoked activity in MTCs was gated to periods outside phasic respiratory mediated firing, causing net shifts in MTC activity across the cycle. In contrast, odor evoked inhibitory responses appear to be permitted throughout the respiratory cycle. Computational models were used to further explore mechanisms of inhibition that can be activated by respiratory activity and influence MTC responses. In silico results indicate that both periglomerular and granule cell inhibition can be activated by respiration to internally gate sensory responses in the olfactory bulb. Both the respiration rate and strength of lateral connectivity influenced inhibitory mechanisms that gate sensory evoked responses. PMID:28005923

  16. Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

    Science.gov (United States)

    Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

    2016-03-01

    Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.

    Directory of Open Access Journals (Sweden)

    Stephen D Freeman

    Full Text Available During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner.

  18. Dynamic properties of sensory stimulation evoked responses in mouse cerebellar granule cell layer and molecular layer.

    Science.gov (United States)

    Bing, Yan-Hua; Zhang, Guang-Jian; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-01-12

    Sensory information coming from climbing fiber and mossy fiber-granule cell pathways, generates motor-related outputs according to internal rules of integration and computation in the cerebellar cortex. However, the dynamic properties of sensory information processing in mouse cerebellar cortex are less understood. Here, we studied the dynamic properties of sensory stimulation-evoked responses in the cerebellar granule cell layer (GCL) and molecular layer (ML) by electrophysiological recordings method. Our data showed that air-puff stimulation (5-10 ms in duration) of the ipsilateral whisker pad evoked single-peak responses in the GCL and ML; whereas a duration of stimulation ≥30 ms in GCL and ≥60 ms in ML, evoked double-peak responses that corresponded with stimulation-on and -off responses via mossy fiber pathway. The highest frequency of stimulation train for evoking GCL responses was 33 Hz. In contrast, the highest frequency of stimulation train for evoking ML responses was 4 Hz. These results indicate that the cerebellar granule cells transfer the high-fidelity sensory information from mossy fibers, which is cut-off by molecular layer interneurons (MLIs). Our results suggest that the MLIs network acts as a low-pass filter during the processing of high-frequency sensory information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  1. Effect of gabazine on sensory stimulation train evoked response in mouse cerebellar Purkinje cells.

    Science.gov (United States)

    Bing, Yan-Hua; Jin, Wen-Zhe; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-02-01

    Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber and mossy fiber-granule cell pathways, and generate motor-related outputs according to internal rules of integration and computation. However, the dynamic properties of sensory information processed by PC in mouse cerebellar cortex are currently unclear. In the present study, we examined the effects of the gamma-aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation train on the simple spike firing of PCs by electrophysiological recordings method. Our data showed that the output of cerebellar PCs could be significantly affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation train, but only by the 1st and 2nd pulses of the high-frequency (≥ 4 Hz) sensory stimulation train. In the presence of gabazine (20 μM), each pulse of 1 Hz facial stimulation evoked simple spike firing in the PCs, but only the 1st and 2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the PCs. These results indicated that GABAA receptor-mediated inhibition did not significantly affect the frequency properties of sensory stimulation evoked responses in the mouse cerebellar PCs.

  2. Differential and Cooperative Cell Adhesion Regulates Cellular Pattern in Sensory Epithelia.

    Science.gov (United States)

    Togashi, Hideru

    2016-01-01

    Animal tissues are composed of multiple cell types arranged in complex and elaborate patterns. In sensory epithelia, including the auditory epithelium and olfactory epithelium, different types of cells are arranged in unique mosaic patterns. These mosaic patterns are evolutionarily conserved, and are thought to be important for hearing and olfaction. Recent progress has provided accumulating evidence that the cellular pattern formation in epithelia involves cell rearrangements, movements, and shape changes. These morphogenetic processes are largely mediated by intercellular adhesion systems. Differential adhesion and cortical tension have been proposed to promote cell rearrangements. Many different types of cells in tissues express various types of cell adhesion molecules. Although cooperative mechanisms between multiple adhesive systems are likely to contribute to the production of complex cell patterns, our current understanding of the cooperative roles between multiple adhesion systems is insufficient to entirely explain the complex mechanisms underlying cellular patterning. Recent studies have revealed that nectins, in cooperation with cadherins, are crucial for the mosaic cellular patterning in sensory organs. The nectin and cadherin systems are interacted with one another, and these interactions provide cells with differential adhesive affinities for complex cellular pattern formations in sensory epithelia, which cannot be achieved by a single mechanism.

  3. Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.

    Science.gov (United States)

    Slattery, Eric L; Speck, Judith D; Warchol, Mark E

    2009-09-01

    The sensory hair cells of the cochlea and vestibular organs are essential for normal hearing and balance function. The mammalian ear possesses a very limited ability to regenerate hair cells and their loss can lead to permanent sensory impairment. In contrast, hair cells in the avian ear are quickly regenerated after acoustic trauma or ototoxic injury. The very different regenerative abilities of the avian vs. mammalian ear can be attributed to differences in injury-evoked expression of genes that either promote or inhibit the production of new hair cells. Gene expression is regulated both by the binding of cis-regulatory molecules to promoter regions as well as through structural modifications of chromatin (e.g., methylation and acetylation). This study examined effects of histone deacetylases (HDACs), whose main function is to modify histone acetylation, on the regulation of regenerative proliferation in the chick utricle. Cultures of regenerating utricles and dissociated cells from the utricular sensory epithelia were treated with the HDAC inhibitors valproic acid, trichostatin A, sodium butyrate, and MS-275. All of these molecules prevent the enzymatic removal of acetyl groups from histones, thus maintaining nuclear chromatin in a "relaxed" (open) configuration. Treatment with all inhibitors resulted in comparable decreases in supporting cell proliferation. We also observed that treatment with the HDAC1-, 2-, and 3-specific inhibitor MS-275 was sufficient to reduce proliferation and that two class I HDACs--HDAC1 and HDAC2--were expressed in the sensory epithelium of the utricle. These results suggest that inhibition of specific type I HDACs is sufficient to prevent cell cycle entry in supporting cells. Notably, treatment with HDAC inhibitors did not affect the differentiation of replacement hair cells. We conclude that histone deacetylation is a positive regulator of regenerative proliferation but is not critical for avian hair cell differentiation.

  4. Mitochondrial peroxiredoxin 3 regulates sensory cell survival in the cochlea.

    Directory of Open Access Journals (Sweden)

    Fu-Quan Chen

    Full Text Available This study delineates the role of peroxiredoxin 3 (Prx3 in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age. In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss.

  5. Population dynamics in vasopressin cells.

    Science.gov (United States)

    Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

    2008-01-01

    Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

  6. Effects of gamma-irradiation before and after cooking on bacterial population and sensory quality of Dakgalbi

    International Nuclear Information System (INIS)

    Yoon, Young Min; Park, Jong-Heum; Lee, Ji-Hye; Park, Jae-Nam; Park, Jin-Kyu; Sung, Nak-Yun; Song, Beom-Seok; Kim, Jae-Hun; Yoon, Yohan; Gao, Meixu; Yook, Hong-Sun; Lee, Ju-Woon

    2012-01-01

    The purpose of this study was to compare the effect of gamma irradiation on the total bacterial population and the sensory quality of Dakgalbi irradiated before and after cooking. Fresh chicken meat was cut into small pieces and used to prepare Dakgalbi. For the preparation of Dakgalbi cooked with gamma-irradiated chicken meat and sauce (IBC), raw chicken meat and Dakgalbi sauce were irradiated and then stir-fried. For the preparation of Dakgalbi irradiated after cooking with raw chicken meat and sauce (IAC), raw chicken meat and Dakgalbi sauce were first cooked and subsequently irradiated. Under the accelerated storage condition of 35 °C for 7 days, bacteria in IBC were below the detection limit (1 log CFU/g) on day 1 but were detected on day 2 and gradually increased hereafter. In IAC, on the other hand, bacteria were not detected at all. Evaluation of sensory quality also decreased on both samples. However, IAC showed a better trend. Our results indicate that IAC protocol was a more effective method for reducing bacterial growth in Dakgalbi. - Highlights: ► We compared the microbial safety and sensory property of Dakgalbi irradiated before and after cooking. ► Dakgalbi irradiated after cooking can be more effective processing method on microbial safety. ► Sensory property decreased on both Dakgalbis by irradiation-induced off-flavor. ► Dakgalbi irradiated after cooking showed a better tendency on the sensory evaluation.

  7. Cutaneous TRPM8-expressing sensory afferents are a small population of neurons with unique firing properties.

    Science.gov (United States)

    Jankowski, Michael P; Rau, Kristofer K; Koerber, H Richard

    2017-04-01

    It has been well documented that the transient receptor potential melastatin 8 (TRPM8) receptor is involved in environmental cold detection. The role that this receptor plays in nociception however, has been somewhat controversial since conflicting reports have shown different neurochemical identities and responsiveness of TRPM8 neurons. In order to functionally characterize cutaneous TRMP8 fibers, we used two ex vivo somatosensory recording preparations to functionally characterize TRPM8 neurons that innervate the hairy skin in mice genetically engineered to express GFP from the TRPM8 locus. We found several types of cold-sensitive neurons that innervate the hairy skin of the mouse but the TRPM8-expressing neurons were found to be of two specific populations that responded with rapid firing to cool temperatures. The first group was mechanically insensitive but the other did respond to high threshold mechanical deformation of the skin. None of these fibers were found to contain calcitonin gene-related peptide, transient receptor potential vanilloid type 1 or bind isolectin B4. These results taken together with other reports suggest that TRPM8 containing sensory neurons are environmental cooling detectors that may be nociceptive or non-nociceptive depending on the sensitivity of individual fibers to different combinations of stimulus modalities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

    Science.gov (United States)

    Tremblay, Marie-Ève; Zettel, Martha L.; Ison, James R.; Allen, Paul D.; Majewska, Ania K.

    2011-01-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. PMID:22223464

  9. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    Science.gov (United States)

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Involvement of p53 and Bcl-2 in sensory cell degeneration in aging rat cochleae.

    Science.gov (United States)

    Xu, Yang; Yang, Wei Ping; Hu, Bo Hua; Yang, Shiming; Henderson, Donald

    2017-06-01

    p53 and Bcl-2 (B-cell lymphoma 2) are involved in the process of sensory cell degeneration in aging cochleae. To determine molecular players in age-related hair cell degeneration, this study examined the changes in p53 and Bcl-2 expression at different stages of apoptotic and necrotic death of hair cells in aging rat cochleae. Young (3-4 months) and aging (23-24 months) Fisher 344/NHsd rats were used. The thresholds of the auditory brainstem response (ABR) were measured to determine the auditory function. Immunolabeling was performed to determine the expression of p53 and Bcl-2 proteins in the sensory epithelium. Propidium iodide staining was performed to determine the morphologic changes in hair cell nuclei. Aging rats exhibited a significant elevation in ABR thresholds at all tested frequencies (p aging hair cells showing the early signs of apoptotic changes in their nuclei. The Bcl-2 expression increase was also observed in hair cells displaying early signs of necrosis. As the hair cell degenerative process advanced, p53 and Bcl-2 immunoreactivity became reduced or absent. In the areas where no detectable nuclear staining was present, p53 and Bcl-2 immunoreactivity was absent.

  11. Cortically-controlled population stochastic facilitation as a plausible substrate for guiding sensory transfer across the thalamic gateway.

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    Sébastien Béhuret

    Full Text Available The thalamus is the primary gateway that relays sensory information to the cerebral cortex. While a single recipient cortical cell receives the convergence of many principal relay cells of the thalamus, each thalamic cell in turn integrates a dense and distributed synaptic feedback from the cortex. During sensory processing, the influence of this functional loop remains largely ignored. Using dynamic-clamp techniques in thalamic slices in vitro, we combined theoretical and experimental approaches to implement a realistic hybrid retino-thalamo-cortical pathway mixing biological cells and simulated circuits. The synaptic bombardment of cortical origin was mimicked through the injection of a stochastic mixture of excitatory and inhibitory conductances, resulting in a gradable correlation level of afferent activity shared by thalamic cells. The study of the impact of the simulated cortical input on the global retinocortical signal transfer efficiency revealed a novel control mechanism resulting from the collective resonance of all thalamic relay neurons. We show here that the transfer efficiency of sensory input transmission depends on three key features: i the number of thalamocortical cells involved in the many-to-one convergence from thalamus to cortex, ii the statistics of the corticothalamic synaptic bombardment and iii the level of correlation imposed between converging thalamic relay cells. In particular, our results demonstrate counterintuitively that the retinocortical signal transfer efficiency increases when the level of correlation across thalamic cells decreases. This suggests that the transfer efficiency of relay cells could be selectively amplified when they become simultaneously desynchronized by the cortical feedback. When applied to the intact brain, this network regulation mechanism could direct an attentional focus to specific thalamic subassemblies and select the appropriate input lines to the cortex according to the descending

  12. Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons.

    Science.gov (United States)

    Hussar, Cory R; Pasternak, Tatiana

    2012-02-22

    Comparing two stimuli that occur at different times demands the coordination of bottom-up and top-down processes. It has been hypothesized that the dorsolateral prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays a key role in such tasks, contributing to both maintenance and sensory comparisons. We examined this hypothesis by recording from the PFC of monkeys comparing directions of two moving stimuli, S1 and S2, separated by a memory delay. We determined the contribution of the two principal cell types to these processes by classifying neurons into broad-spiking (BS) putative pyramidal cells and narrow-spiking (NS) putative local interneurons. During the delay, BS cells were more likely to exhibit anticipatory modulation and represent the remembered direction. While this representation was transient, appearing at different times in different neurons, it weakened when direction was not task relevant, suggesting its utility. During S2, both putative cell types showed comparison-related activity modulations. These modulations were of two types, each carried by different neurons, which either preferred trials with stimuli moving in the same direction or trials with stimuli of different directions. These comparison effects were strongly correlated with choice, suggesting their role in circuitry underlying decision making. These results provide the first demonstration of distinct contributions made by principal cell types to memory-guided perceptual decisions. During sensory stimulation both cell types represent behaviorally relevant stimulus features contributing to comparison and decision-related activity. However in the absence of sensory stimulation, putative pyramidal cells dominated, carrying information about the elapsed time and the preceding direction.

  13. Directional cell movements downstream of Gbx2 and Otx2 control the assembly of sensory placodes

    Directory of Open Access Journals (Sweden)

    Ben Steventon

    2016-11-01

    Full Text Available Cranial placodes contribute to sensory structures including the inner ear, the lens and olfactory epithelium and the neurons of the cranial sensory ganglia. At neurula stages, placode precursors are interspersed in the ectoderm surrounding the anterior neural plate before segregating into distinct placodes by as yet unknown mechanisms. Here, we perform live imaging to follow placode progenitors as they aggregate to form the lens and otic placodes. We find that while placode progenitors move with the same speed as their non-placodal neighbours, they exhibit increased persistence and directionality and these properties are required to assemble morphological placodes. Furthermore, we demonstrate that these factors are components of the transcriptional networks that coordinate placode cell behaviour including their directional movements. Together with previous work, our results support a dual role for Otx and Gbx transcription factors in both the early patterning of the neural plate border and the later segregation of its derivatives into distinct placodes.

  14. GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz; Radomska, Katarzyna J

    2015-01-01

    throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures...... to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.......The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression...

  15. Assessment of the sensory and physical limitations imposed by leprosy in a Brazilian Amazon Population

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    Cintia Yolette Urbano Pauxis Aben-Athar

    Full Text Available Abstract INTRODUCTION Leprosy often results in sensory and physical limitations. This study aimed to evaluate these limitations using a quantitative approach in leprosy patients in Belém (Pará, Brazil. METHODS This epidemiological, cross-sectional study measured the sensory impairment of smell and taste through the use of a questionnaire and evaluated activity limitations of daily life imposed by leprosy through the Screening of Activity Limitation and Safety Awareness (SALSA Scale. Data were collected from 84 patients and associations between the degree of disability and clinical and epidemiological characteristics were assessed. RESULTS The majority of patients were men (64.3%, married (52.4%, age 31-40 years old (26.2%, had primary education (50%, and were independent laborers (36.9%. The multibacillary operational classification (81%, borderline clinical form (57.1%, and 0 degrees of physical disability (41.7% were predominant. SALSA scores ranged from 17 to 59 points, and being without limitations was predominant (53.6%. The risk awareness score ranged from 0 to 8, with a score of 0 (no awareness of risk being the most common (56%. Evaluation of smell and taste sensory sensitivities revealed that 70.2% did not experience these sensory changes. Patients with leprosy reactions were 7 times more likely to develop activity limitations, and those who had physical disabilities were approximately four times more likely to develop a clinical picture of activity limitations. CONCLUSIONS Most patients showed no sensory changes, but patients with leprosy reactions were significantly more likely to develop activity limitations. Finally, further studies should be performed, assessing a higher number of patients to confirm the present results.

  16. Synaptic communication and signal processing among sensory cells in taste buds.

    Science.gov (United States)

    Chaudhari, Nirupa

    2014-08-15

    Taste buds (sensory structures embedded in oral epithelium) show a remarkable diversity of transmitters synthesized and secreted locally. The known transmitters accumulate in a cell type selective manner, with 5-HT and noradrenaline being limited to presynaptic cells, GABA being synthesized in both presynaptic and glial-like cells, and acetylcholine and ATP used for signalling by receptor cells. Each of these transmitters participates in local negative or positive feedback circuits that target particular cell types. Overall, the role of ATP is the best elucidated. ATP serves as a principal afferent transmitter, and also is the key trigger for autocrine positive feedback and paracrine circuits that result in potentiation (via adenosine) or inhibition (via GABA or 5-HT). While many of the cellular receptors and mechanisms for these circuits are known, their impact on sensory detection and perception remains to be elaborated in most instances. This brief review examines what is known, and some of the open questions and controversies surrounding the transmitters and circuits of the taste periphery. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  17. Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

    Science.gov (United States)

    Kobayashi, Kyogo; Nakano, Shunji; Amano, Mutsuki; Tsuboi, Daisuke; Nishioka, Tomoki; Ikeda, Shingo; Yokoyama, Genta; Kaibuchi, Kozo; Mori, Ikue

    2016-01-05

    Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Incidence, risk, and associated factors of depression in adults with physical and sensory disabilities: A nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Szu-Ching Shen

    Full Text Available Physical disability has been associated with the risk of depression. We examined the incidence, risk, and associated factors of depression in Taiwanese adults with physical/sensory disabilities.Two national databases were used to retrospectively analyze 749,491 ≥20-year-old Taiwanese with physical/sensory disabilities in 2002-2008. The incidence of depression was analyzed by univariate Poisson regression. Risk factors of depression were followed up through 2014 and examined with a Cox proportional hazards model.Among the study subjects, the incidence of depression was 6.29 per 1000 person-years, with 1.83 per 1000 person-years corresponding to major depression. The subjects' depression risk was affected by disability type, disability severity, gender, age, education, marital status, aboriginal status, monthly salary, residence urbanization level, and Charlson comorbidity index (CCI. Subjects with rare diseases, mild disability, female gender, age 35-44 years, a high school education level, divorced/widowed status, non-aboriginal status, a NT$22,801-28,800 monthly salary, a highly urbanized residence area, or a CCI≥3 were at higher risk for depression.Adults with physical/sensory disabilities have a 3.7-fold higher incidence of depression than the general population. Social services departments and family members should take extra measures toward preventing and treating depression in this subpopulation.

  19. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  20. Diversity in cell motility reveals the dynamic nature of the formation of zebrafish taste sensory organs.

    Science.gov (United States)

    Soulika, Marina; Kaushik, Anna-Lila; Mathieu, Benjamin; Lourenço, Raquel; Komisarczuk, Anna Z; Romano, Sebastian Alejo; Jouary, Adrien; Lardennois, Alicia; Tissot, Nicolas; Okada, Shinji; Abe, Keiko; Becker, Thomas S; Kapsimali, Marika

    2016-06-01

    Taste buds are sensory organs in jawed vertebrates, composed of distinct cell types that detect and transduce specific taste qualities. Taste bud cells differentiate from oropharyngeal epithelial progenitors, which are localized mainly in proximity to the forming organs. Despite recent progress in elucidating the molecular interactions required for taste bud cell development and function, the cell behavior underlying the organ assembly is poorly defined. Here, we used time-lapse imaging to observe the formation of taste buds in live zebrafish larvae. We found that tg(fgf8a.dr17)-expressing cells form taste buds and get rearranged within the forming organs. In addition, differentiating cells move from the epithelium to the forming organs and can be displaced between developing organs. During organ formation, tg(fgf8a.dr17) and type II taste bud cells are displaced in random, directed or confined mode relative to the taste bud they join or by which they are maintained. Finally, ascl1a activity in the 5-HT/type III cell is required to direct and maintain tg(fgf8a.dr17)-expressing cells into the taste bud. We propose that diversity in displacement modes of differentiating cells acts as a key mechanism for the highly dynamic process of taste bud assembly. © 2016. Published by The Company of Biologists Ltd.

  1. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    Science.gov (United States)

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  2. Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus

    Directory of Open Access Journals (Sweden)

    Andrea eBader

    2012-11-01

    Full Text Available Olfactory sensory neurons which express a member from the OR37 subfamily of odorant receptor genes are wired to the main olfactory bulb in a unique monoglomerular fashion; from these glomeruli an untypical connectivity into higher brain centers exists. In the present study we have investigated by DiI and transsynaptic tracing approaches how the connection pattern from these glomeruli into distinct hypothalamic nuclei is organized. The application of DiI onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in the labeling of fibers within the paraventricular and supraoptic nucleus of the hypothalamus; some of these fibers were covered with varicose-like structures. No DiI-labeled cell somata were detectable in these nuclei. The data indicate that projection neurons which originate in the OR37 region of the main olfactory bulb form direct connections into these nuclei. The cells that were labeled by the transsynaptic tracer WGA in these nuclei were further characterized. Their distribution pattern in the paraventricular nucleus was reminiscent of cells which produce distinct neuropeptides. Double labeling experiments confirmed that they contained vasopressin, but not the related neuropeptide oxytocin. Morphological analysis revealed that they comprise of magno- and parvocellular cells. A comparative investigation of the WGA-positive cells in the supraoptic nucleus demonstrated that these were vasopressin-positive, as well, whereas oxytocin-producing cells of this nucleus also contained no transsynaptic tracer. Together, the data demonstrate a connectivity from OR37 expressing sensory neurons to distinct hypothalamic neurons with the same neuropeptide content.

  3. Natural bizbenzoquinoline derivatives protect zebrafish lateral line sensory hair cells from aminoglycoside toxicity

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    Matthew eKruger

    2016-03-01

    Full Text Available Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.

  4. Sensory feedback, error correction, and remapping in a multiple oscillator model of place cell activity

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    Joseph D. Monaco

    2011-09-01

    Full Text Available Mammals navigate by integrating self-motion signals (‘path integration’ and occasionally fixing on familiar environmental landmarks. The rat hippocampus is a model system of spatial representation in which place cells are thought to integrate both sensory and spatial information from entorhinal cortex. The localized firing fields of hippocampal place cells and entorhinal grid cells demonstrate a phase relationship with the local theta (6–10 Hz rhythm that may be a temporal signature of path integration. However, encoding self-motion in the phase of theta oscillations requires high temporal precision and is susceptible to idiothetic noise, neuronal variability, and a changing environment. We present a model based on oscillatory interference theory, previously studied in the context of grid cells, in which transient temporal synchronization among a pool of path-integrating theta oscillators produces hippocampal-like place fields. We hypothesize that a spatiotemporally extended sensory interaction with external cues modulates feedback to the theta oscillators. We implement a form of this cue-driven feedback and show that it can retrieve fixed points in the phase code of position. A single cue can smoothly reset oscillator phases to correct for both systematic errors and continuous noise in path integration. Further, simulations in which local and global cues are rotated against each other reveal a phase-code mechanism in which conflicting cue arrangements can reproduce experimentally observed distributions of ‘partial remapping’ responses. This abstract model demonstrates that phase-code feedback can provide stability to the temporal coding of position during navigation and may contribute to the context-dependence of hippocampal spatial representations. While the anatomical substrates of these processes have not been fully characterized, our findings suggest several signatures that can be evaluated in future experiments.

  5. Effects of gamma-irradiation before and after cooking on bacterial population and sensory quality of Dakgalbi

    Science.gov (United States)

    Yoon, Young Min; Park, Jong-Heum; Lee, Ji-Hye; Park, Jae-Nam; Park, Jin-Kyu; Sung, Nak-Yun; Song, Beom-Seok; Kim, Jae-Hun; Yoon, Yohan; Gao, Meixu; Yook, Hong-Sun; Lee, Ju-Woon

    2012-08-01

    The purpose of this study was to compare the effect of gamma irradiation on the total bacterial population and the sensory quality of Dakgalbi irradiated before and after cooking. Fresh chicken meat was cut into small pieces and used to prepare Dakgalbi. For the preparation of Dakgalbi cooked with gamma-irradiated chicken meat and sauce (IBC), raw chicken meat and Dakgalbi sauce were irradiated and then stir-fried. For the preparation of Dakgalbi irradiated after cooking with raw chicken meat and sauce (IAC), raw chicken meat and Dakgalbi sauce were first cooked and subsequently irradiated. Under the accelerated storage condition of 35 °C for 7 days, bacteria in IBC were below the detection limit (1 log CFU/g) on day 1 but were detected on day 2 and gradually increased hereafter. In IAC, on the other hand, bacteria were not detected at all. Evaluation of sensory quality also decreased on both samples. However, IAC showed a better trend. Our results indicate that IAC protocol was a more effective method for reducing bacterial growth in Dakgalbi.

  6. Sensory evaluation of a highly nutritive bread, formulated for populations suffering food emergencies, preserved with ionizing radiation

    International Nuclear Information System (INIS)

    Gonzalez, G.S.; Gómez, B.; Cova, M.C.; Narvaiz, Patricia

    2011-01-01

    The aim of this work was to evaluate with sensorial analysis, the feasibility of extending the shelf life at room temperature of highly nutritive bread, specially formulated for people suffering alimentary emergencies such as floods, earthquakes, geographical isolation or malnourishment, by means of ionizing radiation. The shelf life of any bread is limited by microbial growth, so the food industry uses chemicals and /or refrigeration to control it. Twenty one breads were formulated and manufactured employing wheat and soybean flours, dehydrated whey, skim milk and egg, vegetal oil, water, and some commercial food additives as emulsifiers and water retention substances. A final formulation was chosen by means of a preliminary sensory evaluation. Bibliographic estimations were made on its nutritional quality as compared to that of a regular wheat bread; improvements were found on vitamins, minerals, proteins, lipids and fibre. Forty 450 g breads were manufactured, oven cooked at 220°C for 20 minutes, packaged with polyethylene film, 100 microns thickness, and irradiated at the semi industrial cobalt-60 facility of the Ezeiza Atomic Centre, about 600,000 Ci of activity, with doses of 0, 6 and 10 kilo Grays, dose rate: 10 kGy/h, dose uniformity: 1.1. Control and irradiated samples were stored at room temperature and relative humidity for 43 days. Sensory analysis was performed with a panel of about 50 consumers on days 3, 29 and 43, evaluating aroma, aspect, colour, flavour, texture and general acceptability with hedonic scores ranging from 1 to 9. No significant differences between control and irradiated samples were found, being the latter afforded scores close to 7 even at the end of the storage period. Control samples had to be discarded on day 6 due to visible mould growth. So this bread formulation, suitable to fulfill most of the nutritional requirements of a population under alimentary emergency, attained at least a 7 fold shelf life increase when treated

  7. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

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    Martin Veronica

    2008-04-01

    Full Text Available Abstract Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the

  8. Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

    Science.gov (United States)

    Smith, Michael E; Monroe, J David

    2016-01-01

    Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

  9. The design, calibration, and use of a water microjet for stimulating hair cell sensory hair bundles.

    Science.gov (United States)

    Saunders, J C; Szymko, Y M

    1989-11-01

    The design, calibration, and use of a noninvasive, noncontact device for stimulating hair cell hair bundles in vitro are described. This device employed a piezoelectric crystal, driven at high frequencies, to generate sinusoidal pressure in a contained fluid volume. The pressure was propagated to the tip of a glass micropipette and the oscillating water jet stimulus produced at the tip was used to stimulate sensory hair bundles. The movements of glass microbeads, caught in the oscillating pressure field of the water jet, provided a means of calibrating this stimulus. The linearity of the jet, its waveform and frequency response, the influence of pipette shape and tip diameter, as well as models to explain the operation of the water jet, are described. The use of this stimulus for measuring hair bundle micromechanics at high frequencies is then demonstrated.

  10. Relationship between Sensory Perception and Frailty in a Community-Dwelling Elderly Population.

    Science.gov (United States)

    Somekawa, S; Mine, T; Ono, K; Hayashi, N; Obuchi, S; Yoshida, H; Kawai, H; Fujiwara, Y; Hirano, H; Kojima, M; Ihara, K; Kim, H

    2017-01-01

    Aging anorexia, defined as loss of appetite and/or reduced food intake, has been postulated as a risk factor for frailty. Impairments of taste and smell perception in elderly people can lead to reduced enjoyment of food and contribute to the anorexia of aging. To evaluate the relationship between frailty and taste and smell perception in elderly people living in urban areas. Data from the baseline evaluation of 768 residents aged ≥ 65 years who enrolled in a comprehensive geriatric health examination survey was analyzed. Fourteen out of 29-items of Appetite, Hunger, Sensory Perception questionnaire (AHSP), frailty, age, sex, BMI, chronic conditions and IADL were evaluated. AHSP was analyzed as the total score of 8 taste items (T) and 6 smell items (S). Frailty was diagnosed using a modified Fried's frailty criteria. The area under the receiver operator curves for detection of frailty demonstrated that T (0.715) had moderate accuracy, but S (0.657) had low accuracy. The cutoffs, sensitivity, specificity and Youden Index (YI) values for each perception were T: Cutoff 26.5 (YI: 0.350, sensitivity: 0.639, specificity: 0.711) and S: Cutoff 18.5 (YI: 0.246, sensitivity: 0.690, specificity: 0.556). Results from multiple logistic regression models, after adjusting for age, sex, IADL and chronic conditions showed that participants under the T cutoff were associated with exhaustion and those below the S cutoff were associated with slow walking speed. The adjusted logistic models for age, sex, IADL and chronic conditions showed significant association between T and frailty (OR 2.81, 95% CI 1.29-6.12), but not between S and frailty (OR 1.73, 95% CI 0.83-3.63). Taste and smell perception, particularly taste perception, were associated with a greater risk of frailty in community-dwelling elderly people. These results suggest that lower taste and smell perception may be an indicator of frailty in old age.

  11. HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

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    Geoffrey C Horwitz

    Full Text Available The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.

  12. Localization of calcium in the sensory cells of the Dionaea trigger hair by laser micro-mass analysis (LAMMA)

    International Nuclear Information System (INIS)

    Buchen, B.; Schröder, W.H.

    1986-01-01

    In Dionaea, mechanical bending of the trigger hair induces action potentials which spread over the trap lobes to the motor cells (review Bentrup 1979). The perception of the stimulus and its transformation into a physiological signal occurs in a ring of specialized epidermal cells in the indentation zone of the trigger hair. These sensory cells (Haberlandt 1906) are characterized by a highly evolved ER complex at the apical and the basal cell pole. The ER surrounds several vacuoles containing poly phenols (Buchen et al. 1983). In order to study the function of these cell structures in sensory transduction, we examined the development of the trigger hair (Casser et al. 1985). During its development, a change in the membrane potential could be measured for the first time when the structural polarity of the sensory cell was established. Yet the short action potentials which are necessary for trap closure were fired only if the typical ER complex in the cell poles was visible. Since membrane potential changes are mediated by ions, we tried to identify and to localize ions possibly involved in these processes. Here we present the first results

  13. Identification and Characterization of Mouse Otic Sensory Lineage Genes

    Directory of Open Access Journals (Sweden)

    Byron H. Hartman

    2015-03-01

    Full Text Available Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5 as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting

  14. Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

    Science.gov (United States)

    Schendzielorz, Philipp; Vollmer, Maike; Rak, Kristen; Wiegner, Armin; Nada, Nashwa; Radeloff, Katrin; Hagen, Rudolf; Radeloff, Andreas

    2017-10-01

    A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  15. Hebbian plasticity realigns grid cell activity with external sensory cues in continuous attractor models

    Directory of Open Access Journals (Sweden)

    Marcello eMulas

    2016-02-01

    Full Text Available After the discovery of grid cells, which are an essential component to understand how the mammalian brain encodes spatial information, three main classes of computational models were proposed in order to explain their working principles. Amongst them, the one based on continuous attractor networks (CAN, is promising in terms of biological plausibility and suitable for robotic applications. However, in its current formulation, it is unable to reproduce important electrophysiological findings and cannot be used to perform path integration for long periods of time. In fact, in absence of an appropriate resetting mechanism, the accumulation of errors overtime due to the noise intrinsic in velocity estimation and neural computation prevents CAN models to reproduce stable spatial grid patterns. In this paper, we propose an extension of the CAN model using Hebbian plasticity to anchor grid cell activity to environmental landmarks. To validate our approach we used as input to the neural simulations both artificial data and real data recorded from a robotic setup. The additional neural mechanism can not only anchor grid patterns to external sensory cues but also recall grid patterns generated in previously explored environments. These results might be instrumental for next generation bio-inspired robotic navigation algorithms that take advantage of neural computation in order to cope with complex and dynamic environments.

  16. Phenotype heterogeneity in cancer cell populations

    International Nuclear Information System (INIS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-01-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  17. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  18. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  19. Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

    Science.gov (United States)

    Benitez, Suzana U.; Barbizan, Roberta; Spejo, Aline B.; Ferreira, Rui S.; Barraviera, Benedito; Góes, Alfredo M.; de Oliveira, Alexandre L. R.

    2014-01-01

    Root lesions may affect both dorsal and ventral roots. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. The loss of such sensorial input directly disturbs the spinal circuits thus affecting the functionality of the injuried limb. The present study evaluated the motor and sensory improvement following dorsal root reimplantation with fibrin sealant (FS) plus bone marrow mononuclear cells (MC) after dorsal rhizotomy. MC were used to enhance the repair process. We also analyzed changes in the glial response and synaptic circuits within the spinal cord. Female Lewis rats (6–8 weeks old) were divided in three groups: rhizotomy (RZ group), rhizotomy repaired with FS (RZ+FS group) and rhizotomy repaired with FS and MC (RZ+FS+MC group). The behavioral tests electronic von-Frey and Walking track test were carried out. For immunohistochemistry we used markers to detect different synapse profiles as well as glial reaction. The behavioral results showed a significant decrease in sensory and motor function after lesion. The reimplantation decreased glial reaction and improved synaptic plasticity of afferent inputs. Cell therapy further enhanced the rewiring process. In addition, both reimplanted groups presented twice as much motor control compared to the non-treated group. In conclusion, the reimplantation with FS and MC is efficient and may be considered an approach to improve sensory-motor recovery following dorsal rhizotomy. PMID:25249946

  20. L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

    Science.gov (United States)

    Pal Choudhuri, Shreoshi; Delay, Rona J.; Delay, Eugene R.

    2015-01-01

    Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. PMID:26110622

  1. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Directory of Open Access Journals (Sweden)

    Elaine Astrand

    Full Text Available Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF: the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  2. Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

    Science.gov (United States)

    Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

    2015-04-20

    During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Interval scanning photomicrography of microbial cell populations.

    Science.gov (United States)

    Casida, L. E., Jr.

    1972-01-01

    A single reproducible area of the preparation in a fixed focal plane is photographically scanned at intervals during incubation. The procedure can be used for evaluating the aerobic or anaerobic growth of many microbial cells simultaneously within a population. In addition, the microscope is not restricted to the viewing of any one microculture preparation, since the slide cultures are incubated separately from the microscope.

  4. Mutations in ap1b1 cause mistargeting of the Na(+/K(+-ATPase pump in sensory hair cells.

    Directory of Open Access Journals (Sweden)

    Rachel Clemens Grisham

    Full Text Available The hair cells of the inner ear are polarized epithelial cells with a specialized structure at the apical surface, the mechanosensitive hair bundle. Mechanotransduction occurs within the hair bundle, whereas synaptic transmission takes place at the basolateral membrane. The molecular basis of the development and maintenance of the apical and basal compartments in sensory hair cells is poorly understood. Here we describe auditory/vestibular mutants isolated from forward genetic screens in zebrafish with lesions in the adaptor protein 1 beta subunit 1 (ap1b1 gene. Ap1b1 is a subunit of the adaptor complex AP-1, which has been implicated in the targeting of basolateral membrane proteins. In ap1b1 mutants we observed that although the overall development of the inner ear and lateral-line organ appeared normal, the sensory epithelium showed progressive signs of degeneration. Mechanically-evoked calcium transients were reduced in mutant hair cells, indicating that mechanotransduction was also compromised. To gain insight into the cellular and molecular defects in ap1b1 mutants, we examined the localization of basolateral membrane proteins in hair cells. We observed that the Na(+/K(+-ATPase pump (NKA was less abundant in the basolateral membrane and was mislocalized to apical bundles in ap1b1 mutant hair cells. Accordingly, intracellular Na(+ levels were increased in ap1b1 mutant hair cells. Our results suggest that Ap1b1 is essential for maintaining integrity and ion homeostasis in hair cells.

  5. Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients with Sickle Cell Disease

    OpenAIRE

    Brandow, Amanda M.; Panepinto, Julie A.

    2016-01-01

    Patients with sickle cell disease (SCD) display significantly lower mean/median thermal and mechanical pain thresholds compared to controls. This suggests impaired pain sensitivity where stimuli produce exaggerated pain. Despite these mean/median differences, clinicians need to understand if patients meet criteria for impaired pain sensitivity. We defined thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients. Using quantitative sensory testing (QST) we assessed c...

  6. Targeting population heterogeneity for optimal cell factories

    DEFF Research Database (Denmark)

    Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

    the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

  7. Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

    Science.gov (United States)

    Jiang, Yanrui; Boll, Werner; Noll, Markus

    2015-01-15

    The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. IMPACT OF THE FERMENTATION PROCESS WITH IMMOBILIZED YEAST CELLS ON THE AROMA PROFILE AND SENSORY QUALITY OF DISTILLATES PRODUCED FROM TWO FIG (Ficus carica L. CULTIVARS

    Directory of Open Access Journals (Sweden)

    Borislav Miličević

    2017-01-01

    Full Text Available The aim of this research was to investigate the influence of immobilized cell fermentation on aroma and sensory characteristics of distillates produced from two fig varieties commonly grown in Croatia (Petrovača bijela and Petrovača crna. Distillate samples were produced both by classical and immobilized yeast fermentation technology. Aroma profile was determined using GC/FID and sensory analysis was conducted according to German DLG model. Results showed that immobilized cell technique gives distillates with higher ethanol and lower ester contents, but of higher sensory quality. It is a promising technique for production of high quality fruit distillates.

  9. Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

    Science.gov (United States)

    Baral, Pankaj; Umans, Benjamin D; Li, Lu; Wallrapp, Antonia; Bist, Meghna; Kirschbaum, Talia; Wei, Yibing; Zhou, Yan; Kuchroo, Vijay K; Burkett, Patrick R; Yipp, Bryan G; Liberles, Stephen D; Chiu, Isaac M

    2018-05-01

    Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 + nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1 + -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1 + afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.

  10. Structural and Functional Substitution of Deleted Primary Sensory Neurons by New Growth from Intrinsic Spinal Cord Nerve Cells: An Alternative Concept in Reconstruction of Spinal Cord Circuits

    Directory of Open Access Journals (Sweden)

    Nicholas D. James

    2017-07-01

    Full Text Available In a recent clinical report, return of the tendon stretch reflex was demonstrated after spinal cord surgery in a case of total traumatic brachial plexus avulsion injury. Peripheral nerve grafts had been implanted into the spinal cord to reconnect to the peripheral nerves for motor and sensory function. The dorsal root ganglia (DRG containing the primary sensory nerve cells had been surgically removed in order for secondary or spinal cord sensory neurons to extend into the periphery and replace the deleted DRG neurons. The present experimental study uses a rat injury model first to corroborate the clinical finding of a re-established spinal reflex arch, and second, to elucidate some of the potential mechanisms underlying these findings by means of morphological, immunohistochemical, and electrophysiological assessments. Our findings indicate that, after spinal cord surgery, the central nervous system sensory system could replace the traumatically detached original peripheral sensory connections through new neurite growth from dendrites.

  11. Identification of new binding partners of the chemosensory signalling protein Gγ13 expressed in taste and olfactory sensory cells.

    Directory of Open Access Journals (Sweden)

    Zhenhui eLiu

    2012-06-01

    Full Text Available Tastant detection in the oral cavity involves selective receptors localized at the apical extremity of a subset of specialized taste bud cells called taste receptor cells (TRCs. The identification of the genes coding for the taste receptors involved in this process have greatly improved our understanding of the molecular mechanisms underlying detection. However, how these receptors signal in TRCs, and whether the components of the signaling cascades interact with each other or are organized in complexes is mostly unexplored. Here we report on the identification of three new binding partners for the mouse G protein gamma 13 subunit (Gγ13, a component of the bitter taste receptors signalling cascade. For two of these Gγ13 associated proteins, namely GOPC and MPDZ, we describe the expression in taste bud cells for the first time. Furthermore, we demonstrate by means of a yeast two-hybrid interaction assay that the C terminal PDZ binding motif of Gγ13 interacts with selected PDZ domains in these proteins. In the case of the PDZ domain-containing protein zona occludens-1 (ZO-1, a major component of the tight junction defining the boundary between the apical and baso-lateral region of TRCs, we identified the first PDZ domain as the site of strong interaction with Gγ13. This association was further confirmed by co-immunoprecipitation experiments in HEK 293 cells. In addition, we present immunohistological data supporting partial co-localization of GOPC, MPDZ or ZO-1 and Gγ13 in taste buds cells. Finally, we extend this observation to olfactory sensory neurons, another type of chemosensory cells known to express both ZO-1 and Gγ13. Taken together our results implicate these new interaction partners in the sub-cellular distribution of Gγ13 in olfactory and gustatory primary sensory cells.

  12. Sensory processing and corollary discharge effects in posterior caudal lobe Purkinje cells in a weakly electric mormyrid fish.

    Science.gov (United States)

    Alviña, Karina; Sawtell, Nathaniel B

    2014-07-15

    Although it has been suggested that the cerebellum functions to predict the sensory consequences of motor commands, how such predictions are implemented in cerebellar circuitry remains largely unknown. A detailed and relatively complete account of predictive mechanisms has emerged from studies of cerebellum-like sensory structures in fish, suggesting that comparisons of the cerebellum and cerebellum-like structures may be useful. Here we characterize electrophysiological response properties of Purkinje cells in a region of the cerebellum proper of weakly electric mormyrid fish, the posterior caudal lobe (LCp), which receives the same mossy fiber inputs and projects to the same target structures as the electrosensory lobe (ELL), a well-studied cerebellum-like structure. We describe patterns of simple spike and climbing fiber activation in LCp Purkinje cells in response to motor corollary discharge, electrosensory, and proprioceptive inputs and provide evidence for two functionally distinct Purkinje cell subtypes within LCp. Protocols that induce rapid associative plasticity in ELL fail to induce plasticity in LCp, suggesting differences in the adaptive functions of the two structures. Similarities and differences between LCp and ELL are discussed in light of these results. Copyright © 2014 the American Physiological Society.

  13. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Defining the cellular environment in the organ of Corti following extensive hair cell loss: a basis for future sensory cell replacement in the Cochlea.

    Directory of Open Access Journals (Sweden)

    Ruth R Taylor

    Full Text Available BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. METHODOLOGY/PRINCIPAL FINDINGS: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. CONCLUSIONS/SIGNIFICANCE: The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals

  15. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

    Directory of Open Access Journals (Sweden)

    Kazuyo Yasuda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

  16. Hair cell regeneration in sensory epithelia from the inner ear of a urodele amphibian.

    Science.gov (United States)

    Taylor, Ruth R; Forge, Andrew

    2005-03-28

    The capacity of urodele amphibians to regenerate a variety of body parts is providing insight into mechanisms of tissue regeneration in vertebrates. In this study the ability of the newt, Notophthalmus viridescens, to regenerate inner ear hair cells in vitro was examined. Intact otic capsules were maintained in organotypic culture. Incubation in 2 mM gentamicin for 48 hours resulted in ablation of all hair cells from the saccular maculae. Thus, any hair cell recovery was not due to repair of damaged hair cells. Immature hair cells were subsequently observed at approximately 12 days posttreatment. Their number increased over the following 7-14 days to reach approximately 30% of the normal number. Following incubation of damaged tissue with bromodeoxyuridine (BrdU), labeled nuclei were confined strictly within regions of hair cell loss, indicating that supporting cells entered S-phase. Double labeling of tissue with two different hair cell markers and three different antibodies to BrdU in various combinations, however, all showed that the nuclei of cells that labeled with hair cell markers did not label for BrdU. This suggested that the new hair cells were not derived from those cells that had undergone mitosis. When mitosis was blocked with aphidicolin, new hair cells were still generated. The results suggest that direct phenotypic conversion of supporting cells into hair cells without an intervening mitotic event is a major mechanism of hair cell regeneration in the newt. A similar mechanism has been proposed for the hair cell recovery phenomenon observed in the vestibular organs of mammals. Copyright 2005 Wiley-Liss, Inc.

  17. A microarray analysis of two distinct lymphatic endothelial cell populations

    Directory of Open Access Journals (Sweden)

    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  18. Sensory evaluation of a highly nutritive bread, formulated for populations suffering food emergencies, preserved with ionizing radiation; Evaluación sensorial de un panificado de alto valor nutricional formulado para poblaciones en emergencia alimentaria, preservado por radiaciones ionizantes

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, G. S.; Gómez, B., E-mail: gabygon22@yahoo.com.ar, E-mail: bgomez@fb.uner.edu.ar [Universidad Nacional de Entre Ríos, Gualeguaychú (Argentina); Cova, M. C.; Narvaiz, Patricia [Comisión Nacional de Energía Atómica, Ezeiza (Argentina). Gerencia de Área Aplicaciones de la Tecnología Nuclear, Gerencia de Aplicaciones y Tecnología de Radiaciones, Sector Irradiación de Alimentos

    2011-07-01

    The aim of this work was to evaluate with sensorial analysis, the feasibility of extending the shelf life at room temperature of highly nutritive bread, specially formulated for people suffering alimentary emergencies such as floods, earthquakes, geographical isolation or malnourishment, by means of ionizing radiation. The shelf life of any bread is limited by microbial growth, so the food industry uses chemicals and /or refrigeration to control it. Twenty one breads were formulated and manufactured employing wheat and soybean flours, dehydrated whey, skim milk and egg, vegetal oil, water, and some commercial food additives as emulsifiers and water retention substances. A final formulation was chosen by means of a preliminary sensory evaluation. Bibliographic estimations were made on its nutritional quality as compared to that of a regular wheat bread; improvements were found on vitamins, minerals, proteins, lipids and fibre. Forty 450 g breads were manufactured, oven cooked at 220°C for 20 minutes, packaged with polyethylene film, 100 microns thickness, and irradiated at the semi industrial cobalt-60 facility of the Ezeiza Atomic Centre, about 600,000 Ci of activity, with doses of 0, 6 and 10 kilo Grays, dose rate: 10 kGy/h, dose uniformity: 1.1. Control and irradiated samples were stored at room temperature and relative humidity for 43 days. Sensory analysis was performed with a panel of about 50 consumers on days 3, 29 and 43, evaluating aroma, aspect, colour, flavour, texture and general acceptability with hedonic scores ranging from 1 to 9. No significant differences between control and irradiated samples were found, being the latter afforded scores close to 7 even at the end of the storage period. Control samples had to be discarded on day 6 due to visible mould growth. So this bread formulation, suitable to fulfill most of the nutritional requirements of a population under alimentary emergency, attained at least a 7 fold shelf life increase when treated

  19. Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.

    Science.gov (United States)

    Sevilla, T; Martínez-Rubio, D; Márquez, C; Paradas, C; Colomer, J; Jaijo, T; Millán, J M; Palau, F; Espinós, C

    2013-06-01

    Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range. © 2012 John Wiley & Sons A/S.

  20. Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

    Science.gov (United States)

    Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

    2016-04-01

    Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

  1. Bridging the Timescales of Single-Cell and Population Dynamics

    Science.gov (United States)

    Jafarpour, Farshid; Wright, Charles S.; Gudjonson, Herman; Riebling, Jedidiah; Dawson, Emma; Lo, Klevin; Fiebig, Aretha; Crosson, Sean; Dinner, Aaron R.; Iyer-Biswas, Srividya

    2018-04-01

    How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to the replication-competent (stalked) stage of the Caulobacter crescentus life cycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For C. crescentus cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time and, thus, yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell-age distribution, and the quiescence timescale.

  2. Gene expression heterogeneities in embryonic stem cell populations

    DEFF Research Database (Denmark)

    Martinez Arias, Alfonso; Brickman, Joshua M

    2011-01-01

    Stem and progenitor cells are populations of cells that retain the capacity to populate specific lineages and to transit this capacity through cell division. However, attempts to define markers for stem cells have met with limited success. Here we consider whether this limited success reflects...... an intrinsic requirement for heterogeneity with stem cell populations. We focus on Embryonic Stem (ES) cells, in vitro derived cell lines from the early embryo that are considered both pluripotent (able to generate all the lineages of the future embryo) and indefinitely self renewing. We examine the relevance...... of recently reported heterogeneities in ES cells and whether these heterogeneities themselves are inherent requirements of functional potency and self renewal....

  3. Progenitor cell populations in the periodontal ligament of mice

    International Nuclear Information System (INIS)

    McCulloch, C.A.

    1985-01-01

    Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3 H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

  4. Composition, functional properties and sensory characteristics of Mozzarella cheese manufactured from different somatic cell counts in milk

    Directory of Open Access Journals (Sweden)

    Evelise Andreatta

    2009-10-01

    Full Text Available In the present study, composition, functional properties and sensory characteristics of Mozzarella cheese produced from milk with somatic cell counts (SCC at low (800,000 cells/mL levels were investigated. Three batches of cheese were produced for each SCC category. The cheeses were vacuum packed in plastic bags and analysed after 2, 9, 16, 23 and 30 days of storage at 4ºC. SCC level did not affect the moisture, fat, total protein and ash content, mesophilic and psychrotrophic bacteria, and sensory parameters of Mozzarella cheese. However, meltability increased in cheese manufactured from high SCC milk. Results indicated that raw milk used to produce Mozzarella cheese should not contain high SCC (>800,000 cells/mL in order to avoid changes in the functional properties of the Mozzarella cheese.No presente estudo foram investigadas a composição, as propriedades funcionais e as características sensoriais do queijo Mussarela produzido a partir de leite com contagens de células somáticas (CCS em níveis baixos (800.000 CS/mL. Foram produzidos 3 lotes de queijo para cada CCS. Os queijos foram embalados a vácuo e analisados após 2, 9, 16, 23 e 30 dias de armazenamento a 4ºC. O nível de CS não afetou a umidade, os teores de gordura, proteína total e cinzas, os níveis de bactérias mesófilas e psicrotróficas, e os parâmetros sensoriais do queijo Mussarela. Entretanto, houve aumento da capacidade de derretimento no queijo fabricado com leite de alta CCS. Os resultados indicam que o leite cru utilizado para a produção de queijo Mussarela não deve conter níveis de CS acima de 800.000/mL, para evitar alterações nas propriedades funcionais do queijo Mussarela.

  5. Age-associated variation in sensory perception of iron in drinking water and the potential for overexposure in the human population.

    Science.gov (United States)

    Mirlohi, Susan; Dietrich, Andrea M; Duncan, Susan E

    2011-08-01

    Humans interact with their environment through the five senses, but little is known about population variability in the ability to assess contaminants. Sensory thresholds and biochemical indicators of metallic flavor perception in humans were evaluated for ferrous (Fe(2+)) iron in drinking water; subjects aged 19-84 years participated. Metallic flavor thresholds for individuals and subpopulations based on age were determined. Oral lipid oxidation and oral pH were measured in saliva as potential biochemical indicators. Individual thresholds were 0.007-14.14 mg/L Fe(2+) and the overall population threshold was 0.17 mg/L Fe(2+) in reagent water. Average thresholds for individuals younger and older than 50 years of age (grouped by the daily recommended nutritional guidelines for iron intake) were significantly different (p = 0.013); the population thresholds for each group were 0.045 mg/L Fe(2+) and 0.498 mg/L Fe(2+), respectively. Many subjects >50 and a few subjects <50 years were insensitive to metallic flavor. There was no correlation between age, oral lipid oxidation, and oral pH. Standardized olfactory assessment found poor sensitivity for Fe(2+) corresponded with conditions of mild, moderate, and total anosmia. The findings demonstrate an age-dependent sensitivity to iron indicating as people age they are less sensitive to metallic perception.

  6. Controlling the diversity of cell populations in a stem cell culture

    NARCIS (Netherlands)

    Heo, Inha; Clevers, Hans

    2015-01-01

    Culturing intestinal stem cells into 3D organoids results in heterogeneous cell populations, reflecting the in vivo cell type diversity. In a recent paper published in Nature, Wang et al. established a culture condition for a highly homogeneous population of intestinal stem cells.

  7. A biophysical signature of network affiliation and sensory processing in mitral cells

    DEFF Research Database (Denmark)

    Angelo, Kamilla; Rancz, Ede A; Pimentel, Diogo

    2012-01-01

    One defining characteristic of the mammalian brain is its neuronal diversity. For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists. Although it is well known that such cellular properties vary considerably according to neuronal type...

  8. On interfaces between cell populations with different mobilities

    KAUST Repository

    Lorenzi, Tommaso

    2016-11-18

    Partial differential equations describing the dynamics of cell population densities from a fluid mechanical perspective can model the growth of avascular tumours. In this framework, we consider a system of equations that describes the interaction between a population of dividing cells and a population of non-dividing cells. The two cell populations are characterised by different mobilities. We present the results of numerical simulations displaying two-dimensional spherical waves with sharp interfaces between dividing and non-dividing cells. Furthermore, we numerically observe how different ratios between the mobilities change the morphology of the interfaces, and lead to the emergence of finger-like patterns of invasion above a threshold. Motivated by these simulations, we study the existence of one-dimensional travelling wave solutions.

  9. Modelling Effects on Grid Cells of Sensory Input During Self-motion

    Science.gov (United States)

    2016-04-20

    individual oscillators. These oscillatory interference models effectively simulate the theta rhythmic firing of grid cells (Hafting et al. 2008; Jeewajee...et al. 2008; Brandon et al. 2011; Koenig et al. 2011; Stensola et al. 2012), and the changes in rhythmic firing frequency based on running speed and...Fiete, 2009; Couey et al. 2013), and equate head direction with movement direction. However, an analysis of behavioural data shows that the head

  10. Artificial Cochlear Sensory Epithelium with Functions of Outer Hair Cells Mimicked Using Feedback Electrical Stimuli

    Directory of Open Access Journals (Sweden)

    Tetsuro Tsuji

    2018-05-01

    Full Text Available We report a novel vibration control technique of an artificial auditory cochlear epithelium that mimics the function of outer hair cells in the organ of Corti. The proposed piezoelectric and trapezoidal membrane not only has the acoustic/electric conversion and frequency selectivity of the previous device developed mainly by one of the authors and colleagues, but also has a function to control local vibration according to sound stimuli. Vibration control is achieved by applying local electrical stimuli to patterned electrodes on an epithelium made using micro-electro-mechanical system technology. By choosing appropriate phase differences between sound and electrical stimuli, it is shown that it is possible to both amplify and dampen membrane vibration, realizing better control of the response of the artificial cochlea. To be more specific, amplification and damping are achieved when the phase difference between the membrane vibration by sound stimuli and electrical stimuli is zero and π , respectively. We also demonstrate that the developed control system responds automatically to a change in sound frequency. The proposed technique can be applied to mimic the nonlinear response of the outer hair cells in a cochlea, and to realize a high-quality human auditory system.

  11. On interfaces between cell populations with different mobilities

    KAUST Repository

    Lorenzi, Tommaso; Lorz, Alexander; Perthame, Benoit

    2016-01-01

    Partial differential equations describing the dynamics of cell population densities from a fluid mechanical perspective can model the growth of avascular tumours. In this framework, we consider a system of equations that describes the interaction

  12. Pregnancy persistently affects memory T cell populations

    NARCIS (Netherlands)

    Kieffer, Tom E. C.; Faas, Marijke M.; Scherjon, Sicco A.; Prins, Jelmer R.

    Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the

  13. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    International Nuclear Information System (INIS)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean; Larsen, Annette K.; Escargueil, Alexandre

    2016-01-01

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  14. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzi, Tommaso [Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Chisholm, Rebecca H. [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia); Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Larsen, Annette K.; Escargueil, Alexandre [Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France); INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris (France)

    2016-06-08

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  15. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

  16. Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm.

    Science.gov (United States)

    Sakaue, Yuko; Bellier, Jean-Pierre; Kimura, Shin; D'Este, Loredana; Takeuchi, Yoshihiro; Kimura, Hiroshi

    2014-01-01

    Cholinergic structures in the arm of the cephalopod Octopus vulgaris were studied by immunohistochemistry using specific antisera for two types (common and peripheral) of acetylcholine synthetic enzyme choline acetyltransferase (ChAT): antiserum raised against the rat common type ChAT (cChAT), which is cross-reactive with molluscan cChAT, and antiserum raised against the rat peripheral type ChAT (pChAT), which has been used to delineate peripheral cholinergic structures in vertebrates, but not previously in invertebrates. Western blot analysis of octopus extracts revealed a single pChAT-positive band, suggesting that pChAT antiserum is cross-reactive with an octopus counterpart of rat pChAT. In immunohistochemistry, only neuronal structures of the octopus arm were stained by cChAT and pChAT antisera, although the pattern of distribution clearly differed between the two antisera. cChAT-positive varicose nerve fibers were observed in both the cerebrobrachial tract and neuropil of the axial nerve cord, while pChAT-positive varicose fibers were detected only in the neuropil of the axial nerve cord. After epitope retrieval, pChAT-positive neuronal cells and their processes became visible in all ganglia of the arm, including the axial and intramuscular nerve cords, and in ganglia of suckers. Moreover, pChAT-positive structures also became detectable in nerve fibers connecting the different ganglia, in smooth nerve fibers among muscle layers and dermal connective tissues, and in sensory cells of the suckers. These results suggest that the octopus arm has two types of cholinergic nerves: cChAT-positive nerves from brain ganglia and pChAT-positive nerves that are intrinsic to the arm.

  17. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15.

    Science.gov (United States)

    Ahmed, Zubair M; Goodyear, Richard; Riazuddin, Saima; Lagziel, Ayala; Legan, P Kevin; Behra, Martine; Burgess, Shawn M; Lilley, Kathryn S; Wilcox, Edward R; Riazuddin, Sheikh; Griffith, Andrew J; Frolenkov, Gregory I; Belyantseva, Inna A; Richardson, Guy P; Friedman, Thomas B

    2006-06-28

    Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formation.

  18. Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis.

    Science.gov (United States)

    MacLean, Adam L; Lo Celso, Cristina; Stumpf, Michael P H

    2017-01-01

    Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. Stem Cells 2017;35:80-88. © 2016 AlphaMed Press.

  19. Identification of the Ulex europaeus agglutinin-I-binding protein as a unique glycoform of the neural cell adhesion molecule in the olfactory sensory axons of adults rats.

    Science.gov (United States)

    Pestean, A; Krizbai, I; Böttcher, H; Párducz, A; Joó, F; Wolff, J R

    1995-08-04

    Histochemical localization of two lectins, Ulex europaeus agglutinin-I (UEA-I) and Tetragonolobus purpureus (TPA), was studied in the olfactory bulb of adult rats. In contrast to TPA, UEA-I detected a fucosylated glycoprotein that is only present in the surface membranes of olfactory sensory cells including the whole course of their neurites up to the final arborization in glomeruli. Immunoblotting revealed that UEA-I binds specifically to a protein of 205 kDa, while TPA stains several other glycoproteins. Affinity chromatography with the use of a UEA-I column identified the 205 kDa protein as a glycoform of neural cell adhesion molecule (N-CAM), specific for the rat olfactory sensory nerves.

  20. Sensory adaptation for timing perception.

    Science.gov (United States)

    Roseboom, Warrick; Linares, Daniel; Nishida, Shin'ya

    2015-04-22

    Recent sensory experience modifies subjective timing perception. For example, when visual events repeatedly lead auditory events, such as when the sound and video tracks of a movie are out of sync, subsequent vision-leads-audio presentations are reported as more simultaneous. This phenomenon could provide insights into the fundamental problem of how timing is represented in the brain, but the underlying mechanisms are poorly understood. Here, we show that the effect of recent experience on timing perception is not just subjective; recent sensory experience also modifies relative timing discrimination. This result indicates that recent sensory history alters the encoding of relative timing in sensory areas, excluding explanations of the subjective phenomenon based only on decision-level changes. The pattern of changes in timing discrimination suggests the existence of two sensory components, similar to those previously reported for visual spatial attributes: a lateral shift in the nonlinear transducer that maps relative timing into perceptual relative timing and an increase in transducer slope around the exposed timing. The existence of these components would suggest that previous explanations of how recent experience may change the sensory encoding of timing, such as changes in sensory latencies or simple implementations of neural population codes, cannot account for the effect of sensory adaptation on timing perception.

  1. In Vitro Analysis of the Role of Schwann Cells on Axonal Degeneration and Regeneration Using Sensory Neurons from Dorsal Root Ganglia.

    Science.gov (United States)

    López-Leal, Rodrigo; Diaz, Paula; Court, Felipe A

    2018-01-01

    Sensory neurons from dorsal root ganglion efficiently regenerate after peripheral nerve injuries. These neurons are widely used as a model system to study degenerative mechanisms of the soma and axons, as well as regenerative axonal growth in the peripheral nervous system. This chapter describes techniques associated to the study of axonal degeneration and regeneration using explant cultures of dorsal root ganglion sensory neurons in vitro in the presence or absence of Schwann cells. Schwann cells are extremely important due to their involvement in tissue clearance during axonal degeneration as well as their known pro-regenerative effect during regeneration in the peripheral nervous system. We describe methods to induce and study axonal degeneration triggered by axotomy (mechanical separation of the axon from its soma) and treatment with vinblastine (which blocks axonal transport), which constitute clinically relevant mechanical and toxic models of axonal degeneration. In addition, we describe three different methods to evaluate axonal regeneration using quantitative methods. These protocols constitute a valuable tool to analyze in vitro mechanisms associated to axonal degeneration and regeneration of sensory neurons and the role of Schwann cells in these processes.

  2. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

    1988-01-01

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  3. Emergence of cytotoxic resistance in cancer cell populations*

    Directory of Open Access Journals (Sweden)

    Lorenzi Tommaso

    2015-01-01

    Full Text Available We formulate an individual-based model and an integro-differential model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  4. Dielectrophoretic capture of low abundance cell population using thick electrodes

    OpenAIRE

    Marchalot, Julien; Chateaux, Jean-François; Faivre, Magalie; Mertani, Hichem C.; Ferrigno, Rosaria; Deman, Anne-Laure

    2015-01-01

    Enrichment of rare cell populations such as Circulating Tumor Cells (CTCs) is a critical step before performing analysis. This paper presents a polymeric microfluidic device with integrated thick Carbon-PolyDimethylSiloxane composite (C-PDMS) electrodes designed to carry out dielectrophoretic (DEP) trapping of low abundance biological cells. Such conductive composite material presents advantages over metallic structures. Indeed, as it combines properties of both the matrix and doping particle...

  5. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.

    Science.gov (United States)

    Tüysüz, Beyhan; Bayrakli, Fatih; DiLuna, Michael L; Bilguvar, Kaya; Bayri, Yasar; Yalcinkaya, Cengiz; Bursali, Aysegul; Ozdamar, Elif; Korkmaz, Baris; Mason, Christopher E; Ozturk, Ali K; Lifton, Richard P; State, Matthew W; Gunel, Murat

    2008-05-01

    Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.

  6. Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

    Directory of Open Access Journals (Sweden)

    Sugimura Kaoru

    2009-10-01

    Full Text Available Abstract Background For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of Drosophila multidendritic sensory neurons - the dendritic arborization (da neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary. Results We identified multidendritic neurons in the adult Drosophila abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4 of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post

  7. Functional heterogeneity and heritability in CHO cell populations.

    Science.gov (United States)

    Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

    2013-01-01

    In this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental Chinese hamster ovary (CHO) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." One-hundred and ninety-nine CHOK1SV clones were isolated from a donor CHOK1SV parental population by limiting dilution cloning and microplate image analysis, followed by primary analysis of variation in cell-specific proliferation rate during extended deep-well microplate suspension culture of individual clones to accelerate genetic drift in isolated cultures. A subset of 100 clones were comparatively evaluated for transient production of a recombinant monoclonal antibody (Mab) and green fluorescent protein following transfection of a plasmid vector encoding both genes. The heritability of both cell-specific proliferation rate and Mab production was further assessed using a subset of 23 clones varying in functional capability that were subjected to cell culture regimes involving both cryopreservation and extended sub-culture. These data showed that whilst differences in transient Mab production capability were not heritable per se, clones exhibiting heritable variation in specific proliferation rate, endocytotic transfectability and N-glycan processing were identified. Finally, for clonal populations most "evolved" by extended sub-culture in vitro we investigated the relationship between cellular protein biomass content, specific proliferation rate and cell surface N-glycosylation. Rapid-specific proliferation rate was inversely correlated to CHO cell size and protein content, and positively correlated to cell surface glycan content, although substantial clone-specific variation in ability to accumulate cell biomass was evident. Taken together, our data reveal the dynamic nature of the CHO cell functional genome and the potential to evolve and

  8. Trail networks formed by populations of immune cells

    International Nuclear Information System (INIS)

    Yang, Taeseok Daniel; Kwon, Tae Goo; Park, Jin-sung; Lee, Kyoung J

    2014-01-01

    Populations of biological cells that communicate with each other can organize themselves to generate large-scale patterns. Examples can be found in diverse systems, ranging from developing embryos, cardiac tissues, chemotaxing ameba and swirling bacteria. The similarity, often shared by the patterns, suggests the existence of some general governing principle. On the other hand, rich diversity and system-specific properties are exhibited, depending on the type of involved cells and the nature of their interactions. The study on the similarity and the diversity constitutes a rapidly growing field of research. Here, we introduce a new class of self-organized patterns of cell populations that we term as ‘cellular trail networks’. They were observed with populations of rat microglia, the immune cells of the brain and the experimental evidence suggested that haptotaxis is the key element responsible for them. The essential features of the observed patterns are well captured by the mathematical model cells that actively crawl and interact with each other through a decomposing but non-diffusing chemical attractant laid down by the cells. Our finding suggests an unusual mechanism of socially cooperative long-range signaling for the crawling immune cells. (paper)

  9. Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture.

    Science.gov (United States)

    Kim, Euiseok J; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E

    2008-08-01

    Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.

  10. Destruction of radiation-resistant cell populations by hyperthermia

    International Nuclear Information System (INIS)

    Roettinger, E.M.; Gerweck, L.E.

    1979-01-01

    Animal experiments with local hyperthermia have shown that the radiauion dose necessary for the local control of 50% of the tumours examined was essentially reduced by heating to 42,5 0 C. In-vitro experients indicated selective destruction of relatively radiation-resistent cell populations by the combination of hyperthermie and reduced hydrogen ion concentration. Experiments with glioblastoma cells confirmed these results qualitatively, but showed quantitatively considerably lower sensitivity towards hyperthermia. (orig.) 891 MG/orig. 892 RDG [de

  11. Prevalence of distal diabetic polyneuropathy using quantitative sensory methods in a population with diabetes of more than 10 years' disease duration.

    Science.gov (United States)

    Miralles-García, José M; de Pablos-Velasco, Pedro; Cabrerizo, Lucio; Pérez, María; López-Gómez, Vanessa

    2010-11-01

    Results of studies on the prevalence of distal diabetic polyneuropathy (DPN) are contradictory. Conventional methods used for the diagnosis of DPN in clinical practice have limited effectiveness. The present study aimed to assess the prevalence of DPN in a population with long-standing diabetes (more than 10 years disease duration) by measuring vibratory, thermal and tactile sensitivities with quantitative sensory devices, as well as their relationship with associated clinical risk factors. A total of 1011 diabetic patients were evaluated in a multicenter, cross-sectional, observational study. The three sensitivities were assessed by ultrabiothesiometer, aesthesiometer and thermoskin devices, respectively. The prevalence of neuropathic pain was validated by the DN4 questionnaire. Of the 1011 cases included, 400 (39.6%) met the diagnostic criteria of DPN, while no DPN was found in the remaining 611 (60.4%). Of the 400 patients with DPN, 253 (63.2%) showed clinical manifestations, while 147 (36.8%) were diagnosed as subclinical DPN. The prevalence of DPN increased with disease duration. There was a progressive loss of the three sensitivities with increased disease duration, particularly thermal and vibratory sensitivities. This loss was statistically significant for the latter two sensitivities. Among patients with clinical DPN, 84.2% had painful neuropathic symptoms. The prevalence of DPN was positively related to micro- and macroangiopathic complications and with dyslipidemia. This study reveals a high degree of underdiagnosis of DPN, most likely due to the asymptomatic nature of the disease in a considerable proportion of patients. Our observations provide evidence of the usefulness of specific equipment for quantitative and objective assessment of polyneuropathy. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  12. A probabilistic model for cell population phenotyping using HCS data.

    Directory of Open Access Journals (Sweden)

    Edouard Pauwels

    Full Text Available High Content Screening (HCS platforms allow screening living cells under a wide range of experimental conditions and give access to a whole panel of cellular responses to a specific treatment. The outcome is a series of cell population images. Within these images, the heterogeneity of cellular response to the same treatment leads to a whole range of observed values for the recorded cellular features. Consequently, it is difficult to compare and interpret experiments. Moreover, the definition of phenotypic classes at a cell population level remains an open question, although this would ease experiments analyses. In the present work, we tackle these two questions. The input of the method is a series of cell population images for which segmentation and cellular phenotype classification has already been performed. We propose a probabilistic model to represent and later compare cell populations. The model is able to fully exploit the HCS-specific information: "dependence structure of population descriptors" and "within-population variability". The experiments we carried out illustrate how our model accounts for this specific information, as well as the fact that the model benefits from considering them. We underline that these features allow richer HCS data analysis than simpler methods based on single cellular feature values averaged over each well. We validate an HCS data analysis method based on control experiments. It accounts for HCS specificities that were not taken into account by previous methods but have a sound biological meaning. Biological validation of previously unknown outputs of the method constitutes a future line of work.

  13. Depletion of resident macrophages does not alter sensory regeneration in the avian cochlea.

    Directory of Open Access Journals (Sweden)

    Mark E Warchol

    Full Text Available Macrophages are the primary effector cells of the innate immune system and are also activated in response to tissue injury. The avian cochlea contains a population of resident macrophages, but the precise function of those cells is not known. The present study characterized the behavior of cochlear macrophages after aminoglycoside ototoxicity and also examined the possible role of macrophages in sensory regeneration. We found that the undamaged chick cochlea contains a large resting population of macrophages that reside in the hyaline cell region, immediately outside the abneural (inferior border of the sensory epithelium. Following ototoxic injury, macrophages appear to migrate out of the hyaline cell region and towards the basilar membrane, congregating immediately below the lesioned sensory epithelium. In order to determine whether recruited macrophages contribute to the regeneration of sensory receptors, we quantified supporting cell proliferation and hair cell recovery after the elimination of most resident macrophages via application of liposomally-encapsulated clodronate. Examination of macrophage-depleted specimens at two days following ototoxic injury revealed no deficits in hair cell clearance, when compared to normal controls. In addition, we found that elimination of macrophages did not affect either regenerative proliferation of supporting cells or the production of replacement hair cells. However, we did find that macrophage-depleted cochleae contained reduced numbers of proliferative mesothelial cells below the basilar membrane. Our data suggest that macrophages are not required for normal debris clearance and regeneration, but that they may play a role in the maintenance of the basilar membrane.

  14. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    Science.gov (United States)

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  15. Localization of SSeCKS in unmyelinated primary sensory neurons

    Directory of Open Access Journals (Sweden)

    Siegel Sandra M

    2008-03-01

    Full Text Available Abstract Background SSeCKS (Src SupprEssed C Kinase Substrate is a proposed protein kinase C substrate/A kinase anchoring protein (AKAP that has recently been characterized in the rat peripheral nervous system. It has been shown that approximately 40% of small primary sensory neurons contain SSeCKS-immunoreactivity in a population largely separate from substance P (95.2%, calcitonin gene related peptide (95.3%, or fluoride resistant acid phosphatase (55.0% labeled cells. In the spinal cord, it was found that SSeCKS-immunoreactive axon collaterals terminate in the dorsal third of lamina II outer in a region similar to that of unmyelinated C-, or small diameter myelinated Aδ-, fibers. However, the precise characterization of the anatomical profile of the primary sensory neurons containing SSeCKS remains to be determined. Here, immunohistochemical labeling at the light and ultrastructural level is used to clarify the myelination status of SSeCKS-containing sensory neuron axons and to further clarify the morphometric, and provide insight into the functional, classification of SSeCKS-IR sensory neurons. Methods Colocalization studies of SSeCKS with myelination markers, ultrastructural localization of SSeCKS labeling and ablation of largely unmyelinated sensory fibers by neonatal capsaicin administration were all used to establish whether SSeCKS containing sensory neurons represent a subpopulation of unmyelinated primary sensory C-fibers. Results Double labeling studies of SSeCKS with CNPase in the dorsal horn and Pzero in the periphery showed that SSeCKS immunoreactivity was observed predominantly in association with unmyelinated primary sensory fibers. At the ultrastructural level, SSeCKS immunoreactivity was most commonly associated with axonal membrane margins of unmyelinated fibers. In capsaicin treated rats, SSeCKS immunoreactivity was essentially obliterated in the dorsal horn while in dorsal root ganglia quantitative analysis revealed a 43

  16. Functional heterogeneity of side population cells in skeletal muscle

    International Nuclear Information System (INIS)

    Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2006-01-01

    Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31 - CD45 - SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31 - CD45 - SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31 - CD45 - SP cells participate in muscle regeneration

  17. Quantitation of DNA repair in brain cell cultures: implications for autoradiographic analysis of mixed cell populations

    International Nuclear Information System (INIS)

    Dambergs, R.; Kidson, C.

    1979-01-01

    Quantitation of DNA repair in the mixed cell population of mouse embryo brain cultures has been assessed by autoradiographic analysis of unscheduled DNA synthesis following UV-irradiation. The proportion of labelled neurons and the grain density over neuronal nuclei were both less than the corresponding values for glial cells. The nuclear geometries of these two classes of cell are very different. Partial correction for the different geometries by relating grain density to nuclear area brought estimates of neuronal and glial DNA repair synthesis more closely in line. These findings have general implications for autoradiographic measurement of DNA repair in mixed cell populations and in differentiated versus dividing cells. (author)

  18. CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter

    2015-01-01

    Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and pro...

  19. Cell mass and cell cycle dynamics of an asynchronous budding yeast population

    DEFF Research Database (Denmark)

    Lencastre Fernandes, Rita; Carlquist, Magnus; Lundin, Luisa

    2013-01-01

    of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate...

  20. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  1. Modeling population dynamics of mitochondria in mammalian cells

    Science.gov (United States)

    Kornick, Kellianne; Das, Moumita

    Mitochondria are organelles located inside eukaryotic cells and are essential for several key cellular processes such as energy (ATP) production, cell signaling, differentiation, and apoptosis. All organisms are believed to have low levels of variation in mitochondrial DNA (mtDNA), and alterations in mtDNA are connected to a range of human health conditions, including epilepsy, heart failure, Parkinsons disease, diabetes, and multiple sclerosis. Therefore, understanding how changes in mtDNA accumulate over time and are correlated to changes in mitochondrial function and cell properties can have a profound impact on our understanding of cell physiology and the origins of some diseases. Motivated by this, we develop and study a mathematical model to determine which cellular parameters have the largest impact on mtDNA population dynamics. The model consists of coupled ODEs to describe subpopulations of healthy and dysfunctional mitochondria subject to mitochondrial fission, fusion, autophagy, and mutation. We study the time evolution and stability of each sub-population under specific selection biases and pressures by tuning specific terms in our model. Our results may provide insights into how sub-populations of mitochondria survive and evolve under different selection pressures. This work was supported by a Grant from the Moore Foundation.

  2. Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

    Science.gov (United States)

    Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

    2017-02-28

    Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

  3. Lattice Boltzmann method with the cell-population equilibrium

    International Nuclear Information System (INIS)

    Zhou Xiaoyang; Cheng Bing; Shi Baochang

    2008-01-01

    The central problem of the lattice Boltzmann method (LBM) is to construct a discrete equilibrium. In this paper, a multi-speed 1D cell-model of Boltzmann equation is proposed, in which the cell-population equilibrium, a direct non-negative approximation to the continuous Maxwellian distribution, plays an important part. By applying the explicit one-order Chapman–Enskog distribution, the model reduces the transportation and collision, two basic evolution steps in LBM, to the transportation of the non-equilibrium distribution. Furthermore, 1D dam-break problem is performed and the numerical results agree well with the analytic solutions

  4. HIV Associated Sensory Neuropathy.

    Science.gov (United States)

    G, Amruth; S, Praveen-Kumar; B, Nataraju; Bs, Nagaraja

    2014-07-01

    In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ≥ 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts ( 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy.

  5. Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

    Science.gov (United States)

    Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

    2015-04-01

    Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

  6. Sensory nerve action potentials and sensory perception in women with arthritis of the hand.

    Science.gov (United States)

    Calder, Kristina M; Martin, Alison; Lydiate, Jessica; MacDermid, Joy C; Galea, Victoria; MacIntyre, Norma J

    2012-05-10

    Arthritis of the hand can limit a person's ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments. Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits. All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception.

  7. Multiple dendritic cell populations activate CD4+ T cells after viral stimulation.

    Directory of Open Access Journals (Sweden)

    Adele M Mount

    2008-02-01

    Full Text Available Dendritic cells (DC are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8alpha DC play a prominent, and sometimes exclusive, role in driving amplification of CD8(+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4(+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4(+ and CD8(+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8alpha DC populations in the amplification of CD8(+ and CD4(+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8(+ T cells are dominated by presentation of antigen by CD8alpha DC but can involve non-CD8alpha DC. In contrast, CD4(+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4(+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity.

  8. Population genetics inside a cell: Mutations and mitochondrial genome maintenance

    Science.gov (United States)

    Goyal, Sidhartha; Shraiman, Boris; Gottschling, Dan

    2012-02-01

    In realistic ecological and evolutionary systems natural selection acts on multiple levels, i.e. it acts on individuals as well as on collection of individuals. An understanding of evolutionary dynamics of such systems is limited in large part due to the lack of experimental systems that can challenge theoretical models. Mitochondrial genomes (mtDNA) are subjected to selection acting on cellular as well as organelle levels. It is well accepted that mtDNA in yeast Saccharomyces cerevisiae is unstable and can degrade over time scales comparable to yeast cell division time. We utilize a recent technology designed in Gottschling lab to extract DNA from populations of aged yeast cells and deep sequencing to characterize mtDNA variation in a population of young and old cells. In tandem, we developed a stochastic model that includes the essential features of mitochondrial biology that provides a null model for expected mtDNA variation. Overall, we find approximately 2% of the polymorphic loci that show significant increase in frequency as cells age providing direct evidence for organelle level selection. Such quantitative study of mtDNA dynamics is absolutely essential to understand the propagation of mtDNA mutations linked to a spectrum of age-related diseases in humans.

  9. Carrier population control and surface passivation in solar cells

    KAUST Repository

    Cuevas, Andres

    2018-05-02

    Controlling the concentration of charge carriers near the surface is essential for solar cells. It permits to form regions with selective conductivity for either electrons or holes and it also helps to reduce the rate at which they recombine. Chemical passivation of the surfaces is equally important, and it can be combined with population control to implement carrier-selective, passivating contacts for solar cells. This paper discusses different approaches to suppress surface recombination and to manipulate the concentration of carriers by means of doping, work function and charge. It also describes some of the many surface-passivating contacts that are being developed for silicon solar cells, restricted to experiments performed by the authors.

  10. Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

    Science.gov (United States)

    Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

    2004-01-01

    In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

  11. Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E

    1978-01-01

    The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

  12. Influence of Cell-Cell Interactions on the Population Growth Rate in a Tumor

    Science.gov (United States)

    Chen, Yong

    2017-12-01

    The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems. Supported by the National Natural Science Foundation of China under Grant Nos. 11675008 and 21434001

  13. Investigating energy deposition within cell populations using Monte Carlo simulations.

    Science.gov (United States)

    Oliver, Patricia A K; Thomson, Rowan M

    2018-06-27

    In this work, we develop multicellular models of healthy and cancerous human soft tissues, which are used to investigate energy deposition in subcellular targets, quantify the microdosimetric spread in a population of cells, and determine how these results depend on model details. Monte Carlo (MC) tissue models combining varying levels of detail on different length scales are developed: microscopically-detailed regions of interest (>1500 explicitly-modelled cells) are embedded in bulk tissue phantoms irradiated by photons (20 keV to 1.25 MeV). Specific energy (z; energy imparted per unit mass) is scored in nuclei and cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy mean, <z>, standard deviation, σz, and distribution, f(z,D), are calculated for a variety of macroscopic doses, D. MC-calculated f(z,D) are compared with normal distributions having the same mean and standard deviation. For mGy doses, there is considerable variation in energy deposition (microdosimetric spread) throughout a cell population: e.g., for 30 keV photons irradiating melanoma with 7.5 μm cell radius and 3 μm nuclear radius, σz/<z> for nuclear targets is 170%, and the fraction of nuclei receiving no energy deposition, fz=0, is 0.31 for a dose of 10 mGy. If cobalt-60 photons are considered instead, then σz/<z> decreases to 84%, and fz=0 decreases to 0.036. These results correspond to randomly arranged cells with cell/nucleus sizes randomly sampled from a normal distribution with a standard deviation of 1 μm. If cells are arranged in a hexagonal lattice and cell/nucleus sizes are uniform throughout the population, then σz/<z> decreases to 106% and 68% for 30 keV and cobalt-60,respectively; fz=0

  14. Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin

    Directory of Open Access Journals (Sweden)

    Wang Shenglan

    2011-05-01

    Full Text Available Abstract Background The transient receptor potential (TRP channel subtype A1 (TRPA1 is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC. Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin. Results We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3, and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors. Conclusions These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.

  15. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    Science.gov (United States)

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  16. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

    Directory of Open Access Journals (Sweden)

    Andrew Parker

    2015-12-01

    Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

  17. CELL POPULATION KINETICS OF EXCISED ROOTS OF PISUM SATIVUM

    Science.gov (United States)

    Van't Hof, Jack

    1965-01-01

    The cell population kinetics of excised, cultured pea roots was studied with the use of tritiated thymidine and colchicine to determine (1) the influence of excision, (2) the influence of sucrose concentration, (3) the average mitotic cycle duration, and (4) the duration of mitosis and the G 1, S, and G 2 periods of interphase.1 The results indicate that the process of excision causes a drop in the frequency of mitotic figures when performed either at the beginning of the culture period or after 100 hours in culture. This initial decrease in frequency of cell division is independent of sucrose concentration, but the subsequent rise in frequency of division, after 12 hours in culture, is dependent upon sucrose concentration. Two per cent sucrose maintains the shortest mitotic cycle duration. The use of colchicine indicated an average cycle duration of 20 hours, whereas the use of tritiated thymidine produced an average cycle duration of 17 hours. PMID:5857253

  18. Cell dualism: presence of cells with alternative membrane potentials in growing populations of bacteria and yeasts.

    Science.gov (United States)

    Ivanov, Volodymyr; Rezaeinejad, Saeid; Chu, Jian

    2013-10-01

    It is considered that all growing cells, for exception of acidophilic bacteria, have negatively charged inside cytoplasmic membrane (Δψ⁻-cells). Here we show that growing populations of microbial cells contain a small portion of cells with positively charged inside cytoplasmic membrane (Δψ⁺-cells). These cells were detected after simultaneous application of the fluorescent probes for positive membrane potential (anionic dye DIBAC⁻) and membrane integrity (propidium iodide, PI). We found in exponentially growing cell populations of Escherichia coli and Saccharomyces cerevisiae that the content of live Δψ⁻-cells was 93.6 ± 1.8 % for bacteria and 90.4 ± 4.0 % for yeasts and the content of live Δψ⁺-cells was 0.9 ± 0.3 % for bacteria and 2.4 ± 0.7 % for yeasts. Hypothetically, existence of Δψ⁺-cells could be due to short-term, about 1 min for bacteria and 5 min for yeasts, change of membrane potential from negative to positive value during the cell cycle. This change has been shown by the reversions of K⁺, Na⁺, and Ca²⁺ ions fluxes across the cell membrane during synchronous yeast culture. The transformation of Δψ(⁻-cells to Δψ⁺-cells can be explained by slow influx of K⁺ ions into Δψ⁻-cell to the trigger level of K⁺ concentration ("compression of potassium spring"), which is forming "alternative" Δψ⁺-cell for a short period, following with fast efflux of K⁺ ions out of Δψ⁺-cell ("release of potassium spring") returning cell to normal Δψ⁻ state. We anticipate our results to be a starting point to reveal the biological role of cell dualism in form of Δψ⁻- and Δψ⁺- cells.

  19. Sickle cell disease in tribal populations in India.

    Science.gov (United States)

    Colah, Roshan B; Mukherjee, Malay B; Martin, Snehal; Ghosh, Kanjaksha

    2015-05-01

    The sickle gene is widespread among many tribal population groups in India with prevalence of heterozygotes varying from 1-40 per cent. Co-inheritance of the sickle gene with β-thalassaemia, HbD Punjab and glucose-6-phosphate dehydrogenase (G6PD) deficiency has also been reported. Most of the screening programmes in India now use high performance liquid chromatography (HPLC) analysis although the solubility test is also sensitive and cheap. Sickle cell disease (SCD) among tribal populations is generally milder than among non-tribal groups with fewer episodes of painful crises, infections, acute chest syndrome and need for hospitalization. This has partly been attributed to the very high prevalence of α-thalassaemia among these tribes as well as higher foetal haemoglobin levels. However, the clinical presentation is variable with many cases having a severe presentation. There is not much information available on maternal and perinatal outcome in tribal women with sickle cell disease. Newborn screening programmes for SCD have recently been initiated in Maharashtra, Gujarat, Orissa and Chattisgarh and monitoring these birth cohorts will help to understand the natural history of SCD in India. Prenatal diagnosis is acceptable by tribal families in India. The Indian Council of Medical Research and the National Rural Health Mission in different States are undertaking outreach programmes for better management and control of the disease.

  20. Biologic characteristics of the side population of human small cell lung cancer cell line H446.

    Science.gov (United States)

    Wang, Bo; Yang, Huan; Huang, Yu-Zheng; Yan, Ru-Hong; Liu, Fen-Ju; Zhang, Jun-Ning

    2010-03-01

    Recently, the theory of cancer stem cells (CSCs) has presented new targets and orientations for tumor therapy. The major difficulties in researching CSCs include their isolation and purification. The aim of this study is to identify and characterize the side population (SP) cells in small cell lung cancer (SCLC) cell line H446, which lays the foundation for the isolation and purification of CSCs. Fluorescence-activated cell sorting (FACS) was used to sort SP and non-SP (NSP) cells from H446. Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR were used to evaluate the expression levels of the mRNA of CD133, ABCG2, and nucleostemin in both subgroups. The capacity of proliferation and the differences in drug resistance of both subgroups and unsorted cells were tested by the MTT method. The differentiation ability of both subgroups was determined by FACS. Proliferation was determined by subcutaneous tumor formation in nude mice. The percent of Hoechst 33342 negative cells was about (5.1 +/- 0.2)% in H446 by fluorescence microscopy. The percent of SP cells was (6.3 +/- 0.1)% by flow cytometry. SP cells had a stronger capability of forming into tumor spheres than NSP cells. The mRNA expression levels of ABCG2, CD133, and nucleostemin in SP cells were 21.60 +/- 0.26, 7.10 +/- 0.14, and 1.02 +/- 0.08 folds higher than that in NSP cells (P 0.05, respectively). In vivo, SP cells showed better proliferative ability and tougher viability when treated with drugs. SP cells can differentiate into NSP cells, but NSP cells cannot differentiate into SP cells. SP cells had a greater ability to form tumors. The H446 cell line contained some SP cells with stem cell properties. CD133 and ABCG2 may be cancer stem cell markers of SCLC.

  1. Dielectrophoretic capture of low abundance cell population using thick electrodes.

    Science.gov (United States)

    Marchalot, Julien; Chateaux, Jean-François; Faivre, Magalie; Mertani, Hichem C; Ferrigno, Rosaria; Deman, Anne-Laure

    2015-09-01

    Enrichment of rare cell populations such as Circulating Tumor Cells (CTCs) is a critical step before performing analysis. This paper presents a polymeric microfluidic device with integrated thick Carbon-PolyDimethylSiloxane composite (C-PDMS) electrodes designed to carry out dielectrophoretic (DEP) trapping of low abundance biological cells. Such conductive composite material presents advantages over metallic structures. Indeed, as it combines properties of both the matrix and doping particles, C-PDMS allows the easy and fast integration of conductive microstructures using a soft-lithography approach while preserving O2 plasma bonding properties of PDMS substrate and avoiding a cumbersome alignment procedure. Here, we first performed numerical simulations to demonstrate the advantage of such thick C-PDMS electrodes over a coplanar electrode configuration. It is well established that dielectrophoretic force ([Formula: see text]) decreases quickly as the distance from the electrode surface increases resulting in coplanar configuration to a low trapping efficiency at high flow rate. Here, we showed quantitatively that by using electrodes as thick as a microchannel height, it is possible to extend the DEP force influence in the whole volume of the channel compared to coplanar electrode configuration and maintaining high trapping efficiency while increasing the throughput. This model was then used to numerically optimize a thick C-PDMS electrode configuration in terms of trapping efficiency. Then, optimized microfluidic configurations were fabricated and tested at various flow rates for the trapping of MDA-MB-231 breast cancer cell line. We reached trapping efficiencies of 97% at 20 μl/h and 78.7% at 80 μl/h, for 100 μm thick electrodes. Finally, we applied our device to the separation and localized trapping of CTCs (MDA-MB-231) from a red blood cells sample (concentration ratio of 1:10).

  2. Derivation of keratinocytes from chicken embryonic stem cells: Establishment and characterization of differentiated proliferative cell populations

    Directory of Open Access Journals (Sweden)

    Mathilde Couteaudier

    2015-03-01

    Full Text Available A common challenge in avian cell biology is the generation of differentiated cell-lines, especially in the keratinocyte lineage. Only a few avian cell-lines are available and very few of them show an interesting differentiation profile. During the last decade, mammalian embryonic stem cell-lines were shown to differentiate into almost all lineages, including keratinocytes. Although chicken embryonic stem cells had been obtained in the 1990s, few differentiation studies toward the ectodermal lineage were reported. Consequently, we explored the differentiation of chicken embryonic stem cells toward the keratinocyte lineage by using a combination of stromal induction, ascorbic acid, BMP4 and chicken serum. During the induction period, we observed a downregulation of pluripotency markers and an upregulation of epidermal markers. Three homogenous cell populations were derived, which were morphologically similar to chicken primary keratinocytes, displaying intracellular lipid droplets in almost every pavimentous cell. These cells could be serially passaged without alteration of their morphology and showed gene and protein expression profiles of epidermal markers similar to chicken primary keratinocytes. These cells represent an alternative to the isolation of chicken primary keratinocytes, being less cumbersome to handle and reducing the number of experimental animals used for the preparation of primary cells.

  3. Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells.

    Science.gov (United States)

    Wang, Jianyu; Sun, Zhiwei; Liu, Yongli; Kong, Liangsheng; Zhou, Shixia; Tang, Junlin; Xing, Hongmei Rosie

    2017-11-14

    Characterization of the stem-like properties of cancer stem cells (CSCs) remain indirect and qualitative, especially the ability of CSCs to undergo asymmetric cell division for self renewal and differentiation, a unique property of cells of stem origin. It is partly due to the lack of stable cellular models of CSCs. In this study, we developed a new approach for CSC isolation and purification to derive a CSC-enriched cell line (LLC-SE). By conducting five consecutive rounds of single cell cloning using the LLC-SE cell line, we obtained two distinct sub-population of cells within the Lewis lung cancer CSCs that employed largely symmetric division for self-renewal (LLC-SD) or underwent asymmetric division for differentiation (LLC-ASD). LLC-SD and LLC-ASD cell lines could be stably passaged in culture and be distinguished by cell morphology, stem cell marker, spheroid formation and subcutaneous tumor initiation efficiency, as well as orthotopic lung tumor growth, progression and survival. The ability LLC-ASD cells to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division. The more stem-like LLC-SD cells exhibited higher capacity for tumorigenesis and progression and shorter survival. As few as 10 LLC-SD could initiate subcutaneous tumor growth when transplanted to the athymic mice. Collectively, these observations suggest that the SD-type of cells appear to be on the top of the hierarchical order of the CSCs. Furthermore, they have lead to generated cellular models of CSC self-renewal for future mechanistic investigations.

  4. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    International Nuclear Information System (INIS)

    Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun; Juhn, Kyoung-Mi; Woo, Seon Rang; Kim, Hee-Young; Han, Young-Hoon; Hwang, Sang-Gu; Hong, Sung-Hee; Kang, Chang-Mo; Yoo, Young-Do; Park, Won-Bong; Cho, Myung-Haing; Park, Gil Hong; Lee, Kee-Ho

    2010-01-01

    Research highlights: → In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. → The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. → The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. → P53 status is not associated with the occurrence of unsensitized clone. → Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC -/- cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC -/- clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  5. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    Science.gov (United States)

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  6. A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

    Science.gov (United States)

    Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

    2016-06-01

    Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Yeast cells contain a heterogeneous population of peroxisomes that segregate asymmetrically during cell division

    NARCIS (Netherlands)

    Kumar, Sanjeev; de Boer, Rinse; van der Klei, Ida J

    2018-01-01

    Here we used fluorescence microscopy and a peroxisome-targeted tandem fluorescent protein timer to determine the relative age of peroxisomes in yeast. Our data indicate that yeast cells contain a heterogeneous population of relatively old and younger peroxisomes. During budding the peroxisome

  8. The Drosophila T-box transcription factor Midline functions within the Notch–Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc

    Science.gov (United States)

    Das, Sudeshna; Chen, Q. Brent; Saucier, Joseph D.; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M.

    2014-01-01

    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch–Delta signaling pathway essential for specifying the fates of sensory organ precursor cells. This complements an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in diverse neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch–Delta signaling hierarchy and is essential for maintaining cell viability within by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. PMID:23962751

  9. The Drosophila T-box transcription factor Midline functions within the Notch-Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc.

    Science.gov (United States)

    Das, Sudeshna; Chen, Q Brent; Saucier, Joseph D; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M

    2013-01-01

    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch-Delta signaling pathway essential for specifying the fates of sensory organ precursor (SOP) cells. These findings complement an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in unique neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch-Delta signaling hierarchy and is essential for maintaining cell viability by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Shima P Damodaran

    Full Text Available To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers and a significant subpopulation of slowly dividing cells (slow-growers. These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

  11. Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom.

    Science.gov (United States)

    Berger, Philipp; Sirkowski, Erich E; Scherer, Steven S; Suter, Ueli

    2004-11-01

    Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.

  12. The Relationship between Clinical Presentation and Unusual Sensory Interests in Autism Spectrum Disorders: A Preliminary Investigation

    Science.gov (United States)

    Zachor, Ditza A.; Ben-Itzchak, Esther

    2014-01-01

    Unusual responses to sensory stimuli have been described in autism spectrum disorder (ASD).The study examined the frequencies of "unusual sensory interests" and "negative sensory responses" and their relation to functioning in a large ASD population (n = 679). Having "unusual sensory interests" was reported in 70.4%…

  13. Use of Multicolor Flow Cytometry for Isolation of Specific Cell Populations Deriving from Differentiated Human Embryonic Stem Cells

    NARCIS (Netherlands)

    Mengarelli, Isabella; Fryga, Andrew; Barberi, Tiziano

    2016-01-01

    Flow Cytometry-Sorting (FCM-Sorting) is a technique commonly used to identify and isolate specific types of cells from a heterogeneous population of live cells. Here we describe a multicolor flow cytometry technique that uses five distinct cell surface antigens to isolate four live populations with

  14. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    David Fouchet

    Full Text Available BACKGROUND: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. METHODOLOGY AND PRINCIPAL FINDINGS: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. CONCLUSION/SIGNIFICANCE: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.

  15. Enrichment of skin-derived neural precursor cells from dermal cell populations by altering culture conditions.

    Science.gov (United States)

    Bayati, Vahid; Gazor, Rohoullah; Nejatbakhsh, Reza; Negad Dehbashi, Fereshteh

    2016-01-01

    As stem cells play a critical role in tissue repair, their manipulation for being applied in regenerative medicine is of great importance. Skin-derived precursors (SKPs) may be good candidates for use in cell-based therapy as the only neural stem cells which can be isolated from an accessible tissue, skin. Herein, we presented a simple protocol to enrich neural SKPs by monolayer adherent cultivation to prove the efficacy of this method. To enrich neural SKPs from dermal cell populations, we have found that a monolayer adherent cultivation helps to increase the numbers of neural precursor cells. Indeed, we have cultured dermal cells as monolayer under serum-supplemented (control) and serum-supplemented culture, followed by serum free cultivation (test) and compared. Finally, protein markers of SKPs were assessed and compared in both experimental groups and differentiation potential was evaluated in enriched culture. The cells of enriched culture concurrently expressed fibronectin, vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors as compared to control culture. In addition, they possessed a multipotential capacity to differentiate into neurogenic, glial, adipogenic, osteogenic and skeletal myogenic cell lineages. It was concluded that serum-free adherent culture reinforced by growth factors have been shown to be effective on proliferation of skin-derived neural precursor cells (skin-NPCs) and drive their selective and rapid expansion.

  16. The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth

    OpenAIRE

    Jiang, Nan; Soba, Peter; Parker, Edward; Kim, Charles C.; Parrish, Jay Z.

    2014-01-01

    As animals grow, many early born structures grow by cell expansion rather than cell addition; thus growth of distinct structures must be coordinated to maintain proportionality. This phenomenon is particularly widespread in the nervous system, with dendrite arbors of many neurons expanding in concert with their substrate to sustain connectivity and maintain receptive field coverage as animals grow. After rapidly growing to establish body wall coverage, dendrites of Drosophila class IV dendrit...

  17. Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear.

    Science.gov (United States)

    Yu, Xianwen; Lau, Doreen; Ng, Chee Peng; Roy, Sudipto

    2011-02-01

    Ciliary motility is necessary for many developmental and physiological processes in animals. In zebrafish, motile cilia are thought to be required for the deposition of otoliths, which comprise crystals of protein and calcium carbonate, on hair cells of the inner ear. The identity of the motile cilia and their role in otolith biogenesis, however, remain controversial. Here, we show that the ear vesicle differentiates numerous motile cilia, the spatial distribution of which changes as a function of the expression pattern of the ciliogenic gene foxj1b. By contrast, the hair cells develop immotile kinocilia that serve as static tethers for otolith crystallization. In ears devoid of all cilia, otoliths can form but they are of irregular shapes and sizes and appear to attach instead to the hair cell apical membranes. Moreover, overproduction of motile cilia also disrupts otolith deposition through sustained agitation of the precursor particles. Therefore, the correct spatial and temporal distribution of the motile cilia is crucial for proper otolith formation. Our findings support the view that the hair cells express a binding factor for the otolith precursors, while the motile cilia ensure that the precursors do not sediment prematurely and are efficiently directed towards the hair cells. We also provide evidence that the kinocilia are modified motile cilia that depend on Foxj1b for their differentiation. We propose that in hair cells, a Foxj1b-dependent motile ciliogenic program is altered by the proneural Atoh proteins to promote the differentiation of immotile kinocilia.

  18. Stratifying patients with peripheral neuropathic pain based on sensory profiles

    DEFF Research Database (Denmark)

    Vollert, Jan; Maier, Christoph; Attal, Nadine

    2017-01-01

    In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative sensory testing profiles, which are mainly characterized by either sensory loss, intact sensory function and mild thermal hyperalgesia and...... populations that need to be screened to reach a subpopulation large enough to conduct a phenotype-stratified study. The most common phenotype in diabetic polyneuropathy was sensory loss (83%), followed by mechanical hyperalgesia (75%) and thermal hyperalgesia (34%, note that percentages are overlapping...

  19. The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells.

    Directory of Open Access Journals (Sweden)

    Ralf Kist

    2014-10-01

    Full Text Available In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction.

  20. The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells.

    Science.gov (United States)

    Kist, Ralf; Watson, Michelle; Crosier, Moira; Robinson, Max; Fuchs, Jennifer; Reichelt, Julia; Peters, Heiko

    2014-10-01

    In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction.

  1. Partial Aminoglycoside Lesions in Vestibular Epithelia Reveal Broad Sensory Dysfunction Associated with Modest Hair Cell Loss and Afferent Calyx Retraction.

    Science.gov (United States)

    Sultemeier, David R; Hoffman, Larry F

    2017-01-01

    Although the effects of aminoglycoside antibiotics on hair cells have been investigated for decades, their influences on the dendrites of primary afferent neurons have not been widely studied. This is undoubtedly due to the difficulty in disassociating pathology to dendritic processes from that resulting from loss of the presynaptic hair cell. This was overcome in the present investigation through development of a preparation using Chinchilla laniger that enabled direct perilymphatic infusion. Through this strategy we unmasked gentamicin's potential effects on afferent calyces. The pathophysiology of the vestibular neuroepithelia after post-administration durations of 0.5 through 6 months was assessed using single-neuron electrophysiology, immunohistochemistry, and confocal microscopy. Hair cell densities within cristae central zones (0.5-, 1-, 2-, and 6-months) and utricle peri- and extrastriola (6-months) regions were determined, and damage to calretinin-immunoreactive calyces was quantified. Gentamicin-induced hair cell loss exhibited a profile that reflected elimination of a most-sensitive group by 0.5-months post-administration (18.2%), followed by loss of a second group (20.6%) over the subsequent 5.5 months. The total hair cell loss with this gentamicin dose (approximately 38.8%) was less than the estimated fraction of type I hair cells in the chinchilla's crista central zone (approximately 60%), indicating that viable type I hair cells remained. Extensive lesions to afferent calyces were observed at 0.5-months, though stimulus-evoked modulation was intact at this post-administration time. Widespread compromise to calyx morphology and severe attenuation of stimulus-evoked afferent discharge modulation was found at 1 month post-administration, a condition that persisted in preparations examined through the 6-month post-administration interval. Spontaneous discharge was robust at all post-administration intervals. All calretinin-positive calyces had retracted

  2. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    Science.gov (United States)

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

  3. T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity

    Directory of Open Access Journals (Sweden)

    Verhoef Adrienne

    2005-01-01

    Full Text Available Background Synthetic peptides, representing CD4+ T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. Methods and Findings In this study we address the mechanism of action of peptide immunotherapy (PIT in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4+ cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4neg PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4+ and CD8+ PBMCs. Conclusion This study provides evidence for the induction of a population of CD4+ T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.

  4. Sensory perception in autism.

    Science.gov (United States)

    Robertson, Caroline E; Baron-Cohen, Simon

    2017-11-01

    Autism is a complex neurodevelopmental condition, and little is known about its neurobiology. Much of autism research has focused on the social, communication and cognitive difficulties associated with the condition. However, the recent revision of the diagnostic criteria for autism has brought another key domain of autistic experience into focus: sensory processing. Here, we review the properties of sensory processing in autism and discuss recent computational and neurobiological insights arising from attention to these behaviours. We argue that sensory traits have important implications for the development of animal and computational models of the condition. Finally, we consider how difficulties in sensory processing may relate to the other domains of behaviour that characterize autism.

  5. Ultrastructure of photo-sensory cells and pigment epithelium in the retina of the Antarctic fish Notothenia neglecta Nybelin (Nototheniidae

    Directory of Open Access Journals (Sweden)

    Lucelia Donatti

    2002-03-01

    Full Text Available The Antarctic nototheniid Notothenia neglecta is the dominant fish in its habitat in Admiralty Bay, King George Island. They are predators, often ambush feeders, with accurate visual behaviour. For that reason, the ultrastructure of retinal photoreceptive cells and the pigment epithelium was analysed through electron microscopy. Their retina has a pigment epithelium, five different photoreceptors : rods, short single, long single, double, and triple cones, and neurones and support cells. The pigment epithelium is characterised by infoldings of the basal membrane, basal mitochondria, smooth reticule, large amount of microtubules, melanin granules, phagosomes and detached membranes of photoreceptors. Cones show bimembranous discs in the outer segment, an accessory outer segment, a connecting cilium, calycal processes, microtubules in the inferior ellipsoid and myoid, centrioles in the ellipsoid, interdigitating myoid fins and apical microvilli of Muller cells in the myoid and elliposid region. All these features allow all sorts of adaptations to the environmental photic variations, and situate N. neglecta among fish with a complex retina, with cells that are arranged in ten layers, allowing horizontal and vertical integration among them. This allows optimal visual behaviour and perception of food and environment in every Antarctic season.

  6. LGR4 and LGR5 regulate hair cell differentiation in the sensory epithelium of the developing mouse cochlea

    NARCIS (Netherlands)

    Zak, Magdalena; Van Oort, Thijs; Hendriksen, Ferry G.; Garcia, Marie Isabelle; Vassart, Gilbert; Grolman, Wilko

    2016-01-01

    In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the

  7. Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells

    DEFF Research Database (Denmark)

    Hald, Bjørn Olav; Hendriksen, Morten; Sørensen, Preben Graae

    2013-01-01

    Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredict...

  8. The CEA−/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells

    Science.gov (United States)

    Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-01-01

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies. PMID:27813496

  9. A descriptive study of plasma cell dyscrasias in Egyptian population

    International Nuclear Information System (INIS)

    Kassem, N.M.; Kassem, H.A.; EL Zawam, H.; EL Nahas, T.; Abd El Azeeim, H.; Abd El Azeeim; El Husseiny, N.M.

    2014-01-01

    Background: Plasma cell dyscrasias (PCDs) refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins or their components. These disorders include multiple myeloma (MM) and Waldenstrom’s macroglobulinemia, as well as rare conditions such as light-chain deposition disease (LCDD) and heavy-chain diseases (HCDs). The worldwide annual incidence of MM is estimated at 86,000, which is approximately 0.8% of all new cancer cases. Purpose: Our retrospective study aims to highlight the immunologic and epidemiological features of PCDs mainly MM in Egyptian patients and compare our results with those of other populations. Methods: Two hundred seventeen Egyptian patients with PCD were enrolled in the study. Serum, urine protein electrophoresis and immunofixation were used to demonstrate M protein. Results: One hundred thirty-eight patients (63.6%) had IgG monoclonal band, 38 patients (17.5%) had IgA, 12 patients (5.5%) had Waldenstrom’s macroglobulinemia (IgM monoclonal band) and 29 patients (13.4%) were light chain myeloma. One hundred fifty-one (70%) were Kappa chain positive and 66 patients (30%) were lumbda positive. Conventional cytogenetics was available for 40 patients; of them12 patients (30%) showed 13q-. Mean OS was 37.5 months (1-84 months). Survival analysis was statistically insignificant according to age, sex and ISS or type of treatment (P value >0.05). Conclusion: Long term follow up is required to further define the role of different therapeutic lines of treatment including ASCT in the various stages of PCD based on OS data.

  10. A descriptive study of plasma cell dyscrasias in Egyptian population.

    Science.gov (United States)

    Kassem, Neemat M; El Zawam, Hamdy; Kassem, Heba A; El Nahas, Tamer; El Husseiny, Noha M; El Azeeim, Hamdy Abd

    2014-06-01

    Plasma cell dyscrasias (PCDs) refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins or their components. These disorders include multiple myeloma (MM) and Waldenström's macroglobulinemia, as well as rare conditions such as light-chain deposition disease (LCDD) and heavy-chain diseases (HCDs). The worldwide annual incidence of MM is estimated at 86,000, which is approximately 0.8% of all new cancer cases. Our retrospective study aims to highlight the immunologic and epidemiological features of PCDs mainly MM in Egyptian patients and compare our results with those of other populations. Two hundred seventeen Egyptian patients with PCD were enrolled in the study. Serum, urine protein electrophoresis and immunofixation were used to demonstrate M protein. One hundred thirty-eight patients (63.6%) had IgG monoclonal band, 38 patients (17.5%) had IgA, 12 patients (5.5%) had Waldenström's macroglobulinemia (IgM monoclonal band) and 29 patients (13.4%) were light chain myeloma. One hundred fifty-one (70%) were Kappa chain positive and 66 patients (30%) were lumbda positive. Conventional cytogenetics was available for 40 patients; of them12 patients (30%) showed 13q-. Mean OS was 37.5months (1-84months). Survival analysis was statistically insignificant according to age, sex and ISS or type of treatment (P value>0.05). Long term follow up is required to further define the role of different therapeutic lines of treatment including ASCT in the various stages of PCD based on OS data. Copyright © 2013. Production and hosting by Elsevier B.V.

  11. Making sense of snapshot data: ergodic principle for clonal cell populations.

    Science.gov (United States)

    Thomas, Philipp

    2017-11-01

    Population growth is often ignored when quantifying gene expression levels across clonal cell populations. We develop a framework for obtaining the molecule number distributions in an exponentially growing cell population taking into account its age structure. In the presence of generation time variability, the average acquired across a population snapshot does not obey the average of a dividing cell over time, apparently contradicting ergodicity between single cells and the population. Instead, we show that the variation observed across snapshots with known cell age is captured by cell histories, a single-cell measure obtained from tracking an arbitrary cell of the population back to the ancestor from which it originated. The correspondence between cells of known age in a population with their histories represents an ergodic principle that provides a new interpretation of population snapshot data. We illustrate the principle using analytical solutions of stochastic gene expression models in cell populations with arbitrary generation time distributions. We further elucidate that the principle breaks down for biochemical reactions that are under selection, such as the expression of genes conveying antibiotic resistance, which gives rise to an experimental criterion with which to probe selection on gene expression fluctuations. © 2017 The Author(s).

  12. Design of a microfluidic device with a non-traditional flow profile for on-chip damage to zebrafish sensory cells

    International Nuclear Information System (INIS)

    Kwon, Hyuck-Jin; Xu, Yuhao; Solovitz, Stephen A; Xue, Wei; Xu, Jie; Dimitrov, Alexander G; Coffin, Allison B

    2014-01-01

    Hearing loss affects millions of people worldwide and often results from the death of the sensory hair cells in the inner ear, and exposure to intense noise is one of the leading causes of hair cell damage. Recently, the zebrafish lateral line system has emerged as a powerful in vivo model for real-time studies of hair cell damage and protection. In this research, we designed a microfluidic device for inducing noise damage in hair cells of the zebrafish lateral line. As the first step, a 3D computational fluid dynamics (CFD) simulation was utilized to predict the flow pattern inside the device. An ideal flow pattern for our application should feature higher velocity near the sidewalls to over-stimulate the externally located hair cells, and minimum flow in the middle of the channel to protect the fish from high pressure on the head. Flow induced from ordinary channel geometry with a single inlet/outlet pair would not work because the parabolic velocity profile features the maximum flow speed in the middle of the channel. In order to achieve the desired flow pattern, sidewall inlet/outlet pairs were used to suppress the growth of boundary layers. CFD simulation was used to design parameters such as the dimensions of the microfluidic channel and the angle of the inlets and outlets. It was found that in the case of an empty 2.0 mm wide channel with the inlet/outlet pairs set to 45°, the flow velocity at the side of the channel would be 6.7 times faster than the velocity in the middle, approaching the optimal flow characteristics. In the case of a fish-loaded channel, simulation shows that a 1.0 mm wide channel with a 60° inlet/outlet angle creates the lowest pressure (0.3 Pa) on the fish head while maintaining a reasonably strong shear stress (1.9 Pa) on the lateral line hair cells. (technical note)

  13. Phenotypic switching of populations of cells in a stochastic environment

    Science.gov (United States)

    Hufton, Peter G.; Lin, Yen Ting; Galla, Tobias

    2018-02-01

    In biology phenotypic switching is a common bet-hedging strategy in the face of uncertain environmental conditions. Existing mathematical models often focus on periodically changing environments to determine the optimal phenotypic response. We focus on the case in which the environment switches randomly between discrete states. Starting from an individual-based model we derive stochastic differential equations to describe the dynamics, and obtain analytical expressions for the mean instantaneous growth rates based on the theory of piecewise-deterministic Markov processes. We show that optimal phenotypic responses are non-trivial for slow and intermediate environmental processes, and systematically compare the cases of periodic and random environments. The best response to random switching is more likely to be heterogeneity than in the case of deterministic periodic environments, net growth rates tend to be higher under stochastic environmental dynamics. The combined system of environment and population of cells can be interpreted as host-pathogen interaction, in which the host tries to choose environmental switching so as to minimise growth of the pathogen, and in which the pathogen employs a phenotypic switching optimised to increase its growth rate. We discuss the existence of Nash-like mutual best-response scenarios for such host-pathogen games.

  14. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

    Science.gov (United States)

    Zhang, Bin; Liu, Rui; Shi, Dan; Liu, Xingxia; Chen, Yuan; Dou, Xiaowei; Zhu, Xishan; Lu, Chunhua; Liang, Wei; Liao, Lianming; Zenke, Martin; Zhao, Robert C H

    2009-01-01

    Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

  15. Principle component analysis (PCA) for investigation of relationship between population dynamics of microbial pathogenesis, chemical and sensory characteristics in beef slices containing Tarragon essential oil.

    Science.gov (United States)

    Alizadeh Behbahani, Behrooz; Tabatabaei Yazdi, Farideh; Shahidi, Fakhri; Mortazavi, Seyed Ali; Mohebbi, Mohebbat

    2017-04-01

    Principle component analysis (PCA) was employed to examine the effect of the exerted treatments on the beef shelf life as well as discovering the correlations between the studied responses. Considering the variability of the dimensions of the responses, correlation coefficients were applied to form the matrix and extract the eigenvalue. Antimicrobial effect was evaluated on 10 pathogenic microorganisms through the methods of hole-plate diffusion method, disk diffusion method, pour plate method, minimum inhibitory concentration and minimum bactericidal/fungicidal concentration. Antioxidant potential and total phenolic content were examined through the method of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Folin-Ciocalteu method, respectively. The components were identified through gas chromatography and gas chromatography/mass spectrometry. Barhang seed mucilage (BSM) based edible coating containing 0, 0.5, 1 and 1.5% (w/w) Tarragon (T) essential oil mix were applied on beef slices to control the growth of pathogenic microorganisms. Microbiological (total viable count, psychrotrophic count, Escherichia coli, Staphylococcus aureus and fungi), chemical (thiobarbituric acid, peroxide value and pH) and sensory characteristics (odor, color and overall acceptability) analysis measurements were made during the storage periodically. PCA was employed to examine the effect of the exerted treatments on the beef shelf life as well as discovering the correlations between the studied responses. Considering the variability of the dimensions of the responses, correlation coefficients were applied to form the matrix and extract the eigenvalue. The PCA showed that the properties of the uncoated meat samples on the 9th, 12th, 15th and 18th days of storage are continuously changing independent of the exerted treatments on the other samples. This reveals the effect of the exerted treatments on the samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Medullospheres from DAOY, UW228 and ONS-76 cells: increased stem cell population and proteomic modifications.

    Science.gov (United States)

    Zanini, Cristina; Ercole, Elisabetta; Mandili, Giorgia; Salaroli, Roberta; Poli, Alice; Renna, Cristiano; Papa, Valentina; Cenacchi, Giovanna; Forni, Marco

    2013-01-01

    Medulloblastoma (MB) is an aggressive pediatric tumor of the Central Nervous System (CNS) usually treated according to a refined risk stratification. The study of cancer stem cells (CSC) in MB is a promising approach aimed at finding new treatment strategies. The CSC compartment was studied in three characterized MB cell lines (DAOY, UW228 and ONS-76) grown in standard adhesion as well as being grown as spheres, which enables expansion of the CSC population. MB cell lines, grown in adherence and as spheres, were subjected to morphologic analysis at the light and electron microscopic level, as well as cytofluorimetric determinations. Medullospheres (MBS) were shown to express increasingly immature features, along with the stem cells markers: CD133, Nestin and β-catenin. Proteomic analysis highlighted the differences between MB cell lines, demonstrating a unique protein profile for each cell line, and minor differences when grown as spheres. In MBS, MALDI-TOF also identified some proteins, that have been linked to tumor progression and resistance, such as Nucleophosmin (NPM). In addition, immunocytochemistry detected Sox-2 as a stemness marker of MBS, as well as confirming high NPM expression. Culture conditioning based on low attachment flasks and specialized medium may provide new data on the staminal compartment of CNS tumors, although a proteomic profile of CSC is still elusive for MB.

  17. Medullospheres from DAOY, UW228 and ONS-76 cells: increased stem cell population and proteomic modifications.

    Directory of Open Access Journals (Sweden)

    Cristina Zanini

    Full Text Available BACKGROUND: Medulloblastoma (MB is an aggressive pediatric tumor of the Central Nervous System (CNS usually treated according to a refined risk stratification. The study of cancer stem cells (CSC in MB is a promising approach aimed at finding new treatment strategies. METHODOLOGY/PRINCIPAL FINDINGS: The CSC compartment was studied in three characterized MB cell lines (DAOY, UW228 and ONS-76 grown in standard adhesion as well as being grown as spheres, which enables expansion of the CSC population. MB cell lines, grown in adherence and as spheres, were subjected to morphologic analysis at the light and electron microscopic level, as well as cytofluorimetric determinations. Medullospheres (MBS were shown to express increasingly immature features, along with the stem cells markers: CD133, Nestin and β-catenin. Proteomic analysis highlighted the differences between MB cell lines, demonstrating a unique protein profile for each cell line, and minor differences when grown as spheres. In MBS, MALDI-TOF also identified some proteins, that have been linked to tumor progression and resistance, such as Nucleophosmin (NPM. In addition, immunocytochemistry detected Sox-2 as a stemness marker of MBS, as well as confirming high NPM expression. CONCLUSIONS/SIGNIFICANCE: Culture conditioning based on low attachment flasks and specialized medium may provide new data on the staminal compartment of CNS tumors, although a proteomic profile of CSC is still elusive for MB.

  18. UNCOMMON SENSORY METHODOLOGIES

    Directory of Open Access Journals (Sweden)

    Vladimír Vietoris

    2015-02-01

    Full Text Available Sensory science is the young but the rapidly developing field of the food industry. Actually, the great emphasis is given to the production of rapid techniques of data collection, the difference between consumers and trained panel is obscured and the role of sensory methodologists is to prepare the ways for evaluation, by which a lay panel (consumers can achieve identical results as a trained panel. Currently, there are several conventional methods of sensory evaluation of food (ISO standards, but more sensory laboratories are developing methodologies that are not strict enough in the selection of evaluators, their mechanism is easily understandable and the results are easily interpretable. This paper deals with mapping of marginal methods used in sensory evaluation of food (new types of profiles, CATA, TDS, napping.

  19. Probabilistic sensory recoding.

    Science.gov (United States)

    Jazayeri, Mehrdad

    2008-08-01

    A hallmark of higher brain functions is the ability to contemplate the world rather than to respond reflexively to it. To do so, the nervous system makes use of a modular architecture in which sensory representations are dissociated from areas that control actions. This flexibility however necessitates a recoding scheme that would put sensory information to use in the control of behavior. Sensory recoding faces two important challenges. First, recoding must take into account the inherent variability of sensory responses. Second, it must be flexible enough to satisfy the requirements of different perceptual goals. Recent progress in theory, psychophysics, and neurophysiology indicate that cortical circuitry might meet these challenges by evaluating sensory signals probabilistically.

  20. In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice

    Directory of Open Access Journals (Sweden)

    Bradley J. Walters

    2017-04-01

    Full Text Available Summary: Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs declines abruptly after postnatal maturation. We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27Kip1 deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional therapeutic targets for ATOH1-mediated HC regeneration. : Auditory hair cells are nonregenerative, resulting in persistent hearing loss upon damage. Walters et al. find that manipulating two genes, p27Kip1 and Atoh1, induces the conversion of nonsensory cells to hair cells in adult mice. This effect is mediated by GATA3 and POU4F3, where POU4F3 alone was found to convert nonsensory cells. Keywords: regeneration, aging, differentiation, proliferation, development, cancer, sensory, cochlea, hearing

  1. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

    2013-05-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

  2. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K.

    2013-01-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities

  3. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  4. Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Fabian Duttenhoefer

    2015-01-01

    Full Text Available In bone tissue engineering (TE endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs are a rich source of mesenchymal stem cells (MSCs able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+ were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+ or medium containing platelet lysate (PL. MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

  5. What Population Reveals about Individual Cell Identity: Single-Cell Parameter Estimation of Models of Gene Expression in Yeast.

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    Artémis Llamosi

    2016-02-01

    Full Text Available Significant cell-to-cell heterogeneity is ubiquitously observed in isogenic cell populations. Consequently, parameters of models of intracellular processes, usually fitted to population-averaged data, should rather be fitted to individual cells to obtain a population of models of similar but non-identical individuals. Here, we propose a quantitative modeling framework that attributes specific parameter values to single cells for a standard model of gene expression. We combine high quality single-cell measurements of the response of yeast cells to repeated hyperosmotic shocks and state-of-the-art statistical inference approaches for mixed-effects models to infer multidimensional parameter distributions describing the population, and then derive specific parameters for individual cells. The analysis of single-cell parameters shows that single-cell identity (e.g. gene expression dynamics, cell size, growth rate, mother-daughter relationships is, at least partially, captured by the parameter values of gene expression models (e.g. rates of transcription, translation and degradation. Our approach shows how to use the rich information contained into longitudinal single-cell data to infer parameters that can faithfully represent single-cell identity.

  6. Specialized Cilia in Mammalian Sensory Systems

    Directory of Open Access Journals (Sweden)

    Nathalie Falk

    2015-09-01

    Full Text Available Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies.

  7. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis of sensory hair cells in the mouse inner ear

    Directory of Open Access Journals (Sweden)

    Neil eSegil

    2015-05-01

    Full Text Available Aminoglycoside antibiotics are the drug of choice for treating many bacterial infections, but their administration results in hearing loss in nearly one fourth of the patients who receive them. Several biochemical pathways have been implicated in aminoglycoside antibiotic ototoxicity; however, little is known about how hair cells respond to aminoglycoside antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the aminoglycoside antibiotic gentamicin. Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from FACS-purified hair cells. Within 3 hours of gentamicin treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the JNK pathway and the NF-κB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to gentamicin share a considerable similarity with those previously observed in gentamicin-induced nephrotoxicity. Our findings suggest that previously observed early responses to gentamicin in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternative pathway regulating gentamicin-induced hair cell death. This work provides a more comprehensive view of aminoglycoside antibiotic ototoxicity, and thus contribute to identifying potential pathways or therapeutic targets to alleviate this important side effect of aminoglycoside

  8. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers

    NARCIS (Netherlands)

    Almeida, Afonso R. M.; Legrand, Nicolas; Papiernik, Martine; Freitas, António A.

    2002-01-01

    We show that the lymphoid hyperplasia observed in IL-2Ralpha- and IL-2-deficient mice is due to the lack of a population of regulatory cells essential for CD4 T cell homeostasis. In chimeras reconstituted with bone marrow cells from IL-2Ralpha-deficient donors, restitution of a population of

  9. Accessibility and sensory experiences

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2010-01-01

    and accessibility. Sensory accessibility accommodates aspects of a sensory disability and describes architectural design requirements needed to ensure access to architectural experiences. In the context of architecture accessibility has become a design concept of its own. It is generally described as ensuring...... physical access to the built environment by accommodating physical disabilities. While the existing concept of accessibility ensures the physical access of everyone to a given space, sensory accessibility ensures the choice of everyone to stay and be able to participate and experience....

  10. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  11. A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells.

    Science.gov (United States)

    Takamatsu, H-H; Denyer, M S; Wileman, T E

    2002-09-10

    A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated with antigen presenting cells (APCs), and are able to take up soluble antigen very effectively. Functional antigen presentation by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin (OVA). After removing all conventional APCs from the peripheral blood of immunised pigs, the remaining lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA specific proliferation was abolished, but reconstitution with gammadelta T cells restored proliferation. The proliferation was blocked by monoclonal antibodies (mAb) against MHC class II or CD4, and by pre-treatment of gammadelta T cells with chloroquine. These results indicate that a sub-population of circulating porcine gammadelta T cells act as APCs and present antigen via MHC class II.

  12. Thin Layer Sensory Cues Affect Antarctic Krill Swimming Kinematics

    Science.gov (United States)

    True, A. C.; Webster, D. R.; Weissburg, M. J.; Yen, J.

    2013-11-01

    A Bickley jet (laminar, planar free jet) is employed in a recirculating flume system to replicate thin shear and phytoplankton layers for krill behavioral assays. Planar laser-induced fluorescence (LIF) and particle image velocimetry (PIV) measurements quantify the spatiotemporal structure of the chemical and free shear layers, respectively, ensuring a close match to in situ hydrodynamic and biochemical conditions. Path kinematics from digitized trajectories of free-swimming Euphausia superba examine the effects of hydrodynamic sensory cues (deformation rate) and bloom level phytoplankton patches (~1000 cells/mL, Tetraselamis spp.) on krill behavior (body orientation, swimming modes and kinematics, path fracticality). Krill morphology is finely tuned for receiving and deciphering both hydrodynamic and chemical information that is vital for basic life processes such as schooling behaviors, predator/prey, and mate interactions. Changes in individual krill behavior in response to ecologically-relevant sensory cues have the potential to produce population-scale phenomena with significant ecological implications. Krill are a vital trophic link between primary producers (phytoplankton) and larger animals (seabirds, whales, fish, penguins, seals) as well as the subjects of a valuable commercial fishery in the Southern Ocean; thus quantifying krill behavioral responses to relevant sensory cues is an important step towards accurately modeling Antarctic ecosystems.

  13. Membrane potential correlates of sensory perception in mouse barrel cortex.

    Science.gov (United States)

    Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

    2013-11-01

    Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

  14. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous hMSC...... population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high...... and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone...

  15. Neuromorphic sensory systems.

    Science.gov (United States)

    Liu, Shih-Chii; Delbruck, Tobi

    2010-06-01

    Biology provides examples of efficient machines which greatly outperform conventional technology. Designers in neuromorphic engineering aim to construct electronic systems with the same efficient style of computation. This task requires a melding of novel engineering principles with knowledge gleaned from neuroscience. We discuss recent progress in realizing neuromorphic sensory systems which mimic the biological retina and cochlea, and subsequent sensor processing. The main trends are the increasing number of sensors and sensory systems that communicate through asynchronous digital signals analogous to neural spikes; the improved performance and usability of these sensors; and novel sensory processing methods which capitalize on the timing of spikes from these sensors. Experiments using these sensors can impact how we think the brain processes sensory information. 2010 Elsevier Ltd. All rights reserved.

  16. Sensory evaluation techniques

    National Research Council Canada - National Science Library

    Meilgaard, Morten; Civille, Gail Vance; Carr, B. Thomas

    1991-01-01

    ..., #2 as a textbook for courses at the academic level, it aims to provide just enough theoretical background to enable the student to understand which sensory methods are best suited to particular...

  17. [Treatment of sensory information in neurodevelopmental disorders].

    Science.gov (United States)

    Zoenen, D; Delvenne, V

    2018-01-01

    The processing of information coming from the elementary sensory systems conditions the development and fulfilment of a child's abilities. A dysfunction in the sensory stimuli processing may generate behavioural patterns that might affect a child's learning capacities as well as his relational sphere. The DSM-5 recognizes the sensory abnormalities as part of the symptomatology of Autism Spectrum Disorders. However, similar features are observed in other neurodevelopmental disorders. Over the years, these conditions have been the subject of numerous controversies. Nowadays, they are all grouped together under the term of Neurodevelopmental Disorders in DSM-5. The semiology of these disorders is rich and complex due to the frequent presence of comorbidities and their impact on cognitive, behavioural, and sensorimotor organization but also on a child's personality, as well as his family, his school, or his social relationships. We carried out a review of the literature on the alterations in the treatment of sensory information in ASD but also on the different neurodevelopmental clinical panels in order to show their impact on child development. Atypical sensory profiles have been demonstrated in several neurodevelopmental clinical populations such as Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorders, Dysphasia and Intellectual Disability. Abnomalies in the processing of sensory information should be systematically evaluated in child developmental disorders.

  18. 3-Bromopyruvate inhibits cell proliferation and induces apoptosis in CD133+ population in human glioma.

    Science.gov (United States)

    Xu, Dong-Qiang; Tan, Xiao-Yu; Zhang, Bao-Wei; Wu, Tao; Liu, Ping; Sun, Shao-Jun; Cao, Yin-Guang

    2016-03-01

    The study was aimed to investigate the role of 3-bromopyruvate in inhibition of CD133+ U87 human glioma cell population growth. The results demonstrated that 3-bromopyruvate inhibited the viability of both CD133+ and parental cells derived from U87 human glioma cell line. However, the 3-bromopyruvate-induced inhibition in viability was more prominent in CD133+ cells at 10 μM concentration after 48 h. Treatment of CD133+ cells with 3-bromopyruvate caused reduction in cell population and cell size, membrane bubbling, and degradation of cell membranes. Hoechst 33258 staining showed condensation of chromatin material and fragmentation of DNA in treated CD133+ cells after 48 h. 3-Bromopyruvate inhibited the migration rate of CD133+ cells significantly compared to the parental cells. Flow cytometry revealed that exposure of CD133+ cells to 3-bromopyruvate increased the cell population in S phase from 24.5 to 37.9 % with increase in time from 12 to 48 h. In addition, 3-bromopyruvate significantly enhanced the expression of Bax and cleaved caspase 3 in CD133+ cells compared to the parental cells. Therefore, 3-bromopyruvate is a potent chemotherapeutic agent for the treatment of glioma by targeting stem cells selectively.

  19. Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro

    International Nuclear Information System (INIS)

    Yang, Min; Zhang, Rui; Yan, Ming; Ye, Zhengxu; Liang, Wei; Luo, Zhuojing

    2010-01-01

    Dye exclusion is a valuable technique to isolate cancer stem cells (CSCs) based on an ability of stem cell to efflux fluorescent DNA-binding dye, especially for tumors without unique surface markers. It has been proven that side population (SP) cells that exclude Hoechst 33342 dye are enriched with stem-like cells in several cancer cell lines. In this study, we isolated and characterized SP cells from human Ewing's sarcoma cell line SK-ES-1 in vitro. SP cells were detected in SK-ES-1 and comprised 1.2% of total cell population. Only SP cells had the capacity to regenerate both SP and non-SP cells. The proliferation rates were similar between SP and non-SP cells. However, the clonogenicity and invasiveness of SP cells were significantly higher than that of non-SP cells. Further characterization of this SP phenotype presented other properties. SP cells exhibited increased multi-drug resistance and the ATP binding cassette protein (ABC) transporters were up-regulated in SP population. These findings suggest that SP cells derived from Ewing's sarcoma play the critical role in tumor metastasis and recurrence and might be an ideal target for clinical therapy.

  20. A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population

    Science.gov (United States)

    WATANABE, YUSAKU; YOSHIMURA, KIYOSHI; YOSHIKAWA, KOICHI; TSUNEDOMI, RYOICHI; SHINDO, YOSHITARO; MATSUKUMA, SOU; MAEDA, NORIKO; KANEKIYO, SHINSUKE; SUZUKI, NOBUAKI; KURAMASU, ATSUO; SONODA, KOUHEI; TAMADA, KOJI; KOBAYASHI, SEI; SAYA, HIDEYUKI; HAZAMA, SHOICHI; OKA, MASAAKI

    2014-01-01

    Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLCenriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy. PMID:25118635

  1. Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat

    Directory of Open Access Journals (Sweden)

    Boudreaux Crystal E

    2012-05-01

    Full Text Available Abstract Background An appropriate balance in placental regulatory T cells (Tregs, an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation. Methods We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6. Results FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals. Conclusion Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.

  2. Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.

    Science.gov (United States)

    Cosette, Jérémie; Moussy, Alice; Onodi, Fanny; Auffret-Cariou, Adrien; Neildez-Nguyen, Thi My Anh; Paldi, Andras; Stockholm, Daniel

    2015-12-09

    Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.

  3. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

    Full Text Available Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay.ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells.We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP

  4. Physically disconnected non-diffusible cell-to-cell communication between neuroblastoma SH-SY5Y and DRG primary sensory neurons.

    Science.gov (United States)

    Chaban, Victor V; Cho, Taehoon; Reid, Christopher B; Norris, Keith C

    2013-01-01

    Cell-cell communication occurs via a variety of mechanisms, including long distances (hormonal), short distances (paracrine and synaptic) or direct coupling via gap junctions, antigen presentation, or ligand-receptor interactions. We evaluated the possibility of neuro-hormonal independent, non-diffusible, physically disconnected pathways for cell-cell communication using dorsal root ganglion (DRG) neurons. We assessed intracellular calcium ([Ca(2+)]) in primary culture DRG neurons that express ATP-sensitive P2X3, capsaicinsensitive TRPV1 receptors modulated by estradiol. Physically disconnected (dish-in-dish system; inner chamber enclosed) mouse DRG were cultured for 12 hours near: a) media alone (control 1), b) mouse DRG (control 2), c) human neuroblastoma SHSY-5Y cells (cancer intervention), or d) mouse DRG treated with KCl (apoptosis intervention). Chemosensitive receptors [Ca(2+)](i) signaling did not differ between control 1 and 2. ATP (10 μM) and capsaicin (100nM) increased [Ca(2+)](i) transients to 425.86 + 49.5 nM, and 399.21 ± 44.5 nM, respectively. 17β-estradiol (100 nM) exposure reduced ATP (171.17 ± 48.9 nM) and capsaicin (175.01±34.8 nM) [Ca(2+)](i) transients. The presence of cancer cells reduced ATP- and capsaicin-induced [Ca(2+)](i) by >50% (pcommunication.

  5. Novel microchip-based tools facilitating live cell imaging and assessment of functional heterogeneity within NK cell populations

    Directory of Open Access Journals (Sweden)

    Elin eForslund

    2012-10-01

    Full Text Available Each individual has a heterogeneous pool of NK cells consisting of cells that may be specialized towards specific functional responses such as secretion of cytokines or killing of tumor cells. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are also transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended times. This paper presents a versatile microchip platform enabling long-term microscopic studies of individual NK cells interacting with target cells. Each microchip contains an array of microwells, optimized for medium or high-resolution time-lapse imaging of single or multiple NK and target cells, or for screening of thousands of isolated NK-target cell interactions. Individual NK cells confined with target cells in small microwells is a suitable setup for high-content screening and rapid assessment of heterogeneity within populations, while microwells of larger dimensions are appropriate for studies of NK cell migration and sequential interactions with multiple target cells. By combining the chip technology with ultrasonic manipulation, NK and target cells can be forced to interact and positioned with high spatial accuracy within individual microwells. This setup effectively and synchronously creates NK-target conjugates at hundreds of parallel positions in the microchip. Thus, this facilitates assessment of temporal aspects of NK-target cell interactions, e.g. conjugation, immune synapse formation and cytotoxic events. The microchip platform presented here can be used to effectively address questions related to fundamental functions of NK cells that can lead to better understanding of how the behavior of individual cells add up to give a functional response at

  6. HOX and TALE signatures specify human stromal stem cell populations from different sources.

    Science.gov (United States)

    Picchi, Jacopo; Trombi, Luisa; Spugnesi, Laura; Barachini, Serena; Maroni, Giorgia; Brodano, Giovanni Barbanti; Boriani, Stefano; Valtieri, Mauro; Petrini, Mario; Magli, Maria Cristina

    2013-04-01

    Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues. Copyright © 2012 Wiley Periodicals, Inc.

  7. Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

    Science.gov (United States)

    de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

    2017-03-01

    An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

  8. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Stroh, Albrecht

    2015-01-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. PMID:26661247

  9. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

    2016-11-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

  10. Verification and clarification of patterns of sensory integrative dysfunction.

    Science.gov (United States)

    Mailloux, Zoe; Mulligan, Shelley; Roley, Susanne Smith; Blanche, Erna; Cermak, Sharon; Coleman, Gina Geppert; Bodison, Stefanie; Lane, Christianne Joy

    2011-01-01

    Building on established relationships between the constructs of sensory integration in typical and special needs populations, in this retrospective study we examined patterns of sensory integrative dysfunction in 273 children ages 4-9 who had received occupational therapy evaluations in two private practice settings. Test results on the Sensory Integration and Praxis Tests, portions of the Sensory Processing Measure representing tactile overresponsiveness, and parent report of attention and activity level were included in the analyses. Exploratory factor analysis identified patterns similar to those found in early studies by Ayres (1965, 1966a, 1966b, 1969, 1972b, 1977, & 1989), namely Visuodyspraxia and Somatodyspraxia, Vestibular and Proprioceptive Bilateral Integration and Sequencing, Tactile and Visual Discrimination, and Tactile Defensiveness and Attention. Findings reinforce associations between constructs of sensory integration and assist with understanding sensory integration disorders that may affect childhood occupation. Limitations include the potential for subjective interpretation in factor analysis and inability to adjust measures available in charts in a retrospective research.

  11. Analysing the Influence of the Spontaneous Aneuploidy Frequency on the Cell Population System Cultivation

    Directory of Open Access Journals (Sweden)

    G. A. Nefedov

    2015-01-01

    Full Text Available The paper provides a qualitative analysis of M.S. Vinogradova's nonlinear model for dynamics of the cell population system. This system describes the stem cells cultivation in vitro under resource constraints. The system consists of two populations, namely: population of normal cells and population of abnormal cells. Resource constraints are considered as linear dependences of mitosis parameters on the normalized densities of each population.One of the key parameters that effects on the realization of the system evolution scenarios is a parameter that determines a share of the normal cells, which pass, when dividing, into population of the abnormal cells. The paper analyses both the existence conditions of the rest points and the changes of the evolution scenarios of population system with changing abovementioned parameter and other system parameters held fixed. It is shown that there is a saddle-node bifurcation in the system; the bifurcation value of the parameter is found. The paper shows the interval of parameter values in which the favorable scenarios of population system evolution are implemented. It also presents results of mathematical modeling.

  12. Late post-irradiation phenomena in mammalain cell populations. Pt. 2. Intraclonal recovery in sublines isolated from X-irradiated L5178Y-S cell populations

    International Nuclear Information System (INIS)

    Beer, J.Z.

    1975-01-01

    Clonal analysis of L5178Y-S cell populations irradiated with 300 rads of X-rays indicates occurence of cell sublines with considerably prolonged mean doubling times up to 22 h as compared to 10-11 h for control. Subsequent observations of growth of the handicapped sublines derived from single cells showed capability of all more than 100 studied sublines to recover normal proliferative activity. This process of intraclonal recovery required in many cases longer periods of time, corresponding to many tens, sometimes more than 200, generations. Late intraclonal recovery was further analysed by subcloning. It was found that although cytochemically assayed viability of the handicapped sublines was normal, cloning efficiency strongly depended on the stage of the recovery process. The recovery processes occuring in clones isolated from irradiated cell populations were compared with analogous processes occuring in slowly growing sublines isolated from non-irradiated cell cultures. Marked differences in kinetics of these processes show that either they are different in sublines derived from irradiated and non-irradiated cell populations or that the mechanisms of the late intraclonal recovery are affected by radiation. The results presented allow to conclude that gradual post-irradiation recovery of growth depends primarily on formation, in the developing populations, of cells with higher proliferative activities. Possible nature of the recovery processes is discussed in the light of available information on mammalian somatic cell variants with altered drug or temperature sensitivity, or with nutritional requirements. A sequence is proposed of changes leading from radiation-induced disturbance of the normably existing equilibrium between three basic cell subpopulations to ultimate restoration of this equilibrium. (author)

  13. Topological defects in confined populations of spindle-shaped cells

    Science.gov (United States)

    Duclos, Guillaume; Erlenkämper, Christoph; Joanny, Jean-François; Silberzan, Pascal

    2017-01-01

    Most spindle-shaped cells (including smooth muscles and sarcomas) organize in vivo into well-aligned `nematic’ domains, creating intrinsic topological defects that may be used to probe the behaviour of these active nematic systems. Active non-cellular nematics have been shown to be dominated by activity, yielding complex chaotic flows. However, the regime in which live spindle-shaped cells operate, and the importance of cell-substrate friction in particular, remains largely unexplored. Using in vitro experiments, we show that these active cellular nematics operate in a regime in which activity is effectively damped by friction, and that the interaction between defects is controlled by the system’s elastic nematic energy. Due to the activity of the cells, these defects behave as self-propelled particles and pairwise annihilate until all displacements freeze as cell crowding increases. When confined in mesoscopic circular domains, the system evolves towards two identical +1/2 disclinations facing each other. The most likely reduced positions of these defects are independent of the size of the disk, the cells’ activity or even the cell type, but are well described by equilibrium liquid crystal theory. These cell-based systems thus operate in a regime more stable than other active nematics, which may be necessary for their biological function.

  14. Carrier population control and surface passivation in solar cells

    KAUST Repository

    Cuevas, Andres; Wan, Yimao; Yan, Di; Samundsett, Christian; Allen, Thomas; Zhang, Xinyu; Cui, Jie; Bullock, James

    2018-01-01

    Controlling the concentration of charge carriers near the surface is essential for solar cells. It permits to form regions with selective conductivity for either electrons or holes and it also helps to reduce the rate at which they recombine

  15. small cell lung cancer in a Chinese population

    African Journals Online (AJOL)

    clinical significance in patients with non-small cell lung cancer (NSCLC) in Hubei province ... diagnosis, tumor stage, treatment, progression .... Table 4: Association between EGFR mutation, gender and histologic type in 138 NSCLC patients.

  16. Merging Mixture Components for Cell Population Identification in Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Greg Finak

    2009-01-01

    Full Text Available We present a framework for the identification of cell subpopulations in flow cytometry data based on merging mixture components using the flowClust methodology. We show that the cluster merging algorithm under our framework improves model fit and provides a better estimate of the number of distinct cell subpopulations than either Gaussian mixture models or flowClust, especially for complicated flow cytometry data distributions. Our framework allows the automated selection of the number of distinct cell subpopulations and we are able to identify cases where the algorithm fails, thus making it suitable for application in a high throughput FCM analysis pipeline. Furthermore, we demonstrate a method for summarizing complex merged cell subpopulations in a simple manner that integrates with the existing flowClust framework and enables downstream data analysis. We demonstrate the performance of our framework on simulated and real FCM data. The software is available in the flowMerge package through the Bioconductor project.

  17. Irradiation of liquid egg, frozen egg, powdered egg, egg yolk and white of egg: reducing the population of Salmonella enteritidis and sensory aspects and physico-chemical

    International Nuclear Information System (INIS)

    Froehlich, Angela

    2004-01-01

    Eggs and their products have been incriminated in foodborne disease outbreaks due to Salmonella enteritidis contamination. Irradiation is a food preservation technology that could be applied to minimize the problem. The aim of this study was to determine the effect of irradiation in liquid and frozen egg as well as in powdered egg, egg yolk and egg white spiked with Salmonella enteritidis. Spiked samples of liquid egg, egg white and egg yolk were exposed to 0,5; 1,0; 1,5; 2,0; 2,5; 3,0 kGy and spiked samples of frozen and powdered egg were exposed to 0,5; 1,0; 1,5; 2,0; 2,5; 3,0; 3,5 e 4,0 kGy. Raw odour, cooked odour and taste of non inoculated and irradiated samples and non irradiated samples of egg and egg products were analysed by a trained penal. Viscosity and lipid oxidation (malonaldehyde concentration) were also determined. Doses of 2,0; 3,0; 3,5; 3,0 e 3,5 kGy reduced in 5 log the population of S. Enteritidis in liquid and frozen egg, powdered egg yolk, egg white and egg, respectively, with moderate alterations in relation to non irradiated samples detected by the trained penal. Viscosity and lipid oxidation in the powdered products, however, showed more intense alterations. Therefore, irradiation can be considered a feasible process for liquid and frozen egg while when applied to powdered products it should be considered the type of food product to which they will be added due to alterations in viscosity. (author)

  18. Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

    OpenAIRE

    Fidel, Paul L.; Luo, Wei; Steele, Chad; Chabain, Joseph; Baker, Marc; Wormley, Floyd

    1999-01-01

    Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leuko...

  19. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

    Directory of Open Access Journals (Sweden)

    Fierro Leonardo

    2005-11-01

    Full Text Available Abstract Background ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1 ASIC3 might trigger ischemic pain in heart and muscle; 2 it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. Results Less than half (40% of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small ( Conclusion Our data indicates that: 1 ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2 co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.

  20. Heterogeneity within populations of recombinant Chinese hamster ovary cells expressing human interferon-gamma.

    Science.gov (United States)

    Coppen, S R; Newsam, R; Bull, A T; Baines, A J

    1995-04-20

    The Chinese hamster ovary (CHO) cell line has great commercial importance in the production of recombinant human proteins, especially those for therapeutic use. Much attention has been paid to CHO cell population physiology in order to define factors affecting product fidelity and yield. Such studies have revealed that recombinant proteins, including human interferon-gamma (IFN-gamma), can be heterogeneous both in glycosylation and in proteolytic processing. The type of heterogeneity observed depends on the growth physiology of the cell population, although the relationship between them is complex. In this article we report results of a cytological study of the CHO320 line which expresses recombinant human IFN-gamma. When grown in suspension culture, this cell line exhibited three types of heterogeneity: (1) heterogeneity of the production of IFN-gamma within the cell population, (2) heterogeneity of the number of nuclei and mitotic spindles in dividing cells, and (3) heterogeneity of cellular environment. The last of these arises from cell aggregates which form in suspension culture: Some cells are exposed to the culture medium; others are fully enclosed within the mass with little or no direct access to the medium. Thus, live cells producing IFN-gamma are heterogeneous in their environment, with variable access to O(2) and nutrients. Within the aggregates, it appears that live cells proliferate on a dead cell mass. The layer of live cells can be several cells deep. Specific cell-cell attachments are observed between the living cells in these aggregates. Two proteins, known to be required for the formation of certain types of intercellular junctions, spectrin and vinculin, have been localized to the regions of cell-cell contact. The aggregation of the cells appears to be an active process requiring protein synthesis. (c) 1995 John Wiley & Sons, Inc.

  1. Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

    Science.gov (United States)

    Fazleabas, A. T.; Braundmeier, A. G.; Markham, R.; Fraser, I. S.; Berbic, M.

    2011-01-01

    Mounting evidence suggests that immunological responses may be altered in endometriosis. The baboon (Papio anubis) is generally considered the best model of endometriosis pathogenesis. The objective of the current study was to investigate for the first time immunological changes within uterine and peritoneal draining lymph nodes in a nonhuman primate baboon model of endometriosis. Paraffin-embedded femoral lymph nodes were obtained from 22 normally cycling female baboons (induced endometriosis n = 11; control n = 11). Immunohistochemical staining was performed with antibodies for endometrial stromal cells, T cells, immature and mature dendritic cells, and B cells. Lymph nodes were evaluated using an automated cellular imaging system. Endometrial stromal cells were significantly increased in lymph nodes from animals with induced endometriosis, compared to control animals (P = .033). In animals with induced endometriosis, some lymph node immune cell populations including T cells, dendritic cells and B cells were increased, suggesting an efficient early response or peritoneal drainage. PMID:21617251

  2. Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

    Science.gov (United States)

    Fidel, Paul L.; Luo, Wei; Steele, Chad; Chabain, Joseph; Baker, Marc; Wormley, Floyd

    1999-01-01

    Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection. PMID:10338532

  3. Cellular population dynamics control the robustness of the stem cell niche

    Directory of Open Access Journals (Sweden)

    Adam L. MacLean

    2015-11-01

    Full Text Available Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

  4. In vitro expansion of the mammary stem/progenitor cell population by xanthosine treatment

    Directory of Open Access Journals (Sweden)

    Choudhary Ratan K

    2012-06-01

    Full Text Available Abstract Background Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore are of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo, and hepatic and hair follicle stem cells in vitro. In the latter, xanthosine promoted the symmetrical division of hepatic and hair follicle stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC with xanthosine increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells. Results In vitro treatment with xanthosine increased the population of MEC during the exponential phase of cell growth, reducing the doubling time from 86 h in control cultures to 60 h in xanthosine-treated cultures. The bromodeoxyuridine (BrdU labeling index and the proportion of MEC in S-phase both were increased by xanthosine treatment, indicating that increased cell accretion was due to increased cell proliferation. Analysis of daughter-pairs indicated that xanthosine promoted a shift from asymmetric to symmetric cell division. Moreover, the 30 % increase in symmetric cell division was concomitant with an increase in the proportion of MEC that were positive for a putative stem cell marker (FNDC3B and a trend toward increased telomerase activity. These results suggest that xanthosine treatment in vitro can increase cell proliferation, promote symmetric cell division and enhance stem/progenitor cell activity. Conclusions Xanthosine treatment increased the proliferation rate of bovine MEC in vitro. This was likely to be mediated by an increase in the proportion of stem/progenitor cells in the MEC population due to promotion of symmetrical stem cell division by xanthosine.

  5. Synchronization of glycolytic oscillations in a yeast cell population

    DEFF Research Database (Denmark)

    Dano, S.; Hynne, F.; De Monte, Silvia

    2001-01-01

    The mechanism of active phase synchronization in a suspension of oscillatory yeast cells has remained a puzzle for almost half a century. The difficulty of the problem stems from the fact that the synchronization phenomenon involves the entire metabolic network of glycolysis and fermentation, and...

  6. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    International Nuclear Information System (INIS)

    Lushaj, Entela B.; Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi

    2012-01-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  7. Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    Yanping Zhang

    2018-05-01

    Full Text Available Hair cell (HC loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/β-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5, Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs. Our previous studies showed that Lgr6+ cells are a subpopulation of Lgr5+ progenitor cells and that both Lgr6+ and Lgr5+ progenitors can generate Myosin7a+ HCs in vitro. Thus we hypothesized that Lgr6+ cells are an enriched population of cochlear progenitor cells. However, the detailed distinctions between the Lgr5+ and Lgr6+ progenitors are unclear. Here, we systematically compared the proliferation, HC differentiation, and detailed transcriptome expression profiles of these two progenitor populations. We found that the same number of isolated Lgr6+ progenitors generated significantly more Myosin7a+ HCs compared to Lgr5+ progenitors; however, Lgr5+ progenitors formed more epithelial colonies and more spheres than Lgr6+ progenitors in vitro. Using RNA-Seq, we compared the transcriptome differences between Lgr5+ and Lgr6+ progenitors and identified a list of significantly differential expressed genes that might regulate the proliferation and differentiation of these HC progenitors, including 4 cell cycle genes, 9 cell signaling pathway genes, and 54 transcription factors. In conclusion, we demonstrate that Lgr6+ progenitors are an enriched population of inner ear progenitors that generate more HCs compared to Lgr5+ progenitors in the newborn mouse cochlea, and the our research provides a series of genes that might regulate the proliferation of progenitors

  8. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.

    Directory of Open Access Journals (Sweden)

    Rebecca Williams

    Full Text Available BACKGROUND: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC, are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. METHODS AND FINDINGS: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. CONCLUSIONS: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell

  9. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  10. Reduced satellite cell population may lead to contractures in children with cerebral palsy.

    Science.gov (United States)

    Smith, Lucas R; Chambers, Henry G; Lieber, Richard L

    2013-03-01

    Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle. We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6-15y; Gross Motor Function Classification System [GMFCS] levels II-V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15-18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations. After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p0.05) suggesting the isolation procedure was valid. A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

  11. Mechanism of derivation of radioresistance in HeLa cell population after repeated x-irradiation

    International Nuclear Information System (INIS)

    Kubo, Kihei; Koiwai, Soichiro; Morita, Kazuo

    1982-01-01

    The Radioresistant strain (X-8-5) was obtained from HeLa-SC population X-irradiated repeatedly for five times with 800 rad. The mean lethal dose (D 0 ) was 196 rad for X-8-5 cells, while it was 166 rad for control HeLa-SC cells. The fraction of cells containing an unusually long acrocentric chromosome (LA 2) exclusively increased with increasing number of irradiation of HeLa-SC population. A clonal strain with LA 2 marker was isolated from X-8-5 population and named RC-355. Since the RC-355 cells were more resistant (D 0 = 220 rad)than parental X-8-5 cells (D 0 = 196 rad), it was suggested that the cells with LA 2 were responsible for the radioresistance of X-8-5 population. The RC-355 cells were further subjected to the analysis of Q-banded karyotypes and it was observed that 18 types of specific markers (rm 1-17 and LA 2) were included in RC-355 cells in addition to 12 types of markers observed in most of HeLa-SC cells. Since the analysis of Q-banded karyotypes of RC-355 cells showed that RC-355 specific markers were not produced by radiation-induced rearrangements of HeLa-SC chromosomes, because twelve kinds of HeLa-SC markers were presented in RC-355 cells without any change, it was concluded that a small number of cells with LA 2 marker were originally presented in the control population and the relative fraction of them occupied increased after irradiation. (author)

  12. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

    Science.gov (United States)

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

    2012-12-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations.

  13. Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.

    Science.gov (United States)

    Bouklas, Tejas; Alonso-Crisóstomo, Luz; Székely, Tamás; Diago-Navarro, Elizabeth; Orner, Erika P; Smith, Kalie; Munshi, Mansa A; Del Poeta, Maurizio; Balázsi, Gábor; Fries, Bettina C

    2017-05-01

    Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an

  14. Sensory dissociation in chronic low back pain: Two case reports.

    Science.gov (United States)

    Adamczyk, Wacław M; Luedtke, Kerstin; Saulicz, Oskar; Saulicz, Edward

    2018-08-01

    Patients with chronic low back pain often report that they do not perceive their painful back accurately. Previous studies confirmed that sensory dissociation and/or discrepancy between perceived body image and actual size is one of the specific traits of patients with chronic pain. Current approaches for measuring sensory dissociation are limited to two-point-discrimination or rely on pain drawings not allowing for quantitative analysis. This case study reports the sensory dissociation of two cases with chronic low back pain using a recently published test (point-to-point-test (PTP)) and a newly developed test (two-point-estimation (TPE)). Both patients mislocalized tactile stimuli delivered to the painful location compared to non-painful locations (PTP test). In addition, both patients perceived their painful lumbar region differently from non-painful sites above and below and contralateral to the painful site. TPE data showed two distinct clinical patterns of sensory dissociation: one patient perceived the two-point distance in the painful area as expanded, while the other patient perceived it as shrunk. The latter pattern of sensory dissociation (i.e., pattern shrunk) is likely to respond to sensory training. Whether enlarged patterns of sensory dissociation are more resistant to treatment remains unknown but would explain the low effectiveness of previous studies using sensory training in chronic low back pain populations. Subgrouping patients according to their sensory discrimination pattern could contribute to the choice and effectiveness of the treatment approach.

  15. Shaping bacterial population behavior through computer-interfaced control of individual cells.

    Science.gov (United States)

    Chait, Remy; Ruess, Jakob; Bergmiller, Tobias; Tkačik, Gašper; Guet, Călin C

    2017-11-16

    Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.

  16. Studying Sensory Perception.

    Science.gov (United States)

    Ackerly, Spafford C.

    2001-01-01

    Explains the vestibular organ's role in balancing the body and stabilizing the visual world using the example of a hunter. Describes the relationship between sensory perception and learning. Recommends using optical illusions to illustrate the distinctions between external realities and internal perceptions. (Contains 13 references.) (YDS)

  17. Transcendence and Sensoriness

    DEFF Research Database (Denmark)

    Protestant theology and culture are known for a reserved, at times skeptical, attitude to the use of art and aesthetic forms of expression in a religious context. In Transcendence and Sensoriness, this attitude is analysed and discussed both theoretically and through case studies considered...

  18. Sensory matched filters.

    Science.gov (United States)

    Warrant, Eric J

    2016-10-24

    As animals move through their environments they are subjected to an endless barrage of sensory signals. Of these, some will be of utmost importance, such as the tell-tale aroma of a potential mate, the distinctive appearance of a vital food source or the unmistakable sound of an approaching predator. Others will be less important. Indeed some will not be important at all. There are, for instance, wide realms of the sensory world that remain entirely undetected, simply because an animal lacks the physiological capacity to detect and analyse the signals that characterise this realm. Take ourselves for example: we are completely insensitive to the Earth's magnetic field, a sensory cue of vital importance as a compass for steering the long distance migration of animals as varied as birds, lobsters and sea turtles. We are also totally oblivious to the rich palette of ultraviolet colours that exist all around us, colours seen by insects, crustaceans, birds, fish and lizards (in fact perhaps by most animals). Nor can we hear the ultrasonic sonar pulses emitted by bats in hot pursuit of flying insect prey. The simple reason for these apparent deficiencies is that we either lack the sensory capacity entirely (as in the case of magnetoreception) or that our existing senses are incapable of detecting specific ranges of the stimulus (such as the ultraviolet wavelength range of light). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

    Science.gov (United States)

    Pineda, M.; Eftimie, R.

    2017-12-01

    The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

  20. An efficient and reproducible process for transmission electron microscopy (TEM) of rare cell populations

    Science.gov (United States)

    Kumar, Sachin; Ciraolo, Georgianne; Hinge, Ashwini; Filippi, Marie-Dominique

    2014-01-01

    Transmission electron microscopy (TEM) provides ultra-structural details of cells at the sub-organelle level. However, details of the cellular ultrastructure, and the cellular organization and content of various organelles in rare populations, particularly in the suspension, like hematopoietic stem cells (HSCs) remained elusive. This is mainly due to the requirement of millions of cells for TEM studies. Thus, there is a vital requirement of a method that will allow TEM studies with low cell numbers of such rare populations. We describe an alternative and novel approach for TEM studies for rare cell populations. Here we performed TEM study from 10,000 HSC cells with quite ease. In particular, tiny cell pellets were identified by Evans blue staining after PFA-GA fixation. The cell pellet was pre-embedded in agarose in a small microcentrifuge tube and processed for dehydration, infiltration and embedding. Semi-thin and ultra-thin sections identified clusters of numerous cells per sections with well preserved morphology and ultrastructural details of golgi complex and mitochondria. Together, this method provides an efficient, easy and reproducible process to perform qualitative and quantitative TEM analysis from limited biological samples including cells in suspension. PMID:24291346

  1. Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments.

    Science.gov (United States)

    Alvarez-Berdugo, Daniel; Rofes, Laia; Casamitjana, J Francesc; Padrón, Andreína; Quer, Miquel; Clavé, Pere

    2016-09-01

    Oropharyngeal dysphagia (OD) affects older and neurological patients, causing malnutrition and dehydration and increasing the risk for aspiration pneumonia. There is evidence that sensory deficits in those populations are closely related to swallowing disorders, and several research groups are developing new therapies based on sensory stimulation of this area. More information on the sensory innervation participating in the swallow response is needed to better understand the pathophysiology of OD and to develop new treatments. This review focuses on the sensory innervation of the human oropharynx and larynx in healthy people compared with patients with swallowing disorders in order to unravel the abnormalities that may lead to the loss of sensitivity in patients with OD. We also hypothesize the pathway through which active sensory-enhancement treatments may elicit their therapeutic effect on patients with swallowing dysfunctions. As far as we know, this is the first time a review covers the anatomy, histology, ultrastructure, and molecular biology of the sensory innervation of the swallowing function. © 2016 New York Academy of Sciences.

  2. 75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

    Science.gov (United States)

    2010-09-07

    ...] Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop AGENCY: Food and Drug... Biologics Evaluation and Research (CBER) is announcing a public workshop entitled ``Cell and Gene Therapy... Institutional Review Boards (IRBs), gene and cellular therapy clinical researchers, and other stakeholders...

  3. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  4. Calcium Imaging Reveals Coordinated Simple Spike Pauses in Populations of Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Jorge E. Ramirez

    2016-12-01

    Full Text Available The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic gamma-Aminobutyric acid producing (GABAergic network, and blocking ionotropic gamma-Aminobutyric acid receptor (GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (inactivity between neighboring Purkinje cells, and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

  5. Reconstructing human pancreatic differentiation by mapping specific cell populations during development

    DEFF Research Database (Denmark)

    Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire

    2017-01-01

    . Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic......Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate...... cell types and how such lineage decisions are regulated....

  6. The epidermis comprises autonomous compartments maintained by distinct stem cell populations

    DEFF Research Database (Denmark)

    Page, Mahalia E; Lombard, Patrick; Ng, Felicia

    2013-01-01

    populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells drives hyperplasia but requires auxiliary stimuli for tumor formation....... In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance....

  7. Identification of a population of cells with hematopoietic stem cell properties in mouse aorta-gonad-mesonephros cultures

    International Nuclear Information System (INIS)

    Nobuhisa, Ikuo; Ohtsu, Naoki; Okada, Seiji; Nakagata, Naomi; Taga, Tetsuya

    2007-01-01

    The aorta-gonad-mesonephros (AGM) region is a primary source of definitive hematopoietic cells in the midgestation mouse embryo. In cultures of dispersed AGM regions, adherent cells containing endothelial cells are observed first, and then non-adherent hematopoietic cells are produced. Here we report on the characterization of hematopoietic cells that emerge in the AGM culture. Based on the expression profiles of CD45 and c-Kit, we defined three cell populations: CD45 low c-Kit + cells that had the ability to form hematopoietic cell colonies in methylcellulose media and in co-cultures with stromal cells; CD45 low c-Kit - cells that showed a granulocyte morphology; CD45 high c-Kit low/- that exhibited a macrophage morphology. In co-cultures of OP9 stromal cells and freshly prepared AGM cultures, CD45 low c-Kit + cells from the AGM culture had the abilities to reproduce CD45 low c-Kit + cells and differentiate into CD45 low c-Kit - and CD45 high c-Kit low/- cells, whereas CD45 low c-Kit - and CD45 high c-Kit low/- did not produce CD45 low c-Kit + cells. Furthermore, CD45 low c-Kit + cells displayed a long-term repopulating activity in adult hematopoietic tissue when transplanted into the liver of irradiated newborn mice. These results indicate that CD45 low c-Kit + cells from the AGM culture have the potential to reconstitute multi-lineage hematopoietic cells

  8. Crypt cell population kinetics in mouse jejunum under continuous beta irradiation from tritiated water

    International Nuclear Information System (INIS)

    Bhatia, A.L.; Gupta, M.L.; Saharan, B.R.

    1979-01-01

    The behaviour of crypt cell population in mouse jejunum under continuous beta irradiation from tritiated water (HTO) has been studied. Adult mice were maintained on tritiated drinking water of the activity of 1.25 μCi/ml, after priming injection. The crypts were studied at 1, 5, 7, 15 and 30 days after the initiation of treatment. It is observed that there is a partial recovery in proliferative activity after the first day of the treatment. Again there is a decrease in the crypt cells on the 7th day, after which this population appears to achieve a near-steady-state level at about 8% below normal at the last interval studied. Crypt cell population and mitotic figures showed a simultaneous dip and recovery, while dead cells showed inverse relationship. (orig.) [de

  9. Age-Related Change in Vestibular Ganglion Cell Populations in Individuals With Presbycusis and Normal Hearing.

    Science.gov (United States)

    Gluth, Michael B; Nelson, Erik G

    2017-04-01

    We sought to establish that the decline of vestibular ganglion cell counts uniquely correlates with spiral ganglion cell counts, cochlear hair cell counts, and hearing phenotype in individuals with presbycusis. The relationship between aging in the vestibular system and aging in the cochlea is a topic of ongoing investigation. Histopathologic age-related changes the vestibular system may mirror what is seen in the cochlea, but correlations with hearing phenotype and the impact of presbycusis are not well understood. Vestibular ganglion cells, spiral ganglion cells, and cochlear hair cells were counted in specimens from individuals with presbycusis and normal hearing. These were taken from within a large collection of processed human temporal bones. Correlations between histopathology and hearing phenotype were investigated. Vestibular ganglion cell counts were positively correlated with spiral ganglion cell counts and cochlear hair cell counts and were negatively correlated with hearing phenotype. There was no statistical evidence on linear regression to suggest that the relationship between age and cell populations differed significantly according to whether presbycusis was present or not. Superior vestibular ganglion cells were more negatively correlated with age than inferior ganglion cells. No difference in vestibular ganglion cells was noted based on sex. Vestibular ganglion cell counts progressively deteriorate with age, and this loss correlates closely with changes in the cochlea, as well as hearing phenotype. However, these correlations do not appear to be unique in individuals with presbycusis as compared with those with normal hearing.

  10. Descriptive sensory evaluations

    DEFF Research Database (Denmark)

    Dehlholm, Christian

    A recent trend in descriptive sensory evaluation methodology has been the application of rapid evaluation techniques. The ease in use makes the techniques extremely easy to implement by industry and university environments. Thus, one might not consider validity in the choice of method. The overall...... aim of this thesis is to compare and evaluate selected rapid evaluation techniques for sensory profiling. Method variations have been suggested for evaluations in product development and quality control, and method insight is provided. The thesis includes three original studies, designed...... as a consequence of the current practices and needs faced in the industry. Study I compared applicability and validity of rapid methods across several panels of trained assessors. Two rapid approaches were introduced for the evaluation of foods. The first method, ‘Free Multiple Sorting’, allows subjects to perform...

  11. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    Science.gov (United States)

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  12. Studies on the termination of immunological tolerance in the mouse thymus cell population after irradiation

    International Nuclear Information System (INIS)

    Amagai, Takashi

    1981-01-01

    Immunological tolerance in the mouse thymus cell population induced by the intravenous injection of deaggregated bovine gamma globulin was terminated by whole body irradiation. After irradiation, the weight of the thymus recovered biphasically, and the termination of tolerance occurred as early as in the first phase. Both Thy-1 antigen expression and helper activity of the thymus cell population in irradiated mice recovered in parallel with the recovery of the thymus weight. Sensitivity of the regenerating thymus cells to the tolerogen was not different from that of the normal thymus cells. The first phase of thymus regeneration may be caused by the proliferation and differentiation of relatively radioresistant and tolerogen insensitive precursors residing in the thymus. Tolerogen and/or immunogen reactive thymus cells may originate from the precursor. (author)

  13. The effect of ultraviolet light on arrested human diploid cell populations

    International Nuclear Information System (INIS)

    Kantor, G.J.; Warner, C.; Hull, D.R.

    1977-01-01

    The results of the experiments to determine an effect of UV (254 nm) on human diploid fibroblasts (HDF) arrested with respect to division by using 0.5% fetal calf serum in the culture medium are reported. A fraction of cells from irradiated arrested populations, maintained in the arrested state post-irradiation, was lost from the populations. The extent of cell loss was fluence-dependent and cell strain specific. A Xeroderma pigmentosum cell strain was more sensitive to UV than were normal HDF. No difference in sensitivity were observed when arrested populations established from normal HDF populations of various in vitro ages were used. The length of the pre-irradiation arrested period affected the sensitivity of normal HDF, which appeared more resistant at longer arrested periods, but not the sensitivity of arrested Xeroderma populations. These results suggest that DNA repair processes play a role in maintaining irradiated cells in the arrested state. The suggestion is made that the lethal event caused by UV is an effect on transcription leading to an inhibition of required protein synthesis. (author)

  14. Enthesis fibrocartilage cells originate from a population of Hedgehog-responsive cells modulated by the loading environment.

    Science.gov (United States)

    Schwartz, Andrea G; Long, Fanxin; Thomopoulos, Stavros

    2015-01-01

    Tendon attaches to bone across a specialized tissue called the enthesis. This tissue modulates the transfer of muscle forces between two materials, i.e. tendon and bone, with vastly different mechanical properties. The enthesis for many tendons consists of a mineralized graded fibrocartilage that develops postnatally, concurrent with epiphyseal mineralization. Although it is well described that the mineralization and development of functional maturity requires muscle loading, the biological factors that modulate enthesis development are poorly understood. By genetically demarcating cells expressing Gli1 in response to Hedgehog (Hh) signaling, we discovered a unique population of Hh-responsive cells in the developing murine enthesis that were distinct from tendon fibroblasts and epiphyseal chondrocytes. Lineage-tracing experiments revealed that the Gli1 lineage cells that originate in utero eventually populate the entire mature enthesis. Muscle paralysis increased the number of Hh-responsive cells in the enthesis, demonstrating that responsiveness to Hh is modulated in part by muscle loading. Ablation of the Hh-responsive cells during the first week of postnatal development resulted in a loss of mineralized fibrocartilage, with very little tissue remodeling 5 weeks after cell ablation. Conditional deletion of smoothened, a molecule necessary for responsiveness to Ihh, from the developing tendon and enthesis altered the differentiation of enthesis progenitor cells, resulting in significantly reduced fibrocartilage mineralization and decreased biomechanical function. Taken together, these results demonstrate that Hh signaling within developing enthesis fibrocartilage cells is required for enthesis formation. © 2015. Published by The Company of Biologists Ltd.

  15. Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations.

    Science.gov (United States)

    Logsdon, Michelle M; Aldridge, Bree B

    2018-01-01

    Model bacteria, such as E. coli and B. subtilis , tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

  16. Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations

    Directory of Open Access Journals (Sweden)

    Michelle M. Logsdon

    2018-03-01

    Full Text Available Model bacteria, such as E. coli and B. subtilis, tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

  17. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    International Nuclear Information System (INIS)

    Martins-Neves, Sara R; Lopes, Áurio O; Carmo, Anália do; Paiva, Artur A; Simões, Paulo C; Abrunhosa, Antero J; Gomes, Célia MF

    2012-01-01

    Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma

  18. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Martins-Neves Sara R

    2012-04-01

    Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

  19. Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy.

    Science.gov (United States)

    Shah, Pratikkumar; Zhu, Xuena; Zhang, Xueji; He, Jin; Li, Chen-zhong

    2016-03-09

    The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population.

  20. A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates.

    Science.gov (United States)

    Radtke, Stefan; Adair, Jennifer E; Giese, Morgan A; Chan, Yan-Yi; Norgaard, Zachary K; Enstrom, Mark; Haworth, Kevin G; Schefter, Lauren E; Kiem, Hans-Peter

    2017-11-01

    Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). We observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor cell (HSPC) subsets and compared these to human HSPCs. We demonstrated that the CD34 + CD45RA - CD90 + cell phenotype is highly enriched for HSCs. This population fully supported rapid short-term recovery and robust multilineage hematopoiesis in the nonhuman primate transplant model and quantitatively predicted transplant success and time to neutrophil and platelet recovery. Application of this cell population has potential in the setting of HSC transplantation and gene therapy/editing approaches. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Stimulation of angiogenesis, neurogenesis and regeneration by side population cells from dental pulp.

    Science.gov (United States)

    Ishizaka, Ryo; Hayashi, Yuki; Iohara, Koichiro; Sugiyama, Masahiko; Murakami, Masashi; Yamamoto, Tsubasa; Fukuta, Osamu; Nakashima, Misako

    2013-03-01

    Mesenchymal stem cells (MSCs) have been used for cell therapy in various experimental disease models. However, the regenerative potential of MSCs from different tissue sources and the influence of the tissue niche have not been investigated. In this study, we compared the regenerative potential of dental pulp, bone marrow and adipose tissue-derived CD31(-) side population (SP) cells isolated from an individual porcine source. Pulp CD31(-) SP cells expressed the highest levels of angiogenic/neurotrophic factors and had the highest migration activity. Conditioned medium from pulp CD31(-) SP cells produced potent anti-apoptotic activity and neurite outgrowth, compared to those from bone marrow and adipose CD31(-) SP cells. Transplantation of pulp CD31(-) SP cells in a mouse hindlimb ischemia model produced higher blood flow and capillary density than transplantation of bone marrow and adipose CD31(-) SP cells. Motor function recovery and infarct size reduction were greater with pulp CD31(-) SP cells. Pulp CD31(-) SP cells induced maximal angiogenesis, neurogenesis and pulp regeneration in ectopic transplantation models compared to other tissue sources. These results demonstrate that pulp stem cells have higher angiogenic, neurogenic and regenerative potential and may therefore be superior to bone marrow and adipose stem cells for cell therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso...... their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient...

  3. Lipid droplet organelle distribution in populations of dividing cells studied by simulation

    International Nuclear Information System (INIS)

    Dalhaimer, Paul

    2013-01-01

    One of the key questions in cell biology is how organelles are passed from parent to daughter cells. To help address this question, I used Brownian dynamics to simulate lipid droplets as model organelles in populations of dividing cells. Lipid droplets are dynamic bodies that can form both de novo and by fission, they can also be depleted. The quantitative interplay among these three events is unknown but would seem crucial for controlling droplet distribution in populations of dividing cells. Surprisingly, of the three main events studied: biogenesis, fission, and depletion, the third played the key role in maintaining droplet organelle number—and to a lesser extent volume—in populations of dividing cells where formation events would have seemed paramount. In the case of lipid droplets, this provides computational evidence that they must be sustained, most likely through contacts with the endoplasmic reticulum. The findings also agree with video microscopy experiments over much shorter timescales where droplet depletion in fission yeast cells was not observed. In general, this work shows that organelle maintenance is invaluable and lack thereof cannot necessarily be compensated for by organelle formation. This study provides a time-accurate, physical-based template for long-term cell division studies. (paper)

  4. Lipid droplet organelle distribution in populations of dividing cells studied by simulation

    Science.gov (United States)

    Dalhaimer, Paul

    2013-06-01

    One of the key questions in cell biology is how organelles are passed from parent to daughter cells. To help address this question, I used Brownian dynamics to simulate lipid droplets as model organelles in populations of dividing cells. Lipid droplets are dynamic bodies that can form both de novo and by fission, they can also be depleted. The quantitative interplay among these three events is unknown but would seem crucial for controlling droplet distribution in populations of dividing cells. Surprisingly, of the three main events studied: biogenesis, fission, and depletion, the third played the key role in maintaining droplet organelle number—and to a lesser extent volume—in populations of dividing cells where formation events would have seemed paramount. In the case of lipid droplets, this provides computational evidence that they must be sustained, most likely through contacts with the endoplasmic reticulum. The findings also agree with video microscopy experiments over much shorter timescales where droplet depletion in fission yeast cells was not observed. In general, this work shows that organelle maintenance is invaluable and lack thereof cannot necessarily be compensated for by organelle formation. This study provides a time-accurate, physical-based template for long-term cell division studies.

  5. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells.

    Science.gov (United States)

    Tavazzani, Elisa; Tritto, Simona; Spaiardi, Paolo; Botta, Laura; Manca, Marco; Prigioni, Ivo; Masetto, Sergio; Russo, Giancarlo

    2014-01-01

    The function of the enzyme glutamate decarboxylase (GAD) is to convert glutamate in γ-aminobutyric acid (GABA). Glutamate decarboxylase exists as two major isoforms, termed GAD65 and GAD67, that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

  6. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells

    Directory of Open Access Journals (Sweden)

    Giancarlo eRusso

    2014-12-01

    Full Text Available The function of the enzyme glutamate decarboxylase (GAD is to convert glutamate in -aminobutyric acid (GABA.GAD exists as two major isoforms, termed GAD65 and GAD67,.that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

  7. Identification of cancer stem-like side population cells in purified primary cultured human laryngeal squamous cell carcinoma epithelia.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Wu

    Full Text Available Cancer stem-like side population (SP cells have been identified in many solid tumors; however, most of these investigations are performed using established cancer cell lines. Cancer cells in tumor tissue containing fibroblasts and many other types of cells are much more complex than any cancer cell line. Although SP cells were identified in the laryngeal squamous cell carcinoma (LSCC cell line Hep-2 in our pilot study, it is unknown whether the LSCC tissue contains SP cells. In this study, LSCC cells (LSCCs were primary cultured and purified from a surgically resected LSCC specimen derived from a well-differentiated epiglottic neoplasm of a Chinese male. This was followed by the verification of epithelium-specific characteristics, such as ultrastructure and biomarkers. A distinct SP subpopulation (4.45±1.07% was isolated by Hoechst 33342 efflux analysis from cultured LSCCs by using a flow cytometer. Cancer stem cell (CSC-associated assays, including expression of self-renewal and CSC marker genes, proliferation, differentiation, spheroid formation, chemotherapy resistance, and tumorigenicity were then conducted between SP and non-SP (NSP LSCCs. In vitro and in vivo assays revealed that SP cells manifested preferential expression of self-renewal and CSC marker genes, higher capacity for proliferation, differentiation, and spheroid formation; enhanced resistance to chemotherapy; and greater xenograft tumorigenicity in immunodeficient mice compared with NSP cells. These findings suggest that the primary cultured and purified LSCCs contain cancer stem-like SP cells, which may serve as a valuable model for CSC research in LSCC.

  8. The Sensory Neocortex and Associative Memory.

    Science.gov (United States)

    Aschauer, Dominik; Rumpel, Simon

    2018-01-01

    Most behaviors in mammals are directly or indirectly guided by prior experience and therefore depend on the ability of our brains to form memories. The ability to form an association between an initially possibly neutral sensory stimulus and its behavioral relevance is essential for our ability to navigate in a changing environment. The formation of a memory is a complex process involving many areas of the brain. In this chapter we review classic and recent work that has shed light on the specific contribution of sensory cortical areas to the formation of associative memories. We discuss synaptic and circuit mechanisms that mediate plastic adaptations of functional properties in individual neurons as well as larger neuronal populations forming topographically organized representations. Furthermore, we describe commonly used behavioral paradigms that are used to study the mechanisms of memory formation. We focus on the auditory modality that is receiving increasing attention for the study of associative memory in rodent model systems. We argue that sensory cortical areas may play an important role for the memory-dependent categorical recognition of previously encountered sensory stimuli.

  9. Bet-hedging in bacteriocin producing Escherichia coli populations: the single cell perspective

    Science.gov (United States)

    Bayramoglu, Bihter; Toubiana, David; van Vliet, Simon; Inglis, R. Fredrik; Shnerb, Nadav; Gillor, Osnat

    2017-02-01

    Production of public goods in biological systems is often a collaborative effort that may be detrimental to the producers. It is therefore sustainable only if a small fraction of the population shoulders the cost while the majority reap the benefits. We modelled this scenario using Escherichia coli populations producing colicins, an antibiotic that kills producer cells’ close relatives. Colicin expression is a costly trait, and it has been proposed that only a small fraction of the population actively expresses the antibiotic. Colicinogenic populations were followed at the single-cell level using time-lapse microscopy, and showed two distinct, albeit dynamic, subpopulations: the majority silenced colicin expression, while a small fraction of elongated, slow-growing cells formed colicin-expressing hotspots, placing a significant burden on expressers. Moreover, monitoring lineages of individual colicinogenic cells showed stochastic switching between expressers and non-expressers. Hence, colicin expressers may be engaged in risk-reducing strategies—or bet-hedging—as they balance the cost of colicin production with the need to repel competitors. To test the bet-hedging strategy in colicin-mediated interactions, competitions between colicin-sensitive and producer cells were simulated using a numerical model, demonstrating a finely balanced expression range that is essential to sustaining the colicinogenic population.

  10. Taxonomic separation of hippocampal networks: principal cell populations and adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Roelof Maarten evan Dijk

    2016-03-01

    Full Text Available While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippocampal function, because multiple taxonomic levels need to be considered to associate behavioral and anatomical changes. To provide information on anatomical changes within and across taxonomic ranks, we present a quantitative assessment of hippocampal principal cell populations in 20 species or strain groups, with emphasis on rodents, the taxonomic group that provides most animals used in laboratory research. Of special interest is the importance of adult hippocampal neurogenesis in species-specific adaptations relative to other cell populations. Correspondence analysis of cell numbers shows that across taxonomic units, phylogenetically related species cluster together, sharing similar proportions of principal cell populations. CA3 and hilus are strong separators that place rodent species into a tight cluster based on their relatively large CA3 and small hilus while non-rodent species (including humans and non-human primates are placed on the opposite side of the spectrum. Hilus and CA3 are also separators within rodents, with a very large CA3 and rather small hilar cell populations separating mole-rats from other rodents that, in turn, are separated from each other by smaller changes in the proportions of CA1 and granule cells. When adult neurogenesis is included, the relatively small populations of young neurons, proliferating cells and hilar neurons become main drivers of taxonomic separation within rodents. The observations provide challenges to the computational modeling of hippocampal function, suggest differences in the organization of hippocampal information streams in rodent and non

  11. Approaches for cytogenetic and molecular analyses of small flow-sorted cell populations from childhood leukemia bone marrow samples

    DEFF Research Database (Denmark)

    Obro, Nina Friesgaard; Madsen, Hans O.; Ryder, Lars Peter

    2011-01-01

    defined cell populations with subsequent analyses of leukemia-associated cytogenetic and molecular marker. The approaches described here optimize the use of the same tube of unfixed, antibody-stained BM cells for flow-sorting of small cell populations and subsequent exploratory FISH and PCR-based analyses....

  12. Long-Range Regulatory Synergy Is Required to Allow Control of the TAC1 Locus by MEK/ERK Signalling in Sensory Neurones

    Directory of Open Access Journals (Sweden)

    Lynne Shanley

    2010-12-01

    Full Text Available Changes in the expression of the neuropeptide substance P (SP in different populations of sensory neurones are associated with the progression of chronic inflammatory disease. Thus, understanding the genomic and cellular mechanisms driving the expression of the TAC1 gene, which encodes SP, in sensory neurones is essential to understanding its role in inflammatory disease. We used a novel combination of computational genomics, primary-cell culture and mouse transgenics to determine the genomic and cellular mechanisms that control the expression of TAC1 in sensory neurones. Intriguingly, we demonstrated that the promoter of the TAC1 gene must act in synergy with a remote enhancer, identified using comparative genomics, to respond to MAPK signalling that modulates the expression of TAC1 in sensory neurones. We also reveal that noxious stimulation of sensory neurones triggers this synergy in larger diameter sensory neurones – an expression of SP associated with hyperalgesia. This noxious stimulation of TAC1 enhancer-promotor synergy could be strongly blocked by antagonism of the MEK pathway. This study provides a unique insight into the role of long-range enhancer-promoter synergy and selectivity in the tissue-specific response of promoters to specific signal transduction pathways and suggests a possible new avenue for the development of novel anti-inflammatory therapies.

  13. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  14. Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations.

    Science.gov (United States)

    Adams, Christopher F; Rai, Ahmad; Sneddon, Gregor; Yiu, Humphrey H P; Polyak, Boris; Chari, Divya M

    2015-01-01

    Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, 'magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥90%) of primary neural stem cells (NSCs)-a 'hard-to-label' transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Sensory Science Education

    DEFF Research Database (Denmark)

    Otrel-Cass, Kathrin

    2018-01-01

    little note of the body-mind interactions we have with the material world. Utilizing examples from primary schools, it is argued that a sensory pedagogy in science requires a deliberate sensitization and validation of the senses’ presence and that a sensor pedagogy approach may reveal the unique ways...... in how we all experience the world. Troubling science education pedagogy is therefore also a reconceptualization of who we are and how we make sense of the world and the acceptance that the body-mind is present, imbalanced and complex....

  16. The changing sensory room

    DEFF Research Database (Denmark)

    2018-01-01

    In 2017 the kindergarten The Milky Way in the city Vejle in Denmark made a sensory room that has the special ability change whenever wanted by the children and social educators. Kjetil Sandvik (to the right) from Copenhagen University and Klaus Thestrup from Aarhus University reflects upon what...... they saw, took part in and talked with the social educators about. Jacob Knudsen from VIFIN filmed the two gentlemen and organised the project. it is a room composed around common experiments, many self-made objects, open narrative structures. and a combination of digital and analogue elements....

  17. Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture

    OpenAIRE

    Kim, Euiseok J.; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E.

    2008-01-01

    Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiatin...

  18. Modularity in Sensory Auditory Memory

    OpenAIRE

    Clement, Sylvain; Moroni, Christine; Samson, Séverine

    2004-01-01

    The goal of this paper was to review various experimental and neuropsychological studies that support the modular conception of auditory sensory memory or auditory short-term memory. Based on initial findings demonstrating that verbal sensory memory system can be dissociated from a general auditory memory store at the functional and anatomical levels. we reported a series of studies that provided evidence in favor of multiple auditory sensory stores specialized in retaining eit...

  19. Establishment of reference CD4+ T cell values for adult Indian population

    Directory of Open Access Journals (Sweden)

    Ray Krishnangshu

    2011-10-01

    Full Text Available Abstract Background CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. Methods A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre healthy participants were enrolled in the study. The ratio of male (N = 645 to female (N = 561 of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS, version 15 and Prism software version 5. Results The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. Conclusion The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.

  20. Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

    Directory of Open Access Journals (Sweden)

    Grace E Fox

    Full Text Available Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC, an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA, and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

  1. Therapeutic potential of stem cells in auditory hair cell repair

    Directory of Open Access Journals (Sweden)

    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  2. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    Science.gov (United States)

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  3. SENSORY AND CONSUMER TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — These laboratories conduct a wide range of studies to characterize the sensory properties of and consumer responses to foods, beverages, and other consumer products....

  4. Variable sensory perception in autism.

    Science.gov (United States)

    Haigh, Sarah M

    2018-03-01

    Autism is associated with sensory and cognitive abnormalities. Individuals with autism generally show normal or superior early sensory processing abilities compared to healthy controls, but deficits in complex sensory processing. In the current opinion paper, it will be argued that sensory abnormalities impact cognition by limiting the amount of signal that can be used to interpret and interact with environment. There is a growing body of literature showing that individuals with autism exhibit greater trial-to-trial variability in behavioural and cortical sensory responses. If multiple sensory signals that are highly variable are added together to process more complex sensory stimuli, then this might destabilise later perception and impair cognition. Methods to improve sensory processing have shown improvements in more general cognition. Studies that specifically investigate differences in sensory trial-to-trial variability in autism, and the potential changes in variability before and after treatment, could ascertain if trial-to-trial variability is a good mechanism to target for treatment in autism. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations.

    Directory of Open Access Journals (Sweden)

    Bryan D Moyer

    Full Text Available BACKGROUND: Using fungiform (FG and circumvallate (CV taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive, sour cells (PKD2L1-positive, as well as other taste cell populations. Transmembrane protein 44 (TMEM44, a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1, a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1, a calcium-binding transmembrane protein; and anoctamin 7 (ANO7, a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B, a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins

  6. Processing of Sensory Information in the Olfactory System

    DEFF Research Database (Denmark)

    The olfactory system is an attractive model system due to the easy control of sensory input and the experimental accessibility in animal studies. The odorant signals are processed from receptor neurons to a neural network of mitral and granular cells while various types of nonlinear behaviour can...... and equation-free techniques allow for a better reproduction and understanding of recent experimental findings. Talks: Olfaction as a Model System for Sensory-Processing Neural Networks (Jens Midtgaard, University of Copenhagen, Denmark) Nonlinear Effects of Signal Transduction in Olfactory Sensory Neurons...

  7. More or less-On the influence of labelling strategies to infer cell population dynamics.

    Science.gov (United States)

    Gabel, Michael; Regoes, Roland R; Graw, Frederik

    2017-01-01

    The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

  8. More or less-On the influence of labelling strategies to infer cell population dynamics.

    Directory of Open Access Journals (Sweden)

    Michael Gabel

    Full Text Available The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

  9. Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Oral squamous cell carcinoma (OSCC) is a major oral cancer subtype that is the fourth most common cancer affecting Taiwanese men. Despite known risk behaviors such as cigarette smoking, alcohol drinking, and betel nut chewing often indulged by Taiwanese men, the genetic contribution to the incidence or progression of OSCC has yet been elucidated in the Taiwanese population.

  10. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  11. Cellular and Molecular Characterization of Microglia : A Unique Immune Cell Population

    NARCIS (Netherlands)

    Sousa, Carole; Biber, Knut; Michelucci, Alessandro

    2017-01-01

    Microglia are essential for the development and function of the adult brain. Microglia arise from erythro-myeloid precursors in the yolk sac and populate the brain rudiment early during development. Unlike monocytes that are constantly renewed from bone marrow hematopoietic stem cells throughout

  12. A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

    Directory of Open Access Journals (Sweden)

    Conor Lawless

    Full Text Available Increases in cellular Reactive Oxygen Species (ROS concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage. However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS. We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

  13. A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

    Science.gov (United States)

    Lawless, Conor; Jurk, Diana; Gillespie, Colin S; Shanley, Daryl; Saretzki, Gabriele; von Zglinicki, Thomas; Passos, João F

    2012-01-01

    Increases in cellular Reactive Oxygen Species (ROS) concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage). However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS). We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

  14. Analysis of in vitro secretion profiles from adipose-derived cell populations

    Directory of Open Access Journals (Sweden)

    Blaber Sinead P

    2012-08-01

    Full Text Available Abstract Background Adipose tissue is an attractive source of cells for therapeutic purposes because of the ease of harvest and the high frequency of mesenchymal stem cells (MSCs. Whilst it is clear that MSCs have significant therapeutic potential via their ability to secrete immuno-modulatory and trophic cytokines, the therapeutic use of mixed cell populations from the adipose stromal vascular fraction (SVF is becoming increasingly common. Methods In this study we have measured a panel of 27 cytokines and growth factors secreted by various combinations of human adipose-derived cell populations. These were 1. co-culture of freshly isolated SVF with adipocytes, 2. freshly isolated SVF cultured alone, 3. freshly isolated adipocytes alone and 4. adherent adipose-derived mesenchymal stem cells (ADSCs at passage 2. In addition, we produced an ‘in silico’ dataset by combining the individual secretion profiles obtained from culturing the SVF with that of the adipocytes. This was compared to the secretion profile of co-cultured SVF and adipocytes. Two-tailed t-tests were performed on the secretion profiles obtained from the SVF, adipocytes, ADSCs and the ‘in silico’ dataset and compared to the secretion profiles obtained from the co-culture of the SVF with adipocytes. A p-value of  Results A co-culture of SVF and adipocytes results in a distinct secretion profile when compared to all other adipose-derived cell populations studied. This illustrates that cellular crosstalk during co-culture of the SVF with adipocytes modulates the production of cytokines by one or more cell types. No biologically relevant differences were detected in the proteomes of SVF cultured alone or co-cultured with adipocytes. Conclusions The use of mixed adipose cell populations does not appear to induce cellular stress and results in enhanced secretion profiles. Given the importance of secreted cytokines in cell therapy, the use of a mixed cell population such as the

  15. Cell cycle delays in synchronized cell populations following irradiation with heavy ions

    International Nuclear Information System (INIS)

    Scholz, M.

    1992-11-01

    Mammalian cells subjected to irradiation with heavy ions were investigated for cell cycle delays. The ions used for this purpose included Ne ions in the LET range of 400 keV/μm just as well as uranium ions of 16225 keV/μm. The qualitative changes in cell cycle progression seen after irradiation with Ne ions (400 keV/μm) were similar to those observed in connection with X-rays. Following irradiation with extremely heavy ions (lead, uranium) the majority of cells were even at 45 hours still found to be in the S phase or G 2 M phase of the first cycle. The delay cross section 'σ-delay' was introduced as a quantity that would permit quantitative comparisons to be carried out between the changes in cell progression and other effects of radiation. In order to evaluate the influence of the number of hits on the radiation effect observed, the size of the cell nucleus was precisely determined with reference to the cycle phase and local cell density. A model to simulate those delay effects was designed in such a way that account is taken of this probability of hit and that the results can be extrapolated from the delay effects after X-irradiation. On the basis of the various probabilities of hit for cells at different cycle stages a model was developed to ascertain the intensified effect following fractionated irradiation with heavy ions. (orig./MG) [de

  16. Identification and characterisation of side population cells in the canine pituitary gland.

    Science.gov (United States)

    van Rijn, Sarah J; Gremeaux, Lies; Riemers, Frank M; Brinkhof, Bas; Vankelecom, Hugo; Penning, Louis C; Meij, Björn P

    2012-06-01

    To date, stem/progenitor cells have not been identified in the canine pituitary gland. Cells that efficiently exclude the vital dye Hoechst 33342 can be visualised and identified using fluorescence activated cell sorting (FACS) as a 'side population' (SP), distinct from the main population (MP). Such SPs have been identified in several tissues and display stem/progenitor cell characteristics. In this study, a small SP (1.3%, n=6) was detected in the anterior pituitary glands of healthy dogs. Quantitative PCR indicated significantly higher expression of CD34 and Thy1 in this SP, but no differences in the expression of CD133, Bmi-1, Axin2 or Shh. Pro-opiomelanocortin (POMC) and Lhx3 expression were significantly higher in the MP than in the SP, but no differences in the expression of Tpit, GH or PRL were found. The study demonstrated the existence of an SP of cells in the normal canine pituitary gland, encompassing cells with stem cell characteristics and without POMC expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

    Science.gov (United States)

    Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

    2016-01-01

    Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

  18. Patients' views on early sensory relearning following nerve repair-a Q-methodology study.

    Science.gov (United States)

    Vikström, Pernilla; Carlsson, Ingela; Rosén, Birgitta; Björkman, Anders

    2017-09-26

    Descriptive study. Early sensory relearning where the dynamic capacity of the brain is used has been shown to improve sensory outcome after nerve repair. However, no previous studies have examined how patients experience early sensory relearning. To describe patient's views on early sensory relearning. Statements' scores were analyzed by factor analysis. Thirty-seven consecutive adult patients with median and/or ulnar nerve repair who completed early sensory relearning were included. Three factors were identified, explaining 45% of the variance: (1) "Believe sensory relearning is meaningful, manage to get an illusion of touch and complete the sensory relearning"; (2) "Do not get an illusion of touch easily and need support in their sensory relearning" (3) "Are not motivated, manage to get an illusion of touch but do not complete sensory relearning". Many patients succeed in implementing their sensory relearning. However, a substantial part of the patient population need more support, have difficulties to create illusion of touch, and lack motivation to complete the sensory relearning. To enhance motivation and meaningfulness by relating the training clearly to everyday occupations and to the patient's life situation is a suggested way to proceed. The three unique factors indicate motivation and sense of meaningfulness as key components which should be taken into consideration in developing programs for person-centered early sensory relearning. 3. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  19. Desynchronizing electrical and sensory coordinated reset neuromodulation.

    Science.gov (United States)

    Popovych, Oleksandr V; Tass, Peter A

    2012-01-01

    Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

  20. Desynchronizing Electrical and Sensory Coordinated Reset Neuromodulation

    Directory of Open Access Journals (Sweden)

    Oleksandr V. Popovych

    2012-03-01

    Full Text Available Coordinated reset (CR stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS,to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling. Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated excitatory and inhibitory stimulation.Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronalsynchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers of deep brain CR neuromodulation may be similar or even identical. Furthermore, ourresults indicate that an effective desynchronization and anti-kindlingcan even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

  1. An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations.

    Science.gov (United States)

    Sawai, Satoshi; Thomason, Peter A; Cox, Edward C

    2005-01-20

    Nutrient-deprived Dictyostelium amoebae aggregate to form a multicellular structure by chemotaxis, moving towards propagating waves of cyclic AMP that are relayed from cell to cell. Organizing centres are not formed by founder cells, but are dynamic entities consisting of cores of outwardly rotating spiral waves that self-organize in a homogeneous cell population. Spiral waves are ubiquitously observed in chemical reactions as well as in biological systems. Although feedback control of spiral waves in spatially extended chemical reactions has been demonstrated in recent years, the mechanism by which control is achieved in living systems is unknown. Here we show that mutants of the cyclic AMP/protein kinase A pathway show periodic signalling, but fail to organize coherent long-range wave territories, owing to the appearance of numerous spiral cores. A theoretical model suggests that autoregulation of cell excitability mediated by protein kinase A acts to optimize the number of signalling centres.

  2. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

    Directory of Open Access Journals (Sweden)

    Brianna K. Swartwout

    2017-10-01

    Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  3. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

    Science.gov (United States)

    Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

    2017-10-13

    Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  4. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.

    Directory of Open Access Journals (Sweden)

    Natalia Smorodinova

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients.The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR.We examined 46 subjects (19 with AF, and 27 in SR undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry.The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample.An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

  5. CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis.

    Science.gov (United States)

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Davelaar, Nadine; Vroman, Heleen; Hazes, Johanna M W; de Jong, Pascal H P; Lubberts, Erik

    2015-11-30

    Patients with rheumatoid arthritis (RA) can be separated into two major subpopulations based on the absence or presence of serum anti-citrullinated protein antibodies (ACPAs). The more severe disease course in ACPA(+) RA and differences in treatment outcome between these subpopulations suggest that ACPA(+) and ACPA(-) RA are different disease subsets. The identification of T-helper (Th) cells specifically recognizing citrullinated peptides, combined with the strong association between HLA-DRB1 and ACPA positivity, point toward a pathogenic role of Th cells in ACPA(+) RA. In this context we recently identified a potential pathogenic role for CCR6(+) Th cells in RA. Therefore, we examined whether Th cell population distributions differ by ACPA status. We performed a nested matched case-control study including 27 ACPA(+) and 27 ACPA(-) treatment-naive early RA patients matched for disease activity score in 44 joints, presence of rheumatoid factor, sex, age, duration of complaints and presence of erosions. CD4(+)CD45RO(+) (memory) Th cell distribution profiles from these patients were generated based on differential chemokine receptor expression and related with disease duration. ACPA status was not related to differences in total CD4(+) T cell or memory Th cell proportions. However, ACPA(+) patients had significantly higher proportions of Th cells expressing the chemokine receptors CCR6 and CXCR3. Similar proportions of CCR4(+) and CCR10(+) Th cells were found. Within the CCR6(+) cell population, four Th subpopulations were distinguished based on differential chemokine receptor expression: Th17 (CCR4(+)CCR10(-)), Th17.1 (CXCR3(+)), Th22 (CCR4(+)CCR10(+)) and CCR4/CXCR3 double-positive (DP) cells. In particular, higher proportions of Th22 (p = 0.02), Th17.1 (p = 0.03) and CCR4/CXCR3 DP (p = 0.01) cells were present in ACPA(+) patients. In contrast, ACPA status was not associated with differences in Th1 (CCR6(-)CXCR3(+); p = 0.90), Th2 (CCR6(-)CCR4(+); p = 0.27) and T

  6. Glioblastoma formation from cell population depleted of Prominin1-expressing cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nishide

    2009-08-01

    Full Text Available Prominin1 (Prom1, also known as CD133 in human has been widely used as a marker for cancer stem cells (CSCs, which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM. However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreER(TM, and generated glioma-initiating cells (GICs-LD by overexpressing both the SV40 Large T antigen and an oncogenic H-Ras(L61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

  7. Changes in the neuroglial cell populations of the rat spinal cord after local X-irradiation

    International Nuclear Information System (INIS)

    Hubbard, B.M.; Hopewell, J.W.

    1979-01-01

    A 16 mm length of cervical spinal cord of young adult female rats was irradiated with 4000 rad of 250 kV X-rays. Counts of astrocyte and oligodendrocyte nuclei were made in the dorsal columns of both irradiated and control cervical cords during the latent period before the onset of radionecrosis. The numbers of both astrocyte and oligodendrocyte nuclei were reduced one month after exposure to radiation. Both cell populations showed an apparent recovery but this was subsequently followed by a rapid loss of cells prior to the development of white-matter necrosis. The oligodendrocyte population in unirradiated spinal cords increased with age, and mitotic figures were observed among the neuroglia of both irradiated and control cervical spinal cords. A slow, natural turnover of neuroglial cells in the cervical spinal cord is proposed and the relevance of this to the manifestation of delayed white matter necrosis is discussed. (author)

  8. Targeting population heterogeneity in Saccharomyces cerevisiae batch fermentation for optimal cell factories

    DEFF Research Database (Denmark)

    Heins, Anna-Lena; Lencastre Fernandes, Rita; Lundin, L.

    )). Significant gradients of e.g. dissolved oxygen, substrates, and pH are typically observed in many industrial scale fermentation processes. Consequently, the microbial cells experience rapid changes in environmental conditions as they circulate throughout the reactor, which might pose stress on the cells...... and affect their metabolism and consequently affect the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were...... environmental factors on heterogeneity level and amount of living cells. A highly dynamic behavior with regard to subpopulation distribution during the different growth stages was seen for the batch cultivations. Moreover, it could be demonstrated that the glucose concentration had a clear influence...

  9. Use of flow cytometry for high-throughput cell population estimates in fixed brain tissue

    Directory of Open Access Journals (Sweden)

    Nicole A Young

    2012-07-01

    Full Text Available The numbers and types of cells in an area of cortex define its function. Therefore it is essential to characterize the numbers and distributions of total cells in areas of the cortex, as well as to identify numbers of subclasses of neurons and glial cells. To date, the large size of the primate brain and the lack of innovation in cell counting methods have been a roadblock to obtaining high-resolution maps of cell and neuron density across the cortex in humans and non-human primates. Stereological counting methods and the isotropic fractionator are valuable tools for estimating cell numbers, but are better suited to smaller, well-defined brain structures or to cortex as a whole. In the present study, we have extended our flow-cytometry based counting method, the flow fractionator (Collins et al., 2010a, to include high-throughput total cell population estimates in homogenized cortical samples. We demonstrate that our method produces consistent, accurate and repeatable cell estimates quickly. The estimates we report are in excellent agreement with estimates for the same samples obtained using a Neubauer chamber and a fluorescence microscope. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue is more efficient and more precise than manual counting methods. The addition of automated nuclei counting to our flow fractionator method allows for a fully automated, rapid characterization of total cells and neuronal and non-neuronal populations in human and non-human primate brains, providing valuable data to further our understanding of the functional organization of normal, aging and diseased brains.

  10. Attention modulates sensory suppression during back movements.

    Science.gov (United States)

    Van Hulle, Lore; Juravle, Georgiana; Spence, Charles; Crombez, Geert; Van Damme, Stefaan

    2013-06-01

    Tactile perception is often impaired during movement. The present study investigated whether such sensory suppression also occurs during back movements, and whether this would be modulated by attention. In two tactile detection experiments, participants simultaneously engaged in a movement task, in which they executed a back-bending movement, and a perceptual task, consisting of the detection of subtle tactile stimuli administered to their upper or lower back. The focus of participants' attention was manipulated by raising the probability that one of the back locations would be stimulated. The results revealed that tactile detection was suppressed during the execution of the back movements. Furthermore, the results of Experiment 2 revealed that when the stimulus was always presented to the attended location, tactile suppression was substantially reduced, suggesting that sensory suppression can be modulated by top-down attentional processes. The potential of this paradigm for studying tactile information processing in clinical populations is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Monitoring intracellular calcium ion dynamics in hair cell populations with Fluo-4 AM.

    Directory of Open Access Journals (Sweden)

    Kateri J Spinelli

    Full Text Available We optimized Fluo-4 AM loading of chicken cochlea to report hair-bundle Ca(2+ signals in populations of hair cells. The bundle Ca(2+ signal reported the physiological state of the bundle and cell; extruding cells had very high bundle Fluo-4 fluorescence, cells with intact bundles and tip links had intermediate fluorescence, and damaged cells with broken tip links had low fluorescence. Moreover, Fluo-4 fluorescence in the bundle correlated with Ca(2+ entry through transduction channels; mechanically activating transduction channels increased the Fluo-4 signal, while breaking tip links with Ca(2+ chelators or blocking Ca(2+ entry through transduction channels each caused bundle and cell-body Fluo-4 fluorescence to decrease. These results show that when tip links break, bundle and soma Ca(2+ decrease, which could serve to stimulate the hair cell's tip-link regeneration process. Measurement of bundle Ca(2+ with Fluo-4 AM is therefore a simple method for assessing mechanotransduction in hair cells and permits an increased understanding of the interplay of tip links, transduction channels, and Ca(2+ signaling in the hair cell.

  12. The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population

    International Nuclear Information System (INIS)

    Roeske, John C; Stinchcomb, Thomas G

    2006-01-01

    Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10 4 clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome. (note)

  13. Msx genes define a population of mural cell precursors required for head blood vessel maturation.

    Science.gov (United States)

    Lopes, Miguel; Goupille, Olivier; Saint Cloment, Cécile; Lallemand, Yvan; Cumano, Ana; Robert, Benoît

    2011-07-01

    Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs.

  14. Characterization of Cs vapor cell coated with octadecyltrichlorosilane using coherent population trapping spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Hafiz, Moustafa Abdel; Maurice, Vincent; Chutani, Ravinder; Passilly, Nicolas; Gorecki, Christophe; Boudot, Rodolphe [FEMTO-ST, CNRS, UFC, 26 Chemin de l' Epitaphe, 25030 Besançon Cedex (France); Guérandel, Stéphane; Clercq, Emeric de [LNE-SYRTE, Observatoire de Paris, CNRS, UPMC, 61 avenue de l' Observatoire, 75014 Paris (France)

    2015-05-14

    We report the realization and characterization using coherent population trapping (CPT) spectroscopy of an octadecyltrichlorosilane (OTS)-coated centimeter-scale Cs vapor cell. The dual-structure of the resonance lineshape, with presence of a narrow structure line at the top of a Doppler-broadened structure, is clearly observed. The linewidth of the narrow resonance is compared to the linewidth of an evacuated Cs cell and of a buffer gas Cs cell of similar size. The Cs-OTS adsorption energy is measured to be (0.42 ± 0.03) eV, leading to a clock frequency shift rate of 2.7 × 10{sup −9}/K in fractional unit. A hyperfine population lifetime, T{sub 1}, and a microwave coherence lifetime, T{sub 2}, of 1.6 and 0.5 ms are reported, corresponding to about 37 and 12 useful bounces, respectively. Atomic-motion induced Ramsey narrowing of dark resonances is observed in Cs-OTS cells by reducing the optical beam diameter. Ramsey CPT fringes are detected using a pulsed CPT interrogation scheme. Potential applications of the Cs-OTS cell to the development of a vapor cell atomic clock are discussed.

  15. Characterization of Cs vapor cell coated with octadecyltrichlorosilane using coherent population trapping spectroscopy

    International Nuclear Information System (INIS)

    Hafiz, Moustafa Abdel; Maurice, Vincent; Chutani, Ravinder; Passilly, Nicolas; Gorecki, Christophe; Boudot, Rodolphe; Guérandel, Stéphane; Clercq, Emeric de

    2015-01-01

    We report the realization and characterization using coherent population trapping (CPT) spectroscopy of an octadecyltrichlorosilane (OTS)-coated centimeter-scale Cs vapor cell. The dual-structure of the resonance lineshape, with presence of a narrow structure line at the top of a Doppler-broadened structure, is clearly observed. The linewidth of the narrow resonance is compared to the linewidth of an evacuated Cs cell and of a buffer gas Cs cell of similar size. The Cs-OTS adsorption energy is measured to be (0.42 ± 0.03) eV, leading to a clock frequency shift rate of 2.7 × 10 −9 /K in fractional unit. A hyperfine population lifetime, T 1 , and a microwave coherence lifetime, T 2 , of 1.6 and 0.5 ms are reported, corresponding to about 37 and 12 useful bounces, respectively. Atomic-motion induced Ramsey narrowing of dark resonances is observed in Cs-OTS cells by reducing the optical beam diameter. Ramsey CPT fringes are detected using a pulsed CPT interrogation scheme. Potential applications of the Cs-OTS cell to the development of a vapor cell atomic clock are discussed

  16. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  17. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

    Science.gov (United States)

    Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

    2011-02-01

    In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

  18. The CD4+CD26-T-cell population in classical Hodgkin's lymphoma displays a distinctive regulatory T-cell profile

    NARCIS (Netherlands)

    Ma, Yue; Visser, Lydia; Blokzijl, Tjasso; Harms, Geert; Atayar, Cigdem; Poppema, Sibrand; van den Berg, Anke

    Little is known about the gene expression profile and significance of the rosetting CD4+CD26- T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4+CD26- and CD4+CD26+ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL)

  19. Sensory characteristics of camphor.

    Science.gov (United States)

    Green, B G

    1990-05-01

    The perceptual effects of camphor on hairy skin were measured in a psychophysical experiment. Subjects rated the intensity and quality of sensations produced when a solution of 20% camphor (in a vehicle of ethanol and deionized H2O) was applied topically to the volar forearm. Under conditions in which skin temperature was varied either from 33-43 degrees C or from 33-18 degrees C, it was found that camphor increased the perceived intensity of the cutaneous sensations produced during heating and cooling. Although camphor's effect appeared to be greater during warming, neither effect was large. Camphor also produced a significant increase in the frequency of reports of "burning." It is concluded that camphor is a relatively weak sensory irritant that may have a modest excitatory effect on thermosensitive (and perhaps nociceptive) cutaneous fibers.

  20. Assessment of Sensory Processing Characteristics in Children between 3 and 11 Years Old: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Sara Jorquera-Cabrera

    2017-03-01

    Full Text Available The assessment of sensory perception, discrimination, integration, modulation, praxis, and other motor skills, such as posture, balance, and bilateral motor coordination, is necessary to identify the sensory and motor factors influencing the development of personal autonomy. The aim of this work is to study the assessment tools currently available for identifying different patterns of sensory processing. There are 15 tests available that have psychometric properties, primarily for the US population. Nine of them apply to children in preschool and up to grade 12. The assessment of sensory processing is a process that includes the use of standardized tests, administration of caregiver questionnaires, and clinical observations. The review of different studies using PRISMA criteria or Osteba Critical Appraisal Cards reveals that the most commonly used tools are the Sensory Integration and Praxis Test, the Sensory Processing Measure, and the Sensory Profile.

  1. Tic Modulation Using Sensory Tricks

    Directory of Open Access Journals (Sweden)

    Rebecca W. Gilbert

    2013-04-01

    Full Text Available Background: A sensory trick, or geste antagoniste, is defined as a physical gesture (such as a touch on a particular body part that mitigates the production of an involuntary movement. This phenomenon is most commonly described as a feature of dystonia. Here we present a case of successful modulation of tics using sensory tricks.Case Report:: A case report and video are presented. The case and video demonstrate a 19-year-old male who successfully controlled his tics with various sensory tricks.Discussion: It is underappreciated by movement disorder physicians that sensory tricks can play a role in tics. Introducing this concept to patients could potentially help in tic control. In addition, understanding the pathophysiological underpinnings of sensory tricks could help in the understanding of the pathophysiology of tics.

  2. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities. © 2014 Society of Chemical Industry.

  3. Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells.

    Science.gov (United States)

    Hald, Bjørn Olav; Garkier Hendriksen, Morten; Sørensen, Preben Graae

    2013-05-15

    Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem-particularly for phase coherence in oscillating systems. The present article presents a novel strategy for construction of large-scale simulation programs of heterogeneous biological entities. The strategy is designed to be tractable, to handle heterogeneity and to handle computational cost issues simultaneously, primarily by writing a generator of the 'model to be simulated'. We apply the strategy to model glycolytic oscillations among thousands of yeast cells coupled through the extracellular medium. The usefulness is illustrated through (i) benchmarking, showing an almost linear relationship between model size and run time, and (ii) analysis of the resulting simulations, showing that contrary to the experimental situation, synchronous oscillations are surprisingly hard to achieve, underpinning the need for tools to study heterogeneity. Thus, we present an efficient strategy to model the biological heterogeneity, neglected by ordinary mean-field models. This tool is well posed to facilitate the elucidation of the physiologically vital problem of synchronization. The complete python code is available as Supplementary Information. bjornhald@gmail.com or pgs@kiku.dk Supplementary data are available at Bioinformatics online.

  4. Accounting for randomness in measurement and sampling in studying cancer cell population dynamics.

    Science.gov (United States)

    Ghavami, Siavash; Wolkenhauer, Olaf; Lahouti, Farshad; Ullah, Mukhtar; Linnebacher, Michael

    2014-10-01

    Knowing the expected temporal evolution of the proportion of different cell types in sample tissues gives an indication about the progression of the disease and its possible response to drugs. Such systems have been modelled using Markov processes. We here consider an experimentally realistic scenario in which transition probabilities are estimated from noisy cell population size measurements. Using aggregated data of FACS measurements, we develop MMSE and ML estimators and formulate two problems to find the minimum number of required samples and measurements to guarantee the accuracy of predicted population sizes. Our numerical results show that the convergence mechanism of transition probabilities and steady states differ widely from the real values if one uses the standard deterministic approach for noisy measurements. This provides support for our argument that for the analysis of FACS data one should consider the observed state as a random variable. The second problem we address is about the consequences of estimating the probability of a cell being in a particular state from measurements of small population of cells. We show how the uncertainty arising from small sample sizes can be captured by a distribution for the state probability.

  5. Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

    Science.gov (United States)

    Peñas-Cazorla, Raúl; Vilaró, M Teresa

    2015-11-01

    Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

  6. Transcriptional and functional differences in stem cell populations isolated from Extraocular and Limb muscles

    DEFF Research Database (Denmark)

    Pacheco-Pinedo, Eugenia Cristina; Budak, Murat T; Zeiger, Ulrike

    2008-01-01

    The extraocular muscles (EOMs) are a distinct muscle group that displays an array of unique contractile, structural and regenerative properties. They also have differential sensitivity to certain diseases and are enigmatically spared in Duchenne muscular dystrophy (DMD). The EOMs are so distinct...... from other skeletal muscles that the term: allotype has been coined to highlight EOM-group-specific properties. We hypothesized that increased and distinct stem cells may underlie the continual myogenesis noted in EOM. The side population (SP) stem cells were isolated and studied. EOMs had 15x higher...... SP cell content compared to limb muscles. Expression profiling revealed 348 transcripts that define the EOM-SP transcriptome. Over 92% of transcripts were SP-specific, as they were absent in previous whole-muscle microarray studies. Cultured EOM-SP cells revealed superior in vitro proliferative...

  7. The presence of lytic HSV-1 transcripts and clonally expanded T cells with a memory effector phenotype in human sensory ganglia.

    Science.gov (United States)

    Derfuss, Tobias; Arbusow, Viktor; Strupp, Michael; Brandt, Thomas; Theil, Diethilde

    2009-05-01

    Herpes simplex virus type 1 (HSV-1) latent persistence in human trigeminal ganglia (TG) is accompanied by a chronic CD8 T-cell infiltration. Thus far, during HSV-1 latency only a single transcript, namely the latency-associated transcript (LAT), has been identified to be synthesized but not translated into a protein. In contrast, the chronic CD8 T-cell infiltration suggests that an antigen trigger must be present. The focus of the current work was to look for HSV-1 transcription activity as a potential trigger of the immune response and to demonstrate whether the immune cells are clonally expanded and have a phenotype that suggests that they have been triggered by viral antigen. By combining in situ hybridization, laser cutting microscopy, and single-cell real time RT-PCR, we demonstrated expression of the HSV-1 immediate early (IE) genes ICP0 and ICP4 in human trigeminal neurons. Using CDR3 spectratyping, we showed that the infiltrating T cells are clonally expanded, indicating an antigen-driven immune response. Moreover, the persisting CD8(+) T cells had prominent features of the memory effector phenotype. Chemokines CCL5 and CXCL10 were expressed by a subpopulation of infiltrating cells and the corresponding chemokine receptors CCR5 and CXCR3 were co-expressed on virtually all T cells bearing the CD8 phenotype. Thus, HSV-1 IE genes are expressed in human TG, and the infiltrating T cells bear several characteristics that suggest viral antigenic stimulation.

  8. Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.

    Science.gov (United States)

    Patel, Riyaz S; Li, Qunna; Ghasemzadeh, Nima; Eapen, Danny J; Moss, Lauren D; Janjua, A Umair; Manocha, Pankaj; Kassem, Hatem Al; Veledar, Emir; Samady, Habib; Taylor, W Robert; Zafari, A Maziar; Sperling, Laurence; Vaccarino, Viola; Waller, Edmund K; Quyyumi, Arshed A

    2015-01-16

    Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (β=-0.92, P=0.043 and β=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (β=-1.25, P=0.020 and β=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors. Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies. © 2014 American Heart Association, Inc.

  9. Phenotypic characterisation of cell populations in the brains of horses experimentally infected with West Nile virus.

    Science.gov (United States)

    Delcambre, G H; Liu, J; Streit, W J; Shaw, G P J; Vallario, K; Herrington, J; Wenzlow, N; Barr, K L; Long, M T

    2017-11-01

    West Nile virus (WNV), a mosquito borne member of the Flaviviridae, is one of the most commonly diagnosed agents of viral encephalitis in horses and people worldwide. A cassette of markers for formalin-fixed paraffin-embedded tissue and an archive of tissues from experimental infections in the horse were used to investigate the equine neuroimmune response to WNV meningoencephalomyelitis to phenotype the early response to WNV infection in the horse. Quantitative analysis using archived tissue from experimentally infected horses. The thalamus and hindbrain from 2 groups of 6 horses were compared and consisted of a culture positive tissues from WNV experimentally horses, in the other, normal horses. Formalin-fixed paraffin-embedded tissue from the thalamus and hindbrain were immunolabeled for microglia, astrocytes, B cells, macrophages/neutrophils, CD3 + T cells. Fresh frozen tissues were immunolabeled for CD4 + and CD8 + T lymphocyte cell markers. Cell counts were obtained using a computer software program. Differences, after meeting assumptions of abnormality, were computed using a general linear model with a Tukey test (Phorses, Iba-1 + microglia, CD3 + T lymphocyte and MAC387 + macrophage staining were significantly increased. The T cell response for the WNV-challenged horses was mixed, composed of CD4 + and CD8 + T lymphocytes. A limited astrocyte response was also observed in WNV-challenged horses, and MAC387 + and B cells were the least abundant cell populations. The results of this study were limited by a single collection time post-infection. Furthermore, a comprehensive analysis of cellular phenotypes is needed for naturally infected horses. Unfortunately, in clinical horses, there is high variability of sampling in terms of days post-infection and tissue handling. The data show that WNV-challenged horses recruit a mixed T cell population at the onset of neurologic disease. © 2017 EVJ Ltd.

  10. Stochastic adaptation and fold-change detection: from single-cell to population behavior

    Directory of Open Access Journals (Sweden)

    Leier André

    2011-02-01

    Full Text Available Abstract Background In cell signaling terminology, adaptation refers to a system's capability of returning to its equilibrium upon a transient response. To achieve this, a network has to be both sensitive and precise. Namely, the system must display a significant output response upon stimulation, and later on return to pre-stimulation levels. If the system settles at the exact same equilibrium, adaptation is said to be 'perfect'. Examples of adaptation mechanisms include temperature regulation, calcium regulation and bacterial chemotaxis. Results We present models of the simplest adaptation architecture, a two-state protein system, in a stochastic setting. Furthermore, we consider differences between individual and collective adaptive behavior, and show how our system displays fold-change detection properties. Our analysis and simulations highlight why adaptation needs to be understood in terms of probability, and not in strict numbers of molecules. Most importantly, selection of appropriate parameters in this simple linear setting may yield populations of cells displaying adaptation, while single cells do not. Conclusions Single cell behavior cannot be inferred from population measurements and, sometimes, collective behavior cannot be determined from the individuals. By consequence, adaptation can many times be considered a purely emergent property of the collective system. This is a clear example where biological ergodicity cannot be assumed, just as is also the case when cell replication rates are not homogeneous, or depend on the cell state. Our analysis shows, for the first time, how ergodicity cannot be taken for granted in simple linear examples either. The latter holds even when cells are considered isolated and devoid of replication capabilities (cell-cycle arrested. We also show how a simple linear adaptation scheme displays fold-change detection properties, and how rupture of ergodicity prevails in scenarios where transitions between

  11. Heterogenous populations of cytotoxic cells in the peritoneal cavity of BALB/c mice immunized with allogeneic EL4 leukemia cells

    International Nuclear Information System (INIS)

    Zighelboim, J.; Bonavida, B.; Fahey, J.L.

    1974-01-01

    Adherent cells, presumably macrophages, obtained from the peritoneal cavity shortly after rejection of the allogeneic leukemia EL4, produced effective cell-mediated cytotoxicity (CMC) in vitro. These cytotoxic cells were sensitive to anti-macrophage serum and resistant to anti-thymocyte serum and 10,000 roentgen irradiation. In contrast, a second population of specifically cytotoxic cells were nonadherent, sensitive to x-rays and anti-thymocyte serum, but not to anti-macrophage serum. The two cell populations had a cooperative cytotoxic effect in vitro against allogeneic tumor cells

  12. Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

    Science.gov (United States)

    Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

    2017-11-07

    Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

  13. Doped Overoxidized Polypyrrole Microelectrodes as Sensors for the Detection of Dopamine Released from Cell Populations

    DEFF Research Database (Denmark)

    Sasso, Luigi; Heiskanen, Arto; Diazzi, Francesco

    2013-01-01

    A surface modification of interdigitated gold microelectrodes (IDEs) with a doped polypyrrole (PPy) film for detection of dopamine released from populations of differentiated PC12 cells is presented. A thin PPy layer was potentiostatically electropolymerized from an 10 aqueous pyrrole solution onto...... electrode surfaces. The conducting polymer film was doped during electropolymerization by introducing counter ions in the monomer solution. Several counter ions were tested and the resulting electrode modifications were characterized electrochemically to find the optimal dopant that increases sensitivity...... to amperometrically detect dopamine released by populations of cells upon triggering cellular exocytosis with an elevated K+ concentration. A comparison between the generated current on bare gold electrodes and gold electrodes modified with overoxidized doped PPy illustrates the clear advantage of the modification...

  14. Heterogeneity within the spleen colony-forming cell population in rat bone marrow

    International Nuclear Information System (INIS)

    Martens, A.C.; van Bekkum, D.W.; Hagenbeek, A.

    1986-01-01

    The pluripotent hemopoietic stem cell (HSC) of the rat can be enumerated in a spleen colony assay (SCA) in rats as well as mice. After injection of rat bone marrow into lethally irradiated mice, macroscopically visible spleen colonies (CFU-S) are found from day 6 through 14, but the number varies on consecutive days. In normal bone marrow a constant ratio of day-8 to day-12 colony numbers is observed. However, this ratio is changed after in vivo treatment of rats with cyclophosphamide, as well as after in vitro treatment of rat bone marrow with cyclophosphamide derivatives. This indicates that the CFU-S that form colonies on day 8 react differently to this treatment than the CFU-S that form colonies on day 12, and suggests heterogeneity among the CFU-S population. Posttreatment regrowth of day-8 and day-12 CFU-S is characterized by differences in population-doubling times (Td = 0.85 days vs 1.65 days). Another argument in support of the postulate of heterogeneity within the rat CFU-S population is derived from the fact that (in contrast to normal rat spleen) the spleen of leukemic rats contains high numbers of CFU-S that show a ratio of day-8 to day-12 CFU-S of 4.5, which is different than that observed for a CFU-S population in normal bone marrow (a ratio of 2.4). It is concluded that, in rat hemopoiesis, two populations of spleen colony-forming cells can be distinguished using the rat-to-mouse SCA. This indicates that mouse and rat hemopoiesis are comparable in this respect and that heterogeneity in the stem cell compartment is a general phenomenon

  15. Immunohistochemical study of sensory nerve formations in human glabrous skin.

    Science.gov (United States)

    Haro, J J; Vega, J A; del Valle, M E; Calzada, B; Zaccheo, D; Malinovsky, L

    1991-01-01

    The sensory nerve formations (or corpuscles) of normal human glabrous skin from hand and fingers, obtained by punch biopsies, were studied by the streptavidin-biotin method using monoclonal antibodies directed against neurofilament protein (NFP), S-100 protein, glial fibrillary acidic protein (GFAP), cytokeratins, and vimentin. NFP immunoreactivity (IR) was observed in the central axons of most sensory formations, while S-100 protein IR was restricted to non-neuronal cells forming the so-called inner cells core or lamellar cells. Furthermore, vimentin IR was found in the same cells of Meissner's and glomerular corpuscles. None of the sensory nerve formations were stained for GFAP or keratin. The present results suggest that the main nature of the intermediate filaments of the non-neuronal cells of sensory nerve formations from human glabrous skin is represented by vimentin and not by GFAP. Thus, our findings suggest that lamellar and inner core cells of SNF are modified and specialized Schwann cells and not epithelial or perineurial derived cells.

  16. Sensory maps in the claustrum of the cat.

    Science.gov (United States)

    Olson, C R; Graybiel, A M

    1980-12-04

    The claustrum is a telencephalic cell group (Fig. 1A, B) possessing widespread reciprocal connections with the neocortex. In this regard, it bears a unique and striking resemblance to the thalamus. We have now examined the anatomical ordering of pathways linking the claustrum with sensory areas of the cat neocortex and, in parallel electrophysiological experiments, have studied the functional organization of claustral sensory zones so identified. Our findings indicate that there are discrete visual and somatosensory subdivisions in the claustrum interconnected with the corresponding primary sensory areas of the neocortex and that the respective zones contain orderly retinotopic and somatotopic maps. A third claustral region receiving fibre projections from the auditory cortex in or near area Ep was found to contain neurones responsive to auditory stimulation. We conclude that loops connecting sensory areas of the neocortex with satellite zones in the claustrum contribute to the early processing of exteroceptive information by the forebrain.

  17. Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature.

    Science.gov (United States)

    Psaltis, Peter J; Puranik, Amrutesh S; Spoon, Daniel B; Chue, Colin D; Hoffman, Scott J; Witt, Tyra A; Delacroix, Sinny; Kleppe, Laurel S; Mueske, Cheryl S; Pan, Shuchong; Gulati, Rajiv; Simari, Robert D

    2014-07-18

    Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage

  18. Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

    Science.gov (United States)

    ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

    2016-01-01

    Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

  19. Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations

    Czech Academy of Sciences Publication Activity Database

    Stahlberg, A.; Andersson, D.; Aurelius, J.; Faiz, M.; Pekna, M.; Kubista, Mikael; Pekny, M.

    2011-01-01

    Roč. 39, č. 4 (2011) ISSN 0305-1048 R&D Projects: GA AV ČR IAA500970904; GA ČR GAP303/10/1338 Institutional research plan: CEZ:AV0Z50520701 Keywords : EMBRYONIC STEM-CELLS * REAL-TIME PCR * MESSENGER-RNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.026, year: 2011

  20. I Want More and Better Cells! - An Outreach Project about Stem Cells and Its Impact on the General Population.

    Science.gov (United States)

    Varela Amaral, Sara; Forte, Teresa; Ramalho-Santos, João; Girão da Cruz, M Teresa

    2015-01-01

    Although science and technology impact every aspect of modern societies, there is still an extensive gap between science and society, which impairs the full exercise of citizenship. In the particular case of biomedical research increased investment should be accompanied by parallel efforts in terms of public information and engagement. We have carried out a project involving the production and evaluation of educational contents focused on stem cells - illustrated newspaper chronicles, radio interviews, a comic book, and animated videos - and monitored their impact on the Portuguese population. The study of the outreach materials in a heterogeneous sample of the population suggests that they are valuable tools to disseminate scientific messages, and that this is especially true for the comic-book format. Furthermore, the data showed that clear and stimulating outreach materials, that are able to teach new concepts and to promote critical thinking, increase engagement in science at different levels, depending on the depth of the concepts involved. Additionally, these materials can influence political, social and personal attitudes toward science. These results, together with the importance attributed to scientific research in stem cells by the population sampled, validates the diffusion of such materials as a significant contribution towards an overall public understanding and engagement in contemporary science, and this strategy should thus be considered in future projects. Regardless, stringent quality control must be implemented in order to efficiently communicate accurate scientific developments, and the public stimulated in terms of finding additional sources of reliable information.

  1. I Want More and Better Cells! – An Outreach Project about Stem Cells and Its Impact on the General Population

    Science.gov (United States)

    Varela Amaral, Sara; Forte, Teresa; Ramalho-Santos, João; Girão da Cruz, M. Teresa

    2015-01-01

    Although science and technology impact every aspect of modern societies, there is still an extensive gap between science and society, which impairs the full exercise of citizenship. In the particular case of biomedical research increased investment should be accompanied by parallel efforts in terms of public information and engagement. We have carried out a project involving the production and evaluation of educational contents focused on stem cells - illustrated newspaper chronicles, radio interviews, a comic book, and animated videos - and monitored their impact on the Portuguese population. The study of the outreach materials in a heterogeneous sample of the population suggests that they are valuable tools to disseminate scientific messages, and that this is especially true for the comic-book format. Furthermore, the data showed that clear and stimulating outreach materials, that are able to teach new concepts and to promote critical thinking, increase engagement in science at different levels, depending on the depth of the concepts involved. Additionally, these materials can influence political, social and personal attitudes toward science. These results, together with the importance attributed to scientific research in stem cells by the population sampled, validates the diffusion of such materials as a significant contribution towards an overall public understanding and engagement in contemporary science, and this strategy should thus be considered in future projects. Regardless, stringent quality control must be implemented in order to efficiently communicate accurate scientific developments, and the public stimulated in terms of finding additional sources of reliable information. PMID:26222053

  2. Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.

    Directory of Open Access Journals (Sweden)

    József Jászai

    2011-03-01

    Full Text Available Besides being a marker of various somatic stem cells in mammals, prominin-1 (CD133 plays a role in maintaining the photoreceptor integrity since mutations in the PROM1 gene are linked with retinal degeneration. In spite of that, little information is available regarding its distribution in eyes of non-mammalian vertebrates endowed with high regenerative abilities. To address this subject, prominin-1 cognates were isolated from axolotl, zebrafish and chicken, and their retinal compartmentalization was investigated and compared to that of their mammalian orthologue. Interestingly, prominin-1 transcripts--except for the axolotl--were not strictly restricted to the outer nuclear layer (i.e., photoreceptor cells, but they also marked distinct subdivisions of the inner nuclear layer (INL. In zebrafish, where the prominin-1 gene is duplicated (i.e., prominin-1a and prominin-1b, a differential expression was noted for both paralogues within the INL being localized either to its vitreal or scleral subdivision, respectively. Interestingly, expression of prominin-1a within the former domain coincided with Pax-6-positive cells that are known to act as progenitors upon injury-induced retino-neurogenesis. A similar, but minute population of prominin-1-positive cells located at the vitreal side of the INL was also detected in developing and adult mice. In chicken, however, prominin-1-positive cells appeared to be aligned along the scleral side of the INL reminiscent of zebrafish prominin-1b. Taken together our data indicate that in addition to conserved expression of prominin-1 in photoreceptors, significant prominin-1-expressing non-photoreceptor retinal cell populations are present in the vertebrate eye that might represent potential sources of stem/progenitor cells for regenerative therapies.

  3. HCMV spread and cell tropism are determined by distinct virus populations.

    Directory of Open Access Journals (Sweden)

    Laura Scrivano

    Full Text Available Human cytomegalovirus (HCMV can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells.

  4. Dendritic cell populations in patients with self-reported food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Lied GA

    2011-05-01

    Full Text Available Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38

  5. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.

    Science.gov (United States)

    Forman, Oliver P; Hitti, Rebekkah J; Pettitt, Louise; Jenkins, Christopher A; O'Brien, Dennis P; Shelton, G Diane; De Risio, Luisa; Quintana, Rodrigo Gutierrez; Beltran, Elsa; Mellersh, Cathryn

    2016-09-08

    Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population. Copyright © 2016 Forman et al.

  6. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

    Directory of Open Access Journals (Sweden)

    Oliver P. Forman

    2016-09-01

    Full Text Available Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population.

  7. Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease.

    Science.gov (United States)

    Lepoutre, Veronique; Jain, Pooja; Quann, Kevin; Wigdahl, Brian; Khan, Zafar K

    2009-01-01

    Human T cell leukemia virus type 1 (HTLV-1), the first human retrovirus discovered, is the etiologic agent for a number of disorders; the two most common pathologies include adult T cell leukemia (ATL) and a progressive demyelinating neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The neurologic dysfunction associated with HAM/TSP is a result of viral intrusion into the central nervous system (CNS) and the generation of a hyperstimulated host response within the peripheral and central nervous system that includes expanded populations of CD4+ and CD8+ T cells and proinflammatory cytokines/chemokines in the cerebrospinal fluid (CSF). This robust, yet detrimental immune response likely contributes to the death of myelin producing oligodendrocytes and degeneration of neuronal axons. The mechanisms of neurological degeneration in HAM/TSP have yet to be fully delineated in vivo and may involve the immunogenic properties of the HTLV-1 transactivator protein Tax. This comprehensive review characterizes the available knowledge to date concerning the effects of HTLV-1 on CNS resident cell populations with emphasis on both viral and host factors contributing to the genesis of HAM/TSP.

  8. Application of phasor plot and autofluorescence correction for study of heterogeneous cell population

    Science.gov (United States)

    Szmacinski, Henryk; Toshchakov, Vladimir; Lakowicz, Joseph R.

    2014-01-01

    Abstract. Protein-protein interactions in cells are often studied using fluorescence resonance energy transfer (FRET) phenomenon by fluorescence lifetime imaging microscopy (FLIM). Here, we demonstrate approaches to the quantitative analysis of FRET in cell population in a case complicated by a highly heterogeneous donor expression, multiexponential donor lifetime, large contribution of cell autofluorescence, and significant presence of unquenched donor molecules that do not interact with the acceptor due to low affinity of donor-acceptor binding. We applied a multifrequency phasor plot to visualize FRET FLIM data, developed a method for lifetime background correction, and performed a detailed time-resolved analysis using a biexponential model. These approaches were applied to study the interaction between the Toll Interleukin-1 receptor (TIR) domain of Toll-like receptor 4 (TLR4) and the decoy peptide 4BB. TLR4 was fused to Cerulean fluorescent protein (Cer) and 4BB peptide was labeled with Bodipy TMRX (BTX). Phasor displays for multifrequency FLIM data are presented. The analytical procedure for lifetime background correction is described and the effect of correction on FLIM data is demonstrated. The absolute FRET efficiency was determined based on the phasor plot display and multifrequency FLIM data analysis. The binding affinity between TLR4-Cer (donor) and decoy peptide 4BB-BTX (acceptor) was estimated in a heterogeneous HeLa cell population. PMID:24770662

  9. Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

    Science.gov (United States)

    Uematsu, Akira; Tan, Bao Zhen

    2015-01-01

    Noradrenergic neurons in the locus coeruleus (LC) play a critical role in many functions including learning and memory. This relatively small population of cells sends widespread projections throughout the brain including to a number of regions such as the amygdala which is involved in emotional associative learning and the medial prefrontal cortex which is important for facilitating flexibility when learning rules change. LC noradrenergic cells participate in both of these functions, but it is not clear how this small population of neurons modulates these partially distinct processes. Here we review anatomical, behavioral, and electrophysiological studies to assess how LC noradrenergic neurons regulate these different aspects of learning and memory. Previous work has demonstrated that subpopulations of LC noradrenergic cells innervate specific brain regions suggesting heterogeneity of function in LC neurons. Furthermore, noradrenaline in mPFC and amygdala has distinct effects on emotional learning and cognitive flexibility. Finally, neural recording data show that LC neurons respond during associative learning and when previously learned task contingencies change. Together, these studies suggest a working model in which distinct and potentially opposing subsets of LC neurons modulate particular learning functions through restricted efferent connectivity with amygdala or mPFC. This type of model may provide a general framework for understanding other neuromodulatory systems, which also exhibit cell type heterogeneity and projection specificity. PMID:26330494

  10. Modeling and Analysis of a Nonlinear Age-Structured Model for Tumor Cell Populations with Quiescence

    Science.gov (United States)

    Liu, Zijian; Chen, Jing; Pang, Jianhua; Bi, Ping; Ruan, Shigui

    2018-05-01

    We present a nonlinear first-order hyperbolic partial differential equation model to describe age-structured tumor cell populations with proliferating and quiescent phases at the avascular stage in vitro. The division rate of the proliferating cells is assumed to be nonlinear due to the limitation of the nutrient and space. The model includes a proportion of newborn cells that enter directly the quiescent phase with age zero. This proportion can reflect the effect of treatment by drugs such as erlotinib. The existence and uniqueness of solutions are established. The local and global stabilities of the trivial steady state are investigated. The existence and local stability of the positive steady state are also analyzed. Numerical simulations are performed to verify the results and to examine the impacts of parameters on the nonlinear dynamics of the model.

  11. Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine.

    Directory of Open Access Journals (Sweden)

    Hui Kuang

    2010-12-01

    Full Text Available Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.

  12. SEPARATION OF CELL POPULATIONS BY SUPER-PARAMAGNETIC PARTICLES WITH CONTROLLED SURFACE FUNCTIONALITY

    Directory of Open Access Journals (Sweden)

    Lootsik M. D.

    2014-02-01

    Full Text Available The recognition and isolation of specific mammalian cells by the biocompatible polymer coated super-paramagnetic particles with determined surface functionality were studied. The method of synthesis of nanoscaled particles on a core of iron III oxide (Fe2O3, magemit coated with a polymer shell containing reactive oligoperoxide groups for attachment of ligands is described. By using the developed superparamagnetic particles functionalized with peanut agglutinin (PNA we have separated the sub-populations of PNA+ and PNA– cells from ascites of murine Nemeth-Kellner lymphoma. In another type of experiment, the particles were opsonized with proteins of the fetal calf serum that improved biocompatibility of the particles and their ingestion by cultivated murine macrophages J774.2. Macrophages loaded with the particles were effeciently separated from the particles free cells by using the magnet. Thus, the developed surface functionalized superparamagnetic particles showed to be a versatile tool for cell separation independent on the mode of particles’ binding with cell surface or their engulfment by the targeted cells.

  13. Single cell genomics indicates horizontal gene transfer and viral infections in a deep subsurface Firmicutes population

    Directory of Open Access Journals (Sweden)

    Jessica eLabonté

    2015-04-01

    Full Text Available A major fraction of Earth's prokaryotic biomass dwells in the deep subsurface, where cellular abundances per volume of sample are lower, metabolism is slower, and generation times are longer than those in surface terrestrial and marine environments. How these conditions impact biotic interactions and evolutionary processes is largely unknown. Here we employed single cell genomics to analyze cell-to-cell genome content variability and signatures of horizontal gene transfer (HGT and viral infections in five cells of Candidatus Desulforudis audaxviator, which were collected from a three km-deep fracture water in the 2.9 Ga-old Witwatersrand Basin of South Africa. Between 0 and 32 % of genes recovered from single cells were not present in the original, metagenomic assembly of Desulforudis, which was obtained from a neighboring subsurface fracture. We found a transposable prophage, a retron, multiple clustered regularly interspaced short palindromic repeats (CRISPRs and restriction-modification systems, and an unusually high frequency of transposases in the analyzed single cell genomes. This indicates that recombination, HGT and viral infections are prevalent evolutionary events in the studied population of microorganisms inhabiting a highly stable deep subsurface environment.

  14. Joint modeling and registration of cell populations in cohorts of high-dimensional flow cytometric data.

    Directory of Open Access Journals (Sweden)

    Saumyadipta Pyne

    Full Text Available In biomedical applications, an experimenter encounters different potential sources of variation in data such as individual samples, multiple experimental conditions, and multivariate responses of a panel of markers such as from a signaling network. In multiparametric cytometry, which is often used for analyzing patient samples, such issues are critical. While computational methods can identify cell populations in individual samples, without the ability to automatically match them across samples, it is difficult to compare and characterize the populations in typical experiments, such as those responding to various stimulations or distinctive of particular patients or time-points, especially when there are many samples. Joint Clustering and Matching (JCM is a multi-level framework for simultaneous modeling and registration of populations across a cohort. JCM models every population with a robust multivariate probability distribution. Simultaneously, JCM fits a random-effects model to construct an overall batch template--used for registering populations across samples, and classifying new samples. By tackling systems-level variation, JCM supports practical biomedical applications involving large cohorts. Software for fitting the JCM models have been implemented in an R package EMMIX-JCM, available from http://www.maths.uq.edu.au/~gjm/mix_soft/EMMIX-JCM/.

  15. Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

    Directory of Open Access Journals (Sweden)

    Jean-Marc Good

    2017-11-01

    Full Text Available Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF to Purkinje cell (PC network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.

  16. Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations

    International Nuclear Information System (INIS)

    Wong, Nelson K Y; Fuller, Megan; Sung, Sandy; Wong, Fred; Karsan, Aly

    2012-01-01

    Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population

  17. Analyzing sensory data with R

    CERN Document Server

    Le, Sebastien

    2014-01-01

    Quantitative Descriptive Approaches When panelists rate products according to one single list of attributes Data, sensory issues, notations In practice For experienced users: Measuring the impact of the experimental design on the perception of the products? When products are rated according to one single list of attributesData, sensory issues, notations In practice For experienced users: Adding supplementary information to the product space When products are rated according to several lists

  18. Sensory Dissonance Using Memory Model

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2015-01-01

    Music may occur concurrently or in temporal sequences. Current machine-based methods for the estimation of qualities of the music are unable to take into account the influence of temporal context. A method for calculating dissonance from audio, called sensory dissonance is improved by the use of ...... of a memory model. This approach is validated here by the comparison of the sensory dissonance using memory model to data obtained using human subjects....

  19. Population attributable fraction of Esophageal squamous cell carcinoma due to smoking and alcohol in Uganda

    International Nuclear Information System (INIS)

    Okello, Samson; Churchill, Cristina; Owori, Rogers; Nasasira, Benson; Tumuhimbise, Christine; Abonga, Charles Lagoro; Mutiibwa, David; Christiani, David C.; Corey, Kathleen E.

    2016-01-01

    Despite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown. We conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy. Our study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40–64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively. In this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown

  20. Distribution of binding sites for the plant lectin Ulex europaeus agglutinin I on primary sensory neurones in seven different mammalian species.

    Science.gov (United States)

    Gerke, Michelle B; Plenderleith, Mark B

    2002-01-01

    There is an increasing body of evidence to suggest that different functional classes of neurones express characteristic cell-surface carbohydrates. Previous studies have shown that the plant lectin Ulex europaeus agglutinin-I (UEA) binds to a population of small to medium diameter primary sensory neurones in rabbits and humans. This suggests that a fucose-containing glycoconjugate may be expressed by nociceptive primary sensory neurones. In order to determine the extent to which this glycoconjugate is expressed by other species, in the current study, we have examined the distribution of UEA-binding sites on primary sensory neurones in seven different mammals. Binding sites for UEA were associated with the plasma membrane and cytoplasmic granules of small to medium dorsal root ganglion cells and their axon terminals in laminae I-III of the grey matter of the spinal cord, in the rabbit, cat and marmoset monkey. However, no binding was observed in either the dorsal root ganglia or spinal cord in the mouse, rat, guinea pig or flying fox. These results indicate an inter-species variation in the expression of cell-surface glycoconjugates on mammalian primary sensory neurones.

  1. The Significance of Memory in Sensory Cortex.

    Science.gov (United States)

    Muckli, Lars; Petro, Lucy S

    2017-05-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. The significance of memory in sensory cortex

    OpenAIRE

    Muckli, Lars; Petro, Lucy S.

    2017-01-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

  3. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    International Nuclear Information System (INIS)

    Silva, Andrew Oliveira; Dalsin, Eloisa; Onzi, Giovana Ravizzoni; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido

    2016-01-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  4. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Andrew Oliveira, E-mail: andrewbiomed@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Dalsin, Eloisa, E-mail: dalsineloisa@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Onzi, Giovana Ravizzoni, E-mail: gioonzi@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Filippi-Chiela, Eduardo Cremonese, E-mail: eduardochiela@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Lenz, Guido, E-mail: lenz@ufrgs.br [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)

    2016-11-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  5. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

    Czech Academy of Sciences Publication Activity Database

    van Gorp, S.; Leerink, M.; Kakinohana, O.; Platoshyn, O.; Santucci, C.; Galik, J.; Joosten, E. A.; Hruška-Plocháň, Marian; Goldberg, D.; Marsala, S.; Johe, K.; Ciacci, J. D.; Marsala, M.

    2013-01-01

    Roč. 4, č. 57 (2013) ISSN 1757-6512 Institutional support: RVO:67985904 Keywords : spinal cord injury * human neural stem cells * spinal grafting * functional recovery * rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.634, year: 2013

  6. Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

    Directory of Open Access Journals (Sweden)

    Sara J. Hawkins

    2017-11-01

    Full Text Available Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks.

  7. Sensory Supplementation to Enhance Adaptation Following G-transitions and Traumatic Brain Injury

    Science.gov (United States)

    Wood, Scott; Rupert, Angus

    2013-01-01

    Sensory supplementation can be incorporated as online feedback for improving spatial orientation awareness for manual control tasks (e.g. TSAS, Shuttle ZAG study). Preliminary data with vestibular patients and TBI military population is promising for rehabilitation training. Recommend that sensory supplementation be incorporated as a training component in an integrated countermeasure approach.

  8. Neural Correlates of Sensory Hyporesponsiveness in Toddlers at High Risk for Autism Spectrum Disorder

    Science.gov (United States)

    Simon, David M.; Damiano, Cara R.; Woynaroski, Tiffany G.; Ibañez, Lisa V.; Murias, Michael; Stone, Wendy L.; Wallace, Mark T.; Cascio, Carissa J.

    2017-01-01

    Altered patterns of sensory responsiveness are a frequently reported feature of Autism Spectrum Disorder (ASD). Younger siblings of individuals with ASD are at a greatly elevated risk of a future diagnosis of ASD, but little is known about the neural basis of sensory responsiveness patterns in this population. Younger siblings (n = 20) of children…

  9. Lineage Tracing and Cell Ablation Identify a Post-Aire-Expressing Thymic Epithelial Cell Population

    Directory of Open Access Journals (Sweden)

    Todd C. Metzger

    2013-10-01

    Full Text Available Thymic epithelial cells in the medulla (mTECs play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire, a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire+ mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire− mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance.

  10. Toward compression of small cell population: harnessing stress in passive regions of dielectric elastomer actuators

    Science.gov (United States)

    Poulin, Alexandre; Rosset, Samuel; Shea, Herbert

    2014-03-01

    We present a dielectric elastomer actuator (DEA) for in vitro analysis of mm2 biological samples under periodic compressive stress. Understanding how mechanical stimuli affect cell functions could lead to significant advances in diseases diagnosis and drugs development. We previously reported an array of 72 micro-DEAs on a chip to apply a periodic stretch to cells. To diversify our cell mechanotransduction toolkit we have developed an actuator for periodic compression of small cell populations. The device is based on a novel design which exploits the effects of non-equibiaxial pre-stretch and takes advantage of the stress induced in passive regions of DEAs. The device consists of two active regions separated by a 2mm x 2mm passive area. When connected to an AC high-voltage source, the two active regions periodically compress the passive region. Due to the non-equibiaxial pre-stretch it induces uniaxial compressive strain greater than 10%. Cells adsorbed on top of this passive gap would experience the same uniaxial compressive stain. The electrodes configuration confines the electric field and prevents it from reaching the biological sample. A thin layer of silicone is casted on top of the device to ensure a biocompatible environment. This design provides several advantages over alternative technologies such as high optical transparency of the area of interest (passive region under compression) and its potential for miniaturization and parallelization.

  11. A population balance equation model of aggregation dynamics in Taxus suspension cell cultures.

    Science.gov (United States)

    Kolewe, Martin E; Roberts, Susan C; Henson, Michael A

    2012-02-01

    The nature of plant cells to grow as multicellular aggregates in suspension culture has profound effects on bioprocess performance. Recent advances in the measurement of plant cell aggregate size allow for routine process monitoring of this property. We have exploited this capability to develop a conceptual model to describe changes in the aggregate size distribution that are observed over the course of a Taxus cell suspension batch culture. We utilized the population balance equation framework to describe plant cell aggregates as a particulate system, accounting for the relevant phenomenological processes underlying aggregation, such as growth and breakage. We compared model predictions to experimental data to select appropriate kernel functions, and found that larger aggregates had a higher breakage rate, biomass was partitioned asymmetrically following a breakage event, and aggregates grew exponentially. Our model was then validated against several datasets with different initial aggregate size distributions and was able to quantitatively predict changes in total biomass and mean aggregate size, as well as actual size distributions. We proposed a breakage mechanism where a fraction of biomass was lost upon each breakage event, and demonstrated that even though smaller aggregates have been shown to produce more paclitaxel, an optimum breakage rate was predicted for maximum paclitaxel accumulation. We believe this is the first model to use a segregated, corpuscular approach to describe changes in the size distribution of plant cell aggregates, and represents an important first step in the design of rational strategies to control aggregation and optimize process performance. Copyright © 2011 Wiley Periodicals, Inc.

  12. An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry.

    Science.gov (United States)

    Burel, Julie G; Qian, Yu; Lindestam Arlehamn, Cecilia; Weiskopf, Daniela; Zapardiel-Gonzalo, Jose; Taplitz, Randy; Gilman, Robert H; Saito, Mayuko; de Silva, Aruna D; Vijayanand, Pandurangan; Scheuermann, Richard H; Sette, Alessandro; Peters, Bjoern

    2017-02-15

    In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. In this study, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed the technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC samples, we found that most cell populations showed low intraindividual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high interindividual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naive T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these covariates in immune profiling studies. We also exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. CD71(high) population represents primitive erythroblasts derived from mouse embryonic stem cells.

    Science.gov (United States)

    Chao, Ruihua; Gong, Xueping; Wang, Libo; Wang, Pengxiang; Wang, Yuan

    2015-01-01

    The CD71/Ter119 combination has been widely used to reflect dynamic maturation of erythrocytes in vivo. However, because CD71 is expressed on all proliferating cells, it is unclear whether it can be utilized as an erythrocyte-specific marker during differentiation of embryonic stem cells (ESCs). In this study, we revealed that a population expressing high level of CD71 (CD71(high)) during mouse ESC differentiation represented an in vitro counterpart of yolk sac-derived primitive erythroblasts (EryPs) isolated at 8.5days post coitum. In addition, these CD71(high) cells went through "maturational globin switching" and enucleated during terminal differentiation in vitro that were similar to the yolk sac-derived EryPs in vivo. We further demonstrated that the formation of CD71(high) population was regulated differentially by key factors including Scl, HoxB4, Eaf1, and Klf1. Taken together, our study provides a technical advance that allows efficient segregation of EryPs from differentiated ESCs in vitro for further understanding molecular regulation during primitive erythropoiesis. Copyright © 2014. Published by Elsevier B.V.

  14. Host–virus dynamics and subcellular controls of cell fate in a natural coccolithophore population

    Science.gov (United States)

    Vardi, Assaf; Haramaty, Liti; Van Mooy, Benjamin A. S.; Fredricks, Helen F.; Kimmance, Susan A.; Larsen, Aud; Bidle, Kay D.

    2012-01-01

    Marine viruses are major evolutionary and biogeochemical drivers in marine microbial foodwebs. However, an in-depth understanding of the cellular mechanisms and the signal transduction pathways mediating host–virus interactions during natural bloom dynamics has remained elusive. We used field-based mesocosms to examine the “arms race” between natural populations of the coccolithophore Emiliania huxleyi and its double-stranded DNA-containing coccolithoviruses (EhVs). Specifically, we examined the dynamics of EhV infection and its regulation of cell fate over the course of bloom development and demise using a diverse suite of molecular tools and in situ fluorescent staining to target different levels of subcellular resolution. We demonstrate the concomitant induction of reactive oxygen species, caspase-specific activity, metacaspase expression, and programmed cell death in response to the accumulation of virus-derived glycosphingolipids upon infection of natural E. huxleyi populations. These subcellular responses to viral infection simultaneously resulted in the enhanced production of transparent exopolymer particles, which can facilitate aggregation and stimulate carbon flux. Our results not only corroborate the critical role for glycosphingolipids and programmed cell death in regulating E. huxleyi–EhV interactions, but also elucidate promising molecular biomarkers and lipid-based proxies for phytoplankton host–virus interactions in natural systems. PMID:23134731

  15. Derivation and characterization of human embryonic stem cell lines from the Chinese population

    Institute of Scientific and Technical Information of China (English)

    Zhao Wu; Huimin Dai; Lei Qian; Qing Tian; Lei Xiao; Xiaojun Tan; Hui Li; Lingjun Rao; Lixiazi He; Lei Bao; Jing Liao; Chun Cui; Zhenyu Zuo; Qiao Li

    2011-01-01

    Human embryonic stem cells (hESCs) can self-renew indefinitely and differentiate into all cell types in the human body. Therefore, they are valuable in regenerative medicine, human developmental biology and drug discovery. A number of hESC lines have been derived from the Chinese population,but limited of them are available for research purposes. Here we report the derivation and characterization of two hESC lines derived from human blastocysts of Chinese origin. These hESCs express alkaline phosphatase and hESC-specific markers, including Oct4, Nanog, SSEA-3, SSEA-4,TRA-1-60 and TRA-1-81. They also have high levels of telomerase activity and normal karyotypes. These cells can form embryoid body in vitro and can be differentiated into all three germ layers in vivo by teratoma formation. The newly established hESCs will be distributed for research purposes.The availability of hESC lines from the Chinese population will facilitate studies on the differences in hESCs from different ethnic groups.

  16. Sensory Neuropathy Due to Loss of Bcl-w

    Science.gov (United States)

    Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.

    2010-01-01

    Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w −/− mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w −/− sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w −/− mice as an animal model of small fiber sensory neuropathy, and provide new insight regarding the role of bcl-w and of mitochondria in preventing axonal degeneration. PMID:21289171

  17. Quantitative gene expression profiling of CD45(+) and CD45(-) skeletal muscle-derived side population cells

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Kristiansen, Gitte Qvistgaard; Jensen, Line

    2011-01-01

    transcripts associated with endothelial cells, Notch signaling and myogenic precursors. By comparing the mRNA signatures of mSPs with those of adipose tissue-derived SP populations, a common endothelial component seemed to reside in both muscle and fat-derived SPCD45(-) entities. However, each SP subset......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

  18. Neuropathic sensory symptoms: association with pain and psychological factors

    Directory of Open Access Journals (Sweden)

    Shaygan M

    2014-05-01

    Full Text Available Maryam Shaygan,1 Andreas Böger,2 Birgit Kröner-Herwig11Department of Clinical Psychology and Psychotherapy, University of Göttingen, Germany; 2Pain Management Clinic at the Red Cross Hospital, Kassel, GermanyBackground: A large number of population-based studies of chronic pain have considered neuropathic sensory symptoms to be associated with a high level of pain intensity and negative affectivity. The present study examines the question of whether this association previously found in non-selected samples of chronic pain patients can also be found in chronic pain patients with underlying pathology of neuropathic sensory symptoms.Methods: Neuropathic sensory symptoms in 306 patients with chronic pain diagnosed as typical neuropathic pain, radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the Pain DETECT Questionnaire. Two separate cluster analyses were performed to identify subgroups of patients with different levels of self-reported neuropathic sensory symptoms and, furthermore, to identify subgroups of patients with distinct patterns of neuropathic sensory symptoms (adjusted for individual response bias regarding specific symptoms.Results: ANOVA (analysis of variance results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no significant differences between the three levels of neuropathic sensory symptoms regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance, and depressive symptoms. However, in nociceptive back pain patients, significant differences were found for all variables except pain chronicity. When controlling for the response bias of patients in ratings of symptoms, none of the patterns of neuropathic sensory symptoms were associated with pain and psychological factors.Conclusion: Neuropathic sensory symptoms are not closely associated with higher levels of pain intensity and cognitive-emotional evaluations in chronic pain patients with underlying pathology of

  19. Uranium-induced sensory alterations in the zebrafish Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Faucher, K., E-mail: kfaucher@hotmail.fr [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France); Floriani, M.; Gilbin, R.; Adam-Guillermin, C. [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France)

    2012-11-15

    The effect of chronic exposure to uranium ions (UO{sub 2}{sup 2+}) on sensory tissues including the olfactory and lateral line systems was investigated in zebrafish (Danio rerio) using scanning electron microscopy. The aim of this study was to determine whether exposure to uranium damaged sensory tissues in fish. The fish were exposed to uranium at the concentration of 250 {mu}g l{sup -1} for 10 days followed by a depuration period of 23 days. Measurements of uranium uptake in different fish organs: olfactory rosettes and bulbs, brain, skin, and muscles, were also determined by ICP-AES and ICP-MS during the entire experimental period. The results showed that uranium displayed a strong affinity for sensory structures in direct contact with the surrounding medium, such as the olfactory and lateral line systems distributed on the skin. A decreasing gradient of uranium concentration was found: olfactory rosettes > olfactory bulbs > skin > muscles > brain. At the end of the experiment, uranium was present in non-negligible quantities in sensory tissues. In parallel, fish exposed to uranium showed severe sensory tissue alterations at the level of the olfactory and lateral line systems. In both sensory systems, the gross morphology was altered and the sensory hair cells were significantly damaged very early after the initiation of exposure (from the 3rd day). At the end of the experiment, after 23 days of depuration, the lateral line system still displayed slight tissue alterations, but approximately 80% of the neuromasts in this system had regenerated. In contrast, the olfactory system took more time to recover, as more than half of the olfactory rosettes observed remained destroyed at the end of the experiment. This study showed, for the first time, that uranium is able to damage fish sensory tissues to such an extent that tissue regeneration is delayed.

  20. Correlation of human papilloma virus with oral squamous cell carcinoma in Chinese population.

    Science.gov (United States)

    Zhou, Jingping; Tao, Detao; Tang, Daofang; Gao, Zhenlin

    2015-01-01

    Previous studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, the relationship between OSCC in a Chinese population and oral HPV infection is still unclear. In this study, we evaluate the relationship of OSCC with HPV infection in a Chinese population via a meta-analysis. The reports on HPV and OSCC in a Chinese population published between January, 1994, and October, 2015 were retrieved via CNKI/WANFANG/pubmed databases. According to the inclusion criteria, we selected 26 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the random effects model. Quantitative meta-analyses showed that, compared with normal oral mucosa the combined odds ratio of OSCC with HPV infection were 1.98 (95% CI: 1.34-2.92). The test for overall effect showed that the P value was less than 0.05 (Z = 3.46). Forest plot analyses were seen in Figures 2 and 3. Publication bias and bias risk analysis using RevMan 5.3 software were measured indicators of the graphics of the basic symmetry. High incidences of HPV infection were found in the samples of Chinese OSCC. For the Chinese population, HPV infection elevates the risk of OSCC tumorigenesis.

  1. Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.

    Directory of Open Access Journals (Sweden)

    Da-Quan Jiang

    Full Text Available We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model and the ordinary differential equation (ODE system model (deterministic model are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium" under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out or 1 (dominate. We also extend our results to non-Markovian cases.

  2. Damage of Inner Ear Sensory Hair Cells via Mitochondrial Loss in a Murine Model of Sleep Apnea With Chronic Intermittent Hypoxia.

    Science.gov (United States)

    Seo, Young Joon; Ju, Hyun Mi; Lee, Sun Hee; Kwak, Sang Hyun; Kang, Min Jung; Yoon, Joo-Heon; Kim, Chang-Hoon; Cho, Hyung-Ju

    2017-09-01

    Investigating the exact pathophysiology of obstructive sleep apnea syndrome (OSAS)-induced hearing loss is critical. We sought to verify the hypothesis that a correlation exists between mitochondrial dysfunction in inner ear hair cells and the auditory dysfunction induced by chronic intermittent hypoxia (CIH) in a murine model of sleep apnea. C57BL/6J adult male mice were randomized to 4 weeks of CIH (n = 12) or normoxia (Sham) (n = 12). Hearing threshold was determined by auditory brainstem response. The activity of mitochondria was compared between CIH and Sham mice. Histological assessment and transmission electron microscopy were performed for assessing morphologic changes in mitochondria. The number of mtDNA copies as well as the levels of PGC1-α, Tfam, and VDAC (voltage-dependent anion channel) were determined in the hair cells of CIH mice. We observed that hearing ability in CIH mice was impaired and hair-cell mitochondria in CIH mice were fewer compared to that in Sham and also displayed an aberrant morphology. The mRNA levels of PGC-1α and Tfam were higher in the CIH group than in the Sham group. Moreover, the expression of VDAC was increased in the tectorial membrane, the basilar membrane, and especially in the inner hair cells of CIH mice. This study using CIH mice as a model for OSAS provides evidence of an association between OSAS and auditory function alteration, as well as of mitochondria being part of the pathophysiology of hearing impairment. Further investigation is required to determine whether mitochondria could serve as a valid target for preventive or therapeutic purposes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  3. Affective and Sensory Correlates of Hair Pulling in Pediatric Trichotillomania

    Science.gov (United States)

    Meunier, Suzanne A.; Tolin, David F.; Franklin, Martin

    2009-01-01

    Hair pulling in pediatric populations has not received adequate empirical study. Investigations of the affective and sensory states contributing to the etiology and maintenance of hair pulling may help to elucidate the classification of trichotillomania (TTM) as an impulse control disorder or obsessive-compulsive spectrum disorder. The current…

  4. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    Science.gov (United States)

    Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

    2016-03-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

  5. Cisplatin Ototoxicity Blocks Sensory Regeneration in the Avian Inner Ear

    OpenAIRE

    Slattery, Eric L.; Warchol, Mark E.

    2010-01-01

    Cisplatin is a chemotherapeutic agent that is widely-used in the treatment of solid tumors. Ototoxicity is a common side effect of cisplatin therapy, and often leads to permanent hearing loss. The sensory organs of the avian ear are able to regenerate hair cells after aminoglycoside ototoxicity. This regenerative response is mediated by supporting cells, which serve as precursors to replacement hair cells. Given the antimitotic properties of cisplatin, we examined whether the avian ear was al...

  6. Deficient GABAergic gliotransmission may cause broader sensory tuning in schizophrenia.

    Science.gov (United States)

    Hoshino, Osamu

    2013-12-01

    We examined how the depression of intracortical inhibition due to a reduction in ambient GABA concentration impairs perceptual information processing in schizophrenia. A neural network model with a gliotransmission-mediated ambient GABA regulatory mechanism was simulated. In the network, interneuron-to-glial-cell and principal-cell-to-glial-cell synaptic contacts were made. The former hyperpolarized glial cells and let their transporters import (remove) GABA from the extracellular space, thereby lowering ambient GABA concentration, reducing extrasynaptic GABAa receptor-mediated tonic inhibitory current, and thus exciting principal cells. In contrast, the latter depolarized the glial cells and let the transporters export GABA into the extracellular space, thereby elevating the ambient GABA concentration and thus inhibiting the principal cells. A reduction in ambient GABA concentration was assumed for a schizophrenia network. Multiple dynamic cell assemblies were organized as sensory feature columns. Each cell assembly responded to one specific feature stimulus. The tuning performance of the network to an applied feature stimulus was evaluated in relation to the level of ambient GABA. Transporter-deficient glial cells caused a deficit in GABAergic gliotransmission and reduced ambient GABA concentration, which markedly deteriorated the tuning performance of the network, broadening the sensory tuning. Interestingly, the GABAergic gliotransmission mechanism could regulate local ambient GABA levels: it augmented ambient GABA around stimulus-irrelevant principal cells, while reducing ambient GABA around stimulus-relevant principal cells, thereby ensuring their selective responsiveness to the applied stimulus. We suggest that a deficit in GABAergic gliotransmission may cause a reduction in ambient GABA concentration, leading to a broadening of sensory tuning in schizophrenia. The GABAergic gliotransmission mechanism proposed here may have an important role in the

  7. BMP4 signaling is involved in the generation of inner ear sensory epithelia

    Directory of Open Access Journals (Sweden)

    Wang Yucheng

    2005-08-01

    Full Text Available Abstract Background The robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments. Results Here we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation. Conclusion Our results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia.

  8. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    Science.gov (United States)

    Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Campbell, Laura; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

    2015-01-01

    The skin of an adult human contains approximately 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All non-recirculating resident memory T cells (TRM) expressed CD69, but the majority were CD4+, CD103− and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions and had a limited proliferative capacity compared to CD103− TRM. TRM of both types had more potent effector functions than recirculating T cells. Induction of CD103 on human T cells was enhanced by keratinocyte contact, depended on TGFβ and was independent of T cell keratinocyte adhesive interactions. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin− T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions and TMM were depleted more slowly from skin after alemtuzumab, suggesting TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. PMID:25787765

  9. Msx1 and Msx2 are expressed in sub-populations of vascular smooth muscle cells.

    Science.gov (United States)

    Goupille, Olivier; Saint Cloment, Cécile; Lopes, Miguel; Montarras, Didier; Robert, Benoît

    2008-08-01

    Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze the expression of these homeogenes in the adult mouse. We observed that Msx genes are prominently expressed in a subset of blood vessels. The Msx2nlacZ allele is mainly expressed in a restricted population of mural cells in peripheral arteries and veins. Msx1nlacZ is expressed to a lesser extent by vascular smooth muscle cells of peripheral arteries, but is highly expressed in arterioles and capillaries, making Msx1 a novel marker for a subpopulation of pericytes. Expression is set up early in developing vessels and maintained throughout life. In addition, expression of both genes is observed in a few endothelial cells of the aorta at fetal stages, and only Msx2 continues to be expressed in this layer at the adult stage. These results suggest major functions for Msx genes in vascular mural cell formation and remodeling. Copyright (c) 2008 Wiley-Liss, Inc.

  10. Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

    Science.gov (United States)

    Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

    2017-03-01

    Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Sensory overload: A concept analysis.

    Science.gov (United States)

    Scheydt, Stefan; Müller Staub, Maria; Frauenfelder, Fritz; Nielsen, Gunnar H; Behrens, Johann; Needham, Ian

    2017-04-01

    In the context of mental disorders sensory overload is a widely described phenomenon used in conjunction with psychiatric interventions such as removal from stimuli. However, the theoretical foundation of sensory overload as addressed in the literature can be described as insufficient and fragmentary. To date, the concept of sensory overload has not yet been sufficiently specified or analyzed. The aim of the study was to analyze the concept of sensory overload in mental health care. A literature search was undertaken using specific electronic databases, specific journals and websites, hand searches, specific library catalogues, and electronic publishing databases. Walker and Avant's method of concept analysis was used to analyze the sources included in the analysis. All aspects of the method of Walker and Avant were covered in this concept analysis. The conceptual understanding has become more focused, the defining attributes, influencing factors and consequences are described and empirical referents identified. The concept analysis is a first step in the development of a middle-range descriptive theory of sensory overload based on social scientific and stress-theoretical approaches. This specification may serve as a fundament for further research, for the development of a nursing diagnosis or for guidelines. © 2017 Australian College of Mental Health Nurses Inc.

  12. Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography.

    Science.gov (United States)

    Thunemann, Martin; Schörg, Barbara F; Feil, Susanne; Lin, Yun; Voelkl, Jakob; Golla, Matthias; Vachaviolos, Angelos; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Olbrich, Marcus; Ehrlichmann, Walter; Reischl, Gerald; Griessinger, Christoph M; Langer, Harald F; Gawaz, Meinrad; Lang, Florian; Schäfers, Michael; Kneilling, Manfred; Pichler, Bernd J; Feil, Robert

    2017-09-05

    Many pathophysiological processes are associated with proliferation, migration or death of distinct cell populations. Monitoring specific cell types and their progeny in a non-invasive, longitudinal and quantitative manner is still challenging. Here we show a novel cell-tracking system that combines Cre/lox-assisted cell fate mapping with a thymidine kinase (sr39tk) reporter gene for cell detection by positron emission tomography (PET). We generate Rosa26-mT/sr39tk PET reporter mice and induce sr39tk expression in platelets, T lymphocytes or cardiomyocytes. As proof of concept, we demonstrate that our mouse model permits longitudinal PET imaging and quantification of T-cell homing during inflammation and cardiomyocyte viability after myocardial infarction. Moreover, Rosa26-mT/sr39tk mice are useful for whole-body characterization of transgenic Cre mice and to detect previously unknown Cre activity. We anticipate that the Cre-switchable PET reporter mice will be broadly applicable for non-invasive long-term tracking of selected cell populations in vivo.Non-invasive cell tracking is a powerful method to visualize cells in vivo under physiological and pathophysiological conditions. Here Thunemann et al. generate a mouse model for in vivo tracking and quantification of specific cell types by combining a PET reporter gene with Cre-dependent activation that can be exploited for any cell population for which a Cre mouse line is available.

  13. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages.

    Science.gov (United States)

    Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J; Fernandez, Anne

    2008-04-01

    Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal beta III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.

  14. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages

    International Nuclear Information System (INIS)

    Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J.; Fernandez, Anne

    2008-01-01

    Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal β III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders

  15. Microbiological, chemical, and sensory changes in irradiated pico de gallo

    International Nuclear Information System (INIS)

    Howard, L.R.; Miller, G.H. Jr.; Wagner, A.B.

    1995-01-01

    The effects of gamma processing (1 kGy) and refrigerated storage (2 degrees C) on microbiological, sensory, and chemical quality of pico de gallo was studied. Color, flavor, texture, odor, and heat sensory attributes were not affected by radiation treatment. The treatment decreased populations of aerobic mesophilic, heterofermentative, and total lactic microflora during storage. L-ascorbic acid content declined 50% in response to gamma processing, but levels were similar in irradiated and non-irradiated samples after 6 wk. Pectin solubility was affected by radiation treatment. Gamma processing caused a reduction in pectin degree of estenfication, and conversion of chelator soluble to dilute alkali soluble and nonextractable pectins

  16. Response of Listeria monocytogenes to disinfection stress at the single-cell and population levels as monitored by intracellular pH measurements and viable-cell counts

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Nielsen, Dennis S.; Arneborg, Nils

    2009-01-01

    of the bacterium. In situ analyses of Listeria monocytogenes single cells were performed during exposure to different concentrations of the disinfectant Incimaxx DES to study a possible population subdivision. Bacterial survival was quantified with plate counting and disinfection stress at the single-cell level...... by measuring intracellular pH (pHi) over time by fluorescence ratio imaging microscopy. pHi values were initially 7 to 7.5 and decreased in both attached and planktonic L. monocytogenes cells during exposure to sublethal and lethal concentrations of Incimaxx DES. The response of the bacterial population...... was homogenous; hence, subpopulations were not detected. However, pregrowth with NaCl protected the planktonic bacterial cells during disinfection with Incimaxx (0.0015%) since pHi was higher (6 to 6.5) for the bacterial population pregrown with NaCl than for cells grown without NaCl (pHi 5 to 5.5) (P

  17. Decoherence in yeast cell populations and its implications for genome-wide expression noise.

    Science.gov (United States)

    Briones, M R S; Bosco, F

    2009-01-20

    Gene expression "noise" is commonly defined as the stochastic variation of gene expression levels in different cells of the same population under identical growth conditions. Here, we tested whether this "noise" is amplified with time, as a consequence of decoherence in global gene expression profiles (genome-wide microarrays) of synchronized cells. The stochastic component of transcription causes fluctuations that tend to be amplified as time progresses, leading to a decay of correlations of expression profiles, in perfect analogy with elementary relaxation processes. Measuring decoherence, defined here as a decay in the auto-correlation function of yeast genome-wide expression profiles, we found a slowdown in the decay of correlations, opposite to what would be expected if, as in mixing systems, correlations decay exponentially as the equilibrium state is reached. Our results indicate that the populational variation in gene expression (noise) is a consequence of temporal decoherence, in which the slow decay of correlations is a signature of strong interdependence of the transcription dynamics of different genes.

  18. Wortmannin efficiently suppresses the recovery from radiation-induced damage in pimonidazole-unlabeled quiescent tumor cell population

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Ono, Koji; Sakurai, Yoshinori; Tanaka, Hiroki; Maruhashi, Akira

    2013-01-01

    Labeling of proliferating (P) cells in mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2'-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after pimonidazole administration followed by caffeine or wortmannin treatment. Twenty-four hours later, assessment of the responses of quiescent (Q) and total (=P+Q) cell populations were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. The pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using an assay performed 24 hours after irradiation, was more clearly observed in Q cells than total cells. In both the pimonidazole-unlabeled and the whole cell fractions, wortmannin efficiently suppressed the reduction in sensitivity due to delayed assay. Wortmannin combined with γ-ray irradiation is useful for suppressing the recovery from radiation-induced damage especially in the pimonidazole-unlabeled cell fraction within the total and Q tumor cell populations. (author)

  19. The beauty of sensory ecology.

    Science.gov (United States)

    Otálora-Luna, Fernando; Aldana, Elis

    2017-08-10

    Sensory ecology is a discipline that focuses on how living creatures use information to survive, but not to live. By trans-defining the orthodox concept of sensory ecology, a serious heterodox question arises: how do organisms use their senses to live, i.e. to enjoy or suffer life? To respond to such a query the objective (time-independent) and emotional (non-rational) meaning of symbols must be revealed. Our program is distinct from both the neo-Darwinian and the classical ecological perspective because it does not focus on survival values of phenotypes and their functions, but asks for the aesthetic effect of biological structures and their symbolism. Our message recognizes that sensing apart from having a survival value also has a beauty value. Thus, we offer a provoking and inspiring new view on the sensory relations of 'living things' and their surroundings, where the innovating power of feelings have more weight than the privative power of reason.

  20. Sensory analysis in grapes benitaka

    Energy Technology Data Exchange (ETDEWEB)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  1. Sensory analysis in grapes benitaka

    International Nuclear Information System (INIS)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H.

    2011-01-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  2. Population pharmacokinetics of hydroxyurea for children and adolescents with sickle cell disease.

    Science.gov (United States)

    Wiczling, Paweł; Liem, Robert I; Panepinto, Julie A; Garg, Uttam; Abdel-Rahman, Susan M; Kearns, Gregory L; Neville, Kathleen A

    2014-09-01

    The objective of this study was to develop a population pharmacokinetic (PK) model sufficient to describe hydroxyurea (HU) concentrations in serum and urine following oral drug administration in pediatric patients with sickle cell disease. Additionally, the measured hydroxyurea concentrations for particular sampling time were correlated with exposure measures (AUC) to find the most predictive relationship. Hydroxyurea concentrations were determined in 21 subjects. Using a population nonlinear mixed-effect modeling, the HU PK was best described by a one-compartment model with two elimination pathways (metabolic and renal) and a transit compartment absorption. The typical mean absorption time was 0.222 hour. The typical apparent volume of distribution was 21.8 L and the apparent systemic clearance was 6.88 L/h for an average weight patient of 30.7 kg. The 50% of the HU dose was renally excreted. Linear correlations were apparent between the plasma HU concentration at 1, 1.5, 2, 4, and 6 hours post-dose and AUC with the most significant (R(2)  = 0.71) observed at 1.5 hours. A population PK model was successful in describing HU disposition in plasma and urine. Data from the model also demonstrated that HU plasma concentrations at 1.5 hours after an oral dose of the drug were highly predictive of systemic drug exposure. © 2014, The American College of Clinical Pharmacology.

  3. Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

    Science.gov (United States)

    Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

    2016-01-28

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

  4. Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.

    Science.gov (United States)

    Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong

    2017-02-21

    Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.

  5. Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure.

    Directory of Open Access Journals (Sweden)

    Sophie Roetynck

    Full Text Available Multiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.We developed polychromatic flow cytometry antibody panels for immunophenotyping the major CD4 T cell subsets as well as broadly characterizing the functional profiles of the CD4 T cells in peripheral blood. We then validated these assays by conducting a pilot study comparing CD4 T cell responses in distinct populations of healthy adults living in either rural or urban Kenya. This study revealed that the expression profile of CD4 T cell activation and memory markers differed significantly between African and European donors but was similar amongst African individuals from either rural or urban areas. Adults from rural Kenya had, however, higher frequencies and greater polyfunctionality among cytokine producing CD4 T cells compared to both urban populations, particularly for "Th1" type of response. Finally, endemic exposure to malaria in rural Kenya may have influenced the expansion of few discrete CD4 T cell populations with specific functional signatures.These findings suggest that environmentally driven T cell activation does not drive the dysfunction of CD4 T cells but is rather associated with greater magnitude and quality of CD4 T cell response, indicating that the level or type of microbial exposure and antigenic experience may influence and shape the functionality of CD4 T cell compartment. Our data confirm that it is possible and mandatory to assess multiple functional attributes of CD4 T cell response in the context of infection.

  6. Statin use and peripheral sensory perception: a pilot study.

    Science.gov (United States)

    West, Brenton; Williams, Cylie M; Jilbert, Elise; James, Alicia M; Haines, Terry P

    2014-06-01

    Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183). This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.

  7. Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia.

    Science.gov (United States)

    Bartley, Angela N; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J; Buckmeier, Julie A; Corley, Lynda; Phipps, Ron A; Gallick, Gary; Lance, Peter; Thompson, Patricia A; Hamilton, Stanley R

    2013-11-01

    Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma ("recurrence"), has not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1-labeling indices (ALI) were similar across patient characteristics and in advanced and nonadvanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (P = 0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (P = 0.03). A best-fit algorithm-based cutoff point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem cell target for chemoprevention. ©2013 AACR

  8. Quantitative gene expression profiling of CD45+ and CD45- skeletal muscle-derived side population cells

    DEFF Research Database (Denmark)

    Ditte Caroline Andersen, Ditte Caroline; Kristiansen, Gitte Qvist; Jensen, Line

    2012-01-01

    The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we desc...... a satellite cell subpopulation) remain in the mSPCD45(-) fraction, and we show that these cells express high levels of many of the known myogenic precursor/stem cell related markers, including Pax7 and Myf5.......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

  9. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

    2009-01-01

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

  10. Structure and development of the saccular sensory epithelium in ...

    African Journals Online (AJOL)

    Structure and development of the saccular sensory epithelium in relation to otolith growth in the perch Perca fluviatilis (Telostei) ... Electron microscopy indicated: 1) The apical surface of each hair cell is covered with a ciliary bundle which varies in length in different epithelial regions. Each bundle is formed from a long ...

  11. Geographic Clusters of Basal Cell Carcinoma in a Northern California Health Plan Population.

    Science.gov (United States)

    Ray, G Thomas; Kulldorff, Martin; Asgari, Maryam M

    2016-11-01

    Rates of skin cancer, including basal cell carcinoma (BCC), the most common cancer, have been increasing over the past 3 decades. A better understanding of geographic clustering of BCCs can help target screening and prevention efforts. Present a methodology to identify spatial clusters of BCC and identify such clusters in a northern California population. This retrospective study used a BCC registry to determine rates of BCC by census block group, and used spatial scan statistics to identify statistically significant geographic clusters of BCCs, adjusting for age, sex, and socioeconomic status. The study population consisted of white, non-Hispanic members of Kaiser Permanente Northern California during years 2011 and 2012. Statistically significant geographic clusters of BCC as determined by spatial scan statistics. Spatial analysis of 28 408 individuals who received a diagnosis of at least 1 BCC in 2011 or 2012 revealed distinct geographic areas with elevated BCC rates. Among the 14 counties studied, BCC incidence ranged from 661 to 1598 per 100 000 person-years. After adjustment for age, sex, and neighborhood socioeconomic status, a pattern of 5 discrete geographic clusters emerged, with a relative risk ranging from 1.12 (95% CI, 1.03-1.21; P = .006) for a cluster in eastern Sonoma and northern Napa Counties to 1.40 (95% CI, 1.15-1.71; P Costa and west San Joaquin Counties, compared with persons residing outside that cluster. In this study of a northern California population, we identified several geographic clusters with modestly elevated incidence of BCC. Knowledge of geographic clusters can help inform future research on the underlying etiology of the clustering including factors related to the environment, health care access, or other characteristics of the resident population, and can help target screening efforts to areas of highest yield.

  12. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

    Energy Technology Data Exchange (ETDEWEB)

    Santamaria-Martinez, Albert [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat de Barcelona, Barcelona (Spain); Barquinero, Jordi [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Banc de Sang i Teixits, Barcelona (Spain); Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Seoane, Joan [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Medical Oncology program, Vall d' Hebron Institute of Oncology, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Poupon, Marie-France [Institut Curie, Paris (France); Morote, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Servei d' Urologia. Hospital Vall d' Hebron, Barcelona (Spain); Reventos, Jaume [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Munell, Francina, E-mail: fmunell@ir.vhebron.net [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain)

    2009-10-15

    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  13. A Multisampling Reporter System for Monitoring MicroRNA Activity in the Same Population of Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chen Huang

    2009-01-01

    Full Text Available MicroRNAs (miRNAs downregulate gene expression by binding to the partially complementary sites in the 3′ untranslated region (UTR of target mRNAs. Several methods, such as Northern blot analysis, quantitative real-time RT-PCR, microarray, and the luciferase reporter system, are commonly used to quantify the relative level or activity of miRNAs. The disadvantage of these methods is the requirement for cell lysis, which means that several sets of wells/dishes of cells must be prepared to monitor changes in miRNA activity in time-course studies. In this study, we developed a multisampling reporter system in which two secretable bioluminescence-generating enzymes are employed, one as a reporter and the other as an internal control. The reporters consist of a pair of vectors containing the Metridia luciferase gene, one with and one without a duplicated miRNA targeting sequence at their 3′UTR, while the other vector coding for the secreted alkaline phosphatase gene is used as an internal control. This method allows miRNA activity to be monitored within the same population of cells over time by withdrawing aliquots of the culture medium. The practicability and benefits of this system are addressed in this report.

  14. Estimation of the target stem-cell population size in chronic myeloid leukemogenesis

    International Nuclear Information System (INIS)

    Radivoyevitch, T.; Ramsey, M.J.; Tucker, J.D.

    1999-01-01

    Estimation of the number of hematopoietic stem cells capable of causing chronic myeloid leukemia (CML) is relevant to the development of biologically based risk models of radiation-induced CML. Through a comparison of the age structure of CML incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program and the age structure of chromosomal translocations found in healthy subjects, the number of CML target stem cells is estimated for individuals above 20 years of age. The estimation involves three steps. First, CML incidence among adults is fit to an exponentially increasing function of age. Next, assuming a relatively short waiting time distribution between BCR-ABL induction and the appearance of CML, an exponential age function with rate constants fixed to the values found for CML is fitted to the translocation data. Finally, assuming that translocations are equally likely to occur between any two points in the genome, the parameter estimates found in the first two steps are used to estimate the number of target stem cells for CML. The population-averaged estimates of this number are found to be 1.86 x 10 8 for men and 1.21 x 10 8 for women; the 95% confidence intervals of these estimates are (1.34 x 10 8 , 2.50 x 10 8 ) and (0.84 x 10 8 , 1.83 x 10 8 ), respectively. (orig.)

  15. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

    Science.gov (United States)

    Arnold, Julia; Barcena de Arellano, Maria L; Rüster, Carola; Vercellino, Giuseppe F; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

    2012-01-01

    To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Activation of Six1 Expression in Vertebrate Sensory Neurons.

    Directory of Open Access Journals (Sweden)

    Shigeru Sato

    Full Text Available SIX1 homeodomain protein is one of the essential key regulators of sensory organ development. Six1-deficient mice lack the olfactory epithelium, vomeronasal organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor neural differentiation in the distal part of the cranial ganglia. Simultaneous loss of both Six1 and Six4 leads to additional abnormalities such as small trigeminal ganglion and abnormal dorsal root ganglia (DRG. The aim of this study was to understand the molecular mechanism that controls Six1 expression in sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we focused on the sensory ganglia-specific Six1 enhancer (Six1-8 conserved between chick and mouse. In vivo reporter assays using both animals identified an important core region comprising binding consensus sequences for several transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU homeodomain and basic-helix-loop-helix proteins. The results provided information on upstream factors and signals potentially relevant to Six1 regulation in sensory neurons. We also report the establishment of a new transgenic mouse line (mSix1-8-NLSCre that expresses Cre recombinase under the control of mouse Six1-8. Cre-mediated recombination was detected specifically in ISL1/2-positive sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination in SOX10-positive glial cells and central nervous system and ability to induce recombination in a subset of neurons derived from the olfactory placode/epithelium. This mouse model can be potentially used to advance research on sensory development.

  17. Hyperthermic survival of Chinese hamster ovary cells as a function of cellular population density at the time of plating

    International Nuclear Information System (INIS)

    Highfield, D.P.; Holahan, E.V.; Holahan, P.K.; Dewey, W.C.

    1984-01-01

    The survival of synchronous G 1 or asynchronous Chinese hamster ovary cells in vitro to heat treatment may depend on the cellular population density at the time of heating and/or as the cells are cultured after heating. The addition of lethally irradiated feeder cells may increase survival at 10 -3 by as much as 10- to 100-fold for a variety of conditions when cells are heated either in suspension culture or as monolayers with or without trypsinization. The protective effect associated with feeder cells appears to be associated with close cell-to-cell proximity. However, when cells are heated without trypsinization about 24 hr or later after plating, when adaptation to monolayer has occurred, the protective effect is reduced; i.e., addition of feeder cells enhances survival much less, for example, about 2- to 3-fold at 10 -2 -10 -3 survival. Also, the survival of a cell to heat is independent of whether the neighboring cell in a microcolony is destined to live or die. Finally, if protective effects associated with cell density do occur and are not controlled, serious artifacts can result as the interaction of heat and radiation is studied; for example, survival curves can be moved upward, and thus changed in shape as the number of cells plated is increased with an increase in the hyperthermic treatment or radiation dose following hyperthermia. Therefore, to understand mechanisms and to obtain information relevant to populations of cells in close proximity, such as those in vivo, these cellular population density effects should be considered and understood

  18. Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lecourt, Severine, E-mail: severine.lecourt@sls.aphp.fr [UPMC/AIM UMR S 974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); INSERM U974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); CNRS UMR 7215, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Marolleau, Jean-Pierre, E-mail: Marolleau.Jean-Pierre@chu-amiens.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); CHU Amiens Hopital Sud, Service d' Hematologie Clinique, UPJV, Amiens (France); Fromigue, Olivia, E-mail: olivia.fromigue@larib.inserm.fr [INSERM U606, Universite Paris 07, Hopital Lariboisiere, Paris (France); Vauchez, Karine, E-mail: k.vauchez@institut-myologie.org [UPMC/AIM UMR S 974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); INSERM U974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); CNRS UMR 7215, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Genzyme S.A.S., Saint-Germain en Laye (France); Andriamanalijaona, Rina, E-mail: rinandria@yahoo.fr [Laboratoire de Biochimie des Tissus Conjonctifs, Faculte de Medecine, Caen (France); Ternaux, Brigitte, E-mail: brigitte.ternaux@orange.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Lacassagne, Marie-Noelle, E-mail: mnlacassagne@free.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Robert, Isabelle, E-mail: isa-robert@hotmail.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Boumediene, Karim, E-mail: karim.boumediene@unicaen.fr [Laboratoire de Biochimie des Tissus Conjonctifs, Faculte de Medecine, Caen (France); Chereau, Frederic, E-mail: fchereau@pervasistx.com [Myosix S.A., Saint-Germain en Laye (France); Marie, Pierre, E-mail: pierre.marie@larib.inserm.fr [INSERM U606, Universite Paris 07, Hopital Lariboisiere, Paris (France); and others

    2010-09-10

    Human skeletal muscle is an essential source of various cellular progenitors with potential therapeutic perspectives. We first used extracellular markers to identify in situ the main cell types located in a satellite position or in the endomysium of the skeletal muscle. Immunohistology revealed labeling of cells by markers of mesenchymal (CD13, CD29, CD44, CD47, CD49, CD62, CD73, CD90, CD105, CD146, and CD15 in this study), myogenic (CD56), angiogenic (CD31, CD34, CD106, CD146), hematopoietic (CD10, CD15, CD34) lineages. We then analysed cell phenotypes and fates in short- and long-term cultures of dissociated muscle biopsies in a proliferation medium favouring the expansion of myogenic cells. While CD56{sup +} cells grew rapidly, a population of CD15{sup +} cells emerged, partly from CD56{sup +} cells, and became individualized. Both populations expressed mesenchymal markers similar to that harboured by human bone marrow-derived mesenchymal stem cells. In differentiation media, both CD56{sup +} and CD15{sup +} cells shared osteogenic and chondrogenic abilities, while CD56{sup +} cells presented a myogenic capacity and CD15{sup +} cells presented an adipogenic capacity. An important proportion of cells expressed the CD34 antigen in situ and immediately after muscle dissociation. However, CD34 antigen did not persist in culture and this initial population gave rise to adipogenic cells. These results underline the diversity of human muscle cells, and the shared or restricted commitment abilities of the main lineages under defined conditions.

  19. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  20. Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS Imaging and Quantification from Cell Populations with LC/MS/MS.

    Science.gov (United States)

    Newman, Carla F; Havelund, Rasmus; Passarelli, Melissa K; Marshall, Peter S; Francis, Ian; West, Andy; Alexander, Morgan R; Gilmore, Ian S; Dollery, Colin T

    2017-11-21

    ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.

  1. Sensory processing and cognitive development of preterm and full term infants

    Directory of Open Access Journals (Sweden)

    Flávia Regina Ribeiro Cavalcanti Buffone

    2016-10-01

    Full Text Available Introduction: Current studies show the repercussion of sensory processing disorder in infant neurodevelopment. Little is known about the influence of these disorders in the infant’s cognitive development, however, it is known that they negatively interfere on daily life activities and remain during life course. Objective:To evaluate the relationship between sensory processing and cognitive development in infants and the association between prematurity and sensory processing in this population. Method: This is a cross-sectional study conducted in the Childcare Outpatient Department of the Hospital das Clínicas, Federal Universidade de Pernambuco, from December 2009 to August 2010. The sample consisted of 182 infants from 8 to 15 months, of which 54 (29.7% were born preterm with the prematurity age correction made to 40 weeks of gestational age. We used the Test of Sensory Functions in Infants (TSFI to evaluate the sensory processing and the Bayley Scales of Infant and Toddler Development III to assess cognitive development. Results: There was a significantly higher frequency of at risk and deficient sensory processing among preterm infants (37% when compared to term infants (21.9%. Cognitive delay was significantly higher (8.3% in infants with at risk and deficient sensory processing when compared to those with normal sensory processing (1.5%. Conclusion: Prematurity was a risk factor for sensory processing disorder, and infants diagnosed with this disorder showed cognitive delay more frequently. Prematurity alone was not associated with cognitive delay.

  2. Multi-sensory Sculpting (MSS)

    DEFF Research Database (Denmark)

    von Wallpach, Sylvia; Kreuzer, Maria

    2013-01-01

    -conscious and modality-specific level and use multi-sensory metaphors to express embodied knowledge. Retrieving embodied brand knowledge requires methods that (a) stimulate various senses that have been involved in brand knowledge formation and (b) give consumers the opportunity to express themselves metaphorically...

  3. Effect of normal and tumor factors on different phases of cell populations cycle.

    Science.gov (United States)

    Inda, A M; García, A L; Errecalde, A L; Badrán, A F

    1999-12-01

    In the present experiments we studied the effect of extracts from intact liver (LE), ES2 tumor extract (TE), plasmas from intact mice (PI), and from tumor bearing animals (PT) on different phases of hepatocytes and renocytes cell cycles. C3HS 28-day-old male mice, standardized for periodicity analysis, were injected at 16:00 hours and killed every 4 hours during a circadian cycle at 20:00/04; 00:00/08; 04:00/12; 08:00/16; 12:00/20 and 16:00/24 (time of day/hours post treatment). Colchicine (2 microg/g) was injected 4 hours before killing them. Samples of livers and kidneys were processed for histology and mitotic index determinations. The results were expressed as colchicine arrested metaphases per 1000 nuclei. The TE, LE and PI had a promoting effect on the mitotic activity of hepatocytes during the first 12 hours post treatment. During the subsequent 12 hours, not only these treatments but also the PI had an inhibiting effect on the mitotic activity of the same cell population. Also the TE and the PT had a promoting effect on the mitotic activity of the renocytes during the first 12 hours while the effect of all treatments showed a clear inhibition of the mitotic activity studied during the last 12 hours. Taking into account the time elapsed between the injections and the measurements made in these light-dark synchronized animals, we conclude that the increase in mitotic index observed in those tissues stemmed from a reinitiation of cell-cycle traverse in a subpopulation of G2-arrested, noncycling cells.

  4. Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population.

    Science.gov (United States)

    Ren, Hao-Yu; Khera, Amit; de Lemos, James A; Ayers, Colby R; Rohatgi, Anand

    2017-09-01

    Cell adhesion molecules are key regulators of atherosclerotic plaque development, but circulating levels of soluble fragments, such as intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1), have yielded conflicting associations with atherosclerotic cardiovascular disease (ASCVD). Endothelial cell-selective adhesion molecule (ESAM) is expressed exclusively in platelets and endothelial cells, and soluble ESAM (sESAM) levels have been associated with prevalent subclinical atherosclerosis. We therefore hypothesized that sESAM would be associated with incident ASCVD. sESAM, sICAM-1, and sVCAM-1 were measured in 2,442 participants without CVD in